Search Results (1,249)

In this study, we investigated the effects of air packaging, vacuum packaging and modified atmosphere packaging (CO₂/N₂: 80/20) on the purine metabolism and enzyme activities of refrigerated large yellow croakers. The results showed that modified atmosphere packaging significantly inhibited microbial growth, delayed adenosine triphosphate degradation and maintained higher IMP content (1.93 μmol/g on day 21) compared to the air packaging group (2.82 μmol/g on day 12). The total purine content increased with storage time, with hypoxanthine content increasing significantly and occupying most of the total content, which was the key factor for the elevation of purine, followed by adenine content showing a significant decreasing trend. Hypoxanthine accumulation was significantly suppressed in the modified atmosphere packaging group (2.31 μmol/g on day 18), which was much lower than that in the air packaging group (5.64 μmol/g), whereas xanthine and guanine did not show significant differences among the groups. The key enzymes xanthine oxidase and purine nucleoside phosphorylase were much less active in modified atmosphere packaging, effectively delaying the cascade reaction of inosine monophosphate → hypoxanthine → xanthine. The study confirmed that modified atmosphere packaging intervenes in purine metabolism through enzyme activity regulation, providing a theoretical basis for the preservation of low purine aquatic products. Full article

Poliovirus represents an oncolytic agent for human glioblastoma—one of the most aggressive types of cancer. Since interference of viruses with metabolic and redox pathways is often linked to their pathogenesis, drugs targeting metabolic enzymes are regarded as potential enhancers of oncolysis. Our goal was to reveal an imprint of poliovirus on the metabolism of glioblastoma cell lines and to assess the dependence of the virus on these pathways. Using GC-MS, HPLC, and Seahorse techniques, we show that poliovirus interferes with amino acid, purine and polyamine metabolism, mitochondrial respiration, and glycolysis. However, many of these changes are cell line- and culture medium-dependent. 2-Deoxyglucose, the pharmacologic inhibitor of glycolysis, was shown to enhance the cytopathic effect of poliovirus, pointing to its possible repurposing as an enhancer of oncolysis. Inhibitors of polyamine biosynthesis, pyruvate import into mitochondria, and fatty acid oxidation exhibited antiviral activity, albeit in a cell-dependent manner. We also demonstrate that poliovirus does not interfere with the production of superoxide anions or with levels of H₂O₂, showing an absence of oxidative stress during infection. Finally, we showed that a high rate of poliovirus replication is associated with fragmentation of the mitochondrial network, pointing to the significance of these organelles for the virus. Full article

Background: Salmonella infections pose a serious threat to both animal and human health worldwide. Notably, there is an increasing trend in the resistance of Salmonella to fluoroquinolones, the first-line drugs for clinical treatment. Methods: Utilizing Salmonella Typhimurium CICC 10420 as the test strain, ciprofloxacin was used for in vitro induction to develop the drug-resistant strain H1. Changes in the minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined using the broth microdilution method. Transcriptomic and metabolomic analyses were conducted to investigate alterations in gene and metabolite expression. A combined drug susceptibility test was performed to evaluate the potential of exogenous metabolites to restore antibiotic susceptibility. Results: The MICs of strain H1 for ofloxacin and enrofloxacin increased by 128- and 256-fold, respectively, and the strain also exhibited resistance to ceftriaxone, ampicillin, and tetracycline. A single-point mutation of Glu469Asp in the GyrB was detected in strain H1. Integrated multi-omics analysis showed significant differences in gene and metabolite expression across multiple pathways, including two-component systems, ABC transporters, pentose phosphate pathway, purine metabolism, glyoxylate and dicarboxylate metabolism, amino sugar and nucleotide sugar metabolism, pantothenate and coenzyme A biosynthesis, pyrimidine metabolism, arginine and proline biosynthesis, and glutathione metabolism. Notably, the addition of exogenous glutamine, in combination with tetracycline, significantly reduced the resistance of strain H1 to tetracycline. Conclusion: Ciprofloxacin-induced Salmonella resistance involves both target site mutations and extensive reprogramming of the metabolic network. Exogenous metabolite supplementation presents a promising strategy for reversing resistance and enhancing antibiotic efficacy. Full article

Codonopsis pilosula polysaccharides have demonstrated multiple biological activities including immune regulation, antitumor, and antioxidant properties. The rapid development and integrated application of multi-omics can facilitate the unraveling of the complex network of immune system regulation. In this study, C. pilosula alkali-extracted polysaccharide (CPAP) were prepared, and their effects on gut microbiota compositions, metabolic pathways, and protein expressions in peripheral blood and solid tumors in mice were further evaluated. The 16S rDNA sequencing results showed that CPAP could effectively promote the enrichment of intestinal Lactobacillus in tumor-bearing mice. In addition, it could be inferred from peripheral blood and solid tumor proteomics results that CPAP might activate T cell-mediated antitumor immune functions by regulating purine metabolism and alleviate tumor-caused inflammation by promoting neutrophil degranulation, finally inducing apoptosis in tumor cells by increasing oxidative stress. These results will provide a theoretical foundation and data support for the further development of CPAP as dietary adjuvants targeting immune deficiency-related diseases. Full article

Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC. Methods: Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models. Results: It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2. Conclusions: This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment. Full article

Triticale (Triticosecale Wittmack) is a versatile forage crop valued for its high yield, balanced nutrition, and environmental adaptability. However, the dough-stage triricale has higher dry matter and starch content but lower water-soluble carbohydrate levels than earlier stages, posing fermentation challenges that may impair silage quality. This study aimed to investigate the effects of lactic acid bacteria inoculation on the fermentation quality, bacterial community, and metabolome of whole-plant triticale silage at the dough stage. Fresh triticale was ensiled for 30 days without or with an inoculant containing Lactiplantibacillus plantarum and Streptococcus bovis. Fermentation quality, bacterial succession, and metabolic profiles were analyzed at multiple time points. Inoculation significantly improved fermentation quality, characterized by a rapid pH drop, increased lactic acid production, and better preservation of fiber components. Microbial analysis revealed that inoculation successfully established Lactobacillus as the dominant genus while suppressing spoilage bacteria like Enterobacter and Clostridium. Metabolomic analysis on day 30 identified numerous differential metabolites, indicating that inoculation primarily altered pathways related to amino acid and purine metabolism. In conclusion, inoculating dough-stage triticale with this LAB combination effectively directs the fermentation trajectory. It enhances silage quality not only by optimizing organic acid profiles and microbial succession but also by modulating key metabolic pathways, ultimately leading to improved nutrient preservation. Full article

The paper proposes a putative prebiotic scenario leading to homochirality in the RNA world. In this scenario, racemic ribose, the only chiral moiety in RNA, was enantioseparated (in its pyranose form) on a chiral surface formed by the adsorption of (prochiral) nucleobases (NBs) on a mineral or metal. Purine bases (adenine and guanine) are more likely candidates for this process than pyrimidine bases because they have more H-bond donors and acceptors. Another possible candidate surface for the enantioseparation of ribose would be formed by the adsorption of nucleobase pairs, e.g., guanine–cytosine (GC). Interactions of ribose molecules with hydrogen bond donors and acceptors of NBs or NB pairs (located on the surface) enforced the orientation of ribose molecules in two directions perpendicular to each other and parallel to the surface. Consequently, the energy of interactions of enantiomers of the sugar with the surface was not the same. Thus, a solvent moving along the surface caused the enantiomers of ribose to move with different rates, resulting in the enantioseparation of ribose in a chromatography-like process. The same process would also separate ribose from other monosaccharides in the mix. Hydrogen bonding between nucleobases was also pivotal in the formation of large homochiral domains on the surfaces. Full article

Staphylococcus aureus, a major cause of foodborne illness globally, presents significant challenges due to its multidrug resistance and biofilm-forming capabilities. Pyruvate carboxylase (PycA), a metabolic master switch linking glycolysis and the tricarboxylic acid (TCA) cycle, is a potential target for controlling S. aureus. In this study, a pycA mutant was constructed and analyzed using phenotypic assays and proteomics to investigate its role in virulence and antimicrobial resistance. The results showed that deletion of pycA in the foodborne methicillin-resistant strain ATCC BAA1717 resulted in a 4- to 1024-fold reduction in resistance to β-lactams, aminoglycosides, and macrolides; a 23.24% impairment in biofilm formation; and a 22.32% decrease in staphyloxanthin production, a key antioxidant essential for survival in oxidative food environments. Proteomic analysis revealed downregulation of the TCA cycle, purine biosynthesis, surface adhesins (FnbA/B, SasG), and β-lactamase (BlaZ), linking PycA-mediated metabolism to phenotypes relevant to food safety. These findings underscore the importance of PycA as a metabolic regulator crucial for S. aureus resilience in food systems, suggesting novel strategies to combat foodborne staphylococcal infections through metabolic interference. Full article

Temperature is the most critical factor in fish preservation. Superchilled storage represents a novel technology that effectively retards quality deterioration in aquatic products. This study investigated the flavor variation patterns and deterioration mechanisms in 16 northern pike (Esox lucius) samples during superchilled storage (−3 °C) based on analysis using gas chromatography-ion mobility spectrometry (GC-IMS) and ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The results indicate that GC-MS analysis identified 25 key volatile flavor compounds. These comprised seven ketones, thirteen alcohols, aldehydes including 2-methylbutanal, esters such as 2-heptyl acetate and methyl butyrate, as well as nitrogen-containing compounds, exemplified by pyrazines and indole. Non-targeted metabolomics further revealed four pivotal metabolic pathways, glycerophospholipid metabolism, purine metabolism, the pentose phosphate pathway, and arginine biosynthesis. These metabolic pathways were found to regulate flavor changes through modulation of lipid oxidation, nucleotide degradation, and amino acid metabolism. Notably, the arginine biosynthesis pathway exhibited significant correlations with the development of characteristic cold-storage off-flavors, mediated by glutamate accumulation and fumarate depletion. This investigation provided a theoretical foundation for optimizing preservation strategies in cold-water fish species at the molecular level. Full article

Optimizing the metabolizable protein level in ruminant diets represents a promising strategy to increase nitrogen use efficiency and mitigate environmental pollution. This study explored the impacts of varying metabolizable protein (MP) levels on amino acid (AA) balance, nitrogen (N) utilization, and the ruminal microbiota in Hu lambs. Fifty-four female Hu lambs of 60 d old, with an average body weight (BW) of 18.7 ± 2.37 kg, were randomly allocated to three dietary MP groups: (1) low MP (LMP, 7.38% of DM), (2) moderate MP (MMP, 8.66% of DM), and (3) high MP (HMP, 9.93% of DM). Three lambs with similar BW within each group were housed together in a single pen, serving as one experimental replicate (n = 6). The feeding trial lasted for 60 days with 10 days for adaptation. The final BW of lambs in the MMP and HMP groups increased (p < 0.05) by 5.64% and 5.26%, respectively, compared to the LMP group. Additionally, lambs fed the MMP diet exhibited an 11.6% higher (p < 0.05) average daily gain than those in the LMP group. Increasing dietary MP levels enhanced (p < 0.05) N intake, urinary N, retained N, and percent N retained, but decreased apparent N digestibility (p < 0.05). Urinary uric acid, total purine derivatives, intestinally absorbable dietary protein, microbial crude protein, intestinally absorbable microbial crude protein, and actual MP supply all increased (p < 0.05) with higher MP values in the diet. The plasma concentrations of arginine, lysine, methionine, phenylalanine, threonine, aspartic acid, proline, total essential AAs, and total nonessential AAs were the lowest (p < 0.05) in the LMP group. In the rumen, elevated MP levels led to a significant increase (p < 0.05) in the ammonia N content. The relative abundances of Candidatus_Saccharimonas, Ruminococcus, and Oscillospira were the lowest (p < 0.05), whereas the relative abundances of Terrisporobacter and the Christensenellaceae_R-7_group were the highest (p < 0.05) in the MMP group. In conclusion, the moderate dietary metabolizable protein level could enhance growth performance, balance the plasma amino acid profiles, and increase nitrogen utilization efficiency in Hu lambs, while also altering the rumen bacterial community by increasing beneficial probiotics like the Christensenellaceae_R-7_group. Full article

In recent years, gut microbiota has emerged as a critical regulator of gastrointestinal health and disease, with its role in inflammatory bowel disease (IBD)—including Crohn’s disease and ulcerative colitis—being particularly significant. Among the many factors influencing the gut microbiota, dietary components such as fibers, fats, and polyphenols have received substantial attention. However, nitrogen-containing compounds, such as amino acids, nitrates, urea, and even nucleic acids, such as purines, remain underexplored despite their integral role in shaping microbial ecology, host metabolism, and immune responses. Some of these compounds are metabolized by gut bacteria into bioactive molecules such as short-chain fatty acids, ammonia, and nitric oxide, which exert diverse effects on mucosal integrity and inflammation. IBD pathophysiology is characterized by chronic inflammation, microbial dysbiosis, and compromised epithelial barriers. Nitrogen metabolism contributes significantly to these processes by influencing microbial composition, metabolite production, and host immune pathways. The breakdown of various nitrogen-containing compounds in the body leads to the production of byproducts, such as ammonia and hydrogen sulfide, which have been implicated in mucosal damage and immune dysregulation. At the same time, nitrogen-derived molecules, such as short-chain fatty acids and nitric oxide, exhibit protective effects, underscoring the dual role of dietary nitrogen in health and disease. This narrative review highlights the complex interactions between dietary nitrogen sources, gut microbiota, and IBD pathogenesis. We summarize the mechanisms by which nitrogen compounds influence microbial dynamics, identify their contributions to inflammation and barrier dysfunction, and explore their therapeutic potential. Multidisciplinary approaches integrating clinical, metabolomic, and microbiome research are essential to unravel the full scope of nitrogen’s role in gut health and identify novel therapeutic targets. Full article

Streptococcus agalactiae (SA) is a severe prevalent pathogen, resulting in high morbidity and mortality in the global tilapia industry. With increasing bacterial resistance to antibiotics, alternative strategies are urgently needed. This study aims to investigate the antibacterial activity and the underlying mechanisms of the natural product xanthohumol (XN) against SA infection in tilapia (Oreochromis niloticus). The results showed that XN could significantly reduce the bacterial loads of SA in different tissues (liver, spleen and brain) after treatment with different tested concentrations of XN (12.5, 25.0 and 50.0 mg/kg). Moreover, XN could improve the survival rate of SA-infected tilapia. 16S rRNA gene sequencing demonstrated that the alpha-diversity index (Chao1 and Shannon_e) was significantly increased in the XN-treated group (MX group) compared to the SA-infected group (CG group) (p < 0.05), and the Simpson diversity index significantly decreased. The Bray–Curtis similarity analysis of non-metric multidimensional scaling (NMDS) and principal coordinate analysis (PCA) showed that there were significant differences in microbial composition among groups. At the phylum level, the relative abundance of the phyla Actinobacteria, Proteobacteria and Bacteroidetes decreased in the MX group compared to the CG group, while the relative abundance of the phyla Fusobacteria, Firmicutes and Verrucomicrobia increased. Differences were also observed at the genus level; the relative abundance of Mycobacterium decreased in the MX group, but the abundance of Cetobacterium and Clostridium_sensu_stricto_1 increased. Metabolomics analysis revealed that XN changed the metabolic profile of the liver and significantly enriched aspartate metabolism, glycine and serine metabolism, phosphatidylcholine biosynthesis, arginine and proline metabolism, glutamate metabolism, urea cycle, purine metabolism, methionine metabolism, betaine metabolism, and carnitine synthesis. Correlation analysis indicated an association between the intestinal microbiota and metabolites. In conclusion, XN may be a potential drug for the prevention and treatment of SA infection in tilapia, and its mechanism of action may be related to the regulation of the intestinal microbiota and liver metabolism. Full article

Lesch–Nyhan disease (LND) is associated with a complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity due to mutations in the HPRT1 gene. Although the physiopathology of LND-related neurological manifestations remains unknown, a defective neuronal developmental process is the most widely accepted hypothesis. We generated an HPRT-deficient line from the pluripotent human embryonic cell line NT2/D1 by CRISPR-Cas9 and induced its differentiation along neuroectodermal lineages by retinoic acid treatment. As levels of folic acid in the culture media may affect results in LND models, we employed physiological levels of folate. The effect of HPRT deficiency on neural development-related gene expression was evaluated using two methodological approaches: a directed qPCR array of genes related to neuronal differentiation, and global gene expression by RNAseq. HPRT-deficient pluripotent cells presented altered expression of genes related to pluripotency in human embryonic stem cells, such as DPPA3 and CFAP95, along with genes of the homeobox gene family. HPRT-deficient pluripotent cells were able to differentiate along neuro-ectodermal lineages but presented consistent dysregulation of several genes from the homeobox gene family, including EN1 and LMX1A. GO enrichment analysis of up- and downregulated genes in HPRT-deficient cells showed that the most significant biological processes affected are related to development and nervous system development. Full article

Background/Objectives: The dual targeting of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) represents an effective approach for cancer treatment. The current study involved the design, synthesis, and biological evaluation of a new series of purine-containing hydrazones, 6–24 (a,b), as anticancer agents targeting EGFR and HER2 kinases. Methods: The proposed compounds were initially screened in silico using molecular docking to investigate their binding affinity to the active sites of EGFR and HER2 kinase domains. Subsequently, the compounds were synthesized and evaluated in vitro for their antiproliferative activity, using the MTT assay, against the various cancer cell lines A549, SKOV-3, A2780, and SKBR-3, with lapatinib as the reference drug. The most active derivatives were then examined to determine their inhibitory activity against EGFR and HER2 kinases. Results: Among the assessed compounds, significant antiproliferative activity was demonstrated by 19a, 16b, and 22b. 19a exhibited substantial anticancer efficacy against A549 and SKBR-3, with IC₅₀ values of 0.81 µM and 1.41 µM, respectively. This activity surpassed lapatinib, which has an IC₅₀ of 11.57 µM on A549 and 8.54 µM on SKBR-3 cells. Furthermore, 19a, 16b, and 22b exhibited superior EGFR inhibitory efficacy compared with lapatinib (IC₅₀ = 0.13 µM), with IC₅₀ values of 0.08, 0.06, and 0.07 µM, respectively. Regarding HER2, 22b demonstrated the greatest potency with an IC₅₀ of 0.03 µM, equipotent to lapatinib (IC₅₀ = 0.03 µM). Flow cytometry analysis of A549 cells treated with 19a and 22b indicated their ability to arrest the cell cycle during the G1 phase and to trigger cellular apoptosis. Conclusions: Compounds 19a, 16b, and 22b represent intriguing candidates for the development of an anticancer agent targeting EGFR and HER2 kinases. Full article

This study aimed to investigate the effects of adding 360 mg/kg niacinamide (NAM) to diets on nutrient metabolism, providing insights into how dietary NAM supplementation enhances nitrogen utilization and growth performance in pigs. Forty growing–finishing pigs were randomly assigned to one of four experimental diets as follows: basal diet + 30 mg/kg NAM (CON), basal diet + 360 mg/kg NAM (CON + NAM), low-protein diet + 30 mg/kg NAM (LP), and low-protein diet + 360 mg/kg NAM (LP + NAM). Results showed that supplementation of both the CON and LP diets with 360 mg/kg NAM resulted in decreased urea nitrogen concentrations and carbamyl phosphate synthetase-I activity (p < 0.05). The pyruvate dehydrogenase activity in the serum and liver, as well as the activity of pyruvate dehydrogenase, citrate synthase, and glutamate dehydrogenase 1 in the ileum mucosa, was increased by supplementing the LP diet with 360 mg/kg NAM (p < 0.05). The LP diet with 360 mg/kg NAM increased the villi length to crypt depth, mRNA expression of glucose transporters 1 and 2 and alanine-serine-cysteine transporter 1, and mRNA expression of mechanistic target of the rapamycin 1 in the ileum (p < 0.05). Additionally, 360 mg/kg NAM supplementation in the LP diet reduced ileal Lactobacillus abundance (LDA > 4) and increased ileal microbial nucleotide and purine metabolism (p < 0.05). Our findings suggest that addition of 360 mg/kg NAM to the LP diet reduced urea production in the liver, enhanced glucose and amino acid absorption and transport in the ileum, and improved glucose metabolism. Full article