Search Results (116)

In forensic medicine, spotting signs of an acute myocardial infarction (AMI) right after it happens is still a tough call, especially in sudden-death cases. Standard histology often misses changes in those critical first hours because the tissue damage is too subtle to see. To tackle this, we reviewed research (1990–2023) from PubMed and Web of Science, following PRISMA guidelines. We focused on studies that used immunohistochemistry to identify markers of early AMI in both human autopsies and animal models, specifically in the first six hours post-event. Our selection process narrowed 418 records to 37 key papers. We screened 49 markers in total, but only a handful stood out for reliable diagnosis: C5b-9, cardiac troponins, dystrophin, and H-FABP—all showing high specificity. Markers like S100A1 and IL-15 also showed promise, whereas JunB and connexin-43 appeared less dependable. We believe immunohistochemistry can add real value in early AMI identification, especially when using combinations of markers chosen for complementary strengths. Still, to make this approach practical in forensic settings, we need more studies on human samples and agreement on standardized lab protocols. Full article

To accelerate maturation of intestinal function and promote growth and development, the effect of maternal clofibrate on intestinal fatty acid (FA) metabolism was investigated in suckling piglets. Twenty-seven pregnant sows were fed either 0, 0.25, or 0.5% clofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, during late gestation and early lactation. [1-¹⁴C]-Oleic acid metabolism was measured in vitro in intestinal mucosa of piglets with/without L-carnitine and/or malonate. Clofibrate increased oleic acid metabolism on d1, and the increase was higher from 0.5% than 0.25% of maternal clofibrate (p < 0.005). Flux to CO₂ increased with age, while flux to acid-soluble products (ASP) remained constant after d1. Flux to esterified products (ESP) increased on d7, but the increase was dampened by clofibrate (p < 0.0001). Carnitine increased flux to CO_2, and malonate decreased it (p < 0.0001), but neither affected ASP or ESP. Intestinal non-esterified FA and triglyceride levels decreased linearly, and carnitine palmitoyl-transferase (CPT) activity increased quadratically with age. Clofibrate increased acyl-CoA oxidase (ACOX) abundance but decreased the ratio of CPT1A and CPT1B on d1. Postnatal age increased FA binding protein 2 (FABP2) but decreased PPARα. In conclusion, maternal supplementation of clofibrate promotes intestinal energy generation from fat oxidation in postnatal piglets, but the stimulation is influenced by age, in which ACOX, FABP2, and CPT1 might play modulatory roles. Full article

This study was conducted to investigate the effects of a Chinese herbal medicine compound microecological agent (C-MEA) on the egg production performance, ovarian follicle development, ovary transcriptome, and cecal microbiota of caged laying ducks. A total of 108 black Muscovy ducks (150 days old) were randomly divided into three groups for 30 days in a formal feeding trial. Compared with the control basic diet (Group C) and 16 g/kg C-MEA dosage (Group B), the 8 g/kg C-MEA dosage (Group A) increased egg production (average laying rate 69.35%) and follicle development (5~7 Fs, 6~7 LYFs, 11~13 SYFs) mass (p < 0.05). According to RNA-Seq, the ovaries’ transcriptome among different dietary groups enriched six key pathways, including neuroactive ligand–receptor interaction, the PPAR signaling pathway, ECM–receptor interaction, focal adhesion, the adherens junction, and the FoxO signaling pathway, as well as 46 candidate key genes. According to 16S-Seq, the microbial diversity was significantly increased in Group A, and the genus abundances of Sphaerochaeta and UCG-004 were significantly changed among different dietary groups (p < 0.05). Supplementation with C-MEA may optimize the cecal microflora and the interactions between the intestinal microflora and the host. The results from combining RNA-Seq and 16S-Seq demonstrated that the relationship between Sphaerochaeta and the hub gene cluster (F2, KNG1, C5, PLG, F2RL1, FABP1, and GCG) is the most prominent. In conclusion, the egg performance of caged laying ducks can be modulated through the microbiota–gut–ovary axis. Our findings provide new insights for improving gut health and reproductive performance of caged laying ducks. Full article

Background/Objectives: Non-Hodgkin lymphoma (NHL) is a group of blood cancers that arise in the lymphatic nodes and other tissues after an injury to the DNA of B/T lineage and NK lymphocytes. Recently, we reported that incomptine A (IA) has in vivo antilymphoma properties. This research aimed to evaluate the effects of IA in the treatment of NHL using antilymphoma activity, Tandem Mass Tag (TMT), and bioinformatics approaches. Methods: The antilymphoma activity of IA was tested on male Balb/c mice inoculated with U-937 cells. Also, TMT, gene ontology enrichment, Reactome pathway, Kyoto Encyclopedia of Gene and Genomes pathway, molecular docking, toxicoinformatic, and pharmaceutical analyses were performed. Results: By TMT analysis of the altered levels of proteins present in the lymph nodes of Balb/c mice with NHL and treated with IA, we identified 106 significantly differentially expressed proteins (DEPs), including Il1rap, Ifi44, Timd4, Apoa4, and Fabp3 as well as Myh3, Eno 2, and H4c11. Among these, the Fhl1 result was the most important cluster altered and a potential core target of IA for the treatment of NHL. Network pharmacology studies have revealed that DEPs are associated with processes such as muscle contraction, glycolysis, hemostasis, epigenetic regulation of gene expression, transport of small molecules, neutrophil extracellular trap formation, adrenergic signaling in cardiomyocytes, systemic lupus erythematosus, alcoholism, and platelet activation, signaling, and aggregation. Computational studies revealed strong binding affinities with six proteins associated with cancer, positive pharmacokinetic properties, and no toxicity. Conclusions: Our contribution suggests that IA may be a compound with potential therapeutic effects against NHL. Full article

Intramuscular fat (IMF) content determines the quality of goat meat and is regulated by the comprehensive effect of the proliferation and adipogenesis of intramuscular preadipocytes. Our previous RNA-seq data revealed that cell death-inducing DNA fragmentation factor alpha (DFFA)-like effector (CIDE) A was upregulated during the development of intramuscular fat in the longissimus dorsi muscle tissue, implying an important role in lipid homeostasis. However, the mechanism by which CIDEA, a member of the CIDE family, regulates intramuscular fat deposition in goat muscle is unknown, so we explored the function and underlying mechanism of CIDEA in goat intramuscular preadipocytes. To address this, we altered CIDEA in intramuscular preadipocytes and resolved the effect and mechanism of CIDEA in adipogenesis through RT-PCR, Western blot, triglyceride and LD determinations, CCK-8, and RNA-seq. It was found that CIDEA increased lipid droplets (LDs) and triglyceride contents and inhibited cell proliferation. Meanwhile, the lipid metabolism-related genes PPARγ, C/EBPα, SREBP1c, PLIN1, TIP47, ADFP, DGAT1, ACC, FASN, ACSL1, and FABP3 were upregulated, while the lipolysis and β-oxidation genes HSL, ACOX1, and CPT1B, as well as the proliferation marker gene CDK1, were all downregulated upon CIDEA overexpression. Differentially expressed genes in CIDEA dysregulation groups through RNA-seq were selected and were enriched in the apelin and focal adhesion signaling pathways. Specifically, the Western blot and rescue assays found that focal adhesion, but not apelin, was the key signaling pathway in CIDEA regulating lipid deposition in goat intramuscular preadipocytes. In summary, this study reveals that CIDEA promotes lipid deposition in intramuscular preadipocytes through the focal adhesion pathway and inhibits cell proliferation. This work clarifies the functional role and downstream signaling pathway of CIDEA in intramuscular fat deposition and provides theoretical support for improving meat quality by targeting key phenotype-related genes. Full article

The objective of this experiment was to investigate the effects of tartary buckwheat flavonoids (TBF) and 25-hydroxyvitamin D₃ (25-OHD) on fatty liver syndrome (FLS) in laying hens. A total of 450 35-wk-old Lohmann laying hens were selected and randomly divided into five groups, with six replicates per treatment and 15 laying hens in each replicate. The control group was fed a corn-soybean meal basal diet. The FLS group was fed a high- energy–low-protein (HELP) diet, and the other three experimental groups were fed HELP diets supplemented with 60 mg/kg TBF, 69 μg/kg 25-OHD, and 60 mg/kg TBF plus 69 μg/kg 25-OHD, respectively. The experiment lasted 8 weeks. The results demonstrated that feeding laying hens with a HELP diet led to a significant accumulation of fat in their livers, liver enlargement and yellowing, as well as a decline in liver antioxidant capacity and an aggravation of inflammation. TBF alone, 25-OHD alone, and their combination had no effect on the laying performance of laying hens fed with a HELP diet. However, 25-OHD significantly enhanced the albumin content, eggshell strength, and eggshell thickness of eggs (p < 0.05). Compared with the HELP group, TBF, 25-OHD, or their combination reduced serum LDL-C and TG (p < 0.05). The combined treatment further lowered serum NEFA and MDA, enhanced liver SOD activity (p < 0.05), and unlike TBF alone (which reduced hepatic TG) or 25-OHD alone (which decreased liver index), reduced both liver index and hepatic TG (p < 0.05). Liver gene expression analysis showed that combined TBF and 25-OHD significantly inhibited the expression of fat synthesis-related genes (ACC, FAS, GPAT1, ChREBP1, LXRα, SREBP-1C, SREBP-2, FABP) as well as inflammation-related genes (IL-6, TNF-α, NF-κB, TLR4) (p < 0.05). At the phylum level of the cecal microbiota, TBF increased the abundance of Bacteroidota (p < 0.05), and combined TBF and 25-OHD tended to increase the abundance of Firmicutes_D. At the genus level, TBF increased the abundance of Phocaeicola_A (p < 0.05). Furthermore, TBF, 25-OHD, or their combination reduced the abundance of Faecalibacterium (p < 0.05). These findings suggest that combined TBF and 25-OHD mitigates FLS in laying hens potentially through remodeling gut microbiota and maintaining lipid metabolic homeostasis. Full article

Weaning is challenging for dairy calves, frequently resulting in digestive issues. This highlights the importance of implementing appropriate nutritional strategies to enhance gut health and support optimal growth. Postbiotics is a promising alternative to traditional probiotics, conferring health benefits without the risks associated with live bacteria. This study aimed to investigate the effect of dietary supplementation with a postbiotic from dead-cell Limosilactobacillus ingluviei C37 (postbiotic LIC37) on blood biochemical parameters and jejunal epithelium transcriptomic profiles in calves. Fourteen Holstein bull calves were randomly allocated into two groups (n = 7). The control group (CON) received a basic diet, while the postbiotic group (DCLI) was supplemented with 1 g/d of postbiotic LIC37 for 90 days. Blood samples were collected on days 76, 83, and 90, respectively. The jejunal epithelial tissue was obtained from four randomly selected calves per group at day 90 for transcriptome analysis. The results showed that postbiotic LIC37 supplementation reduced globulin, total protein, neutrophil (Neu) levels, and neutrophil-to-lymphocyte ratio (NLR) levels in the DCLI group (p < 0.05). Transcriptomic analysis identified 76 differentially expressed genes (DEGs), with significant upregulation of genes involved in fatty acid metabolism (FABP1), intestinal barrier function (B4GALNT2), and detoxification (GSTA1), alongside downregulation of immune response regulation (FCRLA, FCRL4). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses highlighted enrichment in pathways related to glutathione metabolism, drug metabolism, and vitamin digestion, indicating that postbiotic supplementation improved detoxification, oxidative stress defense, and nutrient absorption in calves. This study provides novel insights into the molecular mechanisms underlying the benefits of postbiotic LIC37 and supports its potential as a sustainable alternative to probiotics in calf nutrition. Full article

Meat quality traits, particularly WHC and tenderness, are pivotal for consumer satisfaction and economic value in the sheep industry. However, their genetic regulatory mechanisms remain unclear. We used RNA-Seq and WGCNA to identify genes regulating WHC and tenderness. Sixty longissimus thoracis samples were classified into high/low WHC (HWHC vs. LWHC) and high/low tenderness (HTN vs. LTN) groups. Comparative transcriptomics identified 270 differentially expressed genes (DEGs) linked to WHC, enriched in pathways like the regulation of the ATP metabolic process and the inhibition of canonical Wnt signaling. Key DEGs (e.g., SORBS1, FOXO1, PDE4B, CDH1) correlated significantly with WHC-associated traits. For tenderness, 165 DEGs were identified, including LEP, FABP4, PLIN1, and GLP1R, enriched in PPAR signaling, fat cell differentiation, and cAMP signaling pathways. WGCNA revealed modules associated with WHC and tenderness, with hub genes (ATP2C1, GSKIP, PATL1, PPARA, CYLD) involved in ATP metabolism, lipid biosynthesis, and myofibril assembly. Tissue-specific gene integration prioritized muscle-enriched candidates (METTL21C and ACTC1) with strong trait correlations. Our findings unveil interconnected gene networks governing WHC and tenderness, highlighting some candidate genes as potential biomarkers for precision breeding. This study provides novel insights into the molecular determinants of meat quality, offering actionable targets to enhance mutton production sustainability and consumer appeal. Full article

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are major contributors to the rise in metabolic disorders, particularly in developed countries. Despite the need for effective therapies, natural product-based interventions remain underexplored. This study investigated the therapeutic effects of Endarachne binghamiae, a type of brown algae, hot water extract (EB-WE) in ameliorating obesity and MASLD using high-fat diet (HFD)-induced ICR mice for an acute obesity model (4-week HFD feeding) and C57BL/6 mice for a long-term MASLD model (12-week HFD feeding). EB-WE administration significantly reduced body and organ weights and improved serum lipid markers, such as triglycerides (TG), total cholesterol (T-CHO), HDL (high-density lipoprotein), LDL (low-density lipoprotein), adiponectin, and apolipoprotein A1 (ApoA1). mRNA expression analysis of liver and skeletal muscle tissues revealed that EB-WE upregulated Ampkα and Cpt1 while downregulating Cebpα and Srebp1, suppressing lipogenic signaling. Additionally, EB-WE activated brown adipose tissue through Pgc1α and Ucp1, contributing to fatty liver alleviation. Western blot analysis of liver tissues demonstrated that EB-WE enhanced AMPK phosphorylation and modulated lipid metabolism by upregulating PGC-1α and UCP-1 and downregulating PPAR-γ, C/EBP-α, and FABP4 proteins. It also reduced oxidation markers, such as OxLDL (oxidized low-density lipoprotein) and ApoB (apolipoprotein B), while increasing ApoA1 levels. EB-WE suppressed lipid peroxidation by modulating oxidative stress markers, such as SOD (superoxide dismutase), CAT (catalase), GSH (glutathione), and MDA (malondialdehyde), in liver tissues. Furthermore, EB-WE regulated the glucose regulatory pathway in the liver and muscle by inhibiting the expression of Sirt1, Sirt4, Glut2, and Glut4 while increasing the expression of Nrf2 and Ho1. Tentative liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis for EB-WE identified bioactive compounds, such as pyropheophorbide A and digiprolactone, which are known to have antioxidant or metabolic regulatory activities. These findings suggest that EB-WE improves obesity and MASLD through regulation of metabolic pathways, glucose homeostasis, and antioxidant activity, making it a promising candidate for natural product-based functional foods and pharmaceuticals targeting metabolic diseases. Full article

Background: As one of the most important poultry species worldwide, chickens provide substantial amounts of meat, eggs, and other products for human consumption. With continuous improvements in living standards, consumer demand for high-quality animal products is increasing, making it essential to understand the genetic basis of key traits such as egg production, meat quality, and disease resistance for targeted genetic improvement. Methods: In this study, a number of the candidate genes associated with important traits in chickens were screened by various comparative genomics analysis methods. To further clarify the relationship between these candidate genes and important traits in chickens, they were functionally annotated through the KOG, GO, and KEGG databases. Results: These candidate genes are mainly concentrated in the functional categories of transcription and signal transduction mechanisms and are involved in biological processes such as cyclic nucleotide biosynthesis and intracellular signaling, which involve signaling pathways such as ECM–receptor interactions and calcium signaling. Conclusions: Based on the annotation results from various databases, a functional search of the candidate genes and related literature reports, the following results were obtained: genes such as TBX22, LCORL, and GH were associated with chicken growth traits; genes such as A-FABP, H-FABP, and PRKAB2 were associated with chicken meat quality; genes such as IGF-1, SLC25A29, and WDR25 were associated with chicken reproductive traits; and genes such as C1QBP, VAV2 and IL12B were associated with chicken disease resistance traits. Overall, the findings of this study provide novel insights and candidate genes for genetic improvements in chickens, laying a foundation for future research and breeding strategies targeting key economic traits. Full article

The protective effect of cruciferae-derived sulforaphane (SFN) on diabetic cardiomyopathy (DCM) has garnered increasing attention. However, no studies have specifically explored its mechanistic involvement in cardiac substrate metabolism and mitochondrial function. To address this gap, Type 2 diabetes mellitus (T2DM) db/db mice were orally gavaged with vehicle or 10 mg/kg body weight SFN every other day for 16 weeks, with vehicle-treated wild-type mice as controls. SFN intervention (SFN-I) alleviated hyperglycemia, dyslipidemia, HOMA-IR, serum MDA levels, and liver inflammation. Furthermore, SFN-I improved the lipotoxicity-related phenotype of T2DM cardiomyopathy, manifested as attenuation of diastolic dysfunction, cardiac injury, fibrosis, lipid accumulation and peroxidation, ROS generation, and decreased mitochondrial complex I and II activities and ATP content, despite having no effect on ceramide abnormalities. Protein expression data revealed that the model mice exhibited upregulated cardiac CD36, H-FABP, FATP4, CPT1B, PPARα, and PDK4 but downregulated GLUT4, with unchanged MPC1 and MPC2. Notably, SFN-I significantly attenuated the increase in CD36, H-FABP, CPT1B, and PPARα. These results suggest that chronic oral SFN-I protects against DCM by mitigating overall metabolic dysregulation and inhibiting cardiolipotoxicity. The latter might involve controlling cardiac fatty acid metabolism and improving mitochondrial function, rather than promoting glucose metabolism. Full article

(1) Background: Prompt acute coronary syndrome (ACS) recognition remains challenging. This study evaluated the diagnostic and prognostic performance of novel biomarkers for non-ST-elevation myocardial infarction (NSTEMI). (2) Methods: Patients with suspected ACS presenting to Heidelberg University Hospital’s Emergency Department between August 2014 and February 2023 were analyzed. The biomarker panel included high-sensitivity cardiac troponin T (hs-cTnT), cardiac myosin-binding protein C (cMyBP-C), pro-B-type natriuretic peptide (proBNP), total N-terminal pro-B-type natriuretic peptide (t-NtproBNP), Angiotensin II (Ang2), Bone morphogenetic protein 10 (BMP10), Endothelial cell-specific molecule 1 (ESM1), fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor 15 (GDF15), and Copeptin. Negative predictive values (NPVs), sensitivities, and area under the curve (AUC) values were calculated for NSTEMI discrimination. Effectiveness and prognostic performance were assessed based on cardiovascular events at 30 days and 1 year. (3) Results: Of 1765 patients, 212 (12%) were diagnosed with NSTEMI. The European Society of Cardiology (ESC) 0/1 h and 0/3 h algorithms achieved sensitivities of 100% and 96.8%, NPVs of 100% and 99.3%, and effectiveness values of 54.8% and 66.0%. Hs-cTnT (AUC: 0.922) and cMyBP-C (AUC: 0.917) exhibited the highest diagnostic accuracy, followed by FABP3 (AUC: 0.759) and Copeptin (AUC: 0.624). Other biomarkers had lower performance (AUC: 0.516–0.617). At 1 year, event rates ranged from 0.0% to 3.4%, with the ESC algorithms demonstrating superior prognostic performance (0.8%, 2.4%). (4) Conclusions: The ESC 0/1 h and 0/3 h algorithms remain the most effective NSTEMI diagnostic strategies, balancing high sensitivity, prognostic reliability, and effectiveness. Among novel biomarkers, only cMyBP-C demonstrated comparable accuracy to hs-cTnT, supporting its potential as an adjunct to troponin assays. Full article

Pulmonary thromboembolism (PE) is a life-threatening condition that often leads to right ventricular (RV) dysfunction, a key determinant of prognosis and clinical management. Biomarkers play a crucial role in the early detection and risk stratification of RV dysfunction in PE, complementing imaging and hemodynamic assessments. Cardiac troponins, B-type natriuretic peptides, and novel biomarkers, such as heart-type fatty acid-binding protein (H-FABP) and growth differentiation factor-15 (GDF-15), provide valuable insights into myocardial injury, overload, and stress. This article explores the clinical possible significance of these biomarkers, their predictive value, and their potential to guide therapeutic strategies in patients with PE. Understanding the role of biomarkers in RV dysfunction assessment may improve patient outcomes focusing on early intervention and personalized treatment approaches. Full article

MicroRNA-204-5p (miR-204-5p) is a critical regulator of differentiation, structural maintenance, and inflammation in limbal epithelial cells (LECs). This study examined the role of miR-204-5p in modulating the gene expression related to transcription factors, cell structure, extracellular matrix remodeling, and retinoic acid signaling under normal and lipopolysaccharide (LPS)-induced inflammatory conditions. Using qPCR, we analyzed the mRNA levels of FOSL2, FOXC1, Meis2, PPARγ, ABCG2, PTGES2, IL-1β, IL-6, KRT3, KRT12, MMP2, MMP9, RARA, RARB, RXRA, RXRB, CRABP2, RBP1, RDH10, ADH7, ADH1A1, FABP5, CYP1B1, and CYP26A1, while changes in protein levels were assessed via Western blot or ELISA. Our data revealed that the overexpression of miR-204-5p reduced the mRNA levels of FOXC1, KRT12, and RDH10 under normal and inflammatory conditions (p ≤ 0.039). Additionally, it decreased FOSL2 and RXRA mRNA under normal conditions (p = 0.006, p = 0.011) and KRT3 and FABP5 mRNA under inflammatory conditions (p = 0.010, p = 0.001). The IL-6 mRNA expression was significantly increased following the LPS treatment in cells overexpressing miR-204-5p (p = 0.029). A protein analysis revealed significant reductions in FOXC1 and KRT3 in the miR-204-5p-transfected cells during LPS-induced inflammation (p = 0.020, p = 0.030). These findings suggest that miR-204-5p modulates genes critical to the differentiation, migration, and inflammatory response of LECs. The modulation of FOXC1 and KRT3 by miR-204-5p highlights these proteins as novel targets under inflammatory conditions. Full article

Diabetes mellitus has emerged as a global public health crisis, with Type 2 diabetes (T2D) constituting over 90% of cases. Current treatments are palliative, primarily focusing on blood glucose modulation. This review systematically evaluates 181 bioactive compounds isolated from 66 marine fungal strains for their inhibitory activities against key diabetes-related enzymes, including α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), dipeptidyl peptidase-4 (DPP-4), glycogen synthase kinase-3β (GSK-3β), and fatty acid-binding protein 4 (FABP4). These compounds, categorized into polyketides, alkaloids, terpenoids, and lignans, exhibit multitarget engagement and nanomolar-to-micromolar potency. The review highlights the potential of marine fungal metabolites as novel antidiabetic agents, emphasizing their structural novelty and diverse mechanisms of action. Future research should focus on overcoming challenges related to yield and extraction, leveraging advanced technologies such as genetic engineering and synthetic biology to enhance drug development. Full article