Результаты поиска

Cancer anorexia: new pathogenic and therapeutic insights.

During tumor growth, anorexia and reduced food intake markedly contribute to the development of malnutrition, thus worsening overall patients' survival. A better understanding of the pathophysiology of eating behavior may lead to new and more effective therapies, aiming at counteracting the detrimental effects of anorexia and reduced food intake on nutritional status and survival in cancer patients. Brain tryptophan and serotonin concentrations seem to play a pivotal role in the regulation of eating behavior. Increased brain serotonin activity is indeed associated with a reduction of food inta…

Steady-state and time-resolved phosphorescence of wild-type and modified bacteriophage λcI repressors.

We have measured the steady-state phosphorescence and decay times of wild-type λcI repressor and compared it with that of a modified λcI repressor in which > 95% of the tryptophans were replaced with 5-hydroxy-L-tryptophan (5-OHTrp). The wild-type and 5-OHTrp-λcI repressors are spectroscopically distinct such that we can selectively excite the 5-OHTrp-λcI even in the presence of a 15-fold molar excess ofN-acetyltryptophanamide (NATrpA). The phosphorescence band of wild-type λcI is red-shifted by 3 nm relative to NATrpA, characteristic of buried tryptophan. Similarly, the phosphorescence of 5-O…

Immunological alterations in frail older adults: A cross sectional study.

Frailty is a progressive physiologic decline in multiple body systems, characterized by loss of function, loss of physiologic reserve, and i … s), who were classified according to Fried's frailty phenotype. Plasma concentrations of neopterin, tryptophan, kynurenine, phenylalanine, tyrosine as well as kynurenine/tryptophan (Kyn/Trp) and phenylalanine/tyrosine (Phe/Tyr) ratios were analyzed as immune stimulation biomarkers. In addition, nitrite and C-reactive protein levels were measured as indicator …

Reduced kynurenine pathway metabolism and cytokine expression in the prefrontal cortex of depressed individuals.

BACKGROUND: Neuroinflammatory processes are increasingly believed to participate in the pathophysiology of a number of major psychiatric diseases, including depression. Immune activation stimulates the conversion of the amino acid tryptophan to kynurenine, leading to the formation of neuroactive metabolites, such as quinolinic acid and kynurenic acid. These compounds affect glutamatergic neurotransmission, which plays a prominent role in depressive pathology. Increased tryptophan degradation along the kynurenine pathway (KP) has been proposed to contribute to disease etiology. METHODS: We use…

Modulation of central serotonin affects emotional information processing in impulsive aggressive personality disorder.

BACKGROUND: The mechanistic model whereby serotonin affects impulsive aggression is not completely understood. The purpose of this study was to test the hypothesis that depletion of serotonin reserves by tryptophan depletion affects emotional information processing in susceptible individuals. METHODS: The effect of tryptophan (vs placebo) depletion on processing of Ekman emotional faces was compared in impulsive aggressive personality disordered, male and female adults with normal controls. All subjects were free of psychotropic medications, medically healthy, nondepressed, and substance free…

Indole-3-propionic acid is an endogenic agonist of hypoxia-inducible factor-1α to protect the heart against hypoxia.

Tryptophan catabolism by the gut microbiota is increasingly recognized as a hub connecting environmental challenges to cardiovascular health. By systematically profiling tryptophan metabolites in humans who had moved from low altitude to an altitude of 4300 m and in mice exposed to hypobaric hypoxia, we found that circulating and fecal levels of indole-3-propionic acid (IPA), a gut microbiota-derived tryptophan metabolite, are reduced in both settings, and these reductions correlate with the severity of cardiac injury. IPA supplementation in mice ameliorated hypobaric hypoxia-induced cardiac d…

Prediction of postoperative delirium by blood metabolome analysis.

No established blood markers can preoperatively predict postoperative delirium. Blood concentrations of amino acid catabolites and dipeptides, including those secreted extracellularly during T-lymphocyte activation, were investigated as predictors of postoperative delirium using metabolomic analyses to ascertain whether preoperative blood metabolites could predict postoperative delirium. Eighteen and 24 participants were included in the delirium and non-delirium groups, respectively. Higher preoperative levels of amino acid (tryptophan) catabolites, via the indoleamine 2,3-dioxygenase pathway,…

Terahertz spectroscopy of brain tissue from a mouse model of Alzheimer's disease.

The terahertz (THz) absorption and index of refraction of brain tissues from a mouse model of Alzheimer’s disease (AD) and a control wild-type (normal) mouse were compared using THz time-domain spectroscopy (THz-TDS). Three dominating absorption peaks associated to torsional–vibrational modes were observed in AD tissue, at about 1.44, 1.8, and 2.114 THz, closer to the peaks of free tryptophan molecules than in normal tissue. A possible reason is that there is more free tryptophan in AD brain tissue, while in normal brain tissue more tryptophan is attached to other molecules. Our study suggests…

Flavin-induced charge separation in transmembrane model peptides.

Hydrophobic peptide models derived from the α-helical transmembrane segment of the epidermal growth factor receptor were synthetically modified with a flavin amino acid as a photo-inducible charge donor and decorated with tryptophans along the helix as charge acceptors. The helical conformation of the peptides was conserved despite the modifications, notably also in lipid vesicles and multibilayers. Their ability to facilitate photo-induced transmembrane charge transport was examined by means of steady-state and time-resolved optical spectroscopy. The first tryptophan next to the flavin donor …

Prediction of absorption coefficients by pulsed laser induced photoacoustic measurements.

In the current study, a pulsed laser induced photoacoustic spectroscopy setup was designed and developed, aiming its application in clinical diagnostics. The setup was optimized with carbon black samples in water and with various tryptophan concentrations at 281nm excitations. The sensitivity of the setup was estimated by determining minimum detectable concentration of tryptophan in water at the same excitation, and was found to be 0.035mM. The photoacoustic experiments were also performed with various tryptophan concentrations at 281nm excitation for predicting optical absorption coefficients…

Interferon-gamma-induced activation of indoleamine 2,3-dioxygenase in cord blood monocyte-derived macrophages inhibits the growth of group B streptococci.

Neonatal sepsis is most often caused by group B streptococci (GBS) and is a major cause of death in the neonatal period. The response of the … ition of tumor necrosis factor-alpha to the culture conditions. The coincident supplementation of L-tryptophan with the bacteria abrogated the bacterial growth inhibition, thus confirming the causative role of L-tryptophan depletion. Control of the extracellular as well as intracellular L-tryptophan levels may thus be one of the effector mechanisms with whic …

5-HT metabolism in the intestinal wall of the rat-II. The nerves plexuses-interactions between 5-HT containing cells.

The presence of serotonin (5-HT) in dissected intestinal muscular wall of the caecum was demonstrated by the determination of endogenous level of the amine by both spectrofluorimetric and radioenzymatic assays. Biosynthesis of [(3)H]5-HT from [(3)H]tryptophan in in vitro conditions revealed the presence of tryptophan hydroxylase in these muscular layers and therefore strongly suggest the presence of serotoninergic neurons. Following dissection of the mucosa from the muscular layers containing the nerve plexuses, endogenous 5-HT and 5-hydroxyindol acetic acid levels as well as amounts of [(3)H]…

У клеток, инфицированных хламидией трахоматис, и неинфекционных клеток есть диаметрально противоположные реакции на интерферонную гамма.

Внутриклеточный бактериальный патоген, хламидийный трахоматис, это триптофан ауксотроп. Таким образом, ввод носителя триптофана в катаболию фермента, индолемина-2,3-диоксигеназы-1 (IDO1), гамма-интерферон (IFN) является одним из основных средств защиты от хламидиальной инфекции. Тем не менее, несмотря на то, что ИФН (IFN) принимает энергичные ответные меры, в шейных секрециях женщин можно обнаружить активный и воспроизводящий C. trachomatis. Мы предположили, что первичная инфекция Трахоматиса может ускользнуть от реакции ИФН, и что защитный эффект этого цитокина вызван активацией катаболизма т

Совпадение в аннотации оригинала
The intracellular bacterial pathogen, Chlamydia trachomatis, is a tryptophan auxotroph. Therefore, induction of the host tryptophan catabolizing enzyme, indoleamine-2,3-dioxgenase-1 (IDO1), by interferon gamma (IFNγ) is one of the primary protective responses against chlamydial infection. However, despite the presence of a robust IFNγ response, active and re…

BeWo trophoblasts are unable to control replication of Toxoplasma gondii, even in the presence of exogenous IFN-gamma.

The ability of RH strain of Toxoplasma gondii to invade and grow into BeWo cells was investigated in the present study using IFN-gamma, l-tryptophan, or alpha-methyl-tryptophan treatments. HeLa cells were used in the same conditions for comparison purposes. It was demonstrated that BeWo cells are more permissive to T. gondii infection, making them more susceptible to this pathogen when compared to HeLa cells. Infection rates of BeWo cells do not show any significant alteration in different protocols using IFN-gamma. In addition, BeWo treated with l-tryptophan was unable to significantly increa…

The Synergism of Human Lactobacillaceae and Inulin Decrease Hyperglycemia via Regulating the Composition of Gut Microbiota and Metabolic Profiles in db/db Mice.

This study aimed to evaluate the effects of Limosilactobacillus fermentum and Lactiplantibacillus plantarum isolated from human feces coordi … otaustralin, 5-hydroxyindoleacetic acid, and 13(S)-HpODE were increased while L-phenylalanine and L-tryptophan were decreased in the MC group compared with the NC group. However, the intervention of LI reversed the levels of these metabolites in the intestine. Correlation analysis revealed that Lachnoclostridium and Ruminococcus_gnavus_group were negatively …

Characterization of the In Vitro Chlamydia pecorum Response to Gamma Interferon.

Chlamydia pecorum is an important intracellular bacterium that causes a range of diseases in animals, including a native Australian marsupial, the koala. In humans and animals, a gamma interferon (IFN-γ)-mediated immune response is important for the control of intracellular bacteria. The present study tested the hypotheses that C. pecorum can escape IFN-γ-mediated depletion of host cell tryptophan pools. In doing so, we demonstrated that, unlike Chlamydia trachomatis, C. pecorum is completely resistant to IFN-γ in human epithelial cells. While the growth of C. pecorum was inhibited in tryptoph…

Multidimensional Metabolic Engineering for Green and Sustainable Bioproduction of Serotonin from Glucose in Bacillus licheniformis.

Serotonin (5-hydroxytryptamine, 5-HT) plays a critical role in maintaining intestinal health, regulating mood and sleep, and enhancing crop stress tolerance. Here, a Bacillus licheniformis cell factory was developed for the sustainable and efficient synthesis of 5-HT. First, a tryptophan-producing chassis strain, TRP18, was obtained by blocking competitive pathways, modifying the tryptophan operon, and rewiring carbon metabolic flux, and the Trp titer was increased by 23.94-fold over the starting strain, TRP0. Subsequently, a heterologous 5-HT biosynthetic pathway was established, and tryptoph…

Longitudinal associations of plasma kynurenines and ratios with fatigue and quality of life in colorectal cancer survivors up to 12 months post-treatment.

Fatigue is prevalent in colorectal cancer (CRC) survivors, impacting their health-related quality of life (HRQoL). Inflammation-induced activation of the kynurenine pathway may play a role in cancer-related fatigue and HRQoL, but evidence is scarce. Therefore, we aimed to investigate longitudinal associations of plasma tryptophan, kynurenines, and ratios with fatigue and HRQoL in CRC survivors up to 12 months post-treatment. Repeated measurements at 6 weeks, 6 months, and 12 months post-treatment were performed in 249 stage I-III CRC survivors. Plasma tryptophan and eight kynurenines were anal…

Some new bifunctional reagents for the conjugation of a protein with an amino compound in water.

Five symmetrical bifunctional reagents (I-V) have been synthesized and tested for their usefulness for the conjugation of albumin with tryptophan, in aqueous solution. With I and II about 17, with IV and V about 8 tryptophan residues could be introduced in the native protein. The difference is discussed. Reagent III has a very low solubility in water but may be useful if organic solvents are permissible.

Phase-and disorder-specific differences in peripheral metabolites of the kynurenine pathway in major depression, bipolar affective disorder and schizophrenia.

OBJECTIVES: Kynurenine, kynurenic and quinolinic acid are important metabolites in tryptophan metabolism. Due to an involvement in glutamatergic neurotransmission and immune response, previous studies have investigated this pathway in mental disorders such as major depressive disorder (MDD), bipolar disorder (BD) or schizophrenia (SCZ). Tryptophan and kynurenine have been shown to be decreased across disorders, hinting at the missing link how inflammation causes neurotoxicity and psychiatric symptoms. The main aim of our study was to investigate if individual catabolites could serve as diagnos…