Search Results (3,971)

Background: Necrotizing pneumonia is a severe complication of Mycoplasma pneumoniae pneumonia (MPP) in children. Early recognition remains challenging because initial clinical manifestations are often non-specific, highlighting the need for a practical tool for early risk stratification. Methods: We conducted a single-center retrospective study of hospitalized children with MPP. Data from 2015–2023 were used for model development, and patients enrolled in 2024 were reserved for temporal validation. We compared candidate machine-learning algorithms and selected a parsimonious random forest model using routinely available variables obtained during the early hospitalization period. Model performance was evaluated using discrimination, calibration, and decision curve analysis, and model interpretability was assessed using SHapley Additive exPlanations (SHAP). Results: The random forest model showed good discriminatory performance in internal validation and retained acceptable performance in the 2024 temporal cohort. Calibration indicated reasonable agreement between predicted and observed risks. Decision curve analysis suggested potential clinical value as a supportive tool for early risk stratification. SHAP analysis highlighted fever duration, C-reactive protein, pleural effusion, alanine aminotransferase, and gamma-glutamyl transferase as the main contributors to model prediction. Conclusions: We developed and temporally validated a clinical prediction model for necrotizing pneumonia in children hospitalized with MPP. The model may support early risk stratification using routinely available clinical data, but it is intended to complement rather than replace clinical judgment. External prospective validation is required before routine clinical implementation. Full article

This study aimed to investigate the effects of feeding high-moisture corn (HMC) on weight performance, serum immune and antioxidant indices, rumen fermentation, microbial community, and metabolomics in Kazakh rams. A total of 32 healthy Kazakh rams were randomly divided into a control group (CT, diet with only ordinary crushed corn) and an experimental group (GS, diet with 50% ordinary crushed corn + 50% HMC), following a 7-day adaptation period and a 120-day trial period. Results showed that the F/G was significantly lower in the GS group than in the CT group (p < 0.05). FBW, net weight gain and ADG increased by 4.58%, 8.69%, and 8.70%, respectively, while ADFI decreased by 7.04% (p > 0.05). Regarding serum immune indices, IgA in the GS group was significantly higher at 40 d (p < 0.01), and IgM was significantly higher at 40, 80, and 120 d (p < 0.05). For antioxidant indices, the SOD activity in the GS group was significantly higher than that in the CT group at 120 d (p < 0.01). The CAT activity in the GS group was significantly higher at 40, 80, and 120 d (p < 0.01). Among rumen fermentation parameters, the concentration of butyric acid in the GS group was significantly lower than in the CT group (p < 0.01). Microbial diversity analysis indicated no significant differences in Alpha- and Beta-diversity of rumen microorganisms between the two groups. However, the relative abundance of Firmicutes_A at the phylum level was significantly higher in the GS group (p < 0.05), and the abundance of Cryptobacteroides was significantly higher than in the CT group (p < 0.01). Rumen metabolomic analysis identified a total of 1357 differential metabolites, among which 1130 showed significant differences, with 459 upregulated and 671 downregulated. These were mainly enriched in pathways such as Glutathione metabolism, Beta-alanine metabolism, Sphingolipid metabolism, and lysine degradation. In conclusion, feeding HMC can improve feed conversion efficiency and weight performance in Kazakh rams, regulate the structure of dominant rumen microorganisms, and enhance immune and antioxidant capacities. Full article

This study aimed to systematically elucidate the antihyperlipidemic mechanism of paeoniflorin, and we adopted an integrated multi-omics strategy to screen the key molecular targets and regulatory pathways involved in its action, followed by experimental validation to verify the potential regulatory effects of paeoniflorin on the screened targets and metabolic processes. Rats with high-fat diet-induced hyperlipidemia received paeoniflorin treatment. Liver histopathology was evaluated using hematoxylin–eosin and Oil Red O staining. Serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bile acids, activated partial thromboplastin time, prothrombin time, thrombin time, and fibrinogen were measured using a biochemical analyzer. Integrated multi-omics analyses were performed to investigate paeoniflorin’s lipid-lowering mechanism. Critical pathways and targets identified were validated using Western blotting. Paeoniflorin alleviated pathological liver damage in hyperlipidemic rats and improved blood lipid levels, coagulation function, and liver function markers. Multi-omics analyses verified that paeoniflorin downregulated the expression of TREM-1, TLR4, NF-κB, TNF-α, and IL-1β, thereby alleviating hepatic inflammation. Paeoniflorin also upregulated the expression of low-density lipoprotein receptors (LDLR), liver X receptor alpha (LXRα), and ATP-binding cassette subfamily G member 1 (ABCG1), while downregulating proprotein convertase subtilisin/kexin type 9 (PCSK9) expression, contributing to balanced cholesterol metabolism. Paeoniflorin normalized glycerophospholipid and branched-chain amino acid metabolism, which correlated with reduced inflammation and improved cholesterol metabolism. Paeoniflorin ameliorates hyperlipidemia through multitarget mechanisms, potentially by suppressing the TREM-1-TLR4-NF-κB signaling pathway to reduce inflammation and by regulating cholesterol metabolism via the PCSK9-LDLR and LXRα-ABCG1 pathways. Full article

In this study, the active components in the seed of Mangifera indica L. were isolated, the main chemical components were identified, and then their antioxidant activities and their effects on liver injury and intestinal microbiota were evaluated. The results showed that all the components of mango column chromatography exhibited antioxidant activity. F2 had the lowest IC₅₀ value of 93.61 μg/mL and exhibited the strongest DPPH radical scavenging activity. Given its superior overall antioxidant activity, F2 was selected for further compositional analysis and activity evaluation. UPLC-MS/MS analysis showed that the isolated components of mango F2 contained 11 active ingredients, including mangiferin, gallic acid and quercetin. The results showed that specific mango fractions significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and showed a protective effect on liver injury induced by alcohol. rRNA sequencing analysis showed that high alcohol intake could reduce the species diversity of intestinal microbiota in mice, and mango fractions could effectively alleviate this phenomenon. High alcohol intake decreases the relative abundance of Bacteroidota and increases the abundance of Bacillota and Thermodesulfobacteriota phyla. The high-dose mango group alleviated the above changes, which was manifested by an increase in the relative abundance of Bacteroidota and Thermodesulfobacteriota bacteria. The relative abundance of families such as Muribaculaceae in the high-dose mango group decreased compared to the model group. This study provides a scientific basis for the analysis and high-value utilization of mango components, and provides a new alternative for protecting against alcoholic liver injury and regulating intestinal microbiota. Full article

The global prevalence of obesity continues to rise, posing serious risks to human health largely because obesity itself leads to metabolic disorders of carbohydrate and lipids. Currently, effective and healthy interventions for lowering blood glucose, reducing blood lipids, and promoting weight loss remain limited due to the complexity of obesity development. Lactobacillus plantarum (GDMCC 1.140) was shown to promote catabolic processes and reduce hepatic lipid accumulation in largemouth bass fed with high-starch feed (HSF) in our previous study; however, molecular mechanisms underlying the function of this probiotic remain unclear. Here, we evaluated the effects of L-carnosine, one of metabolites produced by Lactobacillus plantarum, on carbohydrate and lipid metabolisms in an obesity model of zebrafish, which was induced by HSF. Histopathological analyses of livers from different groups indicated that a dietary supplement with L-carnosine can alleviate hepatic impairment and reduce lipid accumulation in the hepatocytes of obese zebrafish. Transcriptomic analyses revealed that L-carnosine supplementation can reverse the expression of about 70 HSF-induced genes, mainly gene-specific transcription regulators and metabolite interconversion enzymes. Furthermore, approximately 250 HSF-inhibited genes were found to be up-regulated by L-carnosine, reaching levels comparable to those in normal-starch feed (NSF) zebrafish. These genes, targeted by L-carnosine and inhibited by HSF, are highly enriched in GO terms such as lipid metabolic process, small molecule metabolic process, and cellular response to chemical stimulus, with monocarboxylic acid metabolic process, modified amino acid metabolic process and aldehyde metabolic process following, and in KEGG pathways of carbohydrate, lipid and amino acid metabolisms, such as pentose and glucuronate interconversions, glycolysis/gluconeogenesis, glycerolipid metabolism, pentose phosphate pathways, fatty acid degradation, beta-alanine metabolism and arginine and proline metabolism. These findings provide functional and molecular evidence that L-carnosine can ameliorate HSF-induced disorders of carbohydrate and lipid metabolisms. Full article

Background/Objectives: Sea urchin gonads (“roe”) are a valuable seafood product and a chemically complex matrix whose composition varies with physiology and environment. We present a biphasic extraction and ¹H NMR workflow to build a reusable reference inventory of polar metabolites and apolar lipid features in Paracentrotus lividus. Methods: Gonads from 37 adults (23 males, 14 females) collected at two sites (Alicante and Jávea–Dénia, Spain; October 2024) were lyophilized, extracted with methanol/chloroform/water, and analyzed by 400 MHz ¹H NMR in buffered aqueous solution (polar) and CDCl₃ (apolar). Polar metabolite identification combined 1D patterns with database matching and ¹H–¹³C HSQC confirmation on representative samples, yielding 71 annotated resonances corresponding to 37 metabolites spanning amino acids, osmolytes/quaternary amines, carbohydrates/aminosugars, and nucleoside/purine-related compounds. Results: Polar fingerprints enabled supervised modelling: PLS-LDA separated sexes with low cross-validated error, and SPA/COSS ranking highlighted glycine, alanine, creatine and osmolyte-associated signals as key discriminants; pathway mapping supported the enrichment of amino-acid and one-carbon/purine networks. Apolar spectra were annotated at the motif level and used for lipid-index estimation, indicating substantial unsaturation but low docosahexaenoic acid (DHA) and modest sex effects. Conclusions: The curated peak lists and reporting framework facilitate reproducible NMR annotation and future comparative studies of P. lividus gonads. Full article

Hyperuricemia is associated with liver dysfunction, yet its molecular mechanisms remain unclear. This study investigated high uric acid (HUA)-induced hepatocyte injury using a hyperuricemia mouse model (HUM) and uric acid (UA)-treated L02 cells. HUM exhibited elevated aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and pathological liver changes. Transmission electron microscopy (TEM) confirmed ferroptotic hallmarks, including mitochondrial shrinkage and increased membrane density. UA exposure upregulated NADPH oxidase 4 (NOX4), increased reactive oxygen species (ROS), and promoted lipid peroxidation (LPO), accompanied by intracellular Fe²⁺ accumulation. Mechanistically, UA increased hypoxia-inducible factor-2α (HIF-2α) expression, subsequently upregulating iron transporters divalent metal transporter 1 (DMT1) and transferrin receptor (TFRC). Deferoxamine (DFO) treatment effectively reversed Fe²⁺ overload and alleviated oxidative stress. Notably, pharmacological inhibition or genetic knockdown of HIF-2α specifically suppressed DMT1 upregulation and restored iron homeostasis, while TFRC expression remained unaffected. Blocking the HIF-2α/DMT1 axis significantly reduced LPO and mitochondrial dysfunction. These findings demonstrate that HUA induces hepatocyte ferroptosis through HIF-2α-mediated DMT1 upregulation, leading to Fe²⁺ overload and mitochondrial impairment. This study identifies the HIF-2α/DMT1 pathway as a key driver of HUA-induced liver injury and a potential therapeutic target. Full article

Diabetic cognitive impairment (DCI) is a serious and growing public health concern. The role of N6-methyladenosine (m⁶A), the predominant mRNA modification in the mammalian brain, in DCI pathogenesis remains not fully elucidated. Here, GEO-derived diabetes datasets were combined with in vivo and in vitro models to reveal aberrant expression of m⁶A-related genes. The results showed that the overall level of m⁶A RNA methylation in both the diabetic group and the high-glucose group was significantly decreased compared to the normal group. In addition, the expression of methyltransferase METTL3, which is involved in the regulation of m⁶A RNA methylation, was downregulated in both diabetic and hyperglycemic groups, and was positively correlated with the downregulation of the overall m⁶A level. Neuronal models with stable METTL3 knockdown were generated using lentiviral transduction. Subsequent ¹H-NMR metabolomic and MeRIP-qPCR analyses demonstrated that METTL3 deficiency disrupts key metabolic pathways, including phosphatidylethanolamine and phosphatidylcholine biosynthesis and glucose–alanine metabolism, and identified Fgf15 (the mouse ortholog of human FGF19) and H6PD as candidate downstream targets. Collectively, these data suggest that METTL3-dependent m⁶A RNA methylation alterations may contribute to DCI through metabolic dysregulation, positioning METTL3 as a promising therapeutic target for DCI. Full article

Ischemia and reperfusion (IR) injuries may produce deleterious effects on hepatic tissue after liver surgery and transplantation. The consequences of IR are more evident in pathological steatotic livers. Spirulina (Arthrospira platensis) is known for its potential to modulate inflammatory responses and enhance antioxidant defenses. The current investigation assessed whether spirulina pretreatment mitigates hepatic IR injury exacerbated by steatosis in rats. Thirty male Wistar rats were divided into five groups: sham, IR, HFD, HFD + IR, and SP1000 (HFD + IR + spirulina 1000 mg/kg/day; oral gavage). Liver injury, oxidative stress, inflammatory signaling, and inflammasome/pyroptosis-related markers were assessed using serum transaminases, hematoxylin–eosin staining, immunofluorescence, and qRT-PCR. High-fat diet-fed rats developed steatosis, which significantly worsened IR-induced liver damage, as shown by the respective steatosis histological score, the elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and higher expression of inflammatory markers, including Toll-like receptor (TLR4), nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β) and inflammasome/pyroptosis-related transcripts, namely NOD-like receptor family pyrin domain-containing 3 (NLRP3), interleukin-18 (IL18), and gasdermin D (GSDMD). Oxidative stress was exacerbated, as reflected by higher levels of malondialdehyde (MDA) and reduced antioxidant defenses (superoxide dismutase (SOD) activity, reduced glutathione (GSH) content, glutathione peroxidase (GPx) expression, and heme oxygenase-1 (HO-1) expression). Furthermore, HFD + IR upregulated sterol regulatory element-binding protein-1c (SREBP-1c) expression and downregulated AMP-activated protein kinase (AMPK) expression. Spirulina supplementation significantly attenuated liver injury and transaminase release, reduced MDA, restored antioxidant parameters, downregulated inflammatory and inflammasome-related gene expression, and shifted both SREBP-1c and AMPK expressions toward control levels. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and depression frequently occur together. Identifying the genes that influence both MASLD and depression may facilitate the discovery of biological pathways associated with disease risk. Methods: We recruited 525 participants from Mexican American families living in the Rio Grande Valley of south Texas. We collected clinical data, biometric measurements, hepatic health assessments using Vibration-Controlled Transient Elastography (VCTE), and depression evaluations determined with the Beck Depression Inventory-II. We estimated the heritability (h²) of MASLD-related measures, depression status, aspartate aminotransferase (AST), alanine aminotransferase (ALT), the AST/ALT ratio, and Vibration-Controlled Transient Elastography measurements. For each gene, we derived a genetic endophenotype representing its expression level. We then performed functional network and gene ontology enrichment analyses to characterize the underlying protein pathways. Results: We observed significant associations between the expression of two genes, Thyroid Hormone Receptor-Associated Protein 3 (THRAP3) (h² = 0.56 [0.45, 0.67]) and ADAM Metallopeptidase with Thrombospondin Type 1 Motif 7 (ADAMTS7) (h² = 0.66 [0.55, 0.77]), with depression and multiple MASLD-related phenotypes. We identified 351 genes with expression levels significantly correlated with one or more MASLD phenotypes and depression. Among these, five genes—ADAMTS7, THRAP3, CHPM4A, RAB9A, and PDIA3—were jointly associated with three phenotypes: AST/ALT, ALT, and Controlled Attenuation Parameter (CAP kPa). Based on the Fisher Combined Test, only THRAP3 (p = 3.0 × 10⁻²) and ADAMTS7 (p = 2 × 10⁻²) were jointly significant for depression (BDI-II) and AST, ALT, AST/ALT ratio, FAST, and CAP (kPa). We present a protein–protein interaction network comprising nodes (proteins) and edges (interactions), and a gene ontology enrichment analysis of cellular components. Discussion: Our findings highlight pleiotropic genes underlying MASLD and depression. Two genes, ADAMTS7 and THRAP3, warrant further investigation as potential targets for therapeutic interventions to manage MASLD and depression among Mexican Americans. These results may improve our understanding of the pathways involved in these two diseases, advance current research, and contribute to improvements in personalized medicine. Conclusion: We identified possible shared gene expression phenotypes linking MASLD and depression, which may provide insight into a common molecular underpinning. Pathway enrichment and gene analysis were used to help refine networks and enhance our understanding of complex gene-environmental interactions and their implications for precision medicine. Full article

Salt stress is an injurious concern of global climate change that negatively impacts the growth and yield of rice plants. Identifying salt tolerance genes is essential to understanding the molecular mechanism regulating salt tolerance in rice. In this study, we treated two rice varieties, Xiangxiuzhan (XXZ) and Changxiang (CXG), with 100 mM NaCl to examine the effect on the germination and growth stages. Transcriptome analysis was investigated for changes in gene expression between the two varieties. During the germination stage, the CXG variety had higher germination potential than the XXZ variety, whereas in the growth stage, the XXZ variety showed higher survival efficiency than the CXG variety. Transcriptome analysis showed that the XXZ variety had more DEGs in grains, while CXG displayed greater DEGs in leaves and roots. Gene Ontology (GO) and KEGG pathway showed that beta-alanine metabolism, cutin biosynthesis, and plant hormone signal transduction were over-represented, whereas heatmap analysis showed cellular and environmental signal transduction. This study focuses on the molecular pathways of the salt stress tolerance mechanism of Xiangxiuzhan and Changxiang varieties. Full article

Background: Total parenteral nutrition (TPN) is widely used after major gastrointestinal surgery; however, its early systemic metabolic effects and temporal adaptation patterns remain incompletely characterized. This study applied a longitudinal plasma metabolomics approach to investigate time-dependent metabolic changes during early TPN administration. Methods: Plasma samples were collected from patients undergoing gastrointestinal surgery before TPN initiation (baseline, T0) and at 24 h (T1), 48 h (T2), and 72 h (T3). Untargeted metabolomic profiling was performed using complementary gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS) platforms. In total, 111 metabolites were detected. Analysis of variance (ANOVA) with baseline (T0) as the reference identified time-point–specific metabolic alterations during TPN administration. Results: At 24 h (T1), nominally significant increases were observed in glycine, tryptophan, isoleucine, and methionine, accompanied by decreases in sarcosine and oxalic acid. At 48 h (T2), elevated levels of glycine, isoleucine, valine, and phenylalanine persisted, while sarcosine, oxalic acid, and myo-inositol remained decreased. By 72 h (T3), sustained increases in glycine, isoleucine, valine, phenylalanine, proline, alanine, and tryptophan were accompanied by reduced levels of sarcosine, oxalic acid, and glucopyranose, reflecting coordinated alterations across multiple metabolite classes. Conclusions: Overall, the results demonstrated a distinct longitudinal metabolomic pattern characterized by increases in circulating amino acids and time-dependent changes in carbohydrate- and lipid-related metabolites within the first 72 h of TPN. This exploratory, time-resolved metabolomic study in 37 patients highlights the utility of untargeted metabolomics for characterizing early metabolic adaptation to parenteral nutrition and supporting postoperative metabolic monitoring. Full article

Objective: To evaluate the efficacy of Roux-en-Y gastric bypass (RYGB) in improving glucose regulation and metabolic parameters in feline diabetes mellitus (FDM). Methods: FDM was experimentally induced via partial pancreatectomy, splenectomy, and dexamethasone administration. Following insulin stabilization, the RYGB cohort underwent gastric bypass, while the medical management group received glargine insulin. Untreated diabetic controls were monitored for 12 weeks. Blood glucose (GLU), fructosamine (FRU), biochemical profiles, and metabolic hormones were evaluated pre- and post-intervention. Hepatic and pancreatic tissues were collected for histopathological examination. Results: GLU and FRU concentrations in the RYGB group were significantly lower than in diabetic controls (p < 0.05), remaining comparable to the insulin-treated group (p > 0.05). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were significantly reduced post-RYGB (p < 0.05), closely matching insulin therapy outcomes (p > 0.05). Hormonal assays demonstrated decreased gastric inhibitory polypeptide (GIP) and elevated glucagon-like peptide-1 (GLP-1) in RYGB cats. Histopathologically, the RYGB group exhibited attenuated hepatic steatosis and a higher density of pancreatic islet cells with abundant cytoplasm compared to the control groups. Conclusions: RYGB effectively restores glycemic control and metabolic hormone balance in FDM, promoting morphological improvements in pancreatic islets and offering a highly promising alternative therapy for diabetic felines. Full article

Background and Objectives: Isoniazid monotherapy has been the most widely used treatment for latent tuberculosis infection (LTBI). Although effective, it has been associated with poor adherence and a higher incidence of adverse events. The shorter duration of rifamycin-based regimens has become increasingly preferable. The one month of daily rifapentine plus isoniazid (1HP) has demonstrated low toxicity and higher completion rates in HIV-infected populations. This study aims to compare the completion rate and adverse events between the 1HP and daily isoniazid for 6 months (6H) regimens in the non-HIV adult population. Materials and Methods: Retrospective, observational, longitudinal study, followed at the National Reference Center for Tuberculosis (Lisbon, Portugal), from January 2024 to January 2025. Treatment-related symptoms and liver function were assessed throughout the treatment. Relevant hepatic toxicity was defined as aspartate transaminase (AST) and/or alanine transaminase (ALT) > 1.5 times the upper limit of normal (ULN). Results: A total of 90 and 74 patients were assigned to the 1HP and 6H groups, respectively. No significant differences were observed in the frequency of reported adverse symptoms between the 1HP and 6H groups (28.9% vs. 23.0%, p = 0.4). The 1HP regimen was associated with a significantly lower risk of relevant hepatic toxicity (4.6% vs. 32.9%, p < 0.001) and a higher rate of treatment completion (97.8% vs. 67.6%, p < 0.001). Adverse drug reactions were the leading cause of treatment discontinuation in both groups, with hepatic toxicity and gastrointestinal intolerance being the most frequent events. A therapeutic switch to rifampicin was required in 16.2% of patients receiving the 6H regimen, whereas no switch was needed in the 1HP group. Conclusions: The 1HP regimen was associated with a higher rate of treatment completion and lower hepatic toxicity with no significant differences in the reported adverse symptoms. Full article

Sepsis-induced liver injury (SILI) stands as an independent prognostic factor for mortality among patients diagnosed with sepsis. Maresin-1 (MaR1) is a proresolving lipid mediator. However, its significance in SILI is uncertain. The current study sought to investigate MaR1’s effectiveness in treating SILI, as well as its molecular mechanism. In male C57BL/6J mice, we generated a SILI model by using cecal ligation and puncture (CLP). We further investigated how MaR1 influences inflammation, hepatic autophagy and apoptosis. We showed that treatment with MaR1 ameliorates SILI-induced hepatic injury, as reflected in decreased blood level of the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes, as well as better appearance of liver tissues. Furthermore, this medication markedly reduced the expression of inflammatory mediators. Importantly, MaR1 inhibited hepatocyte apoptosis by regulating the Bax/Bcl-2 ratio, decreasing cleaved caspase-3 expression, lowering apoptotic cell count, and increasing autophagy. The findings demonstrated that MaR1 treatment reduced p62 protein expression while raising Beclin1 levels and the LC3-II/LC3-I ratio, and facilitated autophagosome formation. The observed effects were most likely due to the stimulation of PI3K/Akt signaling, which was completely prevented by LY294002 (LY), a specific PI3K inhibitor. MaR1’s protective effect in SILI may be mediated via stimulation of the PI3K/Akt pathway, which reduces inflammation and regulates apoptosis and autophagy. Our results give additional experimental evidence of the potential therapeutic uses of MaR1 in the treatment of SILI. Full article