Histidine (His) plays an important role in human health and life activities. It will harm human health when His intake is insufficient or excessive. Its residue also will pollute the natural environment. Therefore, establishing a reliable and sensitive method for detecting histidine is particularly important. However, most of the existing detection methods of His rely on the single change of single signal, which are susceptible to interference from testing environmental factors and prone to generating false positive results. In contrast, the fluorescence and colorimetric dual-signal sensing system can not only effectively improve the reliability of detection, but also significantly reduce the risk of false positives. Therefore, the dual-signal sensing system has gradually become the research hotspot. Based on this, 5,10,15,20-tetra-(4-sulfophenyl) porphyrin (TSPP) was selected as the fluorescence and colorimetry dual-signal probe for the rapid detection of His in this study. Since TSPP could interact with many substances due to the specificity of molecular structure, it is the best choice to build an "ON-OFF-ON" sensing system in order to improve the specificity of the sensing system. Therefore, citric acid (CA) as an intermediate based on TSPP probe was successfully developed fluorescence and colorimetric dual-sensing system for the quantitative detection of histidine in real samples. The signal of the dual sensing system was "turned on" when the red TSPP solution obtained the fluorescence emission wavelength of 642 nm at the 514 nm optimal excitation wavelength and the UV-Vis absorption at 413 nm, respectively. The fluorescence intensity and absorbance of TSPP gradually decreased with the introduction of CA. At this time, the signal of the dual-sensing system became "turned off", and the color of the solution changed from light pink to light green. The quenched fluorescence intensity and absorbance, however, was restored upon the introduction of histidine into the system. Simultaneously, the color of the solution changed from light green to light pink, and the dual-sensing system became "turned on". Therefore, a novel fluorescence and colorimetric dual-signal sensing system based on TSPP was proposed for histidine detection. The results indicated that the linear ranges of the fluorescence sensing system were 8.34 × 10-6 M - 1.51 × 10-4 M and 1.85 × 10-4 M - 1.4 × 10-3 M with detection limits of 0.282 μM and 10.91 μM (LOD, S/N = 3), respectively. The linear range of the colorimetric sensing system was 2.04 × 10-4 M-4.35 × 10-4 M with a detection limit of 11.97 μM (LOD, S/N = 3). Meanwhile, the dual-sensing system provided a promising platform for practical samples sensing applications.

L-Histidine monohydrochloride monohydrate (HIS HCl H2O) is a commercially produced crystalline powder used in the food, pharmaceutical, and feed industries. During the commercial distribution and storage of HIS HCl H2O, customer complaints have arisen due to undesired caking. However, the caking mechanism and potential solutions for HIS HCl H2O crystals have not been thoroughly investigated. In this study, we experimentally measured moisture sorption and the degree of caking at various temperatures and relative humidity (RH) conditions to investigate the caking mechanism of HIS HCl H2O crystals. It was found that caking of HIS HCl H2O crystals occurs at a temperature of 70 °C and a RH of 80 %, even with a moisture content of less than 0.1 %. This caking occurred without evaporative crystallization from moisture desorption. During the caking of HIS HCl H2O crystals, fine crystals were removed, and intermediate-sized crystals grew, with increasing mean particle size from 435.7 to 475.1 μm. However, no remarkable polymorphic changes were observed. The caking was more severe for the sample with smaller crystal size. At a temperature of 70 °C and a RH of 80 %, the lump production ratio and breakable ratio of crystals smaller than 125 μm were 99.8 % and 24.9 %, respectively. However, crystals in the size range of 500-1000 μm did not show any lump formation. Based on these findings, decreasing cooling rate during crystallization process was applied as an effective strategy to prevent lump formation by increasing crystal size during the commercial manufacturing process of HIS HCl H2O.

The structural features and antioxidant activities of whey protein hydrolysates (WPHs) were investigated in this study. The secondary structure, fluorescence spectra and molecular weight distribution of WPHs changed with different hydrolysis time and strains. Tricine-SDS-PAGE results presented that some large proteins were hydrolyzed into small peptides (≤15kD). Compared with natural whey protein, the contents of free amino acids (including Tyr, Lys, etc.) in WPHs were increased. In addition, WPHs were not only with excellent scavenging ability to DPPH and hydroxyl radicals, but also could enhance the cell viability, decline ROS level and restore MMP of RAW264.7 cells induced by LPS. Three peptides were synthesized according to the identified results of BIOPEP-UWM database and exhibited high antioxidant activity in vitro and LPS-induced RAW264.7 cells. This study identifies the structural features of WPHs and explore their antioxidant activities and these results will have crucial theoretical significance for commercial development of WPHs.

The challenge of early detection and stratification in Parkinson's disease (PD) is urgent due to the current emergence of mechanism-based disease-modifying treatments. In here, metabolomic and lipidomic parameters obtained by a standardized and targeted in vitro diagnostic research (IVDr) platform have a significant potential to address therapy-related questions and generate improved biomarker panels. Our study aimed to use IVDr nuclear magnetic resonance (NMR) spectroscopy to quantify metabolites and lipoproteins in PD blood serum from different cohorts to stratify metabolically driven subtypes of idiopathic and genetic PD. Serum aliquots from three neurodegeneration biobank cohorts (287 samples in total, including 62 PD patient samples with GBA mutation, 98/43 PD patient samples of early/late stages of disease duration, 20 PD samples from patients with mutations in recessive PD genes and some smaller subgroups of mitochondrial and double mutation cases) were prepared and analyzed with IVDr NMR spectroscopy, covering 39 blood serum metabolites and 112 lipoprotein parameters. Uni- and multivariate statistics were used to identify metabolism-driven changes under consideration of typical confounders such as age, sex and disease duration and set into context with clinical biomarkers such as CSF concentrations of alpha-synuclein, neurofilament light chain, and tau protein. Based on the different PD subgroups we performed a total of eight different comparisons. Highlights from these comparisons include increased citrate and dimethylglycine with a decrease of creatinine and methionine in healthy controls and early PD group compared to GBA, PD late and recessive PD. We furthermore identified decreased HDL-3 free cholesterol in genetic PD cases compared to sporadic subject samples (sum of the PD early and PD late groups). Considering medication, we found that the levodopa equivalent daily dose (LEDD) is mostly positively correlated with tyrosine and citrate in sporadic PD compared to pyruvate and phenylalanine in genetic PD. Cerebrospinal fluid levels of alpha-synuclein were negatively correlated with alanine. Further metabolites and lipoproteins with discriminatory power for double mutation PD cases involved ornithine, 2-aminobutyrate and 2-hydroxybutyrate as well as for mitochondrial phenotypes via LDL phospholipid, apolipoprotein and cholesterol subfractions. Quantitative IVDr NMR serum spectroscopy is able to stratify PD patient samples of different etiology and can contribute to a wider understanding of the underlying metabolism-driven alterations e.g. in energy, amino acid, and lipoprotein metabolism. Though our overall cohort was large, major confounders such as age, sex and medication have a strong impact. That is why absolute quantification and detailed patient knowledge about metabolic confounders, is a premise for future translation of NMR serum spectroscopy to routine PD diagnostics.

This study examined the effects of dietary supplementation with grape seed proanthocyanidins (GSPs) on the growth performance, serum biochemistry, jejunal antioxidant capacity, and jejunal microbiota and metabolites in Chinese indigenous Kangle chicken. In this experiment, 120 female Kangle chickens aged 30 days old were randomly allocated into three treatment groups: a control group (CON) fed a standard diet and two experimental groups fed diets supplemented with 200 mg/kg (LGSP) or 400 mg/kg (HGSP) of GSPs. The experiment consisted of a 7-day adaptation period followed by a 30-day feeding trial. The results demonstrated that GSP supplementation did not significantly improve their average daily gain or feed efficiency. However, the HGSP group showed significant improvements in their liver and jejunal indices, a reduced jejunal crypt depth, and increased villus-height-to-crypt-depth ratios compared to these values in the CON group. Furthermore, the HGSP group also exhibited elevated concentrations of cholesterol in their serum. Additionally, the oxidative stress levels were probably reduced in the jejuna of the HGSP group, as evidenced by reduced malondialdehyde (MDA) contents. Although jejunal microbial diversity remained unchanged, the metabolomic analysis identified significant upregulation of jejunal metabolites, particularly those associated with free radical scavenging, protein nutrition, and bile acid metabolism, which would be beneficial for maintaining intestinal health. These findings indicate that supplementing their diet with 400 mg/kg of GSPs could improve the health of Kangle chickens, underscoring their potential as a functional feed additive in the production of indigenous Chinese chickens.

For more than 25 years, profuse research has aimed to discriminate Iberian-dry-cured hams produced from pigs differing in genetics (pure Iberian vs. crosses) and feeding background (natural resources vs. commercial feeds). Certain advanced MS-based analytical tools have been found useful to characterise and authenticate a variety of meat products. Here, for the first time, the metabolome (more than 3000 identified compounds) of Iberian dry-cured hams from the three most valuable categories, labeled as BLACK, RED and GREEN, is analysed using a Q-Exactive Orbitrap mass-spectrometry (MS) equipment. The chemical structure, plausible origin and role played by the 35 most abundant chemical species in Iberian dry-cured hams, are reported. Additionally, Iberian hams differing in genetic background namely, BLACK (100 % Iberian) and RED (50 % Iberian) were found to differ in 142 discriminating metabolites. Sixty-six distinctive metabolites were found in RED hams, produced from pigs fed on natural resources, while seventy discriminating metabolites were identified in GREEN hams, produced from pigs fed on concentrate. The method applied provided a preliminary metabolic fingerprinting of Iberian dry-cured hams, which may be helpful for authentication purposes.

Current diet assessment tools, such as food frequency questionnaires, may result in misclassification bias from measurement error and misreporting. These limitations can be mitigated by diet-related biomarkers in urine specimens, an emerging approach to characterize dietary intake.

We conducted a systematic review to identify urinary biomarkers with utility in accurately assessing dietary intake, including individual foods and food groups.

We retrieved studies from 2000 to 2022 from databases including Embase, CINAHL, Cochrane, and PubMed. Data extraction from included articles was conducted by two independent reviewers for cross validation. Articles identifying urinary biomarkers in relation to food groups/items with adult populations were included and were evaluated for bias using the Joanna Briggs Institute Critical Appraisal.

A total of 65 articles were included and categorized as biomarkers of fruit (n = 13), vegetables (n = 5), aromatics (n = 5), fruits and vegetables (n = 3), grains/fiber (n = 5), dairy (n = 3), soy (n = 10), coffee/cocoa/tea (n = 9), alcohol (n = 6), meat and proteins (n = 6), nuts/seeds (n = 3), and sugar and sweeteners (n = 4). Results expanded the context to which metabolites of foods were compared across similar and dissimilar food groupings. Plant-based foods were often represented by polyphenols, while others were distinguishable by innate food composition, such as sulfurous compounds in cruciferous vegetables or galactose derivatives in dairy.

Current evidence suggests urinary biomarkers may have utility in describing intake of broad food groups, such as citrus fruits, cruciferous vegetables, whole grains, and soy foods, but may lack the ability to clearly distinguish individual foods. These findings indicate the potential of urinary biomarkers to monitor changes in dietary patterns. The improvement of diet assessment methodology is a key step toward strengthening research data validity and accurately measuring outcomes in chronic disease management.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42022308255, Prospero CRD42022308255.

Ultra-high-performance liquid chromatography-time-of-flight mass spectrometry (UHPLC-TOF-MS) was employed to analyze serum metabolites and metabolic pathways associated with metabolic syndrome (MS) in the Yi and Han populations of Yunnan.

Participants included individuals diagnosed with MS and healthy controls from the Yi and Han populations of Yunnan. Serum nontargeted and amino acid-targeted metabolomics analyses were conducted to identify differential serum metabolites (DEMs) and metabolic pathways associated with MS pathogenesis in these two ethnic groups.

Nontargeted metabolomics analysis revealed 2,762 DEMs in the MS group of the Han population, while 1,535 DEMs were identified in the MS group of the Yi population [variable importance in projection (VIP)>1, P<0.05]. Venn analysis highlighted common and unique DEMs between the two populations. KEGG pathway analysis identified seven significantly enriched pathways in the Han group and five in the Yi group, primarily involving amino acid synthesis and metabolism. To investigate the role of amino acids in MS, serum levels of 71 endogenous amino acids were quantified. In the MS group of the Han population, 19 differential amino acids were identified, significantly enriched in pathways related to D-glutamine and D-glutamate metabolism, as well as cysteine and methionine metabolism. In the Yi population, six differential amino acids were identified, with significant enrichment in D-glutamine and D-glutamate metabolism, sulfur metabolism, and valine, leucine, and isoleucine biosynthesis.

Our study investigates metabolic differences in metabolic syndrome (MS) between Yi and Han populations through nontargeted and targeted metabolomics approaches, identifying both common and unique metabolites and metabolic pathways associated with MS, especially amino acid metabolic disorders, including glycine, serine, and threonine metabolism, D-glutamine and D-glutamate metabolism, which may play critical roles in regulating different metabolic dysfunctions and worth further exploration in MS pathogenesis, which might provide insights for the effective prevention and treatment of MS in various populations.

Acrylamide (AA) and nanoplastics (NPs) are common food toxicants. However, their combined toxicity and health risks call for further studies. This study aimed to investigate the combined toxicity of AA and polystyrene NPs (PS-NPs) in mice through drinking water exposure. Co-exposure to AA and PS-NPs aggravated colon and liver damage, including more severe inflammatory infiltration, higher levels of colonic and hepatic pro-inflammatory cytokines, and elevated serum content of lipopolysaccharide and activities of diamine oxidase, alanine aminotransferase, and aspartate aminotransferase compared to single exposures. Co-exposure also significantly downregulated the expression of colonic tight-junction genes ZO-1 and Claudin-5. Metabolomics revealed that co-exposure induced more profound metabolic disorders in the liver, particularly affecting amino acid and carbohydrate metabolism. 16S amplicon sequencing showed that co-exposure caused more drastic gut microbiota dysbiosis, characterized by a decrease in beneficial bacteria (unclassified_f__Oscillospiraceae, Roseburia, UCG-005, Ruminiclostridium, unclassified_o__Clostridia_UCG-014, Fournierella, and Acetatifactor) and an increase in pathogenic bacteria (Eubacterium_xylanophilum_group and Eubacterium_nodatum_group). Correlation analysis indicated a negative correlation between beneficial bacteria and intestinal-liver toxicity indicators and a positive correlation between pathogenic bacteria and these indicators. Overall, our findings showed that AA and PS-NPs exerted synergistic toxicity to the gut-liver axis in mammals, highlighting the higher health risks of their combined ingestion.

To explore the differences in protein quality among classic medicinal entomopathogenic fungi and to evaluate their metabolic adaptability, we analyzed the amino acid composition and proteomic characteristics of Cordyceps sinensis (CS), Cordyceps militaris (CM), and Cordyceps cicadae (CC). Quantitative analysis showed CM contained the highest crude protein and lysine, methionine, threonine, and valine. CS adapted to high-altitude hypoxia and exhibited lower protein but elevated leucine, isoleucine, and histidine contents, which may contribute to membrane stabilization and oxidative stress resistance. CC displayed higher non-essential amino acids such as arginine, proline, and tyrosine, reflecting active nitrogen metabolism. Four-dimensional data-independent acquisition (4D-DIA) proteomics identified 495 differentially expressed proteins (DEPs). Compared with CS, CM and CC displayed upregulated glutamate oxaloacetate transaminases 2 (GOT2), glutamate dehydrogenase (GDH), and argininosuccinate synthase 1 (ASS1) coordinately regulate nitrogen flux through the alanine-aspartate-glutamate metabolic network and urea cycle, supporting metabolic intermediate replenishment for energy metabolism. The upregulation of branched-chain keto acid dehydrogenase E1 subunit alpha (BCKDHA) and acyl-CoA dehydrogenase short/branched chain (ACADSB) in CM and CC facilitated the integration of branched-chain amino acid catabolism with the TCA cycle, explaining species-specific differences in protein content. This study presents the first application of 4D-DIA proteomics to compare CS, CM, and CC, providing insights into quality divergence mechanisms in medicinal fungi.

Phosphomannomutase-2 (PMM2) deficiency represents the most common congenital disorder of glycosylation (CDG). Currently, little is known about cell metabolic alterations occurring in these patients. Here, we quantified compounds connected to protein glycosylation (GDP-mannose, UDP-derivatives), energy metabolism (high-energy phosphates, nicotinic coenzymes, oxypurines), oxidative/nitrosative stress (GSH, nitrite, nitrate) and free amino acids in extracts of peripheral blood mononucleated cells (PBMCs), of seven PMM2-CDG patients and ten control healthy donors. Besides marked GDP-mannose decrease, PBMCs of PMM2-CDG patients had higher UDP-glucose (UDP-Glc), UDP-galactose (UDP-Gal) and UDP-Glucuronic levels, lower ATP, GTP and UTP levels, abnormal ATP/ADP, ATP/AMP and NAD+/NADH ratios, increased xanthine, uric acid and nitrite + nitrate levels, and decreased GSH and free amino acids concentrations. These results suggest a new, conceivable metabolic route leading to the increase of specific UDP-derivatives (UDP-Glc, UDP-Gal and UDP-Glucuronic), also potentially explaining the glycogen abnormalities recently found in PMM2-CDG patients. Altogether, this study highlighted various metabolic changes caused by PMM2 deficiency, illustrating the widespread effects of PMM2 mutations (beyond N-glycan biosynthesis) that may significantly vary depending on the cell line considered. Using PBMCs, as a cellular model of lower invasiveness than skin fibroblast, may advantage cell metabolism studies to investigate new therapies specifically targeted to PMM2 deficiency.

Lipid nanoparticles (LNPs) effectively protect mRNA and facilitate its entry into target cells for protein synthesis. Despite these successes, cellular entry alone may not be enough for optimal protein expression, as mRNA translation also depends on the availability of essential metabolites, including metabolic energy sources, coenzymes, and amino acids. Without adequate metabolites, mRNA translation may be less efficient, potentially leading to higher dosing requirements or poorer therapeutic outcomes for LNP therapies. To address this, we develop a metabolite co-delivery strategy by encapsulating essential metabolites within mRNA LNPs, hypothesizing that our approach can uniformly improve mRNA delivery. Instead of adding a fifth component to the organic phase, our strategy involves mixing the metabolite with the mRNA payload in the aqueous phase, while maintaining the molar ratio of the components in the organic phase during LNP formulation. We verify our approach in vitro and in vivo, highlighting the broad applicability of our strategy through mechanism and efficacy studies across multiple cell lines, and physiological conditions, such as normoxia (i.e., 21% oxygen), hypoxia (i.e., 1% oxygen), and in mice. Taken collectively, we anticipate that our metabolite co-delivery strategy may serve as a generalizable strategy to enhance in vitro and in vivo protein expression using mRNA LNPs, potentially offering broad applicability for the study and treatment of disease.

This study aimed to assess the medicinal properties of Breynia retusa, a plant rich in phytocompounds predominantly used as an ethnomedicinal agent in Western Ghats, which appeared to be promising for therapeutic use, especially in the treatment of ovarian cancer. Herein, its cytotoxic potential on ovarian cancer cell lines SKOV-3, neurotoxicity, antioxidant activity, and molecular docking was determined to aid in explaining the mechanisms of interactions with proteins related to ovarian cancer. B . retusa methanolic extract demonstrated exuberant antioxidant activity, with 81.91% scavenging ability of DPPH radicals and efficient reduction of phosphomolybdenum (22.98 mg ascorbic acid equivalents antioxidant capacity/g extract). The extract proved to be an important anti-inflammatory agent through membrane stabilization inhibition of 83%. The cytotoxicity study against the SKOV-3 cell line indicated an IC50 value of 34.01 µg/mL and a very negligible neurotoxicity in SH-SY5Y cell lines. The GC-MS and HPLC profiling indicated many anticancer compounds in the extract such as secalciferol, methyl gallate, ricinoleic acid, gallic acid, and naringenin. The docking study showed significant interactions of secalciferol molecules with the key ovarian cancer proteins, which include IGF1 (-6.758 kcal/mol) and c-ERBB2 (-4.281 kcal/mol). Fatty acid derivatives and methyl gallate showed efficient dock scores (< -5.0 kcal/mol) with antioxidant (catalase and superoxide dismutase) enzymes and inflammatory cytokines (IL-6 and COX-1), respectively, as evidences of antioxidant and anti-inflammatory potentials. The bio-accessibility of phenolics and their antioxidant activity ranged above 90%, indicating the promising bioavailability of phytochemicals expected in vivo. Hence the current study emphasizes the anticancer potential of B. retusa phytocompounds that appeared to interact very strongly with ovarian cancer targets and confirms the dose-dependent cytotoxic and antioxidant activities of B. retusa methanolic extract.

The online version contains supplementary material available at 10.1007/s13205-025-04276-8.

Nanoplastics pollution is a global issue, with the digestive tract being one of the first affected organs, requiring further research on its impact on intestinal health. This study involved orally exposing mice to polystyrene nanoplastics (PS-NPs) at doses of 0.1, 0.5, or 2.5 mg/d for 42 days. The effects on intestinal health were thoroughly assessed via microbiomics, metabolomics, transcriptomics, and molecular biology. Our study demonstrated that the administration of all three doses of PS-NPs resulted in increased colonic permeability, heightened colonic and peripheral inflammation, reduced levels of antimicrobial peptides, and shortened colonic length. These effects may be attributed to a reduction in the abundance of probiotic bacteria, such as Clostridia_UCG-014, Roseburia, and Akkermansia, alongside an increase in the abundance of the pathogenic bacterium Desulfovibrionaceae induced by PS-NPs. Furthermore, we underscored the crucial role of histidine metabolism in PS-NPs-induced colonic injury, characterized by a significant reduction of L-histidine, which is closely related to microbial ecological dysregulation. Corresponding to microbiota deterioration and metabolic dysregulation, transcriptome analysis revealed that PS-NPs may disrupt colonic immune homeostasis by activating the TLR4/MyD88/NF-κB/NLRP3 signaling pathway. In conclusion, this study provided novel insights into the mechanisms by which PS-NPs disrupt intestinal homeostasis through integrated multiomics analysis, revealing critical molecular pathway and providing a scientific basis for future risk assessment of nanoplastics exposure.

Histamine, classified as a biogenic amine, plays a crucial role in both pro-inflammatory and immune regulatory processes, thereby establishing itself as a key mediator in allergic diseases and immune responses. This review provides an exhaustive analysis of the structure, function, and regulation of histamine, with particular emphasis on its interaction with four receptor subtypes: histamine H1 receptor (H1R), histamine H2 receptor (H2R), histamine H3 receptor (H3R), and histamine H4 receptor (H4R), all of which are instrumental in mediating a variety of physiological processes, including neurotransmitter release, modulation of immune responses, and gastric acid secretion. The review explores intracellular signaling pathways mediated by the activation of these receptors, highlighting the complex cascades involved in immediate- and delayed-type hypersensitivity reactions. It also examines the broad spectrum of histamine-induced complications, focusing on their effects on the gastrointestinal, cardiovascular, respiratory, and central nervous systems, and emphasizes histamine's potential to cause vascular dysfunction and other pathological changes. Furthermore, the role of histamine in inflammation and immune responses is explored, particularly in the context of allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis. The review also covers pharmacological interventions targeting histamine receptors, including the use of antihistamines and mast cell stabilizers, which are critical for the treatment of symptoms and the inhibition of the progression of histamine-related conditions. Finally, the review addresses emerging research and future directions, identifying potential areas for innovation and improved therapeutic strategies. This comprehensive overview not only deepens understanding of histamine's multifaceted roles in health and disease, but also underscores the importance of developing advanced diagnostic tools and targeted treatments for histamine-associated disorders.

This study investigated the metabolic mechanisms underlying the association between malnutrition and poor prognosis in coronary artery disease (CAD). We hypothesized that specific metabolites associated with nutritional status impact all-cause mortality and Major Adverse Cardiovascular Events in CAD patients. To test this hypothesis, we evaluated the nutritional status of 5182 CAD patients from multiple centers using three nutritional risk screening tools and analyzed the impact on CAD outcomes with restricted cubic splines and Cox regression. Poor nutritional status was found to be linked to increased adverse outcomes. Further analysis using multiple linear regression and mediation analysis identified elevated concentrations of β-pseudouridine and dulcitol, and decreased concentrations of l-tryptophan and LPC (18:2/0:0), among other metabolites, as mediators of this association. Employing Least Absolute Shrinkage and Selection Operator for variable selection, we integrated these metabolites with clinical variables, which significantly improved the predictive accuracy for adverse outcomes. Our results highlight significant metabolic disparities in CAD patients based on nutritional status and provide novel insights into the role of nutrition-associated metabolites in CAD prognosis. These findings suggest that customized nutritional interventions targeting these metabolites could positively influence the progression of CAD.

Regular long-term exercise can benefit the body and reduce the risk of several diseases, such as cardiovascular disease, diabetes, and obesity. However, the proteomic and metabolomic changes, as well as the physiological responses associated with long-term exercise, remain incompletely understood. To investigate the effects of long-term exercise on the human body, 14 subjects with long-term exercise habits and 10 subjects without exercise habits were selected for this study. Morning urine samples were collected and analyzed for untargeted metabolomics and proteomics using liquid chromatography-mass spectrometry. A total of 404 differential metabolites and 394 differential proteins were screened in this research, and the analysis results indicated that long-term exercise may affect energy metabolism, amino acid synthesis and metabolism, nucleotide metabolism, steroid hormone biosynthesis, and the inflammatory response. These findings offer a more comprehensive understanding of the molecular effects of long-term exercise on the human body and provide a basis for future research exploring the underlying mechanisms.

Leccinum crocipodium (Letellier.) Watliag has attracted increasing attention for their biological activity. In this study, the active polysaccharide components (LCSP11 and LCSP22) extracted from the stem of L. crocipodium (Letellier.) Watliag were investigated to assess structural characterization of LCSP11 and LCSP22, their effects on the metabolic profile of Bacteroides thetaiotaomicron, and the immune activities of the resulting fermentation products. The results showed that LCSP11 and LCSP22 were a type of heteropolysaccharide and amorphous state with good stability, which displayed molecular aggregation in aqueous solutions. LCSP11 and LCSP22 were effectively fermented by Bacteroides thetaiotaomicron, producing a variety of microbial metabolites, including organic acids and derivatives (30.13 %), lipids and lipid-like molecules (21.33 %), and organoheterocyclic compounds (17.45 %). Multiple differential metabolites were identified in the fermentation products (F11 and F22), with significant accumulation of peptides, amino acids, nucleotides, steroids, and fatty acids, such as murabutide and L-cystine. KEGG pathway analysis identified six enriched metabolic pathways in F11 and five in F22, with the histidine metabolic pathway significantly enriched in F11. Furthermore, LCSP22 fermentation by Bacteroides thetaiotaomicron produced short-chain fatty acids, including acetic acid, propionic acid, isovaleric acid, and caproic acid. Cellular experiments suggested that these fermentation metabolites exhibited immunoactivating effects on RAW264.7 cells, significantly enhancing phagocytic capacity and promoting the secretion of nitric acid (NO) and cytokines, including TNF-α, IL-6, and IL-2. These results provide new insights into the immunomodulatory activities of polysaccharides from the stem of L. crocipodium (Letellier.) Watliag fermented by Bacteroides thetaiotaomicron and broadens the potential applications of this natural resource in food, nutrition, and biomedicine.

The aim of this study was to investigate the metabolomic changes in the spleens of ducks artificially infected with Clostridium perfringens type A. Twenty-four healthy ducks aged 1 d were used for this purpose. After acclimatization for 37 d, the ducks were divided into 4 treatment groups (n = 6): the control group (normal group), infection Group 1 (66 h), infection Group 2 (90 h) and infection Group 3 (114 h). The ducks in the corresponding infection group were challenged with 8 mL of C. perfringens type A bacterial solution (1 × 108 CFU/mL) for 4 days. The experimental ducks were culled at 0 h, 66 h, 90 h and 114 h after infection, and the ducks were sacrificed for spleen sampling at the end of the experiment. Autopsy observations, spleen pathological changes and pathogen nucleic acid detection were also performed. Finally, the changes in the metabolic profile of the spleen were investigated via a metabolomics approach.

At necropsy, the pathological changes in C. perfringens type A infection included enlarged, haemorrhagic and mottled spleens. Histopathology examination revealed that the ducks in the infection group had damaged spleen tissue structures, dilated spleen sinuses with congestion and bleeding, an extreme decrease in lymphocytes, and massive inflammatory cell infiltration in the splenic tissue. Spleen lesions were observed and PCR tests were positive in ducks in the infection group, indicating that a model of C. perfringens type A infection was successfully established in this study. Compared with those in the normal group, 14, 15 and 20 differentially abundant metabolites were identified after 66, 90 and 114 h, respectively, of C. perfringens type A infection of duck spleens, mainly including indolin-2-one, 3-methylindole, 4-hydroxy-2-quinolinecarboxylic acid, indole-3-methyl acetate, uric acid, 2'-deoxyinosine, urate, xanthine, 3-succinoylpyridine, nicotinic acid, phenylacetylglycine, histamine and phosphoenolpyruvate. Pathway analysis revealed that these metabolites were mainly involved in tryptophan metabolism, purine metabolism, nicotinate and nicotinamide metabolism, phenylalanine metabolism, histidine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, tyrosine metabolism, arginine and proline metabolism, arachidonic acid metabolism, and caffeine metabolism.

These findings suggest that C. perfringens type A infection causes a duck spleen inflammatory response and immune response in infected ducks through indolin-2-one, 3-methylindole, 4-hydroxy-2-quinolinecarboxylic acid and tryptophan metabolism, purine metabolism, nicotinic acid and nicotinamide metabolism, which provides a basis for understanding the pathogenesis of C. perfringens type A in ducks.

Histidine-derived carbon dots (His-CDs) were synthesized to detect staurosporine-induced apoptosis in T lymphoma (Jurkat) cells. The His-CDs were characterized for their physical and chemical properties including size, morphology, fluorescence, and surface functionality. Transmission electron microscopy (TEM) revealed a spherical morphology with an average size of 11.4 ± 3.4 nm. Fluorescence analysis showed maximum excitation at 338 nm and emission at 415 nm, attributed to the carbon dots' quantum confinement effect and surface defects. FTIR and SEM-EDS confirmed the presence of hydroxyl, amine, aromatic rings, and alkyl (C-H) functional groups and carbon, nitrogen, and oxygen elemental composition in ratios of 52%, 24.8%, and 23.3%, respectively. His-CDs were evaluated for cytotoxicity and apoptosis detection in Jurkat cells. Fluorescence microscopy and flow cytometry analysis demonstrated concentration-dependent fluorescence, suggesting effective cellular uptake of His-CDs. The apoptotic-sensing capability of His-CDs was tested using staurosporine, an apoptosis inducer. A concentration-dependent increase in fluorescence was observed with increasing staurosporine concentrations, indicating the His-CDs' sensitivity to apoptosis. The time-dependent fluorescence increases were noted with prolonged staurosporine exposure. Z-DEVD-FMK, a caspase-3 inhibitor, confirmed that the apoptosis detected by His-CDs was caspase-3 dependent, as co-treatment reduced His-CDs' fluorescence in the cell. In conclusion, these results demonstrate that His-CDs are biocompatible, sensitive apoptosis sensors and hold the potential for monitoring apoptotic pathways in cellular systems.

Histidine is a versatile amino acid with metal-binding, nucleophilic, and basic properties that endow many peptides and proteins with biological activity. However, histidine itself is susceptible to oxidative modifications via post-translational modifications, photo-oxidation, and metal-catalyzed oxidation. Despite multiple investigations into these different oxidation systems, the varied attributions and differential outcomes point to significant gaps in our understanding of the coordination requirements, spectral features, and reaction products that accompany the Cu-catalyzed oxidation of histidine-containing peptides. Here, we use model peptides of Histatin-5, a salivary peptide with Cu-potentiated antifungal activity that relies on its histidine residues, to characterize the complex mixture resulting from the reaction with Cu under physiologically relevant reducing and oxidizing conditions. Characterization via LC-MS, MS/MS, UV-vis, and NMR revealed that adjacent histidine residues of the bis-His site are the main target of Cu-catalyzed oxidation, with predominant modifications being 2-oxo-His and His-His cross-links that give rise to distinctive electronic absorption features between 300-400 nm. Doubly- and triply-oxygenated peptides, intramolecular His-His cross-links, and multimers in the case of a shorter model peptide were also observed. The configuration of the bis-His motif may enable Cu reactivity not available in systems where His residues are not adjacent in sequence or space. These results expand the possibilities of oxidative modifications available to other proteins and peptides containing multiple histidines.

The forest musk deer (FMD, Moschus berezovskii), an endangered small ruminant, is listed as a class I protected wild animals in China. However, compared to their wild counterparts, captive FMD are more prone to gastrointestinal diseases caused by gut microbial dysbiosis, which severely limits population growth and increases the risk of mortality. Active dry yeast (ADY), as a commonly used feed additive, has been widely applied in domestic livestock to improve gut microbiota and enhance immune function. Whether dietary supplementation with ADY in captive FMD contributes to gut microbial homeostasis and physical health is still unclear. Thus, the study aimed to evaluate the effects of dietary supplementation with ADY on the immunity, gut microbial composition, and serum metabolites in FMD.

Fourteen male FMD from the Chongqing Institute of Medicinal Plant Cultivation (Chongqing, China), with similar initial bodyweights (7.0±0.3kg) and an average age of 4.5 years, were selected and randomly divided into two groups. The control group was fed a standard diet, while the ADY group received the standard diet supplemented with ADY at a dosage of 10 g/kg DM.

ADY supplementation significantly increased the concentrations of immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) in the serum. ADY improved the richness and diversity of the gut microbiota, increased the relative abundance of the Firmicutes and Bacteroidota, but decreased the relative abundance of the Proteobacteria. A widely targeted metabolomics analysis identified a total of 25 differential metabolites, with 10 being upregulated and 15 downregulated. Many differential metabolites, for example phosphatidylcholine, Glu-His, L-cysteine and other differential metabolites contributed to strengthening the immunity of the FMD by affecting arachidonic acid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, and so on.

Dietary supplementation with ADY positively impacts the immunity of FMD by modulating the composition of the gut microbial communities and serum metabolites.

Bone broth is a traditional nutrient revered by different people from ancient times to the modern era as a remedy for various illnesses. This review investigates the nutritional components of bone broth, focusing primarily on the most abundant amino acids and minerals saturated in bone broth and their impact on health, particularly in the context of intestinal barrier integrity, intestinal permeability, inflammation, and their application in inflammatory bowel disease. Through comprehensive reviews of animal and human studies, this research highlights that bone broth includes amino acids (glutamine, glycine, proline, histidine, arginine), minerals (Ca, P, K, Mg, Zn) that are beneficial and not just a traditional remedy, resolving questions that have been posed for generations. The benefits documented for components in bone broth support the enhancement of gut health, alleviate inflammation in the intestinal barrier, improve intestinal barrier function in health and disease states, particularly in inflammatory bowel disease, as well as enhancing nutrient absorption. Bone broth offers a nutrient-dense option for enhancing overall health and may offer an alternative to dietary supplements with claims for enhanced gut health. We aim to foster interest in and provide evidence to substantiate claims for bone broth as a potential remedy, particularly for maintaining remission in conditions like IBD and possibly functional diarrhea and to encourage further research.

Pregnancy provokes a heightened amino acid requirement, especially in the third trimester. Alterations to late pregnancy amino acid metabolism have been associated with environmental breast carcinogen exposures, including DDT and PFAS. This project examined whether maternal serum amino acids in late pregnancy are associated with subsequent breast cancer risk. Archival third-trimester serum samples from 172 women who were later diagnosed with breast cancer were compared to samples from 351 women without known breast cancer. A prospective metabolome-wide association study (MWAS) for breast cancer cases showed that associated amino acid pathways included lysine, arginine, proline, aspartate, asparagine, alanine, tyrosine, tryptophan, histidine and branched-chain amino acids. Lower mean concentrations of individual amino acids, including histidine, threonine, lysine, and proline, were associated with an increased risk of breast cancer, and network analyses showed that these amino acids were negatively associated with protective breast cancer risk factors. Prospective MWAS for breast cancer cases diagnosed within 15 years of sample collection showed pathway associations for tryptophan, histidine, lysine methionine, and cysteine metabolism. Nutrient stresses caused by low amino acid levels impair immunosurveillance and activate oncogenic mechanisms of cell survival, thereby providing mechanisms by which environmental exposures in late pregnancy can contribute to breast cancer risk.

To elucidate the role of gut microbiota and their metabolites, including short-chain fatty acids (SCFAs) and targeted metabolomics, in the development of postoperative delirium (POD) in elderly patients.

Prospective nested case-control study.

A Chinese tertiary hospital.

Elderly patients underwent elective orthopedic surgery.

Participants were assessed for POD using the 3-min Diagnostic Confusion Assessment Method (3D-CAM). Biological samples, including feces and plasma, were collected. A 1:1 propensity score matching (PSM) was conducted to match POD cases with non-POD cases. 16S ribosomal RNA (rRNA) sequencing and metabolomics analyses were performed on the matched case series. Predictive models were developed using logistic regression analysis, incorporating bacterial genera and metabolites that exhibited significant differences between the two groups as predictors.

Among 234 patients who were followed up, 41 were diagnosed with POD. A total of 39 cases were matched for both the POD and control groups using PSM. No significant differences were found in the α-diversity and β-diversity of preoperative gut microbiota between the two groups. However, specific bacterial genera, including Romboutsia, Bacteroides faecalis, Blautia mucilaginosa, and Eggerthella lenta, exhibited significant differences. The risk of POD was associated with higher postoperative plasma levels of propionic acid, histidine, aspartate, and ornithine. Logistic regression and receiver operating characteristic curve analyses revealed that indicators derived from the gut microbiota and metabolites could predict POD, with an area under the curve of 0.8413 (95 % confidence interval (CI): 0.7393-0.9434).

This study identified four preoperative bacterial genera and four postoperative plasma metabolites associated with an increased risk of POD in elderly orthopedic patients, suggesting the potential of gut microbiota and metabolite profiles as biomarkers for improving risk prediction and guiding interventions.

We previously identified methylglyoxal as a biomarker for early identification and outcome prediction in human sepsis. We hypothesised that methylglyoxal causally impacts disease severity, and the methylglyoxal-scavenging dipeptide anserine can attenuate the detrimental effects of methylglyoxal.

Using a translational approach, secondary analyses of two observational trials were performed to test the initial hypotheses. Afterwards, these results were re-evaluated in different murine models of experimental sepsis in vivo. The detrimental effects of methylglyoxal as well as the underlying mechanisms were further assessed in vitro using transendothelial electrical resistance measurements, fluorescence-activated cell sorting analyses, cytokine assays, gene expression analyses, and enzyme activity assays, as well as immunofluorescence and immunohistochemistry staining.

The secondary analyses confirmed methylglyoxal as an independent marker associated with increased mortality within the first 48 h after sepsis onset and high catecholamine and fluid requirements in the first 24 h after sepsis onset. In the sepsis models, methylglyoxal-derived carbonyl stress significantly contributed to the development of capillary leakage by disrupting endothelial barrier-forming proteins. Mechanistically, a pathway involving the receptor of advanced glycation end products and mitogen-activated protein kinase was identified. The methylglyoxal-scavenging dipeptide anserine (β-alanyl-N-methylhistidine) reduced methylglyoxal-induced advanced glycation end-product formation and disruptions of junctional complexes in vitro. Moreover, anserine reduced capillary leakage and mortality in vivo.

Methylglyoxal causally contributes to capillary leak formation and mortality in experimental sepsis, which can be mitigated by anserine. Therefore, anserine represents an innovative therapeutic option for the treatment of septic shock.

German Research Foundation (grant number BR 4144/2-1).

Metabolomic analysis of boar semen associated with sexual maturation is essential for improving fertility management and breeding, with amino acids and amines playing key roles in the reproductive process. This study aimed to explore changes in amino acids and amines in boar spermatozoa and seminal plasma during puberty to sexual maturity and identify potential biomarkers of sexual maturity. Semen was collected from the same 15 Duroc boars over time at approximately 7 months (Age 1), 8.5 months (Age 2), and 10 months (Age 3). Liquid chromatography-mass spectrometry was used to analyse amino acids and amines in spermatozoa and seminal plasma separately. Multivariate analysis (PLS-DA) revealed pronounced age-dependent changes in amino acids and amines in spermatozoa between Age 1 and Age 3, and more subtle shifts in seminal plasma. Univariate analysis (Repeated measure ANOVA/Friedman) revealed that glutamate and taurine had significant pairwise differences in seminal plasma (P < 0.05). In sperm, 15 amino acids (glutamate, alanine, aspartate, choline, taurine, histidine, methionine, tryptophan, leucine, cystine, tyrosine, arginine, lysine, valine and glycine) exhibited significant pairwise differences (P < 0.05). VIP scoring (>1.5) prioritised glutamate, alanine, aspartate, and choline as key contributors to the variations and pathway analysis implicated alanine, aspartate and glutamate metabolism, and histidine metabolism linked to sexual maturity. Our study highlights metabolic changes during sexual maturation, identifying potential biomarkers for assessing reproductive maturity. These findings are initial steps toward optimising younger boars' usage in breeding, enhancing genetic gain, and reducing costs associated with their non-productive days at AI centres.

Urinary tract infections (UTIs) in humans are common, with uropathogenic Escherichia coli (UPEC) being the primary pathogen. The adhesive capabilities of UPEC are a substantial pathogenicity factor. Due to limitations of first-line antibiotics, Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross, a traditional Chinese medicinal plant, is frequently used to treat various urological disorders. However, its mechanism regarding bacterial adhesion, remain unclear.

To investigate the effects and mechanisms of action of aqueous P. capitata extracts (PCE) on UPEC adhesion in T24 cells and rat models.

Broth microdilution and growth experiments were used to explore the direct antibacterial effects of PCE on UPEC. Additionally, motility assays were conducted. Different microscopy methods were used to further examine the mechanisms of action. Transcriptomic analysis and RT-qPCR were used to explore mechanisms on a molecular level. Relevant molecules were assessed using western blotting and immunohistochemistry.

PCE modulated UPEC motility by disrupting the fimbriae and flagella. UPEC pathways, including those essential for constructing fimbriae and flagella, and bacterial motility, were affected. PCE reduced UPEC adhesion and invasion of T24 cells, altering the protein expression of adhesion-related molecules, by modulating the secretion of extracellular vesicles (EVs). It improved blood and urine parameters, reduced inflammatory markers, and ameliorated pathological changes in the kidneys and bladder of rats. Furthermore, the expression of adhesion-related molecules in bladder tissues decreased in the UTI rat model.

This study provides new insights into the mechanisms of herbal medicines in treating UTIs.

Pancreatic ductal adenocarcinoma (PDAC) is insidious, with only 15-20% of those diagnosed suitable for surgical resection as it is either too advanced and has invaded local structures or has already spread to distant sites. The associated tumor microenvironment provides a protective shield which limits the efficacy of chemotherapeutic agents, but also impairs the delivery of nutrients required for the PDAC cells. To compensate for this, metabolic adaptions occur to provide alternative sources of fuel. The aim of this study is to explore metabolomic differences between participants with resectable PDAC compared to healthy volunteers (HV). The objectives were to use nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) to determine if resectable PDAC induces sufficient metabolic adaptations and variations which could be used to discriminate between the two groups.

Plasma samples were collected from fasted individuals with resectable PDAC (n = 23, median age 68 [IQR 56-75], 69.6% male) and HV (n = 24, median age 63 [IQR 58-71], 54.2% male). Samples were analyzed using NMR and the Biocrates MxP Quant 500 kit at University Hospital Southampton.

NMR spectroscopy identified six independent metabolites that significantly discriminated between the PDAC and HV groups, including elevated plasma concentrations of 3-hydroxybutyrate and citrate, with decreased amounts of glutamine and histidine. MS analysis identified 84 metabolites with a significant difference between the PDAC and HV cohorts. The metabolites with a fold change (FC) > 1.5 in the PDAC population were conjugated bile acids (taurocholic acid, glycocholic acid, and glycochenodexoycholic acid).

In conclusion, using metabolomics, biochemical differences between resectable PDAC and HV were detected. These differences indicate metabolic plasticity and utilization of alternative fuel sources.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition wherein excessive fat accumulates in the liver, leading to inflammation and potential liver damage. In this narrative review, we evaluate the tissue microbiota, how they arise and their constituent microbes, and the role of the intestinal and hepatic microbiota in MASLD. The history of bacteriophages (phages) and their occurrence in the microbiota, their part in the potential causation of MASLD, and conversely, "phage therapy" for antibiotic resistance, obesity, and MASLD, are all described. The microbiota metabolism of bile acids and dietary tryptophan and histidine is defined, together with the impacts of their individual metabolites on MASLD pathogenesis. Both periodontitis and intestinal microbiota dysbiosis may cause MASLD, and how individual microorganisms and their metabolites are involved in these processes is discussed. Novel treatment opportunities for MASLD involving the microbiota exist and include fecal microbiota transplantation, probiotics, prebiotics, synbiotics, tryptophan dietary supplements, intermittent fasting, and phages or their holins and endolysins. Although FDA is yet to approve phage therapy in clinical use, there are multiple FDA-approved clinical trials, and this may represent a new horizon for the future treatment of MASLD.

Arginine metabolism in tumors is often shunted into the pathway producing pro-tumor and immune suppressive polyamines (PAs), while downmodulating the alternative nitric oxide (NO) synthesis pathway. Aiming to correct arginine metabolism in tumors, arginine deprivation therapy and inhibitors of PA synthesis have been developed. Despite some therapeutic advantages, these approaches have often yielded severe side effects, making it necessary to explore an alternative strategy. We previously reported that supplementing sepiapterin (SEP), the endogenous precursor of tetrahydrobiopterin (BH4, the essential NO synthase cofactor), could correct arginine metabolism in tumor cells and tumor-associated macrophages (TAMs) and induce their metabolic and phenotypic reprogramming. We saw that oral SEP treatment effectively suppressed the growth of HER2-positive mammary tumors in animals. SEP also has no reported dose-dependent toxicity in clinical trials for metabolic disorders. In the present study, we tested our hypothesis that a long-term administration of SEP to individuals susceptible to HER2-positive mammary tumor would protect them against tumor occurrence.

We administered SEP, in comparison to control DMSO, to MMTV-neu mice susceptible to HER2-positive mammary tumors for 8 months starting at their pre-pubertal stage. We monitored tumor onsets to determine the rate of tumor-free survival. After 8 months of treatment, we grouped animals into DMSO treatment with or without tumors and SEP treatment with or without tumors. We analyzed blood metabolites, PBMC, and bone marrow of DMSO vs. SEP treated animals.

We found that a long-term use of SEP in animals susceptible to HER2-positive mammary tumors effectively suppressed tumor occurrence. These SEP-treated animals had undergone reprogramming of the systemic metabolism and immunity, elevating total T cell counts in the circulation and bone marrow. Given that bone marrow-resident T cells are mostly memory T cells, it is plausible that chronic SEP treatment promoted memory T cell formation, leading to a potent tumor prevention.

These findings suggest the possible roles of the SEP/BH4/NO axis in promoting memory T cell formation and its potential therapeutic utility for preventing HER2-positive breast cancer.

This study explores the neuropharmacological potential of various molecular and amino acid components derived from Syzygium aromaticum (clove), an aromatic spice with a long history of culinary and medicinal use. Key bioactive compounds such as eugenol, α-humulene, β-caryophyllene, gallic acid, quercetin, and luteolin demonstrate antioxidant, anti-inflammatory, and neuroprotective properties by scavenging free radicals, modulating calcium channels, and reducing neuroinflammation and oxidative stress. Moreover, gallic acid and asiatic acid may exhibit protective effects, including neuronal apoptosis inhibition, while other useful properties of clove phytocompounds include NF-κB pathway inhibition, membrane stabilization, and suppression of pro-inflammatory pathways, possibly in neurons or other relevant cell types, further contributing to neuroprotection and cognitive enhancement. Amino acid analysis revealed essential and non-essential amino acids such as aspartic acid, serine, glutamic acid, glycine, histidine, and arginine in various clove parts (buds, fruits, branches, and leaves). These amino acids play crucial roles in neurotransmitter synthesis, immune modulation, antioxidant defense, and metabolic regulation. Collectively, these bioactive molecules and amino acids contribute to clove's antioxidant, anti-inflammatory, neurotrophic, and neurotransmitter-modulating effects, highlighting its potential as a preventive and therapeutic candidate for neurodegenerative disorders. While preliminary preclinical studies support these neuroprotective properties, further research, including clinical trials, is needed to validate the efficacy and safety of clove-based interventions in neuroprotection.

Background/Objectives:Limosilactobacillus fermentum KUB-D18, a heterofermentative lactic acid bacterium with promising probiotic properties, is known for promoting gut health and nutrient absorption. Originally isolated from chicken intestines, this strain demonstrates versatile metabolic capabilities in diverse gastrointestinal environments. However, the metabolic functions and sugar transport-related genes remain largely unexplored. This study thus aimed to dissect metabolic functions and sugar transports of L. fermentum KUB-D18. Methods: Next-generation and third-generation sequencing techniques using integrative genomic platform towards transportome analysis were performed. Results: The complete genome, sized at 2.12 Mbps with a GC content of 51.36%, revealed 2079 protein-encoding genes, of which 1876 protein functions were annotated and identified in top categories involved in amino acids, nucleotide, energy, and carbohydrate transports and metabolisms. Comparative genes analysis identified 50 core and 12 strain-specific genes linked to probiotic properties, e.g., acid resistances and bile tolerances, antioxidant functions, or anti-inflammatory properties. Further, sugar transportome analysis uncovered 57 transporter genes, demonstrating diverse carbon utilization and phosphotransferase (PTS) systems, corroborated by API 50 CHL test results for carbohydrate metabolism profile. Conclusions: These findings enhance the comprehensive metabolic understanding of L. fermentum KUB-D18, supporting its industrial potential and applications in engineered probiotics.

The traditional Chinese medicine (TCM) Danggui Buxue Decoction (DBD) was initially recorded in Nei Wai Shang Bian Huo Lun. Known for its immune regulatory and hematopoietic effects, DBD improved the quality of life in non-small-cell lung cancer (NSCLC) patients. Previous research confirmed that DBD can alleviate gemcitabine (GEM) induced myelosuppression. However, the specific metabolic mechanisms underlying this action remain unclear.

The aim of our study was to explore the metabolic mechanism of DBD against GEM-induced myelosuppression using non-targeted metabolomics and network pharmacology. Additionally, we aimed to validate our findings through enzyme linked immunosorbent assays (ELISA) and Western blot (WB).

Initially, a GEM-induced myelosuppression model in mice was established by administering GEM (100 mg/kg) twice. Serum, bone marrow nucleated cells (BMNCs) and thymus samples were collected at different time points. Ultra-high-performance liquid chromatography coupled with Q Exactive Orbitrap mass spectrometry (UHPLC-QE-MS/MS) was employed based on non-targeted metabolomics and network pharmacology was conducted to identify the key compounds, core targets and pathways that mediate the effects of DBD. Furthermore, the targets identified through metabolic and network pharmacology were jointly analyzed to select crucial metabolism pathways. Finally, our findings were experimentally validated using ELISA and WB.

The results revealed 116 differential metabolites as metabolic biomarkers of DBD in the treatment of GEM-induced myelosuppression. Among these, pathway analysis was conducted on 32 distinct metabolites with KEGG ID, which were subsequently linked to a joint pathway involving 115 targets of DBD-related disease in the PPI network. Pyrimidine synthesis and histidine (HIS) metabolism were identified as the most critical metabolic pathways for DBD in treating GEM-induced myelosuppression. DBD was found to enhance adenosine production through CD73 and additionally regulate TNF-α IL-8 and IL-10.

In summary, pyrimidine synthesis, HIS metabolism, CD73 and inflammatory factors play significant roles in DBD's alleviation of GEM-induced myelosuppression. In this study, a comprehensive strategy of multi-tissues and multi-time point metabolomics, network pharmacology and pharmacological experiments was used to further illuminate the complex mechanisms of DBD against GEM-induced myelosuppression.

Histidine metabolism is crucial in role in tumor biology, contributing to tumor progression, immune regulation, and metabolic reprogramming. In hepatocellular carcinoma (HCC), dysregulated histidine metabolism may promote tumor growth and immune evasion, although the specific mechanisms remain poorly understood.

Using single-cell RNA sequencing, the expression patterns of histidine metabolism-related genes were evaluated across different cell types in HCC samples. In vivo and in vitro experiments were conducted to validate how histidine treatment affects macrophage and T-cell function. Furthermore, the TCGA database was utilized to construct a prognostic model to identify the key gene BUD23 and to examine its correlation with metabolism and immune infiltration.

The proportion of parenchymal cells exhibiting high histidine metabolism was significantly increased, accompanied by a general reduction in immune and stromal cell infiltration. Notably, macrophages and T cells demonstrated impaired antitumor functions. In the high histidine metabolism group, multiple critical cell communication pathways (e.g., MIF, CLEC, MHC II) were downregulated, macrophages shifted toward immunosuppressive subpopulations, T cells exhibited an exhaustion phenotype, and CD8 + T-cell activation was diminished. Further in vivo and in vitro co-culture experiments confirmed that elevated histidine concentrations promoted M2 polarization in macrophages and weakened T-cell cytotoxicity, accelerating tumor proliferation. According to TCGA analyses, BUD23 was upregulated in the high histidine metabolism group and significantly negatively correlated with patient survival and immune cell infiltration. Silencing BUD23 boosted immune cell activation and cytotoxic effects, effectively reversing the immunosuppressive microenvironment. A multivariable Cox regression-based prognostic model indicated unfavorable outcomes in patients with high histidine metabolism.

Histidine metabolism drives tumor cell metabolic reprogramming and reshapes the tumor immune microenvironment through intercellular communication, thereby promoting tumor progression. BUD23 shows promise as a biomarker for prognosis and immune response prediction in liver cancer. This study provides new therapeutic targets and theoretical support for liver cancer treatment by targeting histidine metabolism.

Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), arise from complex interactions between genetic factors, environmental exposures, and aging. Additionally, gut dysbiosis has been linked to systemic inflammation and neurodegeneration. Advances in microbiome and metabolome profiling techniques have provided deeper insights into how alterations in gut microbiota and dietary patterns affect metabolic pathways and contribute to the progression of NDs. This review explores the profiles of gut microbiome and metabolome derived biomarkers and their roles in NDs. Across phyla, families, and genera, we identified 55 microbial alterations in PD, 24 in AD, 4 in ALS, and 17 in MS. Some notable results include an increase in Akkermansia in PD, AD, and MS and a decrease in short-chain fatty acids (SCFAs) in PD and AD. We examined the effects of probiotics, prebiotics, fecal microbiota transplants (FMT), sleep, exercise, and diet on the microbiota, all of which contributed to delayed onset and alleviation of symptoms. Further, artificial intelligence (AI) and machine learning (ML) algorithms applied to omics data have been crucial in identifying novel therapeutic targets, diagnosing and predicting prognosis, and enabling personalized medicine using microbiota-modulating therapies in NDs patients.

Histidine is an amino acid which plays a critical role in protein synthesis, muscle buffering during anaerobic exercise, and antioxidation. It also acts as a precursor to carnosine, a dipeptide that enhances physical performance by being present in fast-contracting muscle fibers and contributing to buffering capacity. Recent studies have examined other histidine-containing compounds, such as anserine, balenine, and ergothioneine, to assess their potential benefits for physical activity. This narrative review focuses on the literature about the effects of dietary supplementation with these histidine-containing compounds on exercise capacity in animals and humans. The findings indicate that anserine may improve physical performance and reduce fatigue, particularly in quick, repetitive activities. Although balenine has been less extensively studied, it has shown promise in enhancing muscle regeneration and antioxidative defense in animal models. Ergothioneine, a sulfur-containing histidine derivative, displayed antioxidant and anti-inflammatory properties in both animal and human studies, suggesting its potential role in reducing exercise-induced oxidative stress and aiding recovery. The diversity of the presented studies and their limitations do not provide an opportunity to confirm the ergogenic properties of the histidine-containing compounds studied. Nevertheless, supplementation with anserine and ergothioneine shows promise for enhancing physical performance and recovery, though further research is required to better understand their mechanisms and optimize their use in sports and exercise.