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Gut Microbiota Modulation through Akkermansia spp. Supplementation Increases CAR T-cell Potency.

UNLABELLED: This study investigates the clinical relevance of the gut microbiome at taxonomic and metabolic levels in anti-CD19 chimeric ant … ted the CD4/CD8 CAR T-cell ratio, favored Tc1 CD8+ T-cell polarization, and promoted the release of tryptophan-derived indole metabolites, leading to better tumor control. The clinical benefit of Akkermansia spp. supplementation was abolished when CAR T cells were genetically deficient in the indole receptor, aryl hydrocarbon receptor (AhR). AhR-agonistic in …

Asprosin mediates diabetes-associated depression via provoking the cascade of pyroptosis-neuroinflammation-kynurenine pathway disorder in the hippocampus.

Depression is a frequent neuropsychiatric complication of diabetes mellitus, but the underlying molecular mechanisms of diabetes-associated depression remain poorly understood. Asprosin, a recently identified fasting-induced glucogenic adipokine, is significantly elevated in diabetes. Pyroptosis, a form of inflammatory programmed cell death, can induce robust neuroinflammation, which also disrupts the kynurenine pathway (KP) of tryptophan metabolism, implying a potential cascade of pyroptosis-neuroinflammation-KP disorder relevant to depression pathogenesis. Therefore, this study aimed to eluc…

Differences in the Profile of Aromatic Metabolites in the Corresponding Blood Serum and Cerebrospinal Fluid Samples of Patients with Secondary Bacterial Meningitis.

Background: Secondary (nosocomial) bacterial meningitis remains a serious problem in patients with severe brain damage. The aim of this study was to assess the differences in the aromatic metabolites of tryptophan, phenylalanine, and tyrosine, in serum and cerebrospinal fluid (CSF) samples collected simultaneously from patients with long-term sequelae of severe brain damage with suspected secondary bacterial meningitis. Methods: Group I included 16 paired serum and CSF samples from patients (N = 11) without secondary bacterial meningitis; group II included 13 paired serum and CSF samples from …

Unraveling the Gut-Brain-Immune Interplay in Herpes Simplex Virus-Associated Neurodegeneration.

Herpes simplex virus type 1 (HSV-1), a ubiquitous neurotropic virus, has been increasingly associated with neurodegenerative disorders throu … neuroimmune dysfunction, while microbiota-derived signals, such as short-chain fatty acids (SCFAs), tryptophan catabolites, and postbiotics, exert protective effects by reinforcing barrier integrity, regulating glial responses, and restoring proteostatic balance. Finally, we advocate for integrative therapeutic approaches that combine antiviral interventions …

Ось микробиота-гут-мозгов в нейродегенеративных болезнях: молекулярные механизмы и терапевтические цели.

Ось микробиота-гут-мозгов (MGBA) — сложная двунаправленная коммуникационная сеть, связывающая кишечную микробиоту с центральной нервной системой (CNS) через иммунную, нейронную, эндокринную и метаболическую каналы. Появляющиеся данные свидетельствуют о том, что дисрегуляция MGBA играет ключевую роль в наступлении и развитии нейродегенеративных заболеваний. В этом обзоре описываются ключевые молекулярные механизмы, с помощью которых кишечные микробы модифицируют нейроинфламмацию, целостность мозгового барьера, неправильное завязывание белка и нейрональный гомеостаз. Мы обсуждаем вопрос о том, к

Совпадение в аннотации оригинала
The microbiota-gut-brain axis (MGBA) is an intricate bidirectional communication network that links intestinal microbiota with the central n … g, and neuronal homeostasis. We discuss how microbial metabolites, such as short-chain fatty acids, tryptophan derivatives, and bile acids, interact with host to influence CNS functions. Disease-specific features are described across Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and Amyotrophic lateral sclerosis, emphasizing the distinct and …

Hypoglycemic effects of white hyacinth bean polysaccharide on type 2 diabetes mellitus rats involvement with entero-insular axis and GLP-1 via metabolomics study.

The present study aimed to investigate the potential effects of white hyacinth bean polysaccharide (WHBP) against type 2 diabetic mellitus ( … hway analysis showed that WHBP administration significantly regulated the phenylalanine metabolism, tryptophan metabolism, arginine and proline, isoleucine metabolism, and glycerophospholipid metabolism in T2DM rats. Together, our results suggested that WHBP performed hypoglycemic effects and pancreatic protection linked to entero-insular axis involvement wi …

Modulation of Metabolomic Profile in Sepsis According to the State of Immune Activation.

OBJECTIVE: To investigate the metabolomic profiles associated with different immune activation states in sepsis patients. DESIGN: Subgroup … Metabolites were enriched in pathways related to ubiquinone biosynthesis, tyrosine metabolism, and tryptophan metabolism when comparing MALS to immunoparalysis and unclassified patients. When comparing MALS to unclassified, 312 significantly different metabolites were found, and pathway analysis indicated enrichment in multiple pathways. Comparing immunopar …

Urinary metabolic characterization of advanced tuberculous meningitis cases in a South African paediatric population.

Tuberculous meningitis (TBM) is a severe form of tuberculosis with high neuro-morbidity and mortality, especially among the paediatric popul … tic of advanced TBM and categorized in terms of six dysregulated metabolic pathways: 1) upregulated tryptophan catabolism linked to an altered vitamin B metabolism; 2) perturbation of amino acid metabolism; 3) increased energy production-metabolic burst; 4) disrupted gut microbiota metabolism; 5) ketoacidosis; 6) increased nitrogen excretion. We also provide …

Metabolic signatures of metabolic dysfunction-associated steatotic liver disease in severely obese patients.

BACKROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) can lead to liver fibrosis, cirrhosis, and hepatocellular carcin … not with the metabolic disturbances associated with cardiovascular risk. Xanthine, ketoleucine, and tryptophan were positively correlated to lobular inflammation and ballooning but also with insulin resistance, and dyslipidemia, respectively. The results did not change when taking into account the most important genetic risk factors of MASLD. CONCLUSIONS: O …

Type-II IFN inhibits SARS-CoV-2 replication in human lung epithelial cells and ex vivo human lung tissues through indoleamine 2,3-dioxygenase-mediated pathways.

Interferons (IFNs) are critical for immune defense against pathogens. While type-I and -III IFNs have been reported to inhibit SARS-CoV-2 re … SARS-CoV-2 replication restricted by IFNγ in Calu3 cells. We further found that the treatment of l-tryptophan, a substrate of IDO1, partially rescues the IFNγ-mediated inhibitory effect on SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Collectively, these results suggest that type-II IFN potently inhibits SARS-CoV-2 replication t …

Comparative Analysis of Microbial Diversity and Metabolic Profiles during the Spontaneous Fermentation of Jerusalem Artichoke (Helianthus tuberosus L.) Juice.

Jerusalem artichoke juice is valued for its nutritional content and health benefits. Spontaneous fermentation enhances its flavor, quality, … abolic pathways included phenylpropanoid biosynthesis, with significant increases in phenylalanine, tryptophan, and related metabolites. Lipid and nucleotide metabolism also showed significant changes. Flavor compounds, including 134 identified alcohols, esters, acids, and ketones, mostly increased in content after fermentation. Notable increases were seen i …

Integrated metabolomics revealed the photothermal therapy of melanoma by Mo2C nanosheets: toward rehabilitated homeostasis in metabolome combined lipidome.

Melanoma, the most aggressive and life-threatening form of skin cancer, lacks innovative therapeutic approaches and deeper bioinformation. I … idome, while Mo2C-based PTT helped improve amino acid metabolism-related biological events (such as tryptophan metabolism) impaired by melanoma. These findings suggest that Mo2C nanosheets hold significant potential as an effective therapeutic agent for skin tumors, such as melanoma. Moreover, through exploring multidimensional bioinformation, integrated met …

Musculus senhousei peptides alleviated alcoholic liver injury via the gut-liver axis.

Alcoholic liver injury has become a leading threat to human health, with complicated pathogenesis and limited therapeutic options. Our previ … n-3). Further analysis of faecal microbiota and metabolome revealed that MSP promoted the growth of tryptophan-metabolizing bacteria (Clostridiales, Alistipes, and Odoribacter), leading to increased production of indole derivatives (indole-3-lactic acid and N-acetyltryptophan). These results suggested that MSPs may alleviate alcohol-induced liver injury targ …

Plasma Ribonuclease Activity in Antiretroviral Treatment-Naive People With Human Immunodeficiency Virus and Tuberculosis Disease.

BACKGROUND: The role of ribonucleases in tuberculosis among people with human immunodeficiency virus (HIV; PWH) is unknown. We explored ribo … ase activity was correlated with concentrations of interleukin 27, procalcitonin and the kynurenine-tryptophan ratio. CONCLUSIONS: PWH with tuberculosis disease have elevated plasma ribonuclease activity, which is also associated with HIV disease severity and systemic inflammation.

Adjunct antiseizure effect of clotrimazole in a rotenone corneal kindling mouse model of mitochondrial drug-resistant epilepsy.

This study aimed to investigate the therapeutic potential of clotrimazole, an inhibitor of the transient receptor potential cation channel, … .05) in seizure scores suggesting the restoration of antiseizure effects. Neurochemicals, including tryptophan, serotonin, kynurenine, serine, taurine, gamma-aminobutyric acid, and glutamate, were significantly restored post-clotrimazole treatment. Overall, the present study underscores the adjunct antiseizure effect of clotrimazole in a rotenone corneal kin …

Sewer sediment adhesion reduction and hydraulic floating promotion by alkaline treatment.

Deposition of sediment in sewers decreased flow capacity, with harmful gases and pipe erosion. Sediment floating and removal remained challe … ion and solubilization of proteins, polysaccharides and humus. The aromatic protein solubilization (tryptophan-like and tyrosine-like proteins) and humic acid-like substance deconstruction were the major driving factors for sediment cohesion reduction, which disintegrated the bio-aggregation and increased the surface electronegativity. Meanwhile, the variati …

Chronic evoked seizures in young pre-symptomatic APP/PS1 mice induce serotonin changes and accelerate onset on Alzheimer's disease-related neurpathology.

OBJECTIVE: People with early-onset Alzheimer's disease (AD) are at elevated seizure risk. Further, chronic seizures in pre-symptomatic stage … e to chronic kindled seizures. These changes correlated with a marked downregulation of hippocampal tryptophan hydroxylase 2 and monoamine oxidase A protein expression compared to controls; these changes were not detected in PSEN2-N141I mice. Kindled APP/PS1 mice exhibited amyloid beta; overexpression and glial overactivity without plaque deposition. PSEN2 p …

Interaction of organoruthenium(II)-polypyridyl complexes with DNA and BSA.

The interaction of four arene ruthenium complexes [(η6-p-cymene)Ru(Me2dppz)Cl]PF6 (1) with Me2dppz = 11,12-dimethyldipyrido[3,2-a:2',3'-c]ph … ence titration bovine serum albumin by 1, 2, 3 and 4 showed that all complexes significantly quench tryptophan residues fluorescence through a static quenching mechanism. The antimicrobial activity against both Gram-positive and Gram-negative bacteria analyzed. Complex 1 was most active, even on Escherichia coli was more active than positive control compound …

Intestinal Flora-Derived Kynurenic Acid Protects Against Intestinal Damage Caused by Candida albicans Infection via Activation of Aryl Hydrocarbon Receptor.

Colonization of the intestinal tract by Candida albicans (C. albicans) can lead to invasive candidiasis. Therefore, a functional intestinal … blished following intake of 3% dextran sulfate sodium salt (DSS) for 9 days, and found that KynA, a tryptophan metabolite, inhibited inflammation, promoted expression of intestinal tight junction proteins, and protected from intestinal barrier damage caused by invasive Candida infections. We also demonstrated that KynA activated aryl hydrocarbon receptor (AH …

Leveraging metabolic modeling to identify functional metabolic alterations associated with COVID-19 disease severity.

OBJECTIVE: Since the COVID-19 pandemic began in early 2020, SARS-CoV2 has claimed more than six million lives world-wide, with over 510 mill … isms that link these markers to disease progression. RESULTS: Enriched metabolites associated with tryptophan in non-acute COVID-19 samples suggest mitigated innate immune system inflammatory response and immunopathology related lung damage prevention. Increased prevalence of histidine- and ketone-related metabolism in severe COVID-19 samples offers potenti …