Search Results (1,019)

Background/Objectives: Circulating amino acid concentrations and their excretion can provide insights into dietary protein intake and metabolism. Alterations in amino acid homeostasis occur in various disorders due to nutritional imbalances or metabolic changes, including obesity. A ketogenic diet (KD) has gained popularity for weight management; however, its metabolic effects are not fully known. Therefore, the aim of this study was to evaluate the effect of an eight-week, energy-restricted Mediterranean-type KD on the amino acid metabolism in women with overweight and class I obesity. Methods: A randomized, single-center, controlled trial was conducted with 80 women with a BMI of 25.5–35 in age between 18 and 45 years, without any chronic diseases. Randomly divided women received food catering with approximately 1750 kcal daily for eight weeks, containing KD or standard diet (STD), respectively. The concentration of amino acids was assessed by gas chromatography-mass spectrometry after the derivatization with chloroformate in serum and urine collected at the baseline, after 4 weeks, and at the end of the intervention. Results: The results collected from 66 participants were included in the final analyses. Independent of diet type, weight reduction was associated with increased circulating α-aminobutyric acid and decreased proline, glutamate, and tyrosine. The KD led to lower concentrations of alanine, methionine, threonine, and tryptophan, alongside higher levels of branched-chain amino acids (BCAA) and α-aminobutyric acid compared to the STD. Urinary amino acid excretion decreased after weight reduction. KD was associated with higher urinary excretion of BCAA and β-aminoisobutyric acid. Conclusions: In summary, both weight reduction and KD significantly affect the amino acid metabolism, which might have implications for inflammation, oxidative stress, and cardiometabolic risk. Full article

Parkinson’s disease is the second leading neurodegenerative disease of aging. For over five decades, oral levodopa has been used to manage the progressive motor deficits that are the hallmark of the disease. However, individual dose requirements are highly variable, and patients typically require increased levodopa dosage as the disease progresses, which can cause undesirable side effects. It has become increasingly apparent that the gut microbiome can have a major impact on the metabolism and efficacy of therapeutic drugs. In this Perspective, we examine recent studies highlighting the impact of metabolism by Enterococcus faecalis, a common commensal gut bacterium, on levodopa bioavailability. E. faecalis expresses a highly conserved tyrosine decarboxylase that promiscuously converts levodopa to dopamine in the gut, resulting in decreased neuronal uptake of levodopa and reduced dopamine formation in the brain. Mitochondria-targeted antioxidants conjugated to a triphenylphosphonium moiety have shown promise in transiently suppressing the growth of E. faecalis and decreasing microbial levodopa metabolism, providing an approach to modulating the microbiome that is less perturbing than conventional antibiotics. Thus, mitigating metabolism by the gut microbiota is an attractive therapeutic target to preserve and potentiate the efficacy of oral levodopa therapy in Parkinson’s disease. Full article

Foundries represent complex exposure scenarios where metals, particulate matter, and combustion by-products coexist, posing potential cumulative biological effects. Urinary metabolic profiles from 64 foundry workers and 78 residents living in surrounding areas were investigated using multivariate statistical modeling. Differences in urinary metabolite patterns were observed between the two groups, including lower levels of several amino acids (e.g., valine, alanine, tyrosine, and tryptophan) and tricarboxylic acid intermediates (e.g., citrate and succinate), together with higher levels of selected branched-chain amino acid catabolites (e.g., 3-hydroxyisobutyrate and erythro-2,3-dihydroxybutyrate) in workers. Variations in gut microbiota-related metabolites, such as phenylacetylglycine and p-cresol sulphate, were also detected. Based on these metabolic patterns, potential molecular mechanisms related to energy metabolism, oxidative stress and host–microbiome interaction are discussed as interpretative hypotheses. The comparison between workers and residents was interpreted, taking into account differences in demographic and lifestyle characteristics between groups. Overall, the results indicate that occupational exposure in foundries is associated with measurable differences in urinary metabolic profiles, demonstrating that the applied NMR-based metabolomic strategy is capable of capturing early biological effects and supporting its potential as a non-invasive and holistic biomonitoring tool for evaluating the health impact of complex occupational exposures. Full article

Nicotine is the main substance responsible for the development of tobacco addiction. The α3β4 nicotinic acetylcholine receptors (nAChRs) are a potential key target for mitigating nicotine reward. Preliminary studies in our laboratory suggest that α-conotoxin [S9K]TxID serves as a selective and potent antagonist targeting α3β4 nAChRs, which may be beneficial in addressing nicotine addiction. However, the mechanisms of [S9K]TxID treatment in nicotine addiction are still to be determined. This study aimed to identify the differential metabolic profiles of [S9K]TxID treatment in nicotine addiction using an untargeted metabolomic profiling method. As demonstrated by behavioral experiments, [S9K]TxID effectively attenuated nicotine-induced conditioned place preference (CPP) expression without exerting inhibitory effects on the central nervous system (CNS). The results of untargeted metabolomics revealed that eight metabolites were significantly altered after [S9K]TxID treatment, particularly phenylalanine. [S9K]TxID also attenuated nicotine-induced metabolic disorders by regulating phenylalanine, tyrosine and tryptophan biosynthesis. In conclusion, our findings suggest that [S9K]TxID could be a potential therapeutic compound for nicotine addiction. Full article

Salvia miltiorrhiza Bunge is a traditional Chinese medicinal plant whose roots are rich in water-soluble phenolic acids. Rosmarinic acid and salvianolic acid B are representative components that confer antibacterial, antioxidant, and cardio-cerebrovascular protective activities. However, these metabolites often accumulate at low and unstable levels in planta, which limits their efficient development and use. This review summarises recent advances in understanding salvianolic acid biosynthesis and its transcriptional regulation in S. miltiorrhiza. Current evidence supports a coordinated pathway composed of the phenylpropanoid route and a tyrosine-derived branch, which converge to generate rosmarinic acid and subsequently more complex derivatives through oxidative coupling reactions. Key findings on transcription factor families that fine-tune pathway flux by regulating core structural genes are synthesised. Representative positive regulators such as SmMYB111, SmMYC2, and SmTGA2 activate key nodes (e.g., PAL, TAT/HPPR, RAS, and CYP98A14) to promote phenolic acid accumulation. Conversely, negative regulators such as SmMYB4 and SmMYB39 repress pathway genes and/or interfere with activator complexes. Major regulatory features include hormone-inducible signalling, cooperative regulation through transcription factor complexes, and emerging post-transcriptional and post-translational controls. Future directions and challenges are discussed, including overcoming regulatory redundancy and strong spatiotemporal specificity of transcriptional control. Integrating spatial and single-cell omics with functional genomics (e.g., genome editing and rational TF stacking) is highlighted as a promising strategy to enable predictive metabolic engineering for the stable, high-yield production of salvianolic acid-type compounds. Full article

Silkie (SK) chickens, valued for dark meat, serve as a model to study melanin deposition in muscle. Integrated transcriptomics and metabolomics of SK vs. Arbor Acres (AA) broiler pectoralis were used to identify key molecular drivers of meat color. All birds were cage-raised under standardized temperature and light conditions with free access to feed and water. Pectoralis muscle samples were collected from 24-day-old healthy SK and AA chickens (n = 6). Transcriptome profiling identified 488 differentially expressed genes in SK chickens, with seven conserved melanogenesis genes (TYRP1, MLANA, TYR, MLPH, EDNRB2, PMEL, GPNMB) consistently upregulated across dark-pectoralis breeds, and melanogenesis and WNT pathways were activated. Co-expression network analysis highlighted SOX10 as a key hub regulator. Metabolomics quantified 129 differentially abundant metabolites. A critical finding was the significant depletion of L-tyrosine and its derivatives in SK muscle, despite upregulated melanogenesis genes. It indicates intense metabolic flux toward pigment synthesis. Integrated analyses converged on tyrosine metabolism and redox pathways: oxidized glutathione and p-coumaric acid correlated negatively with pigment deposition, while ADP-ribose and pyridoxal correlated positively. Additionally, novel inhibitors PNMT and HIBADH may modulate melanin deposition. These findings reveal a trade-off between pigment deposition and redox balance, providing molecular markers for poultry melanin-related trait improvement. Full article

Cyclocybe chaxingu is a well-known edible fungus in China, in which pileus size and color are key traits determining its commercial value. However, the molecular genetic mechanisms underlying the morphological development of its pileus remains limited at present. To address this, our study first completed the high-quality genome assembly of the monokaryotic strain Ag.c0002-1 of albino C. chaxingu, anchoring it to 13 chromosomes via Hi-C technology. The final genome size was 51.7 Mb with a GC content of 51.06%, and 11,332 protein-coding genes were annotated. Phenotypic observations and comparative transcriptome analyses were then conducted on the pilei of the brown cultivar Ag.c0067 and the white cultivar Ag.c0002 at the primordium, elongation, and mature stages. Phenotypic analysis revealed continuous pileus expansion accompanied by progressive color lightening in both cultivars during development. Comparative transcriptomic analyses revealed significant differences in gene expression patterns between the two cultivars across developmental stages. KEGG enrichment analysis indicated that pileus expansion is closely associated with pathways related to DNA replication, cell cycle of yeast, carbon metabolism, and carbohydrate digestion and absorption. Among these, differentially expressed genes involved in cell division tended to be downregulated, whereas genes associated with energy metabolism and substance transport were upregulated, providing the necessary energy and material support for pileus growth. Changes in pileus pigmentation were primarily associated with tyrosine metabolism, betalain biosynthesis, tryptophan metabolism, and melanogenesis pathways. Notably, the downregulation of tyrosinase genes and the upregulation of glutathione S-transferase genes during development may represent major molecular mechanisms underlying pileus color lightening. Overall, this study provides important insights into the molecular mechanisms regulating pileus development and pigmentation in C. chaxingu, while also offering valuable theoretical support for genetic analysis of basidiomycete morphogenesis and the molecular breeding of edible mushrooms. Full article

Amaryllidaceae alkaloids are of notable pharmacological relevance. For instance, galanthamine is used in the treatment of Alzheimer’s disease, while other alkaloids (lycorine, crinine, etc.) derived from Amaryllidaceae plants are also of great interest because they exhibit antitumour, antiviral, antibacterial, antifungal, antimalarial, analgesic and cytotoxic properties. Phenolic acids comprise a group of natural bioactive substances that have commercial value in the cosmetic, food and medicinal industries due to their antioxidant, anticancer, anti-inflammatory and cardioprotective potential. In the present study, the effect of temperature (15, 20, 25 and 30 °C) on Amaryllidaceae alkaloid and phenolic acid biosynthesis in Leucojum aestivum in vitro plant cultures was investigated. The highest diversity of alkaloids (i.e., galanthamine, crinan-3-ol, demethylmaritidine, crinine, 11-hydroxyvitattine, lycorine, epiisohaemanthamine, chlidanthine) was noted in plants cultured at 30 °C. By contrast, ismine and tazettine were only present in plants cultured at 15 °C. Temperatures of 20 °C and 30 °C were found to stimulate galanthamine accumulation. The highest lycorine content was noted in plants grown at temperatures of 15 and 30 °C, and it was negatively correlated with the expression of the gene that encodes the cytochrome P450 96T (CYP96T) enzyme which catalyses a key step in the biosynthesis of different types of Amaryllidaceae alkaloids. This observation may reflect temperature-induced shifts in metabolic flux among different branches of Amaryllidaceae alkaloid biosynthesis. The observed stimulating effect of a 15 °C temperature on the chlorogenic, caffeic, p-coumaric, sinapic, ferulic and isoferulic acid content was in line with the highest expression of a gene that encodes the tyrosine decarboxylase (TYDC) enzyme, which is involved in plant stress response mechanisms. At 30 °C, however, the highest content of the caffeic, vanillic, p-coumaric and isoferulic acids was noted. Full article

Bioactive natural products (NPs) may play a critical role in cancer progression by targeting nucleic acids and a wide array of proteins, including enzymes. Furthermore, a large number of derivatives (NPDs), including semi-synthetic products and pharmacophores from NPs, have been developed to enhance the solubility and stability of NPs. Acute myeloid leukemia (AML) is a poor-prognosis hematologic malignancy characterized by the clonal accumulation in the blood and bone marrow of myeloid progenitors with high proliferative capacity, survival and propagation abilities. A number of potential pathways and targets have been identified for development in AML, and include, but are not limited to, Fms-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenases resulting from genetic mutations, BCL2 family members, various signaling kinases and histone deacetylases, as well as tumor-associated antigens (such as CD13, CD33, P-gp). By targeting nucleic acids, FLT3 or CD33, several FDA-approved NPs and NPDs (i.e., cytarabine, anthracyclines, midostaurin, melphalan and calicheamicin linked to anti-CD33) are the major agents of upfront treatment of AML. However, the effective treatment of the disease remains challenging, in part due to the heterogeneity of the disease but also to the involvement of the bone marrow microenvironment and the immune system in favoring leukemic stem cell persistence. This review summarizes the current state of the art, and provides a summary of selected NPs/NPDs which are either entering or have been investigated in preclinical and clinical trials, alone or in combination with current chemotherapy. With multifaceted actions, these biomolecules may target all hallmarks of AML, including multidrug resistance and deregulated metabolism. Full article

Background: Suppressor of Cytokine Signalling 6 (SOCS6) is a cytokine signalling suppressor that regulates receptor tyrosine kinase pathways by promoting degradation of signalling proteins, thereby controlling cell growth and survival. One of these tyrosine kinase receptors, Erythropoietin Receptor (EPOR), plays a critical role in CRC progression by enhancing tumour metabolism, angiogenesis, proliferation, and growth. This study investigates the molecular mechanisms governing SOCS6’s role in CRC pathogenesis using in vitro cell models and examines its interaction with EPOR expression following gene knockdown. Methods: Bioinformatics interaction between SOCS6 and EPOR were investigated using molecular visualization. HT-29 and COLO 320DM colorectal cancer cells were transfected with SOCS6 siRNA followed by measurement of SOCS6 and EPOR expression levels by qRT-PCR. The selected knockdown concentration was used in functional assays assessing cell viability, colony formation, migration, apoptosis, and invasion. Results: Bioinformatic results showed interaction between SOCS6 and EPOR through polar bonds. Furthermore, SOCS6 silencing increased cell viability and colony formation in both cell lines and significantly enhanced migration in COLO 320DM cells. Active caspase-3 levels were elevated markedly in HT-29 cells post SOCS6 knockdown, consistent with caspase-3’s reported oncogenic role in CRC. Moreover, EPOR knockdown selectively altered SOCS6 expression in HT-29 cells, indicating a regulatory feedback loop. EPOR silencing elevated cell viability at 24 h in both cell lines but caused a significant decrease in COLO 320DM cells at 72 h. Conclusions: These findings identify the SOCS6–EPOR axis as a potential target for personalized CRC therapy, supporting SOCS6’s tumour-suppressive and diagnostic roles. Full article

Salinity shock severely impairs the partial denitrification/anammox (PD/A) process, leading to prolonged functional deterioration and slow reactivation of anaerobic ammonium-oxidizing bacteria (anammox). To develop an effective strategy for mitigating salinity-induced inhibition, this study systematically examined the role of exogenous hydroxylamine (NH₂OH) in accelerating PD/A recovery using short-term batch assays and long-term reactor operation. Hydroxylamine exhibited a clear concentration-dependent effect on system reactivation. In batch tests, low-dose hydroxylamine (10 mg/L) markedly enhanced anammox activity, increasing the ammonium oxidation rate to 5.5 mg N/(g VSS·h), representing a 42.5% increase, indicating its potential to stimulate key nitrogen-transforming pathways following salinity stress. During continuous operation, hydroxylamine at 5 mg/L proved optimal for restoring reactor performance, achieving stable nitrogen removal with 87% NH₄⁺-N removal efficiency. The nitrite transformation ratio (NTR) reached approximately 80% within 13 cycles, 46 cycles ahead of the control, while simultaneously promoting the enrichment of key functional microbial taxa, including Thauera and Candidatus Brocadia. Hydroxylamine addition also triggered the production of tyrosine- and tryptophan-like proteins within extracellular polymeric substances, which enhanced protective and metabolic functionality during recovery. In contrast, a higher hydroxylamine dosage (10 mg/L) resulted in persistent NO₂⁻-N accumulation, substantial suppression of Candidatus Brocadia (declining from 0.67% to 0.09%), and impaired system stability, highlighting a dose-sensitive threshold between stimulation and inhibition. Overall, this study demonstrates that controlled low-level hydroxylamine supplementation can effectively reactivate salinity-inhibited PD/A systems by enhancing nitrogen conversion, reshaping functional microbial communities, and reinforcing stress-response mechanisms. These findings provide mechanistic insight and practical guidance for improving the resilience and engineering application of PD/A processes treating saline wastewater. Full article

Background: Polysaccharides modulate host health by interacting with gut microbiota and reshaping the host–microbial metabolome, potentially facilitating immune regulation. Methods: This study evaluated the modulatory effect of Artocarpus heterophyllus Lam. (jackfruit) polysaccharide (JFP-Ps) against cyclophosphamide (Cy)-induced immunosuppression in mice, focusing on gut microbiota modulation and metabolite changes. Results: JFP-Ps effectively increased the beneficial bacteria ratio, such as Lactobacillus and Lachnospiraceae, while inhibiting some species like Akkermansia. Metabolomic analysis showed that JFP-Ps notably regulated gut microbe-associated metabolites, including short-chain fatty acids (SCFAs), amino acids, bile acids, indoles, and derivatives. These metabolites were involved in various metabolic pathways, including primary bile acid synthesis and biosynthesis of phenylalanine, tyrosine, and tryptophan, along with tryptophan catabolism, purine metabolic processes, and unsaturated fatty acid production. Additionally, significant correlations between microbial groups and functional metabolites were identified. Overall, JFP-Ps exerted an immuno-modulatory effect by reshaping gut microbiota and enhancing co-metabolism with the host. Conclusions: These results provided valuable insights into host–microbiota interactions and gut microbiota-targeted intervention strategies of tropical natural bioactive polysaccharides. Full article

The human gut microbiota plays a key role in neurochemical communication, especially through the gut–brain axis. There is growing evidence that the gut microbiota influences dopamine metabolism through both production and consumption mechanisms. Two key bacterial enzymes are central to this process: tyrosine decarboxylase (TDC), which primarily catalyzes the decarboxylation of tyrosine to tyramine but can also act on L-DOPA to produce dopamine in certain bacterial strains, and aromatic L-amino acid decarboxylase (AADC), which can convert precursors such as L-DOPA, tryptophan, or 5-hydroxytryptophan into bioactive amines including dopamine, tryptamine, and serotonin. Identifying the bacterial families corresponding to TDC and AADC enzymes opens new avenues for clinical intervention, particularly in neuropsychiatric and neurodegenerative disorders, such as Parkinson’s disease. Moreover, elucidating strain-specific microbial contribution and host-microbe interactions may enable personalized therapeutic strategies, such as selective microbial enzyme inhibitors or tailored probiotics, to optimize dopamine metabolism. Emerging technologies, including biosensors and organ-on-chip platforms, offer new tools to monitor and manipulate microbial dopamine activity. This article explores the bacterial taxa capable of producing or consuming dopamine, focusing on the enzymatic mechanisms involved and the methodologies available for studying these processes in vivo. Full article

Pasteurella multocida serotype B:2 is a primary agent of hemorrhagic septicemia (HS) in livestock, and the strain NQ01 isolated from yaks highlights its cross-species impact. In this study, a murine intranasal infection model was established using P. multocida NQ01 to assess how acute respiratory infection perturbs gut homeostasis. Mice were intranasally inoculated with NQ01, and at 36 h post-infection, ileal tissues and cecal contents were collected for histopathological examination, 16S rRNA gene sequencing, and untargeted metabolomic analysis. Histopathology revealed obvious acute bronchopneumonia but no overt ileal damage. However, 16S rRNA sequencing of cecal microbiota showed significant dysbiosis: microbial diversity was reduced and community composition shifted, including decreased short-chain fatty-acid-producing taxa and increased opportunistic genera. Metabolomic profiling detected 1444 significantly altered cecal metabolites, and pathway analysis indicated marked disruption of amino acid metabolism, notably the tyrosine metabolism pathway. Key tyrosine pathway metabolites were dysregulated (e.g., elevated L-tyrosine and dopamine with reduced L-DOPA), indicating a breakdown of this metabolic pathway. These findings demonstrate that acute respiratory P. multocida infection profoundly disturbs gut microbiota and metabolism, underscoring disruption of the gut–lung axis. This study provides new insight into the systemic consequences of HS-associated P. multocida infection and offers a basis for exploring the gut–lung interaction in hemorrhagic septicemia pathogenesis. Full article

The aim of the present study was to investigate the effects of different dietary protein levels on the carcass traits, meat quality characteristics, and nutrient composition of slow-growing ducks. At 22 days of age, the ducks were randomly divided into two groups and fed with low- or high-protein diets for 41 days, from 22 to 63 days of age. Each group consisted of six replicates, with each replicate containing 500 ducklings per pen (10 m × 10 m). The results showed that dietary protein had no significant effects on carcass traits, meat quality, amino acid profiles in breast muscle and thigh muscle, and fatty acid contents in breast muscle. However, it increased the contents of C14:0, C16:0, C16:1, C18:1, C20:4, SFA, MUFA, and ω-6 fatty acids (p < 0.05), and reduced the contents of C22:6, ω-3 fatty acids, and ω-3/ω-6 ratio in thigh muscle (p < 0.05). Female ducks fed with a low-protein diet had the contents of aspartic acid, threonine, serine, glutamic acid, glycine, tyrosine, and arginine in the breast muscle, along with a higher pH24 value (p < 0.05). Thigh muscle accumulated more isoleucine and histidine contents, and lower lysine and arginine in female ducks fed with a low-protein diet. Male ducks fed with a low-protein diet had higher contents of alanine, valine, methionine, isoleucine, leucine, and lysine in the breast muscle (p < 0.05). Furthermore, male ducks exhibited higher contents of C16:0, C18:1, C18:2, C18:3, saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), ω-3, and ω-6 in breast muscle (p < 0.05). Male ducks fed with low-protein diets had higher C16:0 content in breast muscle, and female ducks fed with a low-protein diet had lower C16:1 and C17:0 contents (p < 0.05). In conclusion, this study suggests that dietary protein modulation can differentially regulate amino acid and fatty acid deposition in slow-growing ducks through gender-specific metabolic pathways and exert distinct effects on fatty acid metabolism. Full article