Search Results (510)

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. Full article

Biomaterials derived from natural-origin polymers often lack the desired functionality and additional features, such as antibacterial properties, which could be beneficial in the design of modern wound dressings. Our research aimed to fabricate biosafe antibacterial dressings through the modification of curdlan-based hydrogels with triangle-shaped silver nanoparticles (AgTNPs) and poly(L-DOPA) (PL). The prepared hydrogels, including physicochemical, structural, biological, and antibacterial assessments, were thoroughly characterized. All formulations were confirmed to be non-toxic toward eukaryotic cells. The presence of PL in the hydrogels significantly reduced mortality in the zebrafish larvae model, highlighting the improved biocompatibility of the hydrogels. The three-component hydrogel (CUR-PL-AgT) demonstrated a high antibacterial effectiveness against Staphylococcus aureus and Pseudomonas aeruginosa. Additionally, the same three-component material outperformed a hydrogel containing only AgTNPs in promoting blood clot formation. Furthermore, PL enhanced the heat generating capability of hydrogels, showing their potential in medical applications where the temperature effects can stimulate biological processes of different natures. Full article

Parkinson’s disease is the second most common neurodegenerative disease in the world. Natural products can offer a possible option of neuroprotective agents for preventing neurodegenerative diseases. D-Pinitol is a cyclic polyol with anxiolytic and antidepressant effects in acute assays. This work aimed to evaluate the effects of D-Pinitol (10, 50, and 100 mg/kg p.o.) in a chronic reserpine-induced depression model (19 days), using the forced swimming and tail suspension tests in female Balb/c mice, and the neuroprotective effects in an MPTP-induced Parkinsonism model (30 days) in male C57bL/6 mice, using behavioral tests such as wire grip, rotarod, catalepsy, and others. D-Pinitol showed low antidepressant-like effects in the reserpine-induced chronic depression model, compared to amitriptyline (25 mg/kg p.o.). D-Pinitol protected MPTP-treated mice from motor impairment with similar effects to those shown by L-Dopa (25 mg/kg p.o.) as evaluated in different behavioral tests. The inhibition of oxidative stress markers, increase in dopamine levels, and avoidance of apoptosis in neuronal cells were the mechanisms by which D-Pinitol protects MPTP-treated mice from motor impairment. Full article

The human gut microbiota plays a key role in neurochemical communication, especially through the gut–brain axis. There is growing evidence that the gut microbiota influences dopamine metabolism through both production and consumption mechanisms. Two key bacterial enzymes are central to this process: tyrosine decarboxylase (TDC), which primarily catalyzes the decarboxylation of tyrosine to tyramine but can also act on L-DOPA to produce dopamine in certain bacterial strains, and aromatic L-amino acid decarboxylase (AADC), which can convert precursors such as L-DOPA, tryptophan, or 5-hydroxytryptophan into bioactive amines including dopamine, tryptamine, and serotonin. Identifying the bacterial families corresponding to TDC and AADC enzymes opens new avenues for clinical intervention, particularly in neuropsychiatric and neurodegenerative disorders, such as Parkinson’s disease. Moreover, elucidating strain-specific microbial contribution and host-microbe interactions may enable personalized therapeutic strategies, such as selective microbial enzyme inhibitors or tailored probiotics, to optimize dopamine metabolism. Emerging technologies, including biosensors and organ-on-chip platforms, offer new tools to monitor and manipulate microbial dopamine activity. This article explores the bacterial taxa capable of producing or consuming dopamine, focusing on the enzymatic mechanisms involved and the methodologies available for studying these processes in vivo. Full article

Pasteurella multocida serotype B:2 is a primary agent of hemorrhagic septicemia (HS) in livestock, and the strain NQ01 isolated from yaks highlights its cross-species impact. In this study, a murine intranasal infection model was established using P. multocida NQ01 to assess how acute respiratory infection perturbs gut homeostasis. Mice were intranasally inoculated with NQ01, and at 36 h post-infection, ileal tissues and cecal contents were collected for histopathological examination, 16S rRNA gene sequencing, and untargeted metabolomic analysis. Histopathology revealed obvious acute bronchopneumonia but no overt ileal damage. However, 16S rRNA sequencing of cecal microbiota showed significant dysbiosis: microbial diversity was reduced and community composition shifted, including decreased short-chain fatty-acid-producing taxa and increased opportunistic genera. Metabolomic profiling detected 1444 significantly altered cecal metabolites, and pathway analysis indicated marked disruption of amino acid metabolism, notably the tyrosine metabolism pathway. Key tyrosine pathway metabolites were dysregulated (e.g., elevated L-tyrosine and dopamine with reduced L-DOPA), indicating a breakdown of this metabolic pathway. These findings demonstrate that acute respiratory P. multocida infection profoundly disturbs gut microbiota and metabolism, underscoring disruption of the gut–lung axis. This study provides new insight into the systemic consequences of HS-associated P. multocida infection and offers a basis for exploring the gut–lung interaction in hemorrhagic septicemia pathogenesis. Full article

The microbiota–gut–brain axis (MGBA) comprises a complex bidirectional communication network integrating neural, immune, metabolic, and endocrine pathways. Dopamine, traditionally viewed as a central neurotransmitter, also plays essential roles in the gastrointestinal (GI) tract, where it regulates motility, secretion, barrier homeostasis, and mucosal immunity. Growing evidence indicates that the gut microbiota significantly contributes to intestinal dopamine metabolism through specialized enzymatic pathways, particularly tyrosine decarboxylase in Enterococcus species and catechol dehydroxylase in Eggerthella species. These microbial reactions compete with host processes, alter dopaminergic tone, and degrade orally administered levodopa (L-DOPA), providing a mechanistic explanation for the variability in treatment response in Parkinson’s disease (PD). Beyond PD, microbially mediated alterations in dopaminergic signaling have been implicated in mood disorders, neurodevelopmental conditions, metabolic dysfunction, and immune-mediated diseases. This review synthesizes current mechanistic and translational evidence on the dopamine–microbiota interface, outlines microbial pathways shaping dopaminergic activity, and highlights therapeutic opportunities including microbiota modulation, dietary strategies, fecal microbiota transplantation, and targeted inhibitors of microbial dopamine metabolism. Understanding this interface offers a foundation for developing personalized approaches in neurogastroenterology and neuromodulatory therapies. Full article

Reactive oxygen species (ROS) are well-known as major contributors to skin aging, and the application of antioxidants to suppress ROS has been increasingly emphasized in the field of cosmetics. Traditionally, plant-derived or synthetic antioxidants have been predominantly used. More recently, antioxidant, anti-aging, and anti-inflammatory effects of mussel extracts or mussel-derived hydrolysates have also been explored and proposed for cosmetic applications. However, there is still a lack of scientific research on the antioxidant and anti-aging effects of specific mussel foot proteins, particularly engineered recombinant proteins such as NGT-M001 (hybrid fp-151). Natural mussel adhesive proteins are characterized by an amino acid composition rich in tyrosine and catechol groups such as DOPA, which are believed to possess potent antioxidant activity. In this study, we quantitatively evaluated the antioxidant and anti-aging properties of a recombinant mussel adhesive protein (rMAP) lacking DOPA modification, and a rationally designed protein, NGT-M001. Antioxidant activity was assessed using ABTS and DPPH radical scavenging assays, while anti-aging potential was evaluated through collagenase and hyaluronidase inhibition assays. In the ABTS assay, the antioxidant capacity per molar unit of NGT-M001 was 27.76-fold higher than that of Trolox. NGT-M002 (pvFP-5), NGT-M003 (pvFP-5 fragment) and NGT-M004 (FP-1 fragment) exhibited 9.08-fold, 2.84-fold, and 8.54-fold higher activities, respectively. In the DPPH assay, NGT-M001 and NGT-M004 were not detected, whereas NGT-M002 and NGT-M003 showed 3.45-fold and 1.59-fold higher activity than Trolox, respectively. These findings suggest that recombinant mussel adhesive proteins such as NGT-M001 exhibit antioxidant activity and may serve as promising next-generation bioactive ingredients for functional medicine and cosmetic applications to improve skin health and radical scavenging. Full article

L-DOPA-induced dyskinesia (LID) remains the most challenging complication of dopamine replacement therapy in Parkinson’s disease, correlated with maladaptive plasticity within corticostriatal circuits. Perineuronal nets (PNNs), extracellular matrix structures enwrapping mainly parvalbumin interneurons (PV-INs), are key regulators of neuronal stability and plasticity, yet their contribution to LID is unknown. Using a unilateral 6-hydroxydopamine rat model of Parkinsonism followed by chronic L-DOPA administration, we quantified PNN–PV associations by Wisteria floribunda agglutinin (WFA) and PV immunolabeling across striatal and motor cortical territories. Dopamine loss markedly reduced PNN density and intensity in the dorsolateral striatum (DLS), which only partially recovered after L-DOPA. In LID, canonical WFA⁺/PV⁺ cells remained low, whereas non-canonical WFA⁻/PV⁺ populations expanded in both DLS and M1 motor cortex (M1), indicating region-specific remodeling toward a high-plasticity state. To assess causality, we used Chondroitinase ABC (ChABC) for PNN degradation. DLS-targeted ChABC exacerbated abnormal involuntary movements and increased local PV density, while M1-ChABC had no behavioral effect but altered PV metrics within the DLS–M1 axis. These findings identify the DLS as a critical node where PNN fragility amplifies dyskinesia, highlight a functional coupling between striatal and cortical PNN–PV remodeling, and suggest that stabilizing extracellular matrix integrity could mitigate maladaptive plasticity underlying LID. Full article

Background: Large-scale data on the diagnostic performance of functional imaging in metastatic pheochromocytoma/paraganglioma (PPGL) are scarce. Objective: To analyze the diagnostic accuracy of functional imaging for the assessment of metastases during long-term follow-up (FU). Design: Retrospective cohort study, 1991–2025. Setting: Referral center. Outcomes: Sensitivity and specificity of ¹²³MIBG-, ¹⁸F-DOPA-, ⁶⁸GaDOTA-based and ¹⁸FDG PET/CT. Patients: Patients with metastatic PPGL and without PPGL, ≥1 functional imaging prior to first diagnosis and/or during FU and FU ≥ 3 months. Results: 59 ¹²³MIBG-, 101 ¹⁸F-DOPA-, 11 ¹⁸FDG- and 74 ⁶⁸GaDOTA-based PET/CT were performed in 57 patients with metastatic PPGL and 37 ¹²³MIBG-, 323 ¹⁸F-DOPA-, 259 ¹⁸FDG- and 641 ⁶⁸GaDOTA-based imaging in 527 patients without PPGL. FU was 11.6 ± 11.4 and 5.1 ± 4.7 years, respectively. Sensitivity for the detection of all metastases (total cohort) by patient-based analysis was comparable between ¹⁸F-DOPA (77%), both ⁶⁸GaDOTA-based tracers combined (67%) and ¹²³MIBG (72%); lesion-based analysis was better for ¹⁸F-DOPA (94%) than for ⁶⁸GaDOTA (85%) and ¹²³MIBG (67%). Specificity (patient- and lesion-based) of ¹⁸F-DOPA vs. ⁶⁸GaDOTA (96–99%) was comparable and better than ¹²³MIBG (73%) and ¹⁸FDG (75%). Conclusions: Sensitivity of ¹⁸F-DOPA was superior to ⁶⁸GaDOTA for the detection of all and bone metastases in the total cohort and in patients with PCC, that of ⁶⁸GaDOTA was better for bone metastases with PGL, specificity was comparable and for both was better than for ¹⁸FDG and ¹²³MIBG. Given the beneficial pharmaceutical properties and favorable diagnostic performance, ¹⁸F-DOPA may be a good alternative to ⁶⁸GaDOTA-based tracers for the functional imaging of metastatic PPGL. Full article

Food wanting in honeybees is closely associated with the neurotransmitter dopamine; however, the regulatory role of non-coding RNAs in this process remains unclear. In this study, using the honeybee (Apis mellifera) as a model organism, we systematically investigated the molecular network and functional mechanisms by which long non-coding RNAs (lncRNAs) regulate the dopaminergic signaling pathway to mediate food wanting. By establishing two appetite-state models, fed honeybees (FB) and starved honeybees (SB), and combining brain dopamine quantification with behavioral assays, we found that dopamine levels in the honeybee brain were significantly elevated during starvation. Using transcriptome sequencing, we identified 1146 lncRNAs in the honeybee brain, among which 174 were differentially expressed long noncoding RNAs (DElncRNAs) between the two states, predominantly upregulated. Cis- and trans-acting analyses revealed that these DElncRNAs could target multiple genes involved in neural signal transmission, synaptic function, and dopaminergic pathways. KEGG enrichment analysis showed that their target genes were significantly enriched in pathways such as taste transduction, dopaminergic synapse, and neuroactive ligand–receptor interaction. Furthermore, a ceRNA network revealed that several DElncRNAs may regulate dopamine synthesis genes, including DOPA decarboxylase (Ddc), by competing for dopamine-associated miRNAs such as miR-375-3p, influencing food wanting in honeybees. Overall, our findings provide a foundation for uncovering the potential regulatory mechanisms of DElncRNAs in honeybee food wanting and offer new insights into the connection between neural regulation and behavioral manifestation in insects. Full article

Parkinson’s disease (PD) therapy is challenged by the multifactorial nature of neurodegeneration, necessitating an approach combining dopamine replenishment and combating oxidative stress. This study characterizes the neuroprotective potential of MQPD, a novel hybrid molecule containing dopamine with a quinone fragment structurally analogous to coenzyme Q. We evaluated MQPD’s antioxidant capacity in vitro using DPPH radical scavenging and lipid peroxidation assays, its neuroprotective efficacy against mitochondrial toxins (rotenone, paraquat) in neuronal cultures, and its ability to modulate striatal dopamine levels in mice. MQPD demonstrated significant antioxidant activity, reduced reactive oxygen species, and was more effective than dopamine or L-DOPA in mitigating toxin-induced cell death. While MQPD itself showed low brain bioavailability, its administration resulted in a sustained increase in striatal dopamine levels for up to four days. The results indicate that MQPD is a potent neuroprotective agent whose effects are likely mediated by direct antioxidant activity and a long-acting mechanism that stabilizes tissue dopamine levels, offering a promising alternative to current therapies for PD. Full article

Skin hyperpigmentation is primarily regulated by melanogenesis, in which tyrosinase and related enzymes play pivotal roles. Probiotics have recently been attracting attention as a cosmetic ingredient due to their skin-friendly and eco-friendly properties. In particular, microbial metabolites, known as postbiotics, are gaining attention for their superior safety, stability, and efficacy compared with probiotics. In this study, we investigated the whitening effect and molecular mechanisms of phenyllactic acid (PLA), a metabolite derived from Limosilactobacillus reuteri (L. reuteri) culture broth. In B16F10 melanoma cells, the effects of PLA were evaluated by measuring melanin content, cellular tyrosinase activity, enzyme kinetics, and the expression of melanogenesis-related proteins. PLA significantly inhibited melanin production and cellular tyrosinase activity in α-MSH–stimulated B16F10 melanoma cells without inducing cytotoxicity. PLA downregulated tyrosinase-related proteins such as TRP-1 and TRP-2, and competitively inhibited tyrosinase. The inhibition constants (Ki) for L-tyrosine and L-DOPA were 12.63 mM and 0.68 mM, respectively. These findings suggest that PLA, a postbiotic derived from lactic acid bacteria, may serve as a safe and effective whitening ingredient, providing a scientific basis for the development of functional skin-whitening cosmetics. Full article

Background/Objectives: The Glutamate Chemical Exchange Saturation Transfer (GluCEST) technique is an advanced imaging modality that enables non-invasive glutamate quantification using MRI. Methods: This study evaluated glutamate dynamics in Parkinson’s disease (PD) using a unilateral PD rat model, in which Wistar rats received 6-hydroxydopamine (6-OHDA) injections into the medial forebrain bundle, selectively eliminating dopaminergic neurons in the substantia nigra–striatum pathway. Results: The PD rat model exhibited a significant GluCEST increase (MTR Values: 3.0 ppm) compared to the sham-operated group, which was suppressed by administration of L-DOPA, a dopamine precursor drug (Sham: 0.9 ± 0.4%, PD: 2.0 ± 0.2%, Sham L-DOPA: 0.9 ± 0.5%, PD_L-DOPA: 0.8 ± 0.7%, p < 0.01). Additionally, magnetic resonance spectroscopy-derived glutamate data were consistent with GluCEST findings (Sham: 1.4 ± 0.03, PD: 1.7 ± 0.06, Sham_L-DOPA: 1.4 ± 0.12, PD_L-DOPA: 1.4 ± 0.10, p < 0.01). Conclusions: These findings suggest that GluCEST and magnetic resonance spectroscopy are valuable for assessing abnormal glutamate dynamics in the 6-OHDA-induced rat PD model. Furthermore, GluCEST may detect suppressed glutamate secretion following L-DOPA treatment, underscoring its potential for monitoring disease progression and therapeutic responses in PD. Full article

Background/Objectives: Spatio-temporal gait parameters have been proposed as surrogate markers for objective, remote monitoring of global motor status in Parkinson’s disease (PD). Our observational, cross-sectional pilot study tested whether gait metrics, derived from wearable sensors, reflect dopaminergic responsiveness in both axial and appendicular functions. Methods: Twenty-two PD patients were evaluated both under and not under L-Dopa (ON and OFF states, respectively). Motor performance was assessed using wearable inertial sensors during standardized tasks involving gait and upper/lower limb movements. From the recorded kinematics, measures of movement amplitude, speed, rhythm, and consistency were extracted, and dopaminergic response was compared in appendicular and axial functions. Results: Treatment effects were more pronounced on the more affected body side. Improvements in appendicular amplitude, speed, and consistency closely matched those observed in spatio-temporal gait parameters. In contrast, rhythm measures displayed a divergent pattern, with reduced gait cadence but increased hand movement frequency, showing an inverse correlation. No significant correlations emerged between axial and appendicular domains for amplitude, velocity, or consistency, whereas improvements in step length and gait velocity were associated with MDS-UPDRS III motor scores. Conclusions: These findings overall suggest that specific gait metrics, particularly those reflecting amplitude and velocity, may provide reliable, sensor-based indicators of overall motor status in PD, supporting their use in remote monitoring. Full article

Betalains are nitrogen-containing pigments found only in Caryophyllales plants and a few Basidiomycetes; no Ascomycota species have been found to contain them. Here, global untargeted metabolomics analysis revealed that the violet pigment generated by the ascomycete Aspergillus sydowii H-1 under standard conditions of cultivation contains six distinct betalains compounds. Genetic analysis revealed tyrosinase (AsTYRs) and DOPA 4,5-dioxygenase (AsDODA1) as key enzymes essential for the synthesis of both the violet pigment and betalains. In addition, AsTYRs and AsDODA1 were found to regulate hyphal development and branching, mycelial pellet compactness, redox homeostasis, and stress responses, all of which had a significant impact on A. sydowii H-1 secondary metabolism. Crucially, two MYB transcription factors, AsMYB1 and AsMYB3, were identified to be negative regulators of violet pigment synthesis. Deletion of AsMYB1 or AsMYB3 boosted pigment yield by 6.7 and 7.3 times, respectively, and increased betalain accumulation, whereas overexpressing them completely eliminated pigment production. Yeast one-hybrid assays and luciferase reporter assays revealed AsMYB1 and AsMYB3 directly bind to the promoters of AsTYR1 and AsTYR2 to suppress the synthesis of betalains and the violet pigment. Our study reported the first betalain-producing ascomycete species and elucidated the molecular basis of its pigment regulation, providing valuable insights for the microbial synthesis of natural colorants. Full article