Search Results (187)

Background/Objectives: A newly developed nine-protein serum signature has been utilized to enhance the accuracy of an existing three-protein signature used as a blood-based diagnostic tool. This study used the new nine-protein serum signature to evaluate the clinical sensitivity and specificity of a medical device designed to test the clinical performance of an artificial intelligence algorithm. Methods: A blood-based test using multiple reaction monitoring via mass spectrometry was performed to quantify nine proteins (APOC1, CHL1, FN1, VWF, PPBP, CLU, PRDX6, PRG4, and MMP9) in serum samples from 243 healthy controls and 222 patients with breast cancer. Results: Based on cutoff values determined by an artificial intelligence-based deep learning model, the sensitivity and specificity of the nine-protein signature in diagnosing breast cancer among all participants was 83.3% and 88.1%, respectively, whereas those of the three-protein signature were 71.6% and 85.3%, respectively. The assay yielded a positive predictive value of 86.5% for breast cancer and 13.6% for healthy controls, with corresponding negative predictive values of 14.7% and 85.3%, respectively. The accuracies of nine- and three-protein signatures were 85.8% (area under the receiver operating characteristic curve: 0.8526) and 77.0%, respectively. Conclusions: The nine-protein signature may help detect breast cancer more accurately and effectively than the three-protein signature. Full article

Objective: This study aims to identify clinically relevant lactylation-related biomarkers in chronic obstructive pulmonary disease (COPD) and investigate their potential mechanistic roles in COPD pathogenesis. Methods: Differentially expressed genes (DEGs) were identified from the GSE21359 dataset, followed by weighted gene co-expression network analysis (WGCNA) to detect COPD-associated modules. Least absolute shrinkage and selection operator (LASSO) regression and support vector machine–recursive feature elimination (SVM–RFE) algorithms were applied to screen lactylation-related biomarkers, with diagnostic performance evaluated through the ROC curve. Candidates were validated in the GSE76925 dataset for expression and diagnostic robustness. Immune cell infiltration patterns were exhibited using EPIC deconvolution. Single-cell transcriptomics (from GSE173896) were processed via the ‘Seurat’ package encompassing quality control, dimensionality reduction, and cell type annotation. Cell-type-specific markers and intercellular communication networks were delineated using the ‘FindAllMarkers’ package and the ‘CellChat’ R package, respectively. In vitro validation was conducted using a cigarette smoke extract (CSE)-induced COPD model. Results: Integrated transcriptomic approaches and multi-algorithm screening (LASSO/Boruta/SVM–RFE) revealed carbonyl reductase 1 (CBR1) and peroxiredoxin 1 (PRDX1) as core COPD biomarkers enriched in oxidation–reduction and inflammatory pathways, with high diagnostic accuracy (AUC > 0.85). Immune profiling and scRNA-seq delineated macrophage and cancer-associated fibroblasts (CAFs) infiltration with oxidative-redox transcriptional dominance in COPD. CBR1 was significantly upregulated in T cells, neutrophils, and mast cells; and PRDX1 showed significant upregulation in endothelial, macrophage, and ciliated cells. Experimental validation in CSE-induced models confirmed significant upregulation of both biomarkers via transcription PCR (qRT-PCR) and immunofluorescence. Conclusions: CBR1 and PRDX1 are lactylation-associated diagnostic markers, with lactylation-driven redox imbalance implicated in COPD progression. Full article

Oxidative stress (OS), defined as an imbalance between pro-oxidant and antioxidant mechanisms, contributes to DNA and protein oxidation as well as cellular injury, and plays a pivotal role in the pathogenesis of chronic kidney disease (CKD). Peroxiredoxins (PRDXs) are key antioxidant enzymes that regulate intracellular peroxide levels and maintain redox homeostasis. Beyond its renal implications, OS is closely intertwined with hypertension and atherosclerosis, both common comorbidities that accelerate CKD progression. As previously reported, serum concentrations of PRDXs 1-5 may help to differentiate between IgA nephropathy (IgAN), membranous nephropathy (MN), and lupus nephritis (LN). This study aimed to assess the utility of baseline serum PRDX levels in predicting longitudinal changes in kidney function and proteinuria in patients with IgAN, MN, and LN. We analyzed data from 80 patients (IgAN, n = 36; MN, n = 23; LN, n = 21) drawn from an initial cohort of 108 in whom baseline serum concentrations of PRDX 1–5 were measured. Patients were stratified into low, medium, and high PRDX level groups at baseline, and associations between these strata and longitudinal changes in eGFR and proteinuria were assessed over a follow-up period of up to five years. Across all groups, the follow-up eGFR was significantly associated with low baseline serum PRDX 1, 2, 3, and 5 (p = 0.043; p = 0.001; p = 0.036; p = 0.007, respectively). Significant associations were also observed between 24 h follow-up proteinuria and low baseline serum PRDX 2, 3, and 5 (p = 0.025; p = 0.025; p = 0.005, respectively), medium PRDX 4 (p = 0.010), and high PRDX 2 (p = 0.019). No significant associations were found within the study groups; however, these associations were more pronounced in IgAN and MN patients. These findings suggest a potential role for PRDXs in predicting and monitoring CKD progression, especially eGFR decline. Full article

Carassius auratus exhibits significant physiological and behavioral alterations under the combined stress of temperature and dissolved oxygen (DO) fluctuations, which are common challenges in aquaculture. In this investigation, we employed controlled thermal and DO gradients to characterize the multidimensional response profile of this species. The key findings revealed that thermal elevation profoundly influenced blood glucose and cortisol concentrations. Notably, exposure to hyperoxic conditions markedly attenuated stress responses relative to hypoxia at equivalent temperatures: cortisol levels were significantly suppressed (reductions of 60.11%, 118.06%, and 34.72%), while blood glucose levels exhibited concurrent increases (16.42%, 26.43%, and 26.34%). Distinctive behavioral patterns, including floating head behavior, surface swimming behavior, and rollover behavior, were identified as indicative behaviors of thermal–oxygen stress. Molecular analysis demonstrated the upregulated expression of stress-associated genes (HSP70, HSP90, HIF-1α, and Prdx3), which correlated temporally with elevated cortisol and glucose concentrations and the manifestation of stress behaviors. Furthermore, a muscle texture assessment indicated that increased DO availability mitigated the textural deterioration induced by heat stress. Collectively, this work establishes an authentic biomarker framework, providing crucial threshold parameters essential for the development of intelligent, real-time environmental monitoring and dynamic regulation systems to enhance climate-resilient aquaculture management. Full article

Based on the limited hepatic hydroxylation efficiency of dietary VD3 in teleosts and the superior bioavailability of its metabolite, 25(OH)D3, this study investigated the regulatory mechanisms of dietary 25(OH)D3 supplementation in yellow catfish—an economically significant species lacking prior nutritional data on this metabolite. A total of 360 fish were divided into three groups—control (basal diet), VD3 (2500 IU/kg VD3), and 25(OH)D3 (2500 IU/kg 25(OH)D3)—and fed for 8 weeks. Compared to the control, both supplemented groups showed elevated superoxide dismutase (SOD), total antioxidant capacity (T-AOC), catalase (CAT), and transforming growth factor-β (TGF-β) activities, alongside reduced malondialdehyde (MDA), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels. The 25(OH)D3 group exhibited higher T-AOC and CAT activities and lower TNF-α than the VD3 group. Metabolomic and transcriptomic analyses identified 65 differentially expressed metabolites (DEMs) and 3515 differentially expressed genes (DEGs). Enrichment analysis indicated that the DEMs (e.g., indole compounds, organic acids, aldosterone, L-kynurenine) and DEGs (pgd, mthfr, nsdhl, nox5, prdx2, mpx, itih2, itih3, eprs1) that were highly and significantly expressed in the 25(OH)D3 group were primarily associated with antioxidant defense and inflammatory responses. Dietary 25(OH)D3 was more effective than VD3 in promoting antioxidant capacity and modulating inflammation in yellow catfish. Full article

Background: Varicocele is a common condition involving the dilation of veins in the scrotum, often linked to male infertility and testicular dysfunction. This study aimed to elucidate the molecular effects of successful varicocele treatment on sperm proteomes following percutaneous sclero-embolization. Methods: High-resolution tandem mass spectrometry was performed for proteomic profiling of pooled sperm lysates from five patients exhibiting improved semen parameters before and after (3 and 6 months) varicocele sclero-embolization. Data were validated by Western blot analysis. Results: Seven proteins were found exclusively in varicocele patients before surgery—such as stathmin, IFT20, selenide, and ADAM21—linked to inflammation and oxidative stress. After sclero-embolization, 55 new proteins emerged, including antioxidant enzymes like selenoprotein P and GPX3. Thioredoxin (TXN) and peroxiredoxin (PRDX3) were upregulated, indicating restoration of key antioxidant pathways. Additionally, the downregulation of some histones and the autophagy-related protein ATG9A suggests a shift toward an improved chromatin organization and a healthier cellular environment post-treatment. Conclusions: Varicocele treatment that improves sperm quality and fertility parameters leads to significant proteome modulation. These changes include reduced oxidative stress and broadly restored sperm maturation. Despite the limited patient cohort analyzed, these preliminary findings provide valuable insights into how varicocele treatment might enhance male fertility and suggest potential biomarkers for improved male infertility treatment strategies. Full article

Sperm freezability exhibits marked individual variability, yet the mechanisms remain unclear. Using bulls as the experimental model, we integrated proteomic (sperm) and metabolomic (seminal plasma) analyses of high-freezability (HF) and control (CF) bulls to identify key biomarkers associated with sperm freezability. Post-thaw motility and membrane integrity were significantly higher in HF bulls (p < 0.05). Sperm proteome analysis revealed upregulated antioxidant proteins (PRDX2, GSTM4), heat shock proteins (HSP70, HSP90), and key enzymes in arginine and proline metabolism (PRODH, LAP3). Seminal plasma metabolomics revealed elevated spermine in HF bulls. Meanwhile, we found that spermine abundance was positively correlated with post-thaw motility, as well as with the expression levels of both PRODH and LAP3 (r > 0.6, p < 0.05). Functional validation demonstrated that 200 μM spermine supplementation in cryopreservation extenders enhanced post-thaw motility, kinematic parameters (VAP, VSL, VCL), membrane integrity, and acrosome integrity (p < 0.05). Concurrently, spermine enhanced antioxidant enzyme (SOD, CAT, GSH-Px) activity and reduced ROS and MDA levels (p < 0.05). Our study reveals a spermine-driven antioxidant network coordinating sperm–seminal plasma synergy during cryopreservation, offering novel strategies for semen freezing optimization. Full article

The core objective of racehorse breeding is to enhance the speed and endurance of the horses. The Grassland-Thoroughbred is an emerging horse breed developed in northern China in recent years, characterized by excellent speed performance, enduring stamina, and strong environmental adaptability. However, research on the genetic characteristics within this breed and the genes associated with athletic performance remains relatively limited. We conducted whole-genome resequencing of Grassland-Thoroughbred F1, F2, F3, and the crossbred population (CY) and obtained a total of 4056.23 Gb of high-quality data after quality control. The single nucleotide polymorphisms (SNPs) were primarily distributed in intergenic regions, followed by intronic regions. Principal component analysis (PCA) and STRUCTURE revealed clear distinctions among the generations, with a notable overlap between CY and F3. Using the SNP dataset, we analyzed the number and length distribution patterns of runs of homozygosity (ROHs) in the genomes of different generational groups of Grassland-Thoroughbreds. Short ROHs ranging from 0.5 to 2 Mb were the most abundant, with the following distribution: F1 (85.15%) > F2 (82.92%) > CY (78.75%) > F3 (77.51%). Medium-length ROHs (2–8 Mb) and long ROHs (>8 Mb) together exhibited a similar but opposite trend. The average length of ROHs was 1.57 Mb. The inbreeding coefficients (F_ROH) among different generational groups of Grassland-Thoroughbreds were as follows: F1 (0.0942) < F2 (0.1197) < CY (0.1435) < F3 (0.1497). Through ROH island analysis, 10 high-frequency ROH regions were identified and annotated with 120 genes. Genomic regions and candidate genes associated with athletic traits—ACAD8, OPCML, PRDX2, NTM, NDUFB7, SCL25A15, FOXO1, and SLC4A10—were identified. These genes may play important roles in regulating muscle performance, mitochondrial energy supply, and learning and memory processes in horses and are closely associated with the athletic ability of the Grassland-Thoroughbred population. This study is the first to systematically characterize the genomic diversity and inbreeding dynamics of the Grassland-Thoroughbred during the breeding process. It identifies candidate genes that may influence athletic performance, thereby providing an important molecular foundation and theoretical basis for the genetic improvement and performance-based selection of this emerging breed. Full article

CD38, a nicotinamide adenine dinucleotide (NAD⁺) glycohydrolase, increases in old murine macrophages after infection compared to young controls. We aimed to determine whether the increase in CD38 in old murine macrophages after infection is directly associated with enhanced inflammation induced by the oral pathogens Aggregatibacter actinomycetemcomitans (Aa) or Porphyromonas gingivalis (Pg) when compared to young controls. Additionally, we determined the effects of a specific CD38 inhibitor (78c) on CD38, NAD⁺, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α expressions, and anti-oxidative responses in old murine macrophages induced by oral pathogens. Old and young murine macrophages were either uninfected or infected with the oral pathogens Aa or Pg for 1 to 24 h. Protein levels of CD38 and protein kinases, including nuclear factor kappa-B (NF-κB), phosphoinositide 3-kinase (PI3K), and mitogen-activated protein kinases (MAPKs), NAD⁺, and inflammatory cytokine (IL-1β, IL-6, TNF-α) levels were evaluated. Additionally, old murine macrophages were treated with a vehicle or a CD38 inhibitor (78c) and cells were either uninfected or infected with Aa or Pg. CD38, NAD⁺, cytokine (IL-1β, IL-6, TNF-α) levels, reactive oxygen species (ROS), NAPDH oxidase 1 (Nox1), and anti-oxidative enzymes, including superoxide dismutase1 (Sod1), glutathione peroxidase 4 (Gpx4), Peroxiredoxin 1 (Prdx1), thioredoxin reductase 1 (Txnrd1), and catalase (Cat), were evaluated. The results showed that old murine macrophages significantly enhanced CD38 and reduced NAD⁺ levels 24 h after Aa or Pg infection compared to young controls. This enhanced CD38 in old murine macrophages was not directly correlated with the activation of protein kinases (NF-κB, PI3K, and MAPKs), nor the (IL-1β, IL-6, TNF-α) levels in macrophages. The inhibition of CD38 by 78c reduced CD38, enhanced NAD⁺ levels, attenuated IL-1β, IL-6 and TNF-α pro-inflammatory cytokine levels, reduced ROS and Nox1 expressions, and enhanced expressions of Sod1, Gpx4, Prdx1, Txnrd1, and Cat in old murine macrophages infected with Aa or Pg. These results suggest that the inhibition of CD38 by 78c is a promising therapeutic strategy to treat aging-associated periodontitis. Full article

Pneumonia is a major issue that affects calves’ health and performance and causes numerous losses despite treatment. Investigating genetic and molecular differences, as well as immunological and antioxidant responses, in calves at risk for pneumonia was the aim of this study. A total of 225 calves were studied, including 180 Holstein calves with respiratory signs and 45 calves that were apparently healthy. Blood samples were collected for CBC, RNA extractions, and immunological and antioxidant analysis. In contrast to the control group, the pneumonic one showed a considerable (p < 0.05) increase in the expression levels of cytokines and antioxidant genes IL1α, IL-1β, IL-6, IFN-γ, TNF-α, and NOX4. In contrast, the values of IL10, PRDX6, ATG7, and NDUFS6 were in the opposite range. The pneumonic and healthy calves were found to differ in the nucleotide sequences of the genes under analysis. In pneumonic calves, a substantial (p ˂0.05) reduction was detected in RBCs, Hb count, PCV%, and lymphocytes count, and a notable (p ˂ 0.05) increase in WBCs and neutrophil count was correlated with healthy control calves. The findings of the serum profile showed that there was a meaningful (p ˂ 0.05) rise in the serum values of IL-1α, IL-1β, IL-6, TNF-α, IFN-γ, and MDA, with significant reductions in the SOD, GSH, TAC, and IL-10 in the pneumonic compared to the healthy calves. Our results provide valuable information about the nucleotide sequence, gene expression, and serum profile differences of putative indicators for pneumonia in calves. This could be applied in monitoring calves’ pneumonia through the discriminate breeding of naturally resistant animals. Full article

Advancing age in men significantly contributes to declining sperm fertility. Information on age-related proteomic changes in spermatozoa is limited. This study involved normal fertile Arab men in three age groups: young adult (21–30 years; n = 6), late adult (31–40 years; n = 7), and advanced age (40–51 years; n = 5). Gradient-purified spermatozoa were analyzed using LC-MS/MS and proteomic data were processed using Progenesis QI (QIfp) v3.0 and UniProt/SwissProt. Significantly enriched annotations and clustering of proteins in the proteomic datasets were identified (2-fold change; p < 0.05). A total of 588 proteins were identified, with 93% shared across the three groups. Unique proteins were MYLK4 for the young adult group, PRSS57 for the late adult group, and HMGB4, KRT4, LPGAT1, OXCT2, and MGRN1 for the advanced age group. Furthermore, 261 (44%) proteins were differentially expressed (p < 0.05) across the three groups. Functional enrichment analysis suggested an aging-related significant increase in pathways associated with neurodegenerative diseases and protein folding, alongside decreases in glycolysis/gluconeogenesis, flagellated sperm motility, acetylation, phosphoprotein modifications, oxidation processes, and Ubl conjugation. Cluster analysis highlighted significantly upregulated proteins in young adults (e.g., H2BC1, LAP3, SQLE, LTF, PDIA4, DYNLT2) and late adults (e.g., ATP5F1B, ODF2, TUBA3C, ENO1, SPO11, TEX45, TEKT3), whereas most proteins in the advanced age group exhibited downregulation (e.g., SPESP1, RAB10, SEPTIN4, RAB15, PTPN7, USP5, ANXA1, PRDX1). In conclusion, this study revealed aging-associated proteomic changes in spermatozoa that impact critical processes, including spermatogenesis, motility, metabolism, and fertilization, potentially contributing to fertility decline. These changes provide a molecular framework for developing therapies to preserve sperm proteostasis and enhance fertility in older men. Full article

Background: Methylmalonic acidemia combined with homocystinuria (cblC) can lead to infantile maculopathy. Although significant visual deterioration is commonly reported in early-onset cblC, we found poor awareness regarding formal assessments of ocular complications, especially in newborns, and of how these complications relate to the timing of therapy initiation. In this work, we present our experience and perform a literature review. Methods: We performed sequential fundus examinations, optical coherence tomography (OCT) and full-field electroretinography (ERG) under sedation following detection of signs of retinal degeneration. We also assessed visual fields using kinetic attraction perimetry. Results: We report a newborn who was referred on the eighth day of life, following a diagnosis of cblC through newborn screening (NBS), and who began treatment that same day. Close monitoring of retinal changes through fundus examinations allowed the detection of signs of retinal degeneration at 3 months, which progressed when checked at 5 months. At 7 months, OCT showed retinal thinning with the appearance of bull’s eye maculopathy in the corresponding region on fundoscopy; ERG revealed a reduction in the amplitude of both scotopic and photopic components, whereas kinetic attraction perimetry showed no abnormalities. Genetic investigation confirmed the disease, compound heterozygous for a nonsense variant in MMACHC and a splicing one in PRDX1. Conclusions: In cblC, retinal degeneration occurs in the first months of life despite timely treatment and adequate biochemical control, and it may manifest before any signs of visual deprivation appear. However, there is an early, narrow window during which therapy may slow down retinal degeneration enough to prevent sensory nystagmus. We recommend initiating therapy immediately after biochemical diagnosis, along with close ophthalmological monitoring, before the appearance of any signs. Full article

Pingliang Red Cattle, a renowned geographical indication product in China, is distinguished by its superior meat quality, yet the scientific basis for its unique attributes remains underexplored. This study integrated metabolomic and transcriptomic analyses to elucidate the biochemical and physiological factors underlying the enhanced flavor, color stability, and tenderness of Pingliang Red Cattle beef compared to Qinchuan and Simmental cattle. Metabolomic profiling revealed significantly elevated levels of inosine monophosphate (IMP, 2.86–3.96× higher) and glutathione (GSH, 2.42–5.43× higher) in Pingliang Red Cattle, contributing to intense umami flavor and prolonged meat color retention. Notably, ergothioneine (EGT), a potent antioxidant, was identified for the first time in Pingliang Red Cattle beef, with concentrations 2.55× and 4.25× higher than in Qinchuan and Simmental, respectively. Transcriptomic analysis highlighted the upregulation of 21 tenderness-related genes (e.g., FABP3, PRDX6, CAST) and key enzymes in purine and glutathione metabolism pathways (e.g., PDE4D, ADSL, GGT1), correlating with meat tenderness and the improved meat quality. Additionally, Pingliang Red Cattle’s natural forage-rich diet and low-density rearing practices were critical in enhancing these traits. These findings provide a scientific foundation for Pingliang Red Cattle’s premium quality, offering actionable insights for GI product branding, quality optimization, and market competitiveness. The multi-omics approach established here serves as a paradigm for quality assessment and improvement of other GI agricultural products, bridging traditional reputation with molecular evidence. Full article

Superoxide dismutase-rich Tetraselmis chuii (T. chuii) is derived from marine microalgae and has been reported to increase gene expression of nuclear factor erythroid 2-related factor 2 (NRF2) and related antioxidant enzymes in myoblast tissue culture models. Human research has indicated that T. chuii supplementation can improve recovery from exercise-induced muscle damage, but its effects on endurance exercise performance and the molecular bases that may underlie any ergogenic effects are unclear. Healthy participants underwent 14 days of supplementation with 25 mg·day⁻¹T. chuii and placebo in a randomized, double-blind, crossover experimental design. Prior to and following each supplementation period, participants completed a high-intensity cycling test to assess time to exhaustion and peak oxygen uptake (${\dot{\mathrm{V}}\mathrm{O}}_{2\mathrm{peak}}$). A resting skeletal muscle biopsy was collected after both supplementation periods to assess gene expression changes. Compared to pre-supplementation values, ${\dot{\mathrm{V}}\mathrm{O}}_{2\mathrm{peak}}$ was increased following T. chuii (p = 0.013) but not placebo (p = 0.66). Fold-change in glutathione peroxidase 7 [(GPX7) 1.26 ± 1.37], glutathione-disulfide reductase [(GSR) 1.22 ± 1.41], glutathione S-transferase Mu 3 [(GSTM3) 1.34 ± 1.49], peroxiredoxin 6 [(PRDX6) 1.36 ± 1.57], extracellular signal-regulated kinase 3 [(ERK3) 1.92 ± 2.42], NRF2 (1.62 ± 2.16), p38 alpha [(p38a) 1.33 ± 1.58] and sirtuin 1 [(SIRT1) 1.73 ± 2.25] gene expression were higher after T. chuii compared to placebo supplementation (p < 0.05). Short-term T. chuii supplementation increased ${\dot{\mathrm{V}}\mathrm{O}}_{2\mathrm{peak}}$ and skeletal muscle gene expression of key enzymatic antioxidants (GPX7, GSR, GSTM3, and PRDX6), signalling kinases (ERK3 and p38a), post-translational regulators (SIRT1), and transcription factors (NRF2) that may protect against cellular stress insults. Full article

The role of oxidants and antioxidants in inflammatory bowel disease (IBD) has been actively explored since the early 1980s, starting with the role of the respiratory burst of neutrophils and ischemia in bowel pathology. Since that time, the enzymatic components contributing to the pool of reactive oxygen species, including superoxide, H₂O₂, and lipid hydroperoxides, and the counteracting antioxidants—catalase, glutathione peroxidases (Gpx), peroxiredoxins (PRDX), superoxide dismutases, and others—have been fleshed out. My perspective on IBD is from the role of the balance or imbalance of enzymatic oxidant sources and enzymatic antioxidants in the inflammatory process. I will present evidence on the involvement of oxidant and antioxidant processes in IBD based, as much as possible, on my experiences with Gpxs. This evidence will be discussed in terms of both the immune system and local bowel oxidant and antioxidant systems. As Gpxs are generally selenium-dependent, possible deficiencies in selenium uptake in active IBD and the impact on Gpx expression will be explored. The more recently introduced ferroptosis, an iron-dependent lipid peroxidation-based pathological process, will be reviewed for its possible involvement in IBD. Full article