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The Effect of Faecal Microbiota Transplantation on Cognitive Function in Cognitively Healthy Adults with Irritable Bowel Syndrome: Protocol for a Randomised, Placebo-Controlled, Double-Blinded Pilot Study.

Faecal microbiota transplantation (FMT) is an emerging therapy for gastrointestinal and neurological disorders, acting via the microbiota-gu … microbiome composition and plasma biomarkers related to inflammation, short-chain fatty acids, and tryptophan metabolism. Outcomes are assessed at baseline and at one, three, six, and twelve months following treatment. We hypothesise that FMT will lead to greater improvements in cognitive performance than placebo, with benefits extending beyond practice eff …

Leveraging microbiota-metabolites to reduce inflammation and promote functional recovery following spinal cord injury in female mice.

Spinal cord injury induces extensive neurological impairment and drives systemic and tissue-level inflammatory responses that accelerate secondary systemic damage. Emerging evidence suggests that gut microbiota-derived metabolites can influence post-injury inflammation, presenting a potential therapeutic approach. This study examines whether the tryptophan-derived metabolites indole and indole-3-propionic acid modulate inflammatory responses and improve outcomes following spinal cord injury. Female C57BL/6J mice received a severe thoracic-8 contusion-compression injury and were administered in…

A Ketone-Accepting Pictet-Spenglerase for the Asymmetric Construction of 1,1-Disubstituted Tetrahydro-ß-carboline Alkaloids.

In light of the ubiquity of 1,1'-disubstituted tetrahydro-ß-carboline (THBC) motif in alkaloid natural products, developing asymmetric metho … ee method for the construction of densely functionalized THBCs with α-quaternary center by coupling tryptophan derivatives and α-keto acids. We determine the stereochemistry of kitasetalic acid, KslB's physiological product and a key biosynthetic intermediate toward kitasetaline, and established that KslB's selectivity is opposite to what is achieved chemica …

1,3,4-Oxadiazole Sulfonamide Derivatives Containing Pyrazole Structures: Design, Synthesis, Biological Activity Studies, and Mechanism Study.

Sulfonamide derivatives have been widely used for pesticide research in recent years. Herein, 1,3,4-oxadiazole sulfonamide derivatives conta … lysis of transcriptomics and proteomics revealed the capability of A23 to regulate pathways such as tryptophan metabolism and phenylpropanoid biosynthesis, enhancing the innate immunity of rice and activating its disease resistance. Thus, A23 emerges as a potential immunoinducible pesticide lead compound for the discovery of highly active immune-inducing age …

Genome Mining of Isoindolinone-Containing Peptide Natural Products.

Peptide natural products (PNPs) are important sources of bioactive compounds. Recent studies have shown that oligopeptides or pseudopeptides … tetrapeptide formation. From the C. immitis BGC, a flavoenzyme catalyzing the direct oxidation of l-tryptophan to l-oxindolylalanine was discovered. Our work validates ATP-grasp enzymes and ABSs as leads to mine new PNPs and further showcases the biocatalytic potential of these enzymes in catalyzing amide-bond formation.

Flavonoids as Natural Inhibitors of β-Carbolines: Mechanistic Insights.

The inhibitory mechanisms of flavonoids suppressing the formation of foodborne β-carboline heterocyclic amines, Harman and Norharman, remain … flavonoids captured aldehydes to form adducts, thus diminishing THβC formation. Two major adducts, tryptophan-formaldehyde-flavonoid and flavonoid-formaldehyde-flavonoid, were identified by UPLC-MS/MS analysis. These mechanisms were verified in soy sauce brine systems, though their inhibitory efficacy was weakened by preexisting THβCs and β-carbolines, and …

Novel Indoleamine-2,3-Dioxygenase-Targeted Pt(IV) Prodrugs Regulate the Tumor Immune Microenvironment to Achieve Chemoimmunotherapy In Vitro and In Vivo.

Convincing evidence revealed that some platinum-based drugs could stimulate immunological recognition, thereby inducing immunogenic cell death (ICD). Indoleamine-2,3-dioxygenase (IDO) is overexpressed in tumors, which caused exhaustion of tryptophan (T-cell energy) and constructed an immunosuppressive tumor microenvironment. Herein, considering IDO inhibition to improve chemotherapy, a series of IDOi-Pt(IV) prodrugs were designed to not only target DNA and IDO but also facilitate tumor-antigen exposure and immunomodulation. The optimal IDOi-Pt(IV) prodrugs (named compound 10) significantly enh…

Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained fatigue, post-exertional malaise (PEM), and cogn … balance reflected by disturbances in copper-dependent antioxidant pathways and dysregulation of the tryptophan-serotonin-kynurenine pathways. Many of these underlying abnormalities worsened following exercise in ME/CFS patients, but not in healthy subjects; many abnormalities reinforced each other and several were correlated with the intensity of symptoms. O …

B.uniformis IM01-derived IAA alleviates asthma via AhR/NLRP3 pathways in mice.

Symbiotic flora exhibits a strong association with the pathogenesis of allergic disorders. Certain Bacteroides species have demonstrated pot … thelial barrier function in a murine model of asthma. Mechanistically, B.uniformis IM01 upregulated tryptophan metabolism, elevating IAA levels in both colon and serum, which activated the aryl hydrocarbon receptor (AhR) and induced interleukin-22 (IL-22) production. Activated AhR may inhibit NF-κB/NLRP3 signaling pathway and facilitate the splenic different …

Uncovering novel OMPs of Vibrio cholerae: Biophysical insights and epitope prediction of AcfA, Opa, VxrD, LamB, and VpsM for immunotherapy and vaccine design.

AcfA, Opa, VxrD, LamB, and VpsM are outer membrane proteins (OMPs) in Vibrio cholerae that contribute significantly to its virulence and sho … ecovery. Structural confirmation was achieved through circular dichroism spectroscopy and intrinsic tryptophan fluorescence, while additional validation using heat-induced mobility shifts and proteolytic stability assays confirmed that the refolded proteins adopted compact and stable conformations. Furthermore, immunoinformatic screening revealed immunologic …

Воздействие кинуреньиновых метаболитов на клетки В и Т в множественных склерозах и аллергиях.

Хроническое воспаление имеет ключевое значение как для множественных склерозов (MS), так и для аллергических заболеваний, хотя их патологические результаты различаются. В MS воспаление приводит к обезвоживанию и нейродегенерации в центральной нервной системе, в то время как в аллергии оно вызывает локальный опухоль и раздражение тканей. Появляющиеся данные свидетельствуют о том, что повышенная иммунная активность в аллергиях может влиять на подстрекательскую реакцию в MS или усугублять ее, при этом некоторые исследователи предлагают общие иммунопатологические механизмы между аллергической гипе

Совпадение в аннотации оригинала
Chronic inflammation is central to both multiple sclerosis (MS) and allergic conditions, though their pathological outcomes differ. In MS, i … ic hyperactivity and the autoimmune processes underlying MS. The kynurenine pathway, a key route of tryptophan metabolism, has garnered attention for its role in the pathogenesis of neurodegenerative, psychiatric, vascular, and autoimmune diseases. Its metabolites are known to modulate neuroinflammation and immune responses, particularly through their effect …

The roles of the kynurenine pathway in COVID-19 neuropathogenesis.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the highly contagious respiratory disease Corona … re known to activate the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), catalysing the first step of tryptophan (Trp) catabolism through the kynurenine pathway (KP) leading to the production of several neurotoxic and immunosuppressive metabolites. There is already data showing elevation in KP metabolites both acutely and in PASC, especially regarding cognitiv …

Mechanistic insights into EGCG's preventive effects on obesity-induced precocious puberty through multi-omics analyses.

Epigallocatechin gallate (EGCG) has demonstrated potential effects on obesity-induced precocious puberty, but the underlying mechanisms rema … f beneficial bacteria such as Akkermansia. Metabolomic analysis revealed significant alterations in tryptophan metabolism, while transcriptome analysis identified genes involved in metabolic pathways. Correlation analyses underscored the importance of the gut-brain axis in mediating EGCG's effects. Overall, EGCG prevents obesity-induced precocious puberty by …

Electrochemical Sensing of Phenylalanine using Polyaniline-Based Molecularly Imprinted Polymers.

Polyaniline (PANI)-based molecularly imprinted polymers were investigated for their efficacy in sensing phenylalanine (Phe) when fabricated … . We tested the specificity of Phe sensing by PANI-MIP with different amino acids such as cysteine, tryptophan, and tyrosine as well as organic molecules such as ascorbic acid, allantoin, sucrose, and urea, confirming its remarkable electrochemical efficiency. The oxidation response curve yielded a limit of detection of 4.88 μM and a limit of quantification …

Metabolomic signatures associated with fetal growth restriction and small for gestational age: a systematic review.

The pathways involved in the pathophysiology of fetal growth restriction (FGR) and small for gestational age (SGA) are incompletely understo … A: biosynthesis of unsaturated fatty acids in umbilical cord blood, and phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, and phenylalanine metabolism in newborn dried blood spot. Significantly enriched metabolic pathways were not identified in the remaining biological samples. Whether these metabolites are in …

Polysaccharides to postbiotics: Nurturing bone health via modulating "gut-immune axis".

The increasing prevalence of individuals affected by bone pathologies globally has sparked catastrophic concerns. Ankylosing spondylitis, os … biota-derived metabolites, such as branched-chain amino acids, bile acids, short-chain fatty acids, tryptophan, trimethylamine N-oxide, and indole derivatives. Moreover, the modulation of gut microbiota through biotics (prebiotics, probiotics and postbiotics) presents a promising avenue for therapeutic intervention. Biotics selectively promote the growth of …

Exploring serum amino acid signatures as potential biomarkers in Hashimoto's thyroiditis patients.

Hashimoto's thyroiditis (HT) is an autoimmune disease caused by the immune system attacking healthy tissues. However, the exact pathogenesis … e likelihood ratio. Also, according to pathway analysis, degradation of phenylalanine, tyrosine and tryptophan biosynthesis was the highest metabolic pathway according to the impact value (p < 0.001 and impact value = 1.0). We provide serum amino acid profiles of patients with Hashimoto's thyroiditis and identify five potential biomarkers for early diagnosis …

Recent Advances in Microbiota-Associated Metabolites in Heart Failure.

Heart failure is a risk factor for adverse events such as sudden cardiac arrest, liver and kidney failure and death. The gut microbiota and … obiota-derived metabolites such as short chain fatty acids, bile acids, branched-chain amino acids, tryptophan and indole derivatives as well as trimethylamine-derived metabolite, trimethylamine N-oxide, play critical roles in promoting heart failure through various mechanisms. Mainly, they modulate complex signaling pathways such as nuclear factor kappa-lig …

Indole-3-acetic acid improves the hepatic mitochondrial respiration defects by PGC1a up-regulation.

Recent evidences have linked indole-3-acetic acid (I3A), a gut microbiota-derived metabolite from dietary tryptophan, with the protection against non-alcoholic fatty liver disease (NAFLD). However, the values of I3A on mitochondrial homeostasis in NAFLD have yet to be analyzed. In this study, we verified that I3A alleviated dietary-induced metabolic impairments, particularly glucose dysmetabolism and liver steatosis. Importantly, we expanded the understanding of I3A further to enhance mitochondrial oxidative phosphorylation in the liver by RNA-seq. Consistently, I3A restored the deficiency of …

Kynurenic acid ameliorates NLRP3 inflammasome activation by blocking calcium mobilization via GPR35.

The inflammasome has been linked to diverse inflammatory and metabolic diseases, and tight control of inflammasome activation is necessary to avoid excessive inflammation. Kynurenic acid (KA) is a tryptophan metabolite in the kynurenine pathway. However, the roles and mechanisms of the regulation of inflammasome activation by KA have not yet been fully elucidated. Here, we found that KA suppressed caspase-1 activation and IL-1β production in macrophages by specifically inhibiting canonical and noncanonical activation of the NLRP3 inflammasome. Mechanistically, KA reduced calcium mobilization t…