Search Results (577)

Introduction: Endothelial dysfunction is a common feature of end-stage kidney disease, requiring hemodialysis (HD) and antiphospholipid antibody (aPL) persistent positivity. Endothelial dysfunction can be assessed with noninvasive tests such as flow-mediated dilation (FMD). In the HD population, it is not known whether aPL persistent positivity is associated with a more severe endothelial dysfunction. Methods: We performed a cross-sectional study in our HD patients. The FMD of the brachial artery was measured in 17 aPL-positive patients who fulfilled the inclusion criteria and were matched to 17 controls according to age, gender, diabetes mellitus, smoking status and markers of dialysis adequacy (Kt/V). Results: FMD was significantly lower in the aPL group with a mean of 6.9% and 11.8% in the aPL-positive and the control groups, respectively (mean difference (IC 95%): −4.9 (−8.3; −1.6), p = 0.006). aPL was associated with a higher c-reactive protein level, and longer HD vintage. There was no statistical difference between groups in terms of pre-dialysis urea and urinary output, dialysis adequacy (Kt/V), and history of cardiovascular disease or treatments. Conclusions: aPL persistent positivity in HD patients was associated with worse endothelial dysfunction, reflected by FMD measurements. These findings have to be confirmed in larger studies. Full article

Rapid and accurate assessment of nutritional quality, particularly crude protein content and essential nutrient concentrations, remains a major challenge in the food and feed industries. In this study, laser-induced breakdown spectroscopy (LIBS) was combined with advanced chemometric modeling to predict the levels of crude protein and key macro- and micronutrients (Ca, Mg, K, Na, Fe, Mn, P, Zn) in 61 barley forage samples composed of whole aerial plant parts ground prior to analysis. LIBS offers a compelling alternative to traditional analytical methods by enabling real-time analysis with minimal sample preparation. To minimize interference from atmospheric nitrogen, nitrogen spectral lines were excluded from the protein calibration model in favor of spectral lines from elements biochemically associated with proteins. We compared the performance of Partial Least Squares (PLSR) regression and Extreme Learning Machine (ELM) using fivefold cross-validation. ELM outperformed PLS in terms of prediction, achieving a coefficient of determination (R²) close to 1 and a ratio of performance to deviation (RPD) exceeding 2.5 for proteins and several nutrients. These results underscore the potential of LIBS-ELM integration as a robust, non-destructive, and in situ tool for rapid forage quality assessment, particularly in complex and heterogeneous plant matrices. Full article

The preprocessing of infrared spectra can significantly improve predictive accuracy for protein, carbohydrate, lipid, or other nutrition components, yet optimal preprocessing selection is typically empirical, tedious, and dataset specific. This study introduces a Bayesian optimization-based framework designed for the automated selection of optimal spectral preprocessing pipelines within a chemometric modeling context. The framework was applied to mid-infrared spectra of milk to predict compositional parameters for fat, protein, lactose, and total solids. A total of 385 averaged spectra corresponding to 198 unique samples was split into a 70/30 ratio (training/test) using a group-aware Kennard-Stone algorithm, resulting in 269 averaged spectra (135 unique samples) for training and 116 spectra (58 unique samples) for testing. Six regression models: Elastic Net, Gradient Boosting Machines (GBM), Partial Least Squares (PLS), RidgeCV Regression, LassoLarsCV, and Support Vector Regression (SVR) were evaluated across three preprocessing conditions: (1) no preprocessing, (2) literature-derived custom preprocessing (e.g., MSC, SNV, and first and second derivatives), and (3) optimized preprocessing via the proposed Bayesian framework. Optimized preprocessing consistently outperformed other methods, with RidgeCV achieving the best performance for all components except lactose, where PLS slightly outperformed it. Improvements in predictive accuracy, particularly in terms of RMSEP were observed across all milk components. The best RMSEP results were achieved for protein (RMSEP = 0.054, $R^2=0.981$) and lactose (RMSEP = 0.026, $R^2=0.917$), followed by fat (RMSEP = 0.139, $R^2=0.926$) and total solids (RMSEP = 0.154, $R^2=0.960$). Literature-based pipelines demonstrated inconsistent effectiveness, highlighting the limitations of transferring preprocessing methods between datasets. The Bayesian optimization approach identified relatively simple yet highly effective preprocessing pipelines, typically involving few steps. By eliminating manual trial and error, this data-driven strategy offers a robust and generalizable solution that streamlines spectral modeling in dairy analysis and can be readily applied to other types of spectroscopic data across various domains. Full article

Nearly all eukaryotic proteins are turned over by the ubiquitin (Ub)-26S proteasome system (UPS). Despite its broad cellular roles, only a handful of UPS members, particularly the Ub E3 ligases that specifically recognize a protein for ubiquitylation, have been characterized in plants to date. The challenge arises from the transient recognition and rapid degradation of ubiquitylation substrates by the UPS. To tackle this challenge, the emerging biotinylation-based proximity labeling (PL) offers an exciting tool for enriching transient interactors of Ub E3 ligases. In this study, we examined the efficacy of TurboID in identifying substrates of Arabidopsis Skp1-cullin1-F-box (SCF) ligases. We demonstrate that the Arabidopsis Skp1 Like (ASK)1-TurboID is not fully functioning in planta, which led us to discover a novel antagonism between biotinylation and ubiquitylation in regulating protein stability in vivo. This discovery lowers the effectiveness of PL in ubiquitylome studies. However, using one long-known SCF substrate, phytochrome A, we succeeded to apply its TurboID fusion for complementing the far-red-light response of the phyA-211 null mutant allele, suggesting an efficacy of PL in characterizing single ubiquitylation pathways. This study highlighted a limitation of PL in ubiquitylome studies, discovered a new antagonistic pathway of biotinylation, and developed a theoretical guidance for future PL-based characterization of ubiquitylation pathways. Full article

Background: Pancreatic lipase (PL), the principal enzyme catalyzing the hydrolysis of dietary triacylglycerols in the intestinal lumen, is pivotal for efficient lipid absorption and plays a central role in metabolic homeostasis. Enhanced PL activity promotes excessive lipid assimilation and contributes to positive energy balance, key pathophysiological mechanisms underlying the escalating global prevalence of obesity—a complex, multifactorial condition strongly associated with metabolic disorders, including type 2 diabetes mellitus and cardiovascular disease. Inhibition of pancreatic lipase (PL) constitutes a well-established therapeutic approach for attenuating dietary lipid absorption and mitigating obesity. Methods: With the aim to identify putative PL inhibitors, a Structure-Based Virtual Screening (SBVS) of PhytoHub database naturally occurring derivatives was performed. A refined library of 10,404 phytochemicals was virtually screened against a crystal structure of pancreatic lipase. Candidates were filtered out based on binding affinity, Lipinski’s Rule of Five, and structural clustering, resulting in six lead compounds. Results: In vitro, enzymatic assays confirmed theoretical suggestions, highlighting Pinoresinol as the best PL inhibitor. Molecular dynamics simulations, performed to investigate the stability of protein–ligand complexes, revealed key interactions, such as persistent hydrogen bonding to catalytic residues. Conclusions: This integrative computational–experimental workflow highlighted new promising natural PL inhibitors, laying the foundation for future development of safe, plant-derived anti-obesity therapeutics. Full article

Neuronal differentiation is a highly dynamic process marked by coordinated biochemical, structural, and metabolic changes. Rat primary cortical neurons are the preferred cell model to study this process as they can maintain their functional attributes, including functional synapses, and simulate the behavior of neuronal cells in vivo. In this study, we employed Fourier transform infrared (FTIR) spectroscopy to monitor the molecular transformations that occur during the differentiation of rat cortical neurons. Partial least squares regression (PLS-R) analysis from the 1800–1500 cm⁻¹ region further allows the identification of the spectroscopic profile of early and late differentiation stages, highlighting the technique’s ability to detect subtle molecular changes. Further peak intensity analysis revealed significant changes in the cells’ metabolome during differentiation; it was possible to observe remodeling of protein secondary structures and an increase in protein phosphorylation levels, which can imply activation of signaling pathways essential for neuronal differentiation and maturation. Concomitantly, lipid-associated spectral regions demonstrated increased levels of total lipids, lipid esters, and longer acyl chains and decreased unsaturation levels, alterations that can be linked to membrane expansion throughout neuronal differentiation. These findings underscore FTIR spectroscopy as a valuable tool for studying neuronal differentiation, offering insights into the conformational and metabolic shifts underlying the formation of mature neuronal phenotypes. Full article

Motor Neuron Diseases (MNDs) such as Amyotrophic Lateral Sclerosis (ALS), Primary Lateral Sclerosis (PLS), Hereditary Spastic Paraplegia (HSP), Spinal Muscular Atrophy with Respiratory Distress Type 1 (SMARD1), Multisystem Proteinopathy (MSP), Spinal and Bulbar Muscular Atrophy (SBMA), and ALS associated to Frontotemporal Dementia (ALS-FTD), have traditionally been studied as distinct entities, each one with unique genetic and clinical characteristics. However, emerging research reveals that these seemingly disparate conditions converge on shared molecular mechanisms that drive progressive neuroaxonal degeneration. This narrative review addresses a critical gap in the field by synthesizing the most recent findings into a comprehensive, cross-disease mechanisms framework. By integrating insights into RNA dysregulation, protein misfolding, mitochondrial dysfunction, DNA damage, kinase signaling, axonal transport failure, and immune activation, we highlight how these converging pathways create a common pathogenic landscape across MNDs. Importantly, this perspective not only reframes MNDs as interconnected neurodegenerative models but also identifies shared therapeutic targets and emerging strategies, including antisense oligonucleotides, autophagy modulators, kinase inhibitors, and immunotherapies that transcend individual disease boundaries. The diagnostic and prognostic potential of Neurofilament Light Chain (NfL) biomarkers is also emphasized. By shifting focus from gene-specific to mechanism-based approaches, this paper offers a much-needed roadmap for advancing both research and clinical management in MNDs, paving the way for cross-disease therapeutic innovations. Full article

Bamboo shoot boiled liquid (BSBL), a processing byproduct containing soluble proteins, peptides, amino acids, carbohydrates, and phenolics, is typically discarded, causing resource waste and environmental issues. This study analyzed metabolic changes in BSBL during Pediococcus pentosaceus B49 fermentation. The result of partial least squares discriminant analysis (PLS-DA) revealed significant metabolite profile differences across fermentation times (0 h, 24 h, 48 h, 72 h, 96 h). The most substantial alterations occurred within the first 24 h, followed by stabilization. Compared to unfermented BSBL, fermented samples exhibited significantly elevated signal intensities for 5,7-dimethoxyflavone, cinnamic acid, 3,4-dihydro-2H-1-benzopyran-2-one, 6,8-dimethyl-4-hydroxycoumarin, and 2-hydroxycinnamic acid (p < 0.05), showing upward trends over time. Conversely, (+)-gallocatechin intensity decreased gradually. Bitter peptides, such as alanylisoleucine, isoleucylisoleucine, leucylvaline, and phenylalanylisoleucine, in BSBL exhibited a significant reduction following fermentation with P. pentosaceus B49 (p < 0.05). KEGG enrichment indicated tyrosine metabolism (ko00350) and arginine/proline metabolism (ko00330) as the most impacted pathways. These findings elucidate metabolic regulation in BSBL fermentation, supporting development of functional fermented bamboo products. Full article

Background: Diabetic foot ulcers (DFUs) are a serious complication of diabetes and are often difficult to treat. Hyperbaric oxygen therapy (HBOT) has been proposed as an adjunctive treatment to promote healing, but its long-term clinical and biological effects remain insufficiently characterized. This study aimed to evaluate the impact of HBOT on systemic biomarkers, local microvasculature, and clinical outcomes in patients with DFUs. Methods: In this non-randomized prospective study, 20 patients with ischemic DFUs were followed over a 36-month period. Fourteen received HBOT in addition to standard care, while six received standard care alone. Clinical outcomes—including DFU resolution, recurrence, lower extremity amputation (LEA), and mortality—were assessed alongside systemic inflammatory and angiogenic biomarkers and wound characteristics at baseline and at 3, 6, 12, and 36 months. CD31 immunostaining was performed on available tissue samples. Results: The two groups were comparable at baseline (mean age 62 ± 12 years; diabetes duration 18 ± 9 years). At 3 months, the HBOT group showed significant reductions in erythrocyte sedimentation rate and DFU size (p < 0.05), with downward trends observed in C-reactive protein (CRP), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF), and an increase in stromal-derived factor-1 alpha (SDF1-α). No significant changes were observed in the control group. CD31+ microvessel density appeared to increase in HBOT-treated DFU tissue after one month, although the sample size was limited. Patients receiving HBOT had lower rates of LEA and mortality, improved wound healing, and sustained outcomes over three years. DFU recurrence rates were similar between groups. Conclusions: HBOT was associated with improved wound healing and favorable biomarker profiles in patients with treatment-resistant ischemic DFUs. While these findings are encouraging, the small sample size and non-randomized design limit their generalizability, highlighting the need for larger, controlled studies. Full article

This study aimed to investigate the efficacy of a composite coating composed of 150 mg/L ε-Poly-L-lysine (ε-PL) and 5 g/L chitosan (CTS) in extending the shelf life and maintaining the postharvest quality of fresh Tremella fuciformis. Freshly harvested T. fuciformis were treated by surface spraying, with distilled water serving as the control. The effects of the coating on storage quality, physicochemical properties, reactive oxygen species (ROS) metabolism, and membrane lipid metabolism were evaluated during storage at (25 ± 1) °C. The results showed that the ε-PL/CTS composite coating significantly retarded quality deterioration, as evidenced by reduced weight loss, maintained whiteness and color, and higher retention of soluble sugars, soluble solids, and soluble proteins. The coating also effectively limited water migration and loss. Mechanistically, the coated T. fuciformis exhibited enhanced antioxidant capacity, characterized by increased superoxide anion (O₂⁻) resistance capacity, higher activities of antioxidant enzymes (SOD, CAT, APX), and elevated levels of non-enzymatic antioxidants (AsA, GSH). This led to a significant reduction in malondialdehyde (MDA) accumulation, alongside improved DPPH radical scavenging activity and reducing power. Furthermore, the ε-PL/CTS coating preserved cell membrane integrity by inhibiting the activities of lipid-degrading enzymes (lipase, LOX, PLD), maintaining higher levels of key phospholipids (phosphatidylinositol and phosphatidylcholine), delaying phosphatidic acid accumulation, and consequently reducing cell membrane permeability. In conclusion, the ε-PL/CTS composite coating effectively extends the shelf life and maintains the quality of postharvest T. fuciformis by modulating ROS metabolism and preserving membrane lipid homeostasis. This study provides a theoretical basis and a practical approach for the quality control of fresh T. fuciformis. Full article

The popularity of bioactive compounds extracted from sea cucumbers is growing due to their wide application in the pharmaceutical industry, particularly in the development of drugs for neurological disorders. Different types of compounds, such as saponins, phenolic compounds, cerebrosides, and glucocerebrosides, are being studied intensively for their efficacy in assessing the treatment of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and brain tumors, among others. Positive results have been observed in the upregulation in the content of p-CREB, p-PL3K, BDNF, SOD, and MDA. Furthermore, the neuroprotective mechanism of the compounds against Alzheimer’s disease revealed that suppressing the phosphorylation of tau protein by the PI3K/Akt/GSK3β pathway leads to improved synaptic plasticity and reduced nerve fiber tangles. This comprehensive review explores recent findings on the therapeutic potential of sea cucumber bioactives in the treatment of brain-related disorders. Full article

The authenticity of Protected Designation of Origin (PDO) Feta cheese is critical for consumer confidence and market integrity, particularly in light of widespread concerns over economically motivated adulteration. This study evaluated the potential of Attenuated Total Reflectance–Fourier Transform Infrared (ATR-FTIR) spectroscopy combined with chemometric modeling to differentiate authentic Feta from non-Feta white brined cheeses. A total of 90 cheese samples, consisting of verified Feta and cow milk cheeses, were analyzed in both freeze-dried and fresh forms. Spectral data from raw, first derivative, and second derivative spectra were analyzed using principal component analysis–linear discriminant analysis (PCA-LDA) and Partial Least Squares Discriminant Analysis (PLS-DA) to distinguish authentic Feta from non-Feta cheese samples. Derivative processing significantly improved classification accuracy. All classification models performed relatively well, but the PLS-DA model applied to second derivative spectra of freeze-dried samples achieved the best results, with 95.8% accuracy, 100% sensitivity, and 90.9% specificity. The most consistently highlighted discriminatory regions across models included ~2920 cm⁻¹ (C–H stretching in lipids), ~1650 cm⁻¹ (Amide I band, corresponding to C=O stretching in proteins), and the 1300–900 cm⁻¹ range, which is associated with carbohydrate-related bands. These findings support ATR-FTIR spectroscopy as a rapid, non-destructive tool for routine Feta authentication. The approach offers promise for enhancing traceability and quality assurance in high-value dairy products. Full article

Oxidized phospholipids (OxPLs) are increasingly recognized as biologically active lipids involved in various pathologies. Both exposure to pathogenic factors and the efficacy of protective mechanisms are critical to disease development. In this study, we characterized an immunoassay that quantified the total capacity of the plasma to degrade or mask OxPLs, thereby preventing their interaction with cells and soluble proteins. OxLDL-coated plates were first incubated with human blood plasma or a control vehicle, followed by an ELISA using a monoclonal antibody specific to oxidized phosphatidylethanolamine. Pretreatment with the diluted blood plasma markedly inhibited mAb binding. The masking assay was optimized by evaluating the buffer composition, the compatibility with various anticoagulants, potential interfering compounds, the kinetic parameters, pre-analytical stability, statistical robustness, and intra- and inter-individual variability. We propose that this masking assay provides a simple immunological approach to assessing protective mechanisms against lipid peroxidation products. Establishing this robust and reproducible method is essential for conducting clinical association studies that explore masking activity as a potential biomarker of the predisposition to a broad range of lipid-peroxidation-related diseases. Full article

Milk is a nutritionally rich food and a frequent target of economically motivated adulteration, particularly through substitution with lower-cost milk types. Over the past decade, significant progress has been made in the authentication of milk using advanced proteomic and chemometric approaches, with a focus on the discovery and application of protein and peptide biomarkers for species differentiation and fraud detection. Recent innovations in both top-down and bottom-up proteomics have markedly improved the sensitivity and specificity of detecting key molecular targets, including caseins and whey proteins. Peptide-based methods are especially valuable in processed dairy products due to their thermal stability and resilience to harsh treatment, although their species specificity may be limited when sequences are conserved across related species. Robust chemometric approaches are increasingly integrated with proteomic pipelines to handle high-dimensional datasets and enhance classification performance. Multivariate techniques, such as principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), are frequently employed to extract discriminatory features and model adulteration scenarios. Despite these advances, key challenges persist, including the lack of standardized protocols, variability in sample preparation, and the need for broader validation across breeds, geographies, and production systems. Future progress will depend on the convergence of high-resolution proteomics with multi-omics integration, structured data fusion, and machine learning frameworks, enabling scalable, specific, and robust solutions for milk authentication in increasingly complex food systems. Full article

Tissue hypoxia is commonly observed in head cancers and contributes to both molecular and functional changes in tumour cells. It is known to stimulate erythropoiesis, angiogenesis, and metabolic alterations within tumour cells. Glioblastoma, a type of brain tumour, is characterized by rapid proliferation and aggressive growth. Recent studies have indicated that natural products may hold potential as components of cancer therapy. Among these, Polish propolis and its active compound, quercetin, have demonstrated promising anti-cancer properties. The aim of this study was to evaluate the concentrations of selected cytokines—specifically IL-6, IL-9, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB), interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1)—produced by astrocytes of the CCF-STTG1 cell line. The cytotoxic effects of ethanolic extract of propolis (EEP) and quercetin were assessed using the MTT assay. Astrocytes were stimulated with lipopolysaccharide (LPS, 200 ng/mL) and/or IFN-α (100 U/mL), followed by treatment with EEP or quercetin (25–50 µg/mL) under hypoxic conditions for two hours. Cytokine concentrations were measured using the xMAP Luminex Multiplex Immunoassay and the Multiplex Bead-Based Cytokine Kit. Our study demonstrated that Polish propolis and its component quercetin modulate the tumour microenvironment in vitro, primarily by altering the levels of specific cytokines. The HCA analysis revealed that IL-6 and MCP-1 formed a distinct cluster at the highest linkage distance (approximately 100% of Dmax), suggesting that their expression patterns are significantly different from those of the other cytokines and that they are more similar to each other than to the rest. PCA analysis showed that EEP-PL (50 μg/mL) with IFN-α and EEP-PL (50 μg/mL) with LPS exert similar activities on cytokine secretion by astrocytes. Similar effects were demonstrated for EEP-PL 50 μg/mL + LPS + IFN-α, EEP-PL 25 μg/mL + IFN-α and EEP-PL 25 μg/mL + LPS + IFN-α. Our findings suggest that Polish propolis and quercetin may serve as promising natural agents to support the treatment of stage IV malignant astrocytoma. Nonetheless, further research is needed to confirm these results. Full article