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16 pages, 1924 KB  
Communication
Heterogeneous Intermediate Phenotypes of Cancer Cells with Varying Ki-67-Positivity Rates, Including Histologically HCC-Like and NEC-Like Cells, in Liver MiNEN
by Sumie Ohni, Yoko Nakanishi, Yukari Hirotani, Ryosuke Toyonaka, Osamu Aramaki, Yukiyasu Okamura, Shinobu Masuda, Makoto Makishima and Mariko Esumi
Int. J. Mol. Sci. 2026, 27(8), 3390; https://doi.org/10.3390/ijms27083390 (registering DOI) - 9 Apr 2026
Abstract
Mixed hepatocellular carcinoma (HCC)–neuroendocrine carcinoma (NEC) is a major type of liver mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN). Primary liver NEC, which is very rare, is mostly associated with HCC rather than pure NEC. To characterize the cancer cell heterogeneity of the HCC and NEC [...] Read more.
Mixed hepatocellular carcinoma (HCC)–neuroendocrine carcinoma (NEC) is a major type of liver mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN). Primary liver NEC, which is very rare, is mostly associated with HCC rather than pure NEC. To characterize the cancer cell heterogeneity of the HCC and NEC components, we comprehensively analyzed the protein expression of three cancer cell biological markers (TERT, Ki-67, and p53) and five differentiation markers (one hepatocyte marker and four neuroendocrine markers) via immunohistochemistry and immunofluorescence using curative resection tissues from three patients with liver MiNEN. TERT/Ki-67/p53 proteins, which are related to cell proliferation and malignancy, were independently expressed in the HCC and NEC components; Ki-67 was highly expressed among the three proteins in both cancer components, and the expression of all three markers was higher in the NEC component than in the HCC component. Despite the intracomponent and intercomponent heterogeneity, the expression signatures of the three markers were similar between the two components, potentially suggesting a common origin of mixed HCC-NEC. An in-depth exploration of intracomponent heterogeneity using differentiation markers revealed multiple intermediate phenotypes of cancer cells, i.e., HCC-like and NEC-like cells, mainly in the HCC component. Histologically NEC-like cells rather than HCC-like cells tended to have an intermediate percentage of Ki-67-positive cells, compared with NEC cells. The spatial distribution of various intermediate cancer cell phenotypes suggests that mixed HCC-NEC may involve the transdifferentiation from HCC cells to NEC cells through the dedifferentiation of HCC. Full article
24 pages, 6223 KB  
Article
Admission C-Reactive Protein and Mortality After STEMI: A Retrospective Cohort Study Identifying Subgroup-Specific Risk Thresholds
by Kristen Kopp, Magdalena Leitner, Nikolaus Clodi, Michael Lichtenauer, Matthias Hammerer, Uta C. Hoppe, Elke Boxhammer and Mathias C. Brandt
J. Clin. Med. 2026, 15(8), 2864; https://doi.org/10.3390/jcm15082864 (registering DOI) - 9 Apr 2026
Abstract
Background: Inflammation is central to myocardial injury and repair after ST-segment elevation myocardial infarction (STEMI). C-reactive protein (CRP) is an established biomarker of systemic inflammation, but its prognostic thresholds across patient subgroups are not well defined. Methods: In this retrospective cohort study, [...] Read more.
Background: Inflammation is central to myocardial injury and repair after ST-segment elevation myocardial infarction (STEMI). C-reactive protein (CRP) is an established biomarker of systemic inflammation, but its prognostic thresholds across patient subgroups are not well defined. Methods: In this retrospective cohort study, admission CRP was analyzed in 958 consecutive STEMI patients admitted to University Hospital Salzburg 2018–2020 and categorized into four groups (Serum CRP < 5.0, 5.0–9.9, 10.0–15, and >15.0 mg/dL). Mortality was assessed during short- (30, 90, and 180 days) and long-term (1, 3, and 5 years) follow-up. Kaplan–Meier analyses compared survival, Cox regression tested associations, and receiver operating characteristic (ROC) curves determined discriminatory value and optimal cut-offs. Results: Elevated admission CRP was associated with larger infarct size, impaired left ventricular function, and increased mortality. Kaplan–Meier curves showed progressively poorer survival with higher CRP, with worst outcomes at >15 mg/dL. At 30, 90, and 180 days, CRP demonstrated moderate discrimination (AUC 0.628, 0.653, and 0.654; all p < 0.001), with predictive cut-offs 11–15 mg/dL in the overall cohort. Subgroup analyses revealed markedly lower thresholds in vulnerable populations. Diabetic patients showed cut-offs 5–6 mg/dL with the highest AUC values (up to 0.714). Younger patients and smokers exhibited thresholds near 9–10 mg/dL, while subacute STEMI presentations demonstrated lower cut-offs compared with acute infarction. These findings indicate that the prognostic value of CRP is context-dependent rather than uniform. Conclusions: Admission CRP predicts short-term mortality after STEMI, with subgroup-specific cut-offs emerging below conventional thresholds, highlighting profiles where modest inflammatory activation carries disproportionate risk. Full article
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36 pages, 1506 KB  
Review
Chemical Precursors of Flocs in Sweetened Beverages: Mechanisms of Formation, Analytical Methods, and Industrial Strategies
by Ilona Błaszczyk, Radosław Michał Gruska, Magdalena Molska and Alina Kunicka-Styczyńska
Molecules 2026, 31(8), 1246; https://doi.org/10.3390/molecules31081246 - 9 Apr 2026
Abstract
Flocs, visible particles formed in sugar-sweetened beverages, reduce clarity and consumer acceptance of products. Their presence can be caused not only by different types of trace impurities in the sugar but also by interactions among beverage components. In this review, scientific reports on [...] Read more.
Flocs, visible particles formed in sugar-sweetened beverages, reduce clarity and consumer acceptance of products. Their presence can be caused not only by different types of trace impurities in the sugar but also by interactions among beverage components. In this review, scientific reports on acid beverage flocs (ABFs) and alcohol flocs are summarized, the main pathways for their formation are described, and practical options for detecting them and preventing their formation in beverages are compiled. Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 and related guidance, literature searches of Scopus, Web of Science (WoS), PubMed, Food Science and Technology Abstracts (FSTA), CAB Abstracts, and International Commission for Uniform Methods of Sugar Analysis (ICUMSA) resulted in the inclusion of 56 studies. In various types of beverages, complexes formed between proteins (Ps) and polyphenols (PPs) often initiate haze and floc formation, while polysaccharides (dextran, pectin, and starch), silica or silicates, and inorganic ions influence charge balance, particle bridging, and floc growth rate. Ethanol in alcohol beverages can further destabilize colloids and promote aggregation. For beet sugars, saponin–protein interactions are a likely pathway for the formation of ABF, but the available evidence is not consistent. In cane sugars, the reported roles of proteins, polysaccharides, silica, and starch in floc formation vary considerably between studies. For quality assurance, ICUMSA floc tests (GS2-40 and GS2-44) should be complemented by turbidity or haze measurement and colloid characterization such as light scattering, ζ–potential, and infrared IR-based analytical methods supported by chemometrics. Risk mitigation works best as a two-level strategy that combines impurity removal during sugar production and stabilization steps in beverage formulation and storage, including the use of clarification agents and control of pH, temperature, ionic strength, and oxygen exposure. Standardized reporting and validation of rapid predictors against ICUMSA benchmarks remain essential. Full article
(This article belongs to the Special Issue Applied Chemistry in Europe, 2nd Edition)
12 pages, 415 KB  
Article
Impact of Inflammation and Muscle Mass on Prognosis in Hospitalized Patients with Suspected Dysphagia at a Tertiary Hospital
by Mario Alfredo Saavedra-Vásquez, Juan José López-Gómez, Beatriz Ramos-Bachiller, Olatz Izaola-Jauregui, Eva López-Andrés, Isabel Pérez-Mellén, Sara Cuenca-Becerril, María Jesús Villameriel-Galván, Jaime González-Gutiérrez, Lucia Estevez-Asensio, María Ángeles Castro-Lozano and Daniel Antonio De Luis-Román
Geriatrics 2026, 11(2), 42; https://doi.org/10.3390/geriatrics11020042 - 9 Apr 2026
Abstract
Background/Objectives: Dysphagia is associated with an increased risk of in-hospital complications and adverse outcomes. Prognosis in frail hospitalized populations is influenced by systemic inflammation and reduced muscle mass. Calf circumference (CC) and an estimated appendicular skeletal muscle index (ASMI) can serve as indirect [...] Read more.
Background/Objectives: Dysphagia is associated with an increased risk of in-hospital complications and adverse outcomes. Prognosis in frail hospitalized populations is influenced by systemic inflammation and reduced muscle mass. Calf circumference (CC) and an estimated appendicular skeletal muscle index (ASMI) can serve as indirect measures of muscle mass, while inflammatory status may be captured by C-reactive protein (CRP), albumin, and the CRP/albumin ratio. This study aimed to evaluate the prognostic value of indirect biomarkers of inflammation and muscle mass to predict prognosis in hospitalized patients with suspected dysphagia. Methods: A retrospective observational study was conducted at a tertiary hospital and included patients admitted with suspected dysphagia between April 2015 and October 2024. On admission, demographic variables (sex and age), anthropometry (weight, height, and CC), EAT-10 (Eating Assessment Tool) score, and serum laboratory parameters (CRP, albumin) were collected. ASMI was estimated using the formula −10.427 + (CC × 0.768) − (age × 0.029) + (sex × 7.523)/(height2). Outcomes were in-hospital mortality and length of hospital stay. Comparisons were performed between survivors and non-survivors, and multivariable models adjusted for age and sex were used to identify independent associations with mortality. Results: A total of 4241 patients were included (51.2% women), with a median age of 85 (Interquartile range [IQR] 14) years and a mean EAT-10 score of 15.98 (SD 7.79). In-hospital mortality was 18.13% (n = 769). Non-survivors were older (86 [IQR 11] vs. 84 [IQR 14] years; p < 0.001) and displayed a more inflammatory profile, with higher CRP (78.1 [IQR 114.28] vs. 44 [IQR 96] mg/L) and CRP/albumin ratio (27.27 [IQR 43.04] vs. 13.64 [IQR 31.77]; p < 0.001), and lower albumin (3 [IQR 0.8] vs. 3.3 [IQR 0.8] g/dL; p < 0.001). They also had lower muscle mass, with reduced CC and lower ASMI in both sexes. In multivariable analysis, a higher CRP/albumin ratio was independently associated with increased odds of death (OR 1.011; 95% CI 1.008–1.014; p < 0.001), whereas a higher ASMI was protective (OR 0.885; 95% CI 0.801–0.978; p = 0.017). Higher CRP/albumin ratios were also associated with longer hospital stays and lower albumin, CC, and ASMI values. Conclusions: In hospitalized patients with suspected dysphagia, systemic inflammation and lower muscle mass were associated with worse clinical outcomes. The CRP/albumin ratio independently predicted higher in-hospital mortality and prolonged hospitalization, whereas higher estimated ASMI was associated with lower mortality risk, supporting the combined prognostic value of inflammatory and muscle-mass indicators in this population. Full article
(This article belongs to the Section Dysphagia)
19 pages, 7754 KB  
Article
The Oligosaccharyltransferase Catalytic Subunit PsSTT3B Is Required for Asexual Development and Pathogenicity in Phytophthora sojae
by Quanhe Ma, Borui Zhang, Tongshan Cui, Shanshan Chen, Shan Geng, Fan Zhang, Can Zhang and Xili Liu
J. Fungi 2026, 12(4), 274; https://doi.org/10.3390/jof12040274 - 9 Apr 2026
Abstract
N-glycosylation is a fundamental post-translational modification that contributes to protein folding, stability, and secretion in eukaryotes. The catalytic subunit STT3 of the oligosaccharyltransferase complex mediates the transfer of preassembled oligosaccharides to nascent polypeptides in the endoplasmic reticulum. Here, we identified and functionally [...] Read more.
N-glycosylation is a fundamental post-translational modification that contributes to protein folding, stability, and secretion in eukaryotes. The catalytic subunit STT3 of the oligosaccharyltransferase complex mediates the transfer of preassembled oligosaccharides to nascent polypeptides in the endoplasmic reticulum. Here, we identified and functionally characterized PsSTT3B, one of the STT3 paralogs in Phytophthora sojae (P. sojae). PsSTT3B plays an important role in the growth, development, and pathogenicity of P. sojae. CRISPR/Cas9-mediated deletion of PsSTT3B resulted in reduced vegetative growth, sporangia production, and zoospore production in P. sojae. PsSTT3B deletion mutants demonstrated significantly reduced virulence on soybean leaves and etiolated seedlings. Importantly, PsSTT3B deletion mutants also exhibited reduced zoospore germination and diminished chemotaxis toward soybean isoflavones. Moreover, deletion of PsSTT3B increased sensitivity to tunicamycin and dithiothreitol and influenced the ConA-binding glycoprotein profile. Our findings show that PsSTT3B is associated with asexual development, virulence, and sensitivity to ER stress-related conditions of P. sojae. Our study suggests that PsSTT3B represents a potential candidate gene for the prevention and control of P. sojae. Full article
(This article belongs to the Section Fungal Cell Biology, Metabolism and Physiology)
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24 pages, 2940 KB  
Article
Effects of Blood Retention Versus Blood Removal and Freeze-Drying Versus Heat-Processing Plus Drying on the Nutritional Composition of Velvet Antlers
by Xinlong Hao, Yue Zhao, Xilai Zhao, Xu Zhou, Lihong Mu, Youlong Tuo and Wenxi Qian
Processes 2026, 14(8), 1201; https://doi.org/10.3390/pr14081201 - 9 Apr 2026
Abstract
Previous studies on velvet antler processing have mainly evaluated single techniques, and systematic comparisons of processing combinations are limited. This study investigated the effects of different processing combinations on the nutritional composition and physicochemical properties of velvet antler from red deer and sika [...] Read more.
Previous studies on velvet antler processing have mainly evaluated single techniques, and systematic comparisons of processing combinations are limited. This study investigated the effects of different processing combinations on the nutritional composition and physicochemical properties of velvet antler from red deer and sika deer. A 2 × 2 factorial design was applied: Blood-Retained vs. Blood-Removed and Boiled/Fried (zhuzha; no deep-frying) vs. Vacuum Freeze-Dried. In this study, Boiled/Fried was treated as a single processing method. The four processing combinations were analyzed as independent groups using one-way ANOVA. Additionally, two-way ANOVA was conducted to evaluate the main effects of pretreatment, dehydration method, and their interaction on the measured indices. To account for species background, a three-way ANOVA (species × pretreatment × dehydration) was further conducted for key indices. Moisture, crude protein, ash, and crude fat contents were determined. All composition-related indices were evaluated on both wet-weight and dry-weight bases to distinguish moisture-driven concentration or dilution effects from processing-related retention changes. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were conducted for multivariate evaluation. Spearman’s rank correlation was used for association analysis, and Pearson’s correlation with linear regression was applied to quantify linear relationships (reported as r). Freeze-drying significantly reduced moisture content (p < 0.01) and increased crude protein content (p < 0.05). PCA and OPLS-DA demonstrated clear compositional separation among the four processing combinations, with moisture and crude protein as the main contributors (cumulative explained variance > 83%). The effects of Blood-Retained and Blood-Removed treatments differed between species. Three-way ANOVA indicated significant species-dependent effects (e.g., species × pretreatment and or species × dehydration interactions), while the pretreatment × dehydration interaction was significant for TAAs. In the Boiled/Fried groups, total amino acid content (TAA) decreased with increasing moisture. In the Freeze-Dried groups, moisture was significantly negatively correlated with TAAs in the Blood-Retained treatment (Pearson r = −0.886, p < 0.05), whereas no significant correlation was observed in the Blood-Removed treatment (r = 0.429, p > 0.05). Wet- versus dry-basis comparisons indicated that some between-treatment differences were attributable to moisture-related concentration or dilution effects, whereas differences persisting on a dry basis more directly reflected processing-related nutrient retention. Processing combinations produced species-dependent effects in velvet antler. The three-way ANOVA supported species-dependent pretreatment effects and confirmed that the influence of blood retention or removal on amino acid outcomes was contingent on the dehydration regime (pretreatment × dehydration for TAAs). From an application standpoint, no single processing route is universally optimal across all quality attributes; freeze-drying provides a robust baseline, whereas the choice of blood retention or removal should be made in a target-oriented manner (e.g., physicochemical stability versus protein and amino acid retention) while accounting for species background and interaction effects. Therefore, these findings provide a scientific basis for improving product quality, processing efficiency, and standardization in China’s velvet antler industry. Full article
(This article belongs to the Section Food Process Engineering)
31 pages, 3268 KB  
Article
Unraveling the Potential of Giardia Extracellular Vesicles as a Vaccine Candidate
by Clarissa Faria, Sandra Jesus, Bárbara Ferreira, Ágata Lourenço, Ana Isabel Sebastião, Daniela Mateus, Bruno M. Neves, Olga Borges, Maria Teresa Cruz and Maria do Céu Sousa
Pharmaceutics 2026, 18(4), 461; https://doi.org/10.3390/pharmaceutics18040461 - 9 Apr 2026
Abstract
Objectives: This study aimed to investigated the role of Giardia extracellular vesicles (EVs) in intercellular communication and to evaluated their potential as vaccine candidates. Methods: The immunomodulatory effects of Giardia EVs were assessed in mouse macrophages and human monocyte-derived dendritic cells (Mo-DCs), [...] Read more.
Objectives: This study aimed to investigated the role of Giardia extracellular vesicles (EVs) in intercellular communication and to evaluated their potential as vaccine candidates. Methods: The immunomodulatory effects of Giardia EVs were assessed in mouse macrophages and human monocyte-derived dendritic cells (Mo-DCs), with a particular focus on key inflammatory signaling pathways. In vivo immunogenicity was evaluated following EV administration, and the antigenic composition of EV cargo was characterized by proteomic analysis. Results: Giardia EVs activated pro-inflammatory signaling pathways in mouse macrphages, including SAPK/JNK, ERK1/2, and NF-κB. This activation was associated with IκB-α degradation and nuclear translocation of p65. Furthermore, EV stimulation significantly upregulated the expression of pro-inflammatory genes, including Il1β, Il6, Il4, Ptgs2, Nos2, and Tnf, with log₂ fold changes ranging from 3.9 to 15.8. Consistently, EVs increased iNOS protein expression (28–45%) and nitrite production (9.6–12.3-fold). In human Mo-DCs, Giardia EVs promoted cellular maturation, as evidenced by increased expression of MHC-II, CD80, and CD86, and enhanced T-cell proliferation with a Th1-skewed profile. In vivo immunization induced antigen-specific antibody responses, with IgG subclass distribution indicative of a balanced Th1/Th2 response. Proteomic analysis identified immunoreactive EV-associated proteins, including elongation factor 1-alpha, α-7.3 giardin, tubulin, and variant surface proteins (VSPs), which are well-established antigens in Giardia infection, with prominent bands observed at approximately 22 kDa and 50 kDa. Conclusions: Collectively, these findings demonstrate that Giardia EVs modulate innate immune responses in vitro, elicit antigen-specific humoral immunity in vivo, and contain conserved immunogenic proteins. These properties support their potential as a promising cell-free vaccine platform against giardiasis. Full article
(This article belongs to the Special Issue Next-Generation for mRNA Vaccine Delivery)
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15 pages, 3117 KB  
Article
Metabolomics-Based Analysis of Geographical Origin-Driven Quality Variation in Cultivated Pyropia haitanensis
by Wenjing Zhu, Kai Xu, Yan Xu, Dehua Ji, Wenlei Wang and Chaotian Xie
Foods 2026, 15(8), 1299; https://doi.org/10.3390/foods15081299 - 9 Apr 2026
Abstract
Pyropia haitanensis, an economically significant cultivated seaweed in China, exhibits substantial geographical variations in nutritional and sensory qualities that influence its market value. The nutritional quality of the samples, including total sugar, total protein, and amino acid content, as well as color [...] Read more.
Pyropia haitanensis, an economically significant cultivated seaweed in China, exhibits substantial geographical variations in nutritional and sensory qualities that influence its market value. The nutritional quality of the samples, including total sugar, total protein, and amino acid content, as well as color quality, assessed through phycobiliprotein and chlorophyll content, and sensory quality evaluated using an electronic nose and electronic tongue, were determined. To elucidate these quality variations, this study employed an integrated metabolomics and chemometrics approach to analyze samples from five major cultivation regions. Principal component analysis (PCA) effectively differentiated the samples; orthogonal partial least squares discriminant analysis (OPLS-DA) validated this classification with robust model parameters (R2X = 0.791, R2Y = 0.995, Q2 = 0.984) and identified key discriminatory metabolites. Weighted gene co-expression network analysis (WGCNA) identified origin-specific metabolic modules correlated with quality traits, revealing that pathways such as cysteine and methionine metabolism underpin the observed differences in flavor profiles across cultivation regions. Furthermore, mediation analysis quantitatively confirmed that inorganic nitrogen primarily influences key flavor attributes by regulating sulfur-containing amino acid and nucleotide metabolism. This study systematically elucidates the metabolic mechanisms governing quality formation in P. haitanensis, providing a scientific foundation for quality control and geographical origin traceability. Full article
(This article belongs to the Section Food Analytical Methods)
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18 pages, 1238 KB  
Article
Prognostic Value of Inflammatory Status in Patients with Acute Coronary Syndromes: A Single-Center Experience
by Ruxandra-Maria Băghină, Simina Crișan, Silvia Luca, Oana Pătru, Mihai-Andrei Lazăr, Cristina Văcărescu, Marian Morenci, Alina-Gabriela Negru, Constantin-Tudor Luca and Dan Gaiță
J. Clin. Med. 2026, 15(8), 2852; https://doi.org/10.3390/jcm15082852 - 9 Apr 2026
Abstract
Background/Objectives: Acute coronary syndromes (ACS) encompass a spectrum of clinical entities from unstable angina to non–ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI), all associated with significant morbidity and mortality. Inflammation plays a central role in the pathophysiology of [...] Read more.
Background/Objectives: Acute coronary syndromes (ACS) encompass a spectrum of clinical entities from unstable angina to non–ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI), all associated with significant morbidity and mortality. Inflammation plays a central role in the pathophysiology of ACS, contributing to atherosclerotic plaque destabilization, myocardial injury, and adverse clinical outcomes. Inflammatory biomarkers, together with N-terminal pro–B-type natriuretic peptide (NT-proBNP), are increasingly used for risk stratification, yet their prognostic value across different ACS presentations remains unclear. This study aimed to assess the prognostic value of inflammatory status in patients with acute coronary syndromes in a single-center cohort. Methods: This prospective observational study included 100 consecutive patients with ACS and elevated inflammatory biomarkers, enrolled in 2024–2025 at a tertiary cardiovascular center. Inflammatory status was assessed by using C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII); NT-proBNP was also measured. The primary endpoint was in-hospital MACE, defined as cardiovascular death, recurrent myocardial infarction, stroke, urgent coronary revascularization, or acute heart failure requiring escalation of therapy. Multivariable logistic regression and ROC analyses were performed. Results: Among the 100 ACS patients, half experienced in-hospital MACE. Compared with those without events, patients with MACE were older (p = 0.003) and had higher inflammatory biomarkers—CRP (p < 0.001; strongest association), NLR (p = 0.030), and SII (p = 0.042)—as well as higher NT-proBNP (p = 0.002). Patients with MACE also showed reduced renal function (p < 0.001) and lower left ventricular systolic function, reflected by reduced LVEF (p = 0.001), indicating concomitant renal impairment and ventricular dysfunction. Hypertension was more prevalent in the MACE group (p = 0.028), and new-onset atrial fibrillation was significantly more common among these patients (p < 0.001). In multivariable analysis, LVEF emerged as an independent predictor of short-term outcomes (OR 0.934 per 1% increase; p = 0.047). Conclusions: Inflammatory activation appears closely linked to the occurrence of in-hospital adverse events in patients with acute coronary syndromes. While left ventricular ejection fraction remained an independent determinant of short-term outcomes, inflammatory biomarkers may provide complementary insight into the inflammatory burden accompanying ACS. Full article
(This article belongs to the Special Issue Therapies for Heart Failure: Clinical Updates and Perspectives)
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23 pages, 5486 KB  
Article
Phytochemical Characterisation and Bioactivity of Picnomon acarna Extracts: LC–MS/MS Profiling, Antioxidant Capacity and Enzyme Inhibition
by Zeyneb Karakus
Molecules 2026, 31(8), 1240; https://doi.org/10.3390/molecules31081240 - 9 Apr 2026
Abstract
Picnomon acarna (L.) Cass. is a Mediterranean medicinal plant with limited phytochemical and bioactivity characterisation. In this study, methanolic extracts obtained by maceration (MAC), Soxhlet (SOE), and ultrasound-assisted extraction (UAE) were comparatively investigated to determine their phytochemical composition and biological potential. Liquid chromatography–electrospray [...] Read more.
Picnomon acarna (L.) Cass. is a Mediterranean medicinal plant with limited phytochemical and bioactivity characterisation. In this study, methanolic extracts obtained by maceration (MAC), Soxhlet (SOE), and ultrasound-assisted extraction (UAE) were comparatively investigated to determine their phytochemical composition and biological potential. Liquid chromatography–electrospray ionisation–tandem mass spectrometry (LC–ESI–MS/MS) analysis identified and quantified 24 phenolic compounds, with hesperidin, chlorogenic acid, and hyperoside as the dominant constituents. The maceration extract exhibited the highest total phenolic content (29.06 mg GAE/g extract) and showed superior antioxidant performance across six complementary assays [2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), phosphomolybdenum, and ferrous-ion chelation), reflected by the highest relative antioxidant capacity index (RACI = 0.93). Enzyme inhibition assays revealed extraction-dependent activity patterns: Soxhlet and ultrasound extracts demonstrated stronger acetylcholinesterase inhibition (IC50 ≈ 1.23 mg/mL), while Soxhlet extract showed the most potent tyrosinase (AChE) inhibition (IC50 = 1.48 mg/mL). α-Amylase inhibition was comparable among extracts (IC50 = 1.90–2.03 mg/mL). Pearson correlation analysis indicated strong relationships between major phenolics and antioxidant activity. Molecular docking further supported these findings, showing favourable binding affinities of hesperidin, hyperoside, and chlorogenic acid toward α-amylase and acetylcholinesterase, while only chlorogenic acid and hyperoside demonstrated favourable interactions with tyrosinase-related protein-1 (TYRP1), whereas hesperidin did not exhibit a meaningful binding affinity. Overall, the results demonstrate that the extraction strategy significantly influences the phenolic composition and multi-target bioactivity of P. acarna, highlighting its potential as a source of natural antioxidant and enzyme-modulating compounds. Full article
(This article belongs to the Special Issue Biologically Active Molecules from Microbes and Plants)
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23 pages, 2532 KB  
Article
Audiogenic Kindling Stimulation Fails to Induce Cerebral Overexpression of P-Glycoprotein and Limbic Crises in the GASH/Sal Model of Epilepsy
by Laura Zeballos, Jerónimo Auzmendi, Alberto Lazarowski and Dolores E. López
Int. J. Mol. Sci. 2026, 27(8), 3377; https://doi.org/10.3390/ijms27083377 - 9 Apr 2026
Abstract
Experimental evidence indicates that a high seizure burden can induce cerebral overexpression of P-glycoprotein (P-gp) at the blood–brain barrier, a phenomenon associated with drug-resistant epilepsy under the “transporter hypothesis”, but also at the neuronal level, linked to a reduced seizure threshold, increased seizure [...] Read more.
Experimental evidence indicates that a high seizure burden can induce cerebral overexpression of P-glycoprotein (P-gp) at the blood–brain barrier, a phenomenon associated with drug-resistant epilepsy under the “transporter hypothesis”, but also at the neuronal level, linked to a reduced seizure threshold, increased seizure severity (SS), status epilepticus (SE), and a high spontaneous death (SD) rate. In contrast, we recently described a progressive reduction in SS and the absence of SE and SD in GASH/Sal hamsters subjected to 45 audiogenic seizures. Here, we examined SS, SE, and the SD, and the expression of P-gp, erythropoietin receptor (EPO-R), hypoxia-inducible factor 1 alpha subunit (HIF-1α) and cyclooxygenase 2 (COX-2), in the brains of GASH/Sal hamsters following 20 audiogenic kindling stimulations (AUK-20). SS was evaluated using the midbrain and limbic severity scales; gene expression was assessed by RT-qPCR and P-gp protein levels were measured by immunohistochemistry and Western blot (IHC/WB) analysis. A modest decrease in midbrain SS was observed, without an increase in the already low limbic SS scores, and no SE or SD events occurred. P-gp levels remained low in both IHC and WB analyses. At the mRNA level, we detected increased EPO-R expression, decreased HIF-1α, and increased COX-2 without an accompanying increased in Abcb1b. Unlike findings from other experimental epilepsy models, AUK-20 in GASH/Sal hamsters does not enhance limbic SS, trigger SE or SD, or induce P-gp overexpression in the brain. Independently of the implications for drug resistance, the lack of cerebral P-gp overexpression without increased SS in the AUK-20-GASH/Sal model supports a potential role of P-gp in modulating seizure severity and epilepsy-associated mortality risk. Full article
(This article belongs to the Special Issue New Insights into Epilepsy: From Molecular Physiology to Pathology)
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12 pages, 17529 KB  
Article
The Effect of Pediococcus Lactis and Postbiotics on Gut Health and Intestinal Metabolic Profiles
by Jintao Sun, Huaiyu Zhang, Weina Liu, Jinquan Wang, Xiumin Wang, Zhenlong Wang, Hui Tao and Bing Han
Nutrients 2026, 18(8), 1184; https://doi.org/10.3390/nu18081184 - 9 Apr 2026
Abstract
Background: To investigate the effects of probiotics and their postbiotics on mouse health, this study utilized healthy mice randomly assigned to a control group (CK, n = 6), a probiotic group (L, n = 6, oral gavage 200 μL Pediococcus lactis), and [...] Read more.
Background: To investigate the effects of probiotics and their postbiotics on mouse health, this study utilized healthy mice randomly assigned to a control group (CK, n = 6), a probiotic group (L, n = 6, oral gavage 200 μL Pediococcus lactis), and a postbiotic group (PL, n = 6, oral gavage 200 μL Pediococcus lactis postbiotic). Methods: Following 21 days of continuous intervention, changes in gut metabolic profiles, microbial community structure, tissue morphology, and tight junction protein expression were systematically analyzed using metabolomics, 16S rRNA sequencing, hematoxylin and eosin (HE) staining, and immunohistochemistry techniques. Results: The results revealed that screening for significantly altered endogenous metabolites identified core differences concentrated in metabolites related to intestinal barrier repair, anti-inflammation, and antioxidant activity (e.g., 3-indolepropionic acid, astaxanthin, hydroxybenzoic acid). 16S rRNA sequencing revealed that the overall community structure was relatively stable according to principal component analysis, although differences were detected in specific taxa. However, LEfSe analysis identified significantly enriched functional microbial groups at multiple taxonomic levels in the PL group: phylum: Actinomycetota; class: Coriobacteriia; order: Coriobacteriales, Erysipelotrichales; family: Erysipelotrichaceae, Eggerthellaceae; genus: norank_Erysipelotrichaceae, Intestinimonas. These results suggest that although the overall community structure remained relatively stable, specific taxa may have differed between groups. Hematoxylin and eosin staining revealed no pathological lesions in intestinal tissues from either group, with intact mucosal architecture. Immunohistochemistry demonstrated significantly elevated expression of intestinal tight junction proteins Claudin 1, MUC-2, Occludin, and ZO-1 in the PL group compared to the CK group (p < 0.001). Conclusions: In summary, this probiotic (Pediococcus lactis) and its postbiotic showed promising effects, which may be related to changes in specific microbiota taxa, intestinal metabolic profiles, and tight junction protein expression. Beyond maintaining gut microbiota and tissue homeostasis, it enhances intestinal barrier function, suppresses latent inflammation, and boosts antioxidant capacity. Postbiotics may exhibit superior efficacy compared to probiotics. This provides robust experimental evidence for its development and application in gut health products for healthy populations. However, these findings still require further validation in studies with longer intervention periods and in disease models. Full article
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10 pages, 207 KB  
Article
Seroprevalence of Borrelia burgdorferi Antibodies in Patients with Ulcerative Colitis and Its Association with Disease Activity
by Gokhan Aydin and Taner Akyol
Pathogens 2026, 15(4), 408; https://doi.org/10.3390/pathogens15040408 - 9 Apr 2026
Abstract
Background and Aim: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by immune dysregulation. Environmental factors, including infectious agents, have been proposed to influence disease activity in inflammatory bowel disease. Although Borrelia burgdorferi has been shown to exert complex immunomodulatory effects [...] Read more.
Background and Aim: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by immune dysregulation. Environmental factors, including infectious agents, have been proposed to influence disease activity in inflammatory bowel disease. Although Borrelia burgdorferi has been shown to exert complex immunomodulatory effects on host immune responses, its seroprevalence and potential association with disease activity in patients with ulcerative colitis have not been systematically investigated. This study aimed to evaluate the seroprevalence of Borrelia burgdorferi IgG antibodies in patients with ulcerative colitis and to assess the relationship between seropositivity and laboratory markers of disease activity. Methods: In this retrospective observational study, 100 patients with ulcerative colitis (59 males, 41 females; mean age 48.5 ± 17 years) who underwent Borrelia burgdorferi IgG serological testing due to musculoskeletal or neurological symptoms suggestive of possible Lyme disease between October 2020 and October 2024 were included. Demographic characteristics, hematological and biochemical parameters, and inflammatory markers were compared between seropositive and seronegative groups. Due to the retrospective design, validated clinical disease activity indices were not consistently available; therefore, disease activity was indirectly assessed using laboratory inflammatory markers. Results: Among patients with ulcerative colitis, 22% were seropositive for Borrelia burgdorferi IgG. Seropositive patients had significantly lower uric acid, alkaline phosphatase, and C-reactive protein levels compared to seronegative patients (p = 0.001, p = 0.023, and p = 0.020, respectively). Free T4 levels were significantly higher in the seropositive group (p = 0.049). In terms of erythrocyte indices, mean corpuscular volume and mean corpuscular hemoglobin were significantly higher, while RDW-CV values were significantly lower in seropositive patients (all p < 0.05). Conclusion:Borrelia burgdorferi IgG seropositivity in patients with ulcerative colitis was associated with lower laboratory markers of systemic inflammation and a more stable hematological profile. Although causality cannot be established, these findings may suggest a potential association between prior Borrelia exposure and a distinct inflammatory phenotype in UC; however, this relationship should be interpreted with caution. Further prospective and mechanistic studies are warranted to clarify the potential immunological interactions between environmental microbial exposure and inflammatory bowel disease activity. Full article
16 pages, 1435 KB  
Article
Development of High-Internal-Phase Pickering Emulsions Stabilized by Soy Protein Isolate and Sodium Alginate as Innovative Fat Replacers for Emulsified Sausages
by Zhi Wang, Xuefei Wang, Xin Li, Chao Zhang, Fangda Sun, Qian Chen, Qian Liu, Baohua Kong and Haotian Liu
Foods 2026, 15(8), 1294; https://doi.org/10.3390/foods15081294 - 9 Apr 2026
Abstract
In this study, vegetable oil-based high-internal-phase Pickering emulsions (HIPPEs) were formulated from soy protein isolate and sodium alginate, and the effects of different replacement ratios (20–100%) of pork back fat on the quality of emulsified sausages were investigated. With the increase in the [...] Read more.
In this study, vegetable oil-based high-internal-phase Pickering emulsions (HIPPEs) were formulated from soy protein isolate and sodium alginate, and the effects of different replacement ratios (20–100%) of pork back fat on the quality of emulsified sausages were investigated. With the increase in the fat replacement ratio, cooking loss, released fat, and lipid oxidation significantly decreased (p < 0.05). Similarly, as the replacement ratio rose, L*-values, pH and springiness increased, while a*-values, hardness, cohesiveness, and chewiness showed a significant decrease. The reformulated sausages exhibited superior slice compactness, a macroscopic trait corroborated by the dense network structure observed via microstructural analysis. Electronic nose and electronic tongue measurements indicated that the inclusion of HIPPEs modulated both the aroma profiles and taste attributes of the emulsified sausages. Moreover, although differences were observed in some sensory attributes and flavor characteristics, all formulations with HIPPEs remained within an acceptable sensory range. Full article
(This article belongs to the Section Meat)
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19 pages, 1058 KB  
Article
The Causal Relationship Between Blood Zinc, Serum Transferrin and Alzheimer’s Disease in Europeans: A Two-Sample Bidirectional Mendelian Randomization Study
by Yuchen Zhang, Chenyang Hou, Hanliang Xu, Zhanhui Qiu, Ruiqing Yuan, Wei Shao, Xiangsheng Xue, Jiujing Lin, Jia Li, Haoran Zhang and Qingzhi Hou
Green Health 2026, 2(2), 10; https://doi.org/10.3390/greenhealth2020010 - 9 Apr 2026
Abstract
Background: Metal elements have been reported to be associated with Alzheimer’s disease (AD). The available epidemiological evidence for these associations is often inconsistent and prone to confounding and reverse causation. We aimed to explore the causal effects of varying metal element levels [...] Read more.
Background: Metal elements have been reported to be associated with Alzheimer’s disease (AD). The available epidemiological evidence for these associations is often inconsistent and prone to confounding and reverse causation. We aimed to explore the causal effects of varying metal element levels on AD and investigate potential underlying mechanisms. Methods: To investigate the causal link between multiple metals and AD risk, we employed a bidirectional two-sample Mendelian randomization (TSMR) approach and used single nucleotide polymorphisms (SNPs) as instrumental variables. And the participants were extracted from large GWAS databases in the European Cohort. Our analysis primarily utilized methods including inverse variance weighted (IVW), weighted median, and MR-Egger, and used sensitivity analyses to assess pleiotropy and heterogeneity. To verify the mechanism, we further used the metal element-related genes and disease-related genes to construct a protein–protein interaction (PPI) network. Results: The IVW method results from Mendelian randomization (MR) analysis showed that blood zinc was negatively associated with AD risk (OR = 0.96, 95%CI: 0.93–0.99, p = 0.016) in the forward MR analysis, whereas AD was negatively associated with serum transferrin levels (OR = 0.89, 95%CI: 0.81–0.98, p = 0.015) in the reverse MR analysis in Europeans, which was adjusted for BMI, smoking, education, and coffee intake. However, no causal links were found between blood Cu, Mg, Se, and other iron states in serum and AD risk in Europeans. The PPI network suggested that SLC39A1 played a key role in the zinc–AD relationship, and transferrin might interact with ALB, LTF, HFE, TFRC, TF, and SLC40A1 in the context of AD. Conclusions: Our TSMR study suggested that in European populations, higher blood zinc levels might exert a protective effect against AD, whereas pathology of might lead to decreased serum transferrin levels. These findings provided evidence for metal dysregulation in AD, though further validation through randomized controlled trials is required. Full article
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