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This study investigated whether L-tyrosine supplementation enhances endurance performance in mentally fatigued cyclists. Twelve recreational cyclists completed two constant-workload tests to exhaustion cycling tests under two experimental conditions at 80% of maximal endurance power output: L-tyrosine ingestion (300 mg/kg) under mental fatigue (TYR-MF), and placebo under mental fatigue (PLA-MF). Mental fatigue (MF) was induced by a 60-min Stroop task (ST). Oxygen consumption (VO2), rating of perceived exertion (RPE), and heart rate (HR) were measured throughout the cycling test. Time to exhaustion in the TYR-MF condition (459.9 ± 199.6 s) was higher when compared to the PLA-MF experimental condition (398.7 ± 222.1 s) (p = 0.008). The increase (i.e., slope technique) of RPE throughout the cycling to exhaustion was lower in the TYR-MF (0.560 ± 0.184 a.u.) than in PLA-MF (0.673 ± 0.251 a.u.) (p = 0.03) experimental condition. No differences were observed between conditions for VO2 and HR data (p > 0.05). L-tyrosine ingestion increased endurance performance by approximately 16% in mentally fatigued cyclists. This effect was accompanied by a reduction in RPE slope during cycling to exhaustion. Therefore, these preliminary findings suggest that L-tyrosine supplementation may offer moderate benefits in performance for cyclists under mental fatigue conditions, although confirmatory studies with larger samples are needed. © 2026 The Author(s). European Journal of Sport Science published by Wiley‐VCH GmbH on behalf of European College of Sport Science.

BACKGROUND: O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET has a higher specificity than contrast-enhanced T1-weighted MRI (CE-T1MRI) in diagnosing recurrent glioblastoma. We aimed to evaluate whether a FET-PET-based target volume delineation, compared with CE-T1MRI, improves outcomes in patients with recurrent glioblastoma scheduled for re-irradiation. METHODS: GLIAA was a multicentre, open-label, parallel randomised study done in 15 radiation oncology centres in Germany. Patients aged 18 years or older with a Karnofsky performance score greater than 60% and a macroscopic WHO grade IV recurrent glioblastoma (1-6 cm) were randomly assigned (1:1) to receive either FET-PET-based or CE-T1MRI-based target volume delineation followed by re-irradiation with 39 Gy in 13 fractions. Randomisation was performed centrally, using a minimisation technique with a random element and a computer-assisted randomisation tool, stratified by time since first radiotherapy, previous chemotherapy, tumour diameter, MGMT status, and planned chemotherapy. The primary endpoint was progression-free survival from randomisation, assessed in the per-protocol population (patients who initiated treatment per their assigned group). Adverse events were systematically assessed in all patients who commenced therapy. The trial was registered with ClinicalTrials.gov (NCT01252459), German Clinical Trials Registry (DRKS00000634), and European Clinical Trials Database (EudraCT 2012-001121-27), and is completed. FINDINGS: Between Nov 22, 2013, and Aug 18, 2021, 271 patients were recruited and screened for eligibility, 200 of whom were randomly assigned to re-irradiation based on FET-PET (n=100) or CE-T1MRI (n=100). 85 (43%) participants were female and 115 (58%) were male. 98 patients in the FET-PET group and 97 in the CE-T1MRI group were treated per protocol. Median follow-up for censored patients was 12·2 months (IQR 6·6-20·7). Median progression-free survival was 4·0 months (95% CI 3·7-5·2) in the FET-PET group and 4·9 months (3·7-6·0) in the CE-T1MRI group (one-sided stratified log-rank p=0·98; adjusted hazard ratio 1·14 [95% CI 0·85-1·52]; p=0·39; median follow-up for six censored patients 4·1 months [I

IMPORTANCE: Particulate matter exposure has been linked to impaired respiratory health in children, but the respiratory benefits of air purification have not been fully elucidated. OBJECTIVES: To assess the respiratory health outcomes among children exposed to multisetting air purification vs sham purification. DESIGN, SETTING, AND PARTICIPANTS: This cluster randomized, double-blind, crossover trial was conducted among healthy school-aged children (10-12 years) in China from April to December 2021. Data were analyzed from December 2021 to July 2024. INTERVENTIONS: A multisetting (both in classrooms and bedrooms) air purification intervention compared with sham purification in a 2-stage intervention with more than 2 months (76 days) for each period and a washout period (88 days) to estimate the respiratory benefits of air purification. MAIN OUTCOMES AND MEASURES: The primary outcomes were pulmonary function, airway inflammation markers, and metabolites in exhaled breath condensate (EBC) before and after the air purification intervention. Linear mixed-effects models were used to estimate the respiratory benefits of children related to air purification. Differential metabolites in EBC were identified using metabolomics analysis to explore their possible mediation roles. RESULTS: A total of 79 children (38 male [48%]; mean [SD] age, 10.3 [0.5] years) were included in the statistical analyses. During the study period, the mean (SD) concentration of outdoor fine particulate matter (PM2.5) at the school site was 32.53 (24.06) μg/m3. The time-weighted personal PM2.5 concentration decreased by 45.14% during the true air purification period (mean [SD], 21.49 [8.72] μg/m3) compared with the sham air purification period (mean [SD], 39.17 [14.25] μg/m3). Air purification improved forced expiratory volume in 1 second by 8.04% (95% CI, 2.15%-13.93%), peak expiratory flow by 16.52% (95% CI, 2.76%-30.28%), forced vital capacity (FVC) by 5.73% (95% CI, 0.48%-10.98%), forced expiratory flow at 25% to 75% of FVC by 17.22% (95% CI, 3.78%-30.67%), maximal expiratory flow at 75% of FVC by 14.60% (95% CI, 0.35%-28.85%), maximal expiratory flow at 50% of FVC by 17.86% (95% CI, 3.65%-32.

Ingestion of L-theanine and L-tyrosine has been shown to reduce salivary stress biomarkers and improve aspects of cognitive performance in response to stress. However, there have been no studies to concurrently examine the impact of both L-theanine and L-tyrosine ingestion during a mental stress challenge (MSC) involving a brief cognitive challenge and a virtual reality based active shooter training drill. Thus, the purpose of this study was to determine the impact of ingestion of L-theanine and L-tyrosine on markers of stress and cognitive performance in response to a virtual reality active shooter drill and cognitive challenge. The cognitive challenge involved a Stroop challenge and mental arithmetic. Eighty subjects (age = 21 ± 2.6 yrs; male = 46; female = 34) were randomly assigned L-tyrosine (n = 28; 2000 mg), L-theanine (n = 25; 200 mg), or placebo (n = 27) prior to MSC exposure. Saliva samples, state-anxiety inventory (SAI) scales, and heart rate (HR) were collected before and after exposure to the MSC. Saliva was analyzed for stress markers α-amylase (sAA) and secretory immunoglobulin A (SIgA). The MSC resulted in significant increases in sAA, SIgA, HR, and SAI. Ingestion of L-theanine and L-tyrosine did not impact markers of stress. However, the L-tyrosine treatment demonstrated significantly lower missed responses compared to the placebo treatment group during the Stroop challenge. These data demonstrate that ingestion of L-theanine or L-tyrosine does not impact markers of stress in response to a MSC but may impact cognitive performance. This study was pre-registered as a clinical trial ("Impact of supplements on stress markers": NCT05592561).

Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor issues and a range of non-motor symptoms. Microbial therapy may be a useful approach for the treatment of PD. However, comprehensive analyses of the impact of probiotic supplementation on motor and non-motor symptoms are still lacking and the mechanisms whereby the treatment works remain unclear. This study investigated Lacticaseibacillus paracasei strain Shirota (LcS) supplementation on clinical responses, gut microbiota and faecal metabolites in PD patients. Patients (n = 128) were randomised to receive either probiotics (LcS-fermented milk, containing 1 × 1010 living LcS cells) or placebo for 12 weeks. All participants were examined and the basic clinical features were recorded using questionnaires. Fecal and blood samples were collected at the baseline and after 12 weeks for further omics analysis. We found that LcS intervention significantly alleviated patients' constipation-related symptoms and non-motor symptoms. We found no significant shifts in the composition of gut microbiota or faecal metabolites. Several taxa were differentially abundant between the groups, especially with regard to LcS intake, which increased the abundance of the genus Lacticaseibacillus in the probiotic group compared with those at the baseline and in the placebo group. The faecal concentration of L-tyrosine was significantly decreased and the plasma concentration of L-tyrosine was increased in the probiotic group compared with the placebo group. Our study demonstrated that although supplementation with LcS did not induce major changes in the global gut microbiome, the probiotic had favorable effects in managing constipation and other non-motor symptoms in PD patients. This study was registered at the Chinese Clinical Trial Registry: ChiCTR1800016795.

Supplementation with the catecholamine precursor L-Tyrosine might enhance cognitive performance, but overall findings are mixed. Here, we investigate the effect of a single dose of tyrosine (2g) vs. placebo on two catecholamine-dependent trans-diagnostic traits: model-based control during reinforcement learning (2-step task) and temporal discounting, using a double-blind, placebo-controlled, within-subject design (n = 28 healthy male participants). We leveraged drift diffusion models in a hierarchical Bayesian framework to jointly model participants' choices and response times (RTS) in both tasks. Furthermore, comprehensive autonomic monitoring (heart rate, heart rate variability, pupillometry, spontaneous eye blink rate) was performed both pre- and post-supplementation, to explore potential physiological effects of supplementation. Across tasks, tyrosine consistently reduced participants' RTs without deteriorating task-performance. Diffusion modeling linked this effect to attenuated decision-thresholds in both tasks and further revealed increased model-based control (2-step task) and (if anything) attenuated temporal discounting. On the physiological level, participants' pupil dilation was predictive of the individual degree of temporal discounting. Tyrosine supplementation reduced physiological arousal as revealed by increases in pupil dilation variability and reductions in heart rate. Supplementation-related changes in physiological arousal predicted individual changes in temporal discounting. Our findings provide first evidence that tyrosine supplementation might impact psychophysiological parameters, and suggest that modeling approaches based on sequential sampling models can yield novel insights into latent cognitive processes modulated by amino-acid supplementation. Copyright: © 2022 Mathar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

OBJECTIVE: To observe the effect of acupuncture combined with rehabilitation training on cognitive function and amino acid metabolism in children with cerebral palsy. METHODS: Twenty children with cerebral palsy (cerebral palsy group) were randomly divided into an acupuncture and rehabilitation group (11 cases) and a rehabilitation group (9 cases), and 10 healthy children were included as the normal group. The rehabilitation group was treated with rehabilitation training, 30 min each time; on the basis of rehabilitation training, the acupuncture and rehabilitation group was treated with acupuncture at Sishenzhen, Zhisanzhen, Naosanzhen, Niesanzhen, Dazhui (GV 14), Shenzhu (GV 12), Mingmen (GV 4), etc. The Sishenzhen (left and right points) and the ipsilateral Niesanzhen were respectively connected with a group of electrodes, intermittent wave, frequency of 2 Hz for 30 min. Both groups were treated once every other day, three times a week, totaling for 3 months. The Gesell developmental diagnostic scale (GESELL) was used to evaluate the developmental quotient (DQ) scores before and after treatment, and the blood samples of children with cerebral palsy before and after treatment and normal children were collected for amino acid metabolomics. RESULTS: Compared before treatment, the DQ scores of adaptation, fine motor and social in the acupuncture and rehabilitation group was increased after treatment (P<0.05), and the DQ score of fine motor in the rehabilitation group was increased after treatment (P<0.05). Compared with the normal group, the serum L-glutamate, L-ornithine, L-tyrosine, L-methionine and L-arginine in the cerebral palsy group were down-regulated, and L-histidine, L-citrulline, 5-hydroxylysine and L-glutamine were up-regulated before treatment. The functional pathways mapped by different metabolites between the cerebral palsy group and the normal group included arginine biosynthesis, arginine and proline metabolism, etc. Compared with the cerebral palsy group, the serum L-histidine was decreased, and L-citrulline showed decreasing trend in the acupuncture and rehabilitation group after treatment. CONCLUSION: Acupuncture combined with rehabilitation tr

BACKGROUND: Most previous studies used aluminum hydroxide-absorbed allergen extracts in evaluating the potential therapeutic roles of intralymphatic allergen-specific immunotherapy (ILAIT). In this study, we evaluated the therapeutic efficacy and safety of ILAIT with L-tyrosine-adsorbed allergen extracts of Dermatophagoides farinae, D. pteronyssinus, cat, dog, or mixtures thereof, in patients with allergic rhinitis induced by these allergens. METHODS: In this randomized, double-blind, placebo-controlled trial, study subjects received three intralymphatic injections of L-tyrosine-adsorbed allergen extracts (active group) or saline (placebo group) at 4-week intervals. RESULTS: Although ILAIT reduced daily medication use and skin reactivity to HDM and cat allergens at 4 months after treatment, overall symptom score on a visual analog scale (VAS), sinonasal outcome test-20 (SNOT-20), rhinoconjunctivitis quality of life questionnaire (RQLQ), daily symptom score (dSS), daily medication score (dMS), daily symptom medication score (dSMS), nasal reactivity to HDM allergen, and basophil activity to HDM, cat, and dog allergens at 4 months and 1 year after treatment were similar between the treatment and control groups. Intralymphatic injection was more painful than a venous puncture, and pain at the injection site was the most frequent local adverse event (12.8%); dyspnea and wheezing were the most common systemic adverse events (5.3%). CONCLUSIONS: ILAIT with L-tyrosine-adsorbed allergen extracts does not exhibit profound therapeutic efficacy in allergic rhinitis and can provoke moderate-to-severe systemic reactions and cause pain at the injection site. TRIAL REGISTRATION: clinicaltrials.gov: NCT02665754; date of registration: 28 January 2016.

BACKGROUND: The goal of this prospective study was to compare the value of both conventional MRI and O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET for response evaluation in glioblastoma patients treated with bevacizumab plus lomustine (BEV/LOM) at first progression. METHODS: After chemoradiation with concomitant and adjuvant temozolomide, 21 IDH wild-type glioblastoma patients at first progression (age range, 33-75 years; MGMT promoter unmethylated, 81%) were treated with BEV/LOM. Contrast-enhanced MRI and FET-PET scans were performed at baseline and after 8-10 weeks. We obtained FET metabolic tumor volumes (MTV) and tumor/brain ratios. Threshold values of FET-PET parameters for treatment response were established by ROC analyses using the post-progression overall survival (OS) ≤/>9 months as the reference. MRI response assessment was based on RANO criteria. The predictive ability of FET-PET thresholds and MRI changes on early response assessment was evaluated subsequently concerning OS using uni- and multivariate survival estimates. RESULTS: Early treatment response as assessed by RANO criteria was not predictive for an OS>9 months (P = 0.203), whereas relative reductions of all FET-PET parameters significantly predicted an OS>9 months (P < 0.05). The absolute MTV at follow-up enabled the most significant OS prediction (sensitivity, 85%; specificity, 88%; P = 0.001). Patients with an absolute MTV below 5 ml at follow-up survived significantly longer (12 vs. 6 months, P < 0.001), whereas early responders defined by RANO criteria lived only insignificantly longer (9 vs. 6 months; P = 0.072). The absolute MTV at follow-up remained significant in the multivariate survival analysis (P = 0.006). CONCLUSIONS: FET-PET appears to be useful for identifying responders to BEV/LOM early after treatment initiation.

When exposed to ultraviolet radiation, the human skin produces profuse reactive oxygen species (ROS), which in turn activate a variety of biological responses. Mounting ROS levels activate tyrosinase by mobilizing α-melanocyte-stimulating hormone in the epidermis and finally stimulates the melanocytes to produce melanin. Meanwhile, the Keap1-Nrf2/ARE pathway, which removes ROS, is activated at increased ROS levels, and antioxidant compounds facilitates the dissociation of Nrf2. In this study, we explored the possible suppressing effects of antioxidant compounds and tyrosine inhibitors on melanin formation and the promotory effects of these compounds on ROS scavenging. The antioxidant activity of glabridin (GLA), resveratrol (RES), oxyresveratrol (OXYR), and phenylethylresorcinol (PR) were investigated via the stable free radical 2,2-diphenyl-1-picrylhydrazyl method. The inhibitory effects of the four compounds and their mixtures on tyrosinase were evaluated. l-Tyrosine or 3-(3,4-dihydroxyphenyl)-l-alanine (l-DOPA) was used as a substrate. The results showed that all mixtures did not exhibit synergistic effects with the l-tyrosine as a substrate, suggesting that l-tyrosine is not suitable as a substrate. However, the mixtures of "GLA:RES," "GLA:OXYR," "OXYR:RES," and "PR:RES" demonstrated synergistic effects (CI < 0.9, p < 0.05), whereas "GLA:RES" and "PR:OXYR" indicated an additive effect (0.9 ditive1, p < 0.05). Furthermore, we used a molecular docking strategy to study the interactions of the four compounds with tyrosinase and l-DOPA. The molecular docking result is consistent with that of the experiment. Finally, we selected RES + OXYR and used PIG1 cells to verify whether OXYR synergistically promotes RES activity on tyrosinase. The two agents had a synergistic inhibitory effect on tyrosinase activity. These results provided a novel synergistic strategy for antioxidants and tyrosinase inhibitors, and this strategy is useful in skin injury treatment.

Aim of this study was to investigate if cellular [18F]FBPA uptake can be increased upon preloading with amino acids. [18F]FBPA uptake was assessed in HuH-7, CaCo-2 and B16-F1 cells pretreated with different concentrations or incubation times of L-BPA, L-tyrosine or L-DOPA. Without preloading, highest uptake of [18F]FBPA was observed in B16-F1 cells, followed by CaCo-2 cells and HuH-7 cells. In all cell lines higher [18F]FBPA accumulation (up to 1.65-fold) was obtained with increasing L-BPA, L-DOPA and L-tyrosine concentrations.

PURPOSE: Resistance to bevacizumab (BEV) in glioblastoma is believed to occur via activation of molecular networks including the mTOR/PI3K pathway. Using an MR/PET molecular imaging biomarker approach, we investigated the response to combining BEV with the mTOR/PI3K inhibitor BEZ235. METHODS: Tumours were established by orthotopically implanting U87MG-luc2 cells in mice. Animals were treated with BEZ235 and/or BEV, and imaged using diffusion-weighted-MRI, T2-weighted and T2*-weighted before and after administration of superparamagnetic iron oxide contrast agent. Maps for changes in relaxation rates (ΔR2, ΔR2* and apparent diffusion coefficient) were calculated. Vessel size index and microvessel density index were derived. 3'-Deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) PET and O-(2-[(18)F]fluoroethyl)-L-tyrosine ([(18)F]FET) PET were further performed and tumour endothelium/proliferation markers assessed by immunohistochemistry. RESULTS: Treatment with BEV resulted in a pronounced decrease in tumour volume (T2-weighted MRI). No additive effect on tumour volume was observed with the BEV/BEZ235 combination compared with BEV monotherapy. The Ki67 proliferation index and [(18)F]FLT uptake studies were used to support the observations. Using ΔR2* and ΔR2 values, respectively, the BEV/BEZ235 combination significantly reduced tumour microvessel volume in comparison to BEV alone. Decreased microvessel density index was further observed in animals treated with the combination, supported by von Willebrand factor (vWF) immunohistochemistry. [(18)F]FET uptake was decreased following treatment with BEV alone, but was not further reduced following treatment with the combination. vWF immunohistochemistry analysis showed that the mean tumour vessel size was increased in all cohorts. CONCLUSION: Assessing MR imaging biomarker parameters together with [(18)F]FET and [(18)F]FLT PET provided information on mechanism of action of the drug combination and clues as to potential clinical responses. Following translation to clinical use, treatment with a BEV/BEZ235 combination could reduce peritumoral oedema obviating the requirement for steroids. The use of hypothesis-driven molecular

The objective of this study was to assess the structure, anti-tyrosinase activity, and mechanism of proanthocyanidins extracted from Rhododendron pulchrum leaves. Results obtained from mass spectra of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and high performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI-MS) revealed that proanthocyanidins were complex mixtures of procyanidins, prodelphinidins, propelargonidins, and their derivatives, among which procyanidins were the main components. The anti-tyrosinase analysis results indicated that the mixtures were reversible and mixed competitive inhibitors of tyrosinase. Interactions between proanthocyanidins with substrate (L-tyrosine and 3,4-dihydroxyphenylalanine) and with copper ions were the important molecular mechanisms for explaining their efficient inhibition. This research would provide scientific evidence for the use of R. pulchrum leaf proanthocyanidins as new novel tyrosinase inhibitors.

Ultraviolet-A (UV-A)-mediated bactericidal activity was enhanced by combined treatment with trans-ferulic acid (trans-FA, compound 1) or its derivatives. Derivative compounds 4 and 10 contain a phenyl group or an l-tyrosine HCl tert-butyl ester, respectively, linked to the carboxyl group of trans-FA. Of the three compounds, 10 exhibited the highest synergistic activity in a photobactericidal assay based on treating Escherichia coli with a derivative compound and UV-A irradiation (wavelength 350-385 nm). Inactivation of viable cells at a 4.9 J cm(-2) UV-A fluence increased from 1.90 to 5.19 logs in the presence of 10 (100 μm); a 4.95-log inactivation was achieved with 10 (5 μm) and a 7.4 J cm(-2) UV-A fluence. Addition of antioxidants significantly suppressed photosynergistic bactericidal activity, suggesting that reactive oxygen species (ROS) are involved in the combined bactericidal mechanism. Flow cytometry revealed that combined treatment with UV-A and compound 10, which showed the highest photobactericidal activity, generates an excess of oxidative radicals in bacterial cells. The bactericidal activity of compound 10 may be due to electrostatic interaction between the molecule's cationic moiety and the cell surface, followed by amplification of ROS generation in the cells. © 2015 The American Society of Photobiology.

ETHNOPHARMACOLOGICAL RELEVANCE: The compatibility of Angelicae Sinensis Radix (Danggui) and Carthami Flos (Honghua), a famous herb pair Gui-Hong, can produce synergistic and complementary hematinic effects. Our previous studies have indicated that Gui-Hong has therapeutic potential treatment in hemolytic and aplastic anemia (HAA). The present study aimed to investigate the hematinic effects of Danggui, Honghua and Gui-Hong on HAA rats induced by acetyl phenylhydrazine (APH) and cyclophosphamide (CP) and to explore the underlying hematinic regulation mechanisms. MATERIALS AND METHODS: Rats were divided into 5 groups, and drugs were administered by oral gavage one time each day for continuous 7 days from the experiment began. Urine and plasma were analyzed by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Partial least-squares discriminate analysis (PLS-DA) models were built to evaluate the therapeutic effects of Danggui, Honghua and Gui-Hong. Pearson correlation matrix analysis method was used to discover the correlations between potential biomarkers and biochemical indicators of HAA rats. RESULTS: Seven potential biomarkers contribute to the separation of model group and control group were tentatively identified. The levels of l-kynurenine, phenylalanine, nicotinic acid and sphingosine increased significantly (P<0.05) in HAA rats, while the levels of l-isoleucine, l-tyrosine and serotonin decreased significantly (P<0.05) in comparison with control rats. Those endogenous metabolites were chiefly involved in phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, tryptophan metabolism and tyrosine metabolism. The metabolic deviations could be regulated closer to normal level after Danggui, Honghua and Gui-Hong intervention. In term of hematinic effects, Gui-Hong was the most effective as shown by the relative distance in PLS-DA score plots and relative intensity of potential biomarkers. The result reflected the synergic action between Danggui and Honghua. The above results were found to be reasonable in explaining the hematinic effects mechanism of Gui-H

BACKGROUND: Conflicting data exist for anti-cancer effects of anti-placental growth factor (anti-PlGF) in combination with anti-VEGF. Still, this treatment combination has not been evaluated in intracranial glioblastoma (GBM) xenografts. In clinical studies, position emission tomography (PET) using the radiolabeled amino acid O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) and magnetic resonance imaging (MRI) add complementary but distinct information about glioma growth; however, the value of 18F-FET MicroPET combined with MicroMRI has not been investigated preclinically. Here we examined the use of 18F-FET MicroPET and MicroMRI for evaluation of anti-VEGF and anti-PlGF treatment response in GBM xenografts. METHODS: Mice with intracranial GBM were treated with anti-VEGF, anti-PlGF + anti-VEGF or saline. Bioluminescence imaging (BLI), 18F-FET MicroPET and T2-weighted (T2w)-MRI were used to follow tumour development. Primary end-point was survival, and tumours were subsequently analysed for Ki67 proliferation index and micro-vessel density (MVD). Further, PlGF and VEGFR-1 expression were examined in a subset of the xenograft tumours and in 13 GBM patient tumours. RESULTS: Anti-VEGF monotherapy increased survival and decreased 18F-FET uptake, BLI and MVD, while no additive effect of anti-PlGF was observed. 18F-FET SUV max tumour-to-brain (T/B) ratio was significantly lower after one week (114 ± 6%, n = 11 vs. 143 ± 8%, n = 13; p = 0.02) and two weeks of treatment (116 ± 12%, n = 8 vs. 190 ± 24%, n = 5; p = 0.02) in the anti-VEGF group as compared with the control group. In contrast, T2w-MRI volume was unaffected by anti-VEGF. Gene expression of PlGF and VEGFR-1 in xenografts was significantly lower than in patient tumours. CONCLUSION: 18F-FET PET was feasible for anti-angiogenic response evaluation and superior to T2w-MRI; however, no additive anti-cancer effect of anti-PlGF and anti-VEGF was observed. Thus, this study supports use of 18F-FET PET for response evaluation in future studies.

AIMS: In the present study we investigated the intervention of nitric oxide and prostacyclin in the responses to vasopressin of isolated thyroid arteries obtained from multi-organ donors. MAIN METHODS: Paired artery rings from glandular branches of the superior thyroid artery, one normal and the other deendothelised, were mounted in organ baths for isometric recording of tension. Concentration-response curves to vasopressin were determined in the absence and in the presence of either the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP (10(-8)M), the nitric oxide synthase inhibitor N(G)-monomethyl-l-arginine (L-NMMA, 10(-4)M), or the inhibitor of prostaglandins indomethacin (10(-6)M). KEY FINDINGS: In artery rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions. The vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP (10(-8)M) displaced the control curve to vasopressin 19-fold to the right in a parallel manner. The contractile response to vasopressin was unaffected by L-NMMA or by indomethacin. SIGNIFICANCE: Vasopressin causes constriction of human thyroid arteries by stimulation of V1 vasopressin receptors located on smooth muscle cells. These effects are not linked to the presence of an intact endothelium or to the release of nitric oxide or prostaglandins. The constriction of thyroid arteries may be particularly relevant in certain pathophysiological circumstances in which vasopressin is released in amounts that could interfere with the blood supply to the thyroid gland. © 2013.

This study reports the synthesis and biological evaluation of a series of new side-chain-to-side-chain cyclized endomorphin-2 (EM-2) and morphiceptin analogs of a general structure Tyr-c(Xaa-Phe-Phe-Yaa)NH(2) or Tyr-c(Xaa-Phe-D-Pro-Yaa)NH(2), respectively, where Xaa and Yaa were L/D Asp or L/D Lys. Further modification of these analogs was achieved by introduction of 2',6'-dimethyl-L-tyrosine (Dmt) instead of Tyr in position 1. Peptides were synthesized by solid phase method and cleaved from the resin by a microwave-assisted procedure. Dmt(1)-substituted analogs displayed high affinity at the μ-opioid receptors, remained intact after incubation with the rat brain homogenate and showed remarkable, long-lasting μ-opioid receptor-mediated antinociceptive activity after central, but not peripheral administration. Our results demonstrate that cyclization is a promising strategy in the development of new opioid analgesics, but further modifications are necessary to enhance the blood-brain barrier permeability.

OBJECTIVE: This prospective study aimed to evaluate the diagnostic value of fluorine-18-labeled fluoroethyltyrosine (18F-FET) positron emission tomography (PET)/computed tomography (CT) in diagnosing brain tumors within an Asian patient population. METHODS: Patients suspected of having primary or recurrent brain tumors were prospectively recruited. Each patient underwent 18F-FET and fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT on separate days within 1 week. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy to compare the diagnostic performance of the two PET scans. The standardized uptake value (SUV) and tumor-to-background ratio (TBR) of the lesions were determined using static images. Additionally, time-activity curves (TACs) and time-to-peak (TTP) were generated from the dynamic PET images. RESULTS: From September 2019 to December 2023, 33 subjects were enrolled for reasons including suspected brain tumors (n = 20) or suspicious glioma recurrence (n = 8) on magnetic resonance imaging (MRI) and restaging for glioma (n = 5). Among the patients with suspected brain tumors or glioma recurrence on MRI, 25% had false-positive results. 18F-FET PET/CT accurately identified 86% of these false positives. The sensitivity, specificity, PPV, NPV, and accuracy of visual interpretation of 18F-FET PET/CT were 96.2%, 85.7%, 96.2%, 85.7%, and 93.9%, respectively. The corresponding 18F-FDG PET/CT values were 73.1%, 71.4%, 90.5%, 41.7%, and 72.7%. 18F-FET PET/CT demonstrated significantly higher sensitivity and accuracy than 18F-FDG PET (p = 0.031 and p = 0.030, respectively). Using TBRmean as an adjunct reference index enhanced the diagnostic accuracy of 18F-FET PET/CT, achieving a sensitivity and NPV of 100%. Wash-out TAC or TTP < 20 min was associated with a PPV of 100% for brain tumors. CONCLUSIONS: 18F-FET PET/CT appears to be a valuable tool for assessing brain tumors with indeterminate MRI findings in this Asian cohort. 18F-FET PET/CT offers benefits over 18F-FDG PET in differentiating brain tumors from nontumor brain lesions, particularly when using semiquantitative analysis with TBR. This study

Tyrosinase (EC 1.14.18.1) is a binuclear copper enzyme responsible for the rate-limiting steps of melanogenesis, catalyzing the hydroxylation of L-tyrosine and oxidation of L-DOPA into o-quinones that polymerize melanin. Beyond its physiological role in pigmentation, tyrosinase is also implicated in food browning and oxidative stress-related disorders, making it a key target in cosmetic, food, and biomedical industries. This systematic review, conducted following PRISMA guidelines, aimed to identify and analyze microbial metabolites with tyrosinase inhibitory potential as sustainable alternatives to conventional inhibitors such as hydroquinone and kojic acid. Literature searches in Scopus and Web of Science (March 2025) yielded 156 records; after screening and applying inclusion criteria, 11 studies were retained for analysis. The inhibitors identified include indole derivatives, phenolic acids, peptides, and triterpenoids, mainly produced by fungi (e.g., Ganoderma lucidum, Trichoderma sp.), actinobacteria (Streptomyces, Massilia), and microalgae (Spirulina, Synechococcus). Reported IC50 values ranged from micromolar to milli-molar levels, with methyl lucidenate F (32.23 µM) and p-coumaric acid (52.71 mM). Mechanisms involved competitive and non-competitive inhibition, as well as gene-level regulation. However, methodological heterogeneity, the predominance of mushroom tyrosinase assays, and limited human enzyme validation constrain translational relevance. Computational modeling, site-directed mutagenesis, and molecular dynamics are proposed to overcome these limitations. Overall, microbial metabolites exhibit promising efficacy, stability, and biocompatibility, positioning them as emerging preclinical candidates for the development of safer and more sustainable tyrosinase inhibitors.

BACKGROUND: It is often difficult to identify treatment-related changes (TRC) from tumor progression (TP) in patients with glioma, and the current application of PET scanning is expected to improve the diagnosis. PURPOSE: We used a systematic review and meta-analysis to reveal diagnostically more promising tracers by comparing the diagnostic accuracy of different PET tracers in identifying TRC and TP in patients with glioma. DATA SOURCES: We searched PubMed, Web of Science, and EMBASE databases, and we selected studies that used PET scans to identify TP and TRC in patients with glioma. STUDY SELECTION: Twenty-eight studies were identified based on the set criteria. The studies involved a total of 10 different tracers and 1405 patients. TP occurred in 67.4% (947) of patients, while TRC occurred in 32.6% (458) of patients. DATA ANALYSIS: The sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio, and negative likelihood ratio of various PET tracers were calculated and summarized. Moreover, the diagnostic value of various tracers was compared. DATA SYNTHESIS: This systematic review included 28 studies comparing 10 different PET tracers, including 18F-fluoro-deoxy-glucose FDG (18F-FDG), 11C methionine (11C -MET), 18F-fuoroethyl-L-tyrosine (18F-FET), 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine (18F-FDOPA), 18F-fluorothymidine (18F-FLT), 18F-PSMA-1007, 68Ga-PSMA-11, 18F-choline (18F-CHO), 18F-fluciclovine, and [11]C-Alpha-Methyl-Tryptophan(11C-AMT). The results revealed that 11C-MET exhibited the highest diagnostic value, with an overall sensitivity and specificity of 0.89 [0.85, 0.93] and 0.91 [0.84, 0.99], respectively. Although the number of 18F-FDOPA studies is limited, it exhibited high diagnostic value, with an overall sensitivity and specificity of 1.00 [0.91, 1.00] and 0.92 [0.75, 0.99], respectively. LIMITATIONS: Most studies consisted of small sample sizes; however, the included studies differed to some extent regarding the reference standard for the final diagnosis and the standard of care. Additionally, most selected studies were retrospective. CONCLUSIONS: Amino acid-based tracers exhibited the highest diagnostic value in identifying TR

BACKGROUND: 18F-fluoro-ethyl-tyrosine (18F-FET) is recommended to distinguish brain tumours post-therapeutic true progression (including recurrent and metastatic brain tumours) and treatment-related change (TRC). However, many parameters of 18F-FET can be used for this differential diagnosis. Our purpose was to investigate the diagnostic accuracy of various 18F-FET parameters to differentiate true progression from TRC. METHODS: We performed a literature search using the following databases: the PubMed, Embase and Web of Science databases up to 29 November 2020. We included studies that reported the diagnostic test results of 18F-FET to distinguish true progression from TRC. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to evaluate the quality of the included studies. The diagnostic accuracy of various parameters was pooled using a random-effects model. RESULTS: We included 17 eligible studies (nine parameters). For static parameters of 18F-FET, the maximum and mean tumour-to-brain ratios (TBRmax and TBRmean) showed similar pooled sensitivities of 82% [95% confidence interval (CI), 80-85%) and 82% (95% CI, 78-85%), respectively. Among the three kinetic parameters (slope, time to peak and kinetic pattern), the kinetic pattern presented the optimal diagnostic value with a pooled sensitivity of 81% (95% CI, 75-86%). When combining the static and kinetic parameters, the diagnostic performance of 18F-FET was significantly improved, with a pooled sensitivity of 90% (95% CI, 84-94%) in the combination of TBR and kinetic patterns. CONCLUSIONS: 18F-FET static parameters alone showed a comparably high sensitivity in the differentiation between brain tumour true progression and TRC. Combining static and kinetic parameters provided improved diagnostic performance.

Posttreatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent Response Assessment in Neuro-Oncology recommendations, PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and metaanalysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: PubMed, Web of Science, and Embase were searched systematically. Study selection, data extraction, and quality assessment were performed independently by 2 authors. Metaanalysis was performed using a bivariate random-effects model when at least 5 studies were included. Results: The systematic review included 39 studies (11 tracers). 18F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95% confidence interval, 72%-92%) and 84% (95% confidence interval, 69%-93%), respectively. O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) (7 studies, 172 lesions) demonstrated a sensitivity of 90% (95% confidence interval, 81%-95%) and specificity of 85% (95% confidence interval, 71%-93%). For S-11C-methyl)-l-methionine (11C-MET) (8 studies, 151 lesions), sensitivity was 93% (95% confidence interval, 80%-98%) and specificity was 82% (95% confidence interval, 68%-91%). The numbers of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93%-100% and 0%-100%, respectively, for 18F-FLT; 85%-100% and 72%-100%, respectively, for 3,4-dihydroxy-6-18F-fluoro-l-phenylalanine (18F-FDOPA); and 100% and 70%-88%, respectively, for 11C-choline. Conclusion:18F-FET and 11C-MET, both amino-acid tracers, showed a comparably higher sensitivity than 18F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited; thus, 18F-FET and 11C-MET are preferred when available. Our results support the incorporat

BACKGROUND: For the past decade (18)F-fluoro-ethyl-l-tyrosine (FET) and (18)F-fluoro-deoxy-glucose (FDG) positron emission tomography (PET) have been used for the assessment of patients with brain tumor. However, direct comparison studies reported only limited numbers of patients. Our purpose was to compare the diagnostic performance of FET and FDG-PET. METHODS: We examined studies published between January 1995 and January 2015 in the PubMed database. To be included the study should: (i) use FET and FDG-PET for the assessment of patients with isolated brain lesion and (ii) use histology as the gold standard. Analysis was performed on a per patient basis. Study quality was assessed with STARD and QUADAS criteria. RESULTS: Five studies (119 patients) were included. For the diagnosis of brain tumor, FET-PET demonstrated a pooled sensitivity of 0.94 (95% CI: 0.79-0.98) and pooled specificity of 0.88 (95% CI: 0.37-0.99), with an area under the curve of 0.96 (95% CI: 0.94-0.97), a positive likelihood ratio (LR+) of 8.1 (95% CI: 0.8-80.6), and a negative likelihood ratio (LR-) of 0.07 (95% CI: 0.02-0.30), while FDG-PET demonstrated a sensitivity of 0.38 (95% CI: 0.27-0.50) and specificity of 0.86 (95% CI: 0.31-0.99), with an area under the curve of 0.40 (95% CI: 0.36-0.44), an LR+ of 2.7 (95% CI: 0.3-27.8), and an LR- of 0.72 (95% CI: 0.47-1.11). Target-to-background ratios of either FDG or FET, however, allow distinction between low- and high-grade gliomas (P > .11). CONCLUSIONS: For brain tumor diagnosis, FET-PET performed much better than FDG and should be preferred when assessing a new isolated brain tumor. For glioma grading, however, both tracers showed similar performances. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected].