Search Results (335)

Faba bean (Vicia faba L.), a nutrient-rich legume beneficial to human health, is valued for its high L-3,4-dihydroxyphenylalanine (L-DOPA) and phenolic content. This study investigated phytochemical diversity and bioactivity across 29 Chinese faba bean varieties. Phenolics were profiled using ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and quantified via high-performance liquid chromatography (HPLC). Antioxidant capacity was evaluated, including DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid)) radical scavenging activity, and ferric reducing antioxidant power (FRAP), along with α-amylase/α-glucosidase inhibitory effects. Twenty-five phenolics were identified, including L-DOPA (11.96–17.93 mg/g, >70% of total content), seven phenolic acids, and seventeen flavonoids. L-DOPA showed potent enzyme inhibition (IC₅₀ values of 22.45 μM for α-amylase and 16.66 μM for α-glucosidase) but demonstrated limited antioxidant effects. Lincan 13 (Gansu) exhibited the strongest antioxidant activity (DPPH, 16.32 μmol trolox/g; ABTS, 5.85 μmol trolox/g; FRAP, 21.38 mmol Fe²⁺/g), which correlated with it having the highest flavonoid content (40.51 mg rutin/g), while Yican 4 (Yunnan) showed the strongest α-amylase inhibition (43.33%). Correlation analysis confirmed flavonoids as the primary antioxidants, and principal component analysis (PCA) revealed geographical trends (e.g., Jiangsu varieties were particularly phenolic-rich). These findings highlight faba beans’ potential as functional foods and guide genotype selection in targeted breeding programs aimed at enhancing health benefits. Full article

The development of ceria (CeO_2−x)-based nanoantioxidants requires fine-tuning of structural and surface properties for enhancing antioxidant behavior in biological environments. In this contest, here ultrasmall water-dispersible CeO_2−x nanoparticles (NPs), characterized by a high Ce³⁺/Ce⁴⁺ ratio, were synthesized in a non-polar solvent and phase-transfer to an aqueous environment through ligand-exchange reactions using citric acid (CeO_2−x@Cit) and post-treatment with dopamine hydrochloride (CeO_2−x@Dopa). The concept behind this work is to enhance via surface engineering the intrinsic antioxidant properties of CeO_2−x NPs. For this purpose, thanks to electron transfer reactions between dopamine and CeO_2−x, the CeO_2−x@Dopa was obtained, characterized by increased surface Ce³⁺ sites and surface functionalized with polydopamine bearing o-quinone structures as demonstrated by complementary spectroscopic (UV–vis, FT-IR, and XPS) characterizations. To test the antioxidant properties of CeO_2−x NPs, the scavenging activity before and after dopamine treatment against artificial radical 1,1-diphenyl-2-picrylhydrazyl (DPPH^·) and the ability to reduce the reactive oxygen species in Diencephalic Immortalized Type Neural Cell line 1 were evaluated. CeO_2−x@Dopa demonstrated less efficiency in DPPH^· scavenging (%radical scavenging activity 13% versus 42% for CeO_2−x@Cit before dopamine treatment at 33 μM DPPH^· and 0.13 mg/mL loading of NPs), while it markedly reduced intracellular ROS levels (ROS production 35% compared to 66% of CeO_2−x@Cit before dopamine treatment with respect to control—p < 0.001 and p < 0.01, respectively). While steric hindrance from the dopamine-derived polymer layer limited direct electron transfer from CeO_2−x NP surface to DPPH^·, within cells the presence of o-quinone groups contributed with CeO_2−x NPs to break the autoxidation chain of organic substrates, enhancing the antioxidant activity. The functionalization of NPs with o-quinone structures represents a valuable approach to increase the inherent antioxidant properties of CeO_2−x NPs, enhancing their effectiveness in biological systems by promoting additional redox pathways. Full article

Impedance-based cellular assays allow determination of biological functions of cell populations in real-time by measuring electrical impedance. As compared to end-point assays, such as trans-epithelial electrical resistance assays, for example, they enable fast, non-invasive, and easy detection of cell kinetics—their growth, attachment, and interaction can be monitored over time. In our experiment, Caco-2 cells were cultured on E-plates 16. Next, fully differentiated cells were treated with either TNF-α or 3,4-dihydroxy-L-phenylalanine (L-DOPA). We aimed to verify the possibility of real-time testing of the viability, monolayer formation, and integrity (i.e., the presence of a functional and polarized monolayer) of Caco-2 cells by the xCELLigence real-time cell analyzer (RTCA) S16 system (Agilent Technologies). Full article

Antinutritional Factors (ANFs) are compounds produced by plants as defense mechanisms, and in high concentrations, they inhibit nutritional properties. Reducing these ANFs increases the presence of proteins, antioxidants, and vitamins, which is crucial for optimizing animal feed, particularly in developing countries where traditional methods may be costly. Solid-state fermentation (SSF) has the potential to improve the nutritional quality of animal feed derived from cereals and legumes cultivated and non-commercially cultivated by reducing antinutrients and enhancing nutrient availability. This review also considers the potential of non-native species, including those exhibiting invasive behavior and taxonomic similarity to cultivated varieties, as alternative substrates for SSF. Additionally, SSF highlights the biological properties of ANFs when extracted and utilized for technological and industrial advancements. Solid-state fermentation with lactic acid bacteria could be an effective and straightforward method for reducing these antinutritional factors while simultaneously enriching protein content. The aim is to present solid-state fermentation as a biotechnological tool to reduce antinutritional factors and enhance the nutritional content of legumes and cereals that are not cultivated for animal feed. This perspective contributes to expanding the range of raw materials considered for SSF by including taxonomically related but underutilized and ecologically problematic plant resources. Full article

The aim of the study was to investigate the influence of L-DOPA—the gold standard in the treatment of Parkinson’s disease symptoms—on the electroreduction kinetics of Zn²⁺ ions. It was demonstrated that this effect depends not only on the concentration of the drug but also on the environment in which the process takes place. In the experimental part, cyclic voltammetry (CV), square wave voltammetry (SWV), direct current polarography (DC), and electrochemical impedance spectroscopy (EIS) were used. Based on the obtained results, it was determined that the analyzed electrode reaction, both in the absence and presence of L-DOPA, proceeded in two steps. The kinetic parameters of Zn²⁺ ion electroreduction indicated its quasi-reversible nature in solutions with both pH = 2.0 and pH = 6.0. The presence of the drug in the lower pH solution resulted in a slight slowing down of the electrode process, whereas in the pH = 6.0 solution, it led to a significant acceleration. In both low and high pH solutions, the first step was slower and determined the rate of the entire electrode process. Full article

Emerging evidence highlights the gut microbiota as a pivotal determinant of pharmacological efficacy. While Enterococcus faecalis (E. faecalis)-derived tyrosine decarboxylases (tyrDCs) are known to decarboxylate levodopa (L-dopa), compromising systemic bioavailability, the causal mechanisms underlying microbiota-mediated pharmacodynamic variability remain unresolved. In our study, we employed antibiotic-induced microbiota depletion and fecal microbiota transplantation (FMT) to interrogate microbiota-L-dopa interactions in MPTP-induced Parkinson’s disease (PD) mice. The study demonstrated that antibiotic-mediated microbiota depletion enhances L-dopa bioavailability and striatal dopamine (DA) level, correlating with improved motor function. To dissect clinical heterogeneity in the L-dopa response, PD patients were stratified into moderate responders and good responders following standardized L-dopa challenges. In vitro bioconversion assays revealed greater L-dopa-to-DA conversion in fecal samples from moderate responders versus good responders. FMT experiments confirmed mice receiving good-responder microbiota exhibited enhanced L-dopa bioavailability, higher striatal DA concentrations, and a heightened therapeutic effect of L-dopa relative to moderate-responder recipients. Collectively, our study provided evidence that the gut microbiota directly modulates L-dopa metabolism and microbial composition determines interindividual therapeutic heterogeneity. Targeted microbial modulation—through precision antibiotics or donor-matched FMT—is a viable strategy to optimize PD pharmacotherapy, supporting the potential for microbiota-targeted adjuvant therapies in PD management. Full article

Background: Parkinson’s disorder (PD) affects around 1:500 individuals and is associated with enlarged ventricles and symptoms of normal pressure hydrocephalus (NPH). These features suggest disrupted cerebrospinal fluid (CSF) dynamics and folate metabolism. With L-DOPA treatment showing diminishing benefits over time, there is an urgent need to investigate upstream metabolic disruptions, including folate and tetrahydrobiopterin (BH4) pathways, in post-mortem CSF and brain tissue to understand their roles in PD pathogenesis. Methods: CSF and brain tissue from 20 PD patients (mean age 84 years; 55% male; disease duration 10–30 years) and 20 controls (mean age 82 years; 50% male) were analysed. Western and Dot Blots measured proteins and metabolites, spectroscopic assays assessed enzyme activities, BH4 and Neopterin levels were measured using ELISA, and levels of hydrogen peroxide, used as a proxy for reactive oxygen species, and calcium were quantified using horseradish peroxidase and flame photometry assays, respectively. ClinVar genetic data were analysed for variants in genes encoding key enzymes. Statistical significance was assessed using unpaired t-tests (p < 0.05). Results: All enzymes were significantly reduced in PD compared to controls (p < 0.01) except for methyltetrahydrofolate reductase (MTHFR), which was elevated (p < 0.0001). Enzymes were functional in control but undetectable in PD CSF except tyrosine hydroxylase (TH). BH4 and Neopterin were elevated in PD CSF (p < 0.0001, p < 0.001) but significantly reduced (p < 0.001) or unchanged in tissue. Peroxide was increased in both PD CSF (p < 0.001) and tissue (p < 0.0001) selectively inhibiting TH. Calcium was 40% higher in PD than controls (p < 0.05). No pathogenic variants in enzyme genes were found in ClinVar data searches, suggesting the observed deficiencies are physiological. Conclusions: We identified significant disruptions in folate and BH4 pathways in PD, with enzyme deficiencies, oxidative stress and calcium dysregulation pointing to choroid plexus dysfunction. These findings highlight the choroid plexus and CSF as key players in cerebral metabolism and promote further exploration of these as therapeutic targets to address dopaminergic dysfunction and ventricular enlargement in PD. Full article

Cosmetic formulations are complex mixtures of ingredients that must fulfill several requirements. One of the challenges of the cosmetic industry is to find natural alternatives to replace synthetic polymers, preserving desirable sensory characteristics. The aim of this work is to induce the formation of gels, by replacing synthetic polymers with a low-molecular-weight gelator (LMWG), a small molecule able to self-assemble and form supramolecular networks. The impact of low-molecular-weight gelators on the environment is reduced as they are highly biodegradable. Thus, the behavior of solutions containing Boc-L-Dopa(Bn)₂-OH, an LMWG, together with ten different anionic surfactants, was studied to understand if the LMWG may act as a rheological modifier by increasing the viscosity of the formulation or forming gels with these ingredients. An amphoteric surfactant, cocamidopropyl betaine (CAPB), often used to increase cleansing gentleness, was also added to the solutions to better mimic a cosmetic formulation. In most cases, the addition of the gelator at only a 1% w/v concentration induces the gelification or an increase in the viscosity of the solutions, thus showing that this molecule is also able to self-assemble in complex mixtures. Full article

Background/Objectives: Conjugation techniques are increasingly valued in food chemistry for enhancing sensory properties, nutritional profiles, and bioactivity, with potential applications in cosmeceuticals. This study aimed to investigate the potential of Glycine max (L.) Merrill oligopeptide–monosaccharide conjugates as active ingredients in cosmeceuticals, emphasizing their biological activities and stability. Methods: G. max isolate was prepared and subsequently hydrolyzed using alcalase to obtain the oligopeptide (OP). The OP was then conjugated with allulose (AL) or mannose (MN) through a controlled humid-dry heating process to produce the conjugates, OPA and OPM, respectively. Their biological activities, including antioxidant, anti-tyrosinase, anti-collagenase, anti-elastase, and anti-hyaluronidase properties, were assessed and compared to the individual components. Additionally, the irritation potential was evaluated using the hen’s egg test on chorioallantoic membrane (HET-CAM). The stability was examined under varying pH levels, temperatures, and light conditions based on their biological activity profiles. Results: OPA demonstrated the highest antioxidant activity, showing the lowest DPPH^• IC₅₀ value of 198.6 ± 2.7 µg/mL along with a strong ferric reducing power of 1.37 ± 0.04 µg FeSO₄/g sample. Besides, OPM showed superior tyrosinase inhibition on both L-tyrosine and L-DOPA substrates, highlighting its potential for skin whitening. Both OPA and OPM significantly enhanced collagenase inhibition, supporting their anti-aging potential. All samples were non-irritating in the HET-CAM test. The conjugates (OPA and OPM) demonstrated enhanced stability against pH, heat, and light compared to OP, AL, and MN. Conclusions: Oligopeptide–monosaccharide conjugation not only improved bioactivity but also enhanced biological stability, suggesting their potential for use in cosmeceutical applications. Full article

It is well established that certain carboxylic acid compounds can effectively inhibit tyrosinase activity. This study investigated the mechanisms by which four carboxylic acid compounds—3-phenyllactic acid, lactic acid, L-pyroglutamic acid, and malic acid—inhibit tyrosinase and melanogenesis. IC₅₀ values for mushroom tyrosinase inhibition ranged from 3.38 to 5.42 mM, with 3-phenyllactic acid (3.50 mM), lactic acid (5.42 mM), and malic acid (3.91 mM) exhibiting mixed-type inhibition, while L-pyroglutamic acid (3.38 mM) showed competitive inhibition, as determined by enzymatic kinetic analysis. Additionally, the acidification effects of lactic acid, L-pyroglutamic acid, and malic acid contributed to the reduction in tyrosinase activity. Furthermore, all four carboxylic acid compounds effectively inhibited DOPA auto-oxidation (IC₅₀ = 0.38–0.66 mM), ranking in potency as follows: malic acid (0.38 mM) > lactic acid (0.57 mM) > 3-phenyllactic acid (0.63 mM) > L-pyroglutamic acid (0.66 mM). These compounds also demonstrated a dose-dependent reduction in melanin production in B16-F10 cells. Proteomic analysis further revealed that these compounds not only inhibit key proteins involved in melanin synthesis, such as tyrosinase, tyrosinase-related protein 1, and tyrosinase-related protein 2, but also potentially modulate other genes associated with melanogenesis and metabolism, including Pmel, Slc45a2, Ctns, Oca2, and Bace2. Network toxicology analysis indicated that these four compounds exhibit a low risk of inducing dermatitis. These findings suggest that these compounds may indirectly regulate melanin-related pathways through multiple mechanisms, highlighting their potential for further applications in cosmetics and pharmaceuticals. Full article

The α7 nicotinic acetylcholine receptor (α7-nAChR) is a pivotal regulator of neurotransmission, neuroprotection, and immune modulation in the central nervous system. This review explores its structural and functional attributes, highlighting its therapeutic potential in neurodegenerative disorders, particularly Parkinson’s disease (PD). α7-nAChRs mediate synaptic plasticity, modulate inflammatory responses, and influence dopamine release, positioning them as a promising pharmacological target. Positive allosteric modulators (PAMs) enhance α7-nAChR activity mainly by reducing desensitization, offering a superior therapeutic approach compared with direct agonists. Emerging preclinical studies suggest that α7-nAChR activation mitigates dopaminergic neurodegeneration, improves L-dopa-induced dyskinesia, and reduces neuroinflammation. Despite promising findings, clinical trials have yielded mixed results, necessitating further research into optimizing α7-targeted therapies. This review underscores the significance of α7-nAChRs in PD pathophysiology and highlights future directions for their translational potential in neuroprotection and symptomatic relief. Full article

Sepiapterin Reductase Deficiency (SRD) is a rare inherited neurometabolic disorder caused by variants in the SPR gene, which may lead to developmental delays, psychomotor retardation, and cognitive impairments. Two consanguineous North African and Middle Eastern families are reported with multiple affected individuals presenting with developmental delay, ataxia, hypotonia, fatigue, and ptosis, or parkinsonism and cognitive impairment. Exome sequencing revealed a novel homozygous SPR c.560A>G (p.Glu187Gly) mutation that segregates with disease. According to molecular dynamics analysis, the substitution is predicted to compromise structural integrity, likely affecting ligand binding and catalytic activity. Elevated cerebrospinal fluid sepiapterin and biopterin levels, along with low neurotransmitter levels, were concordant with a genetic diagnosis of SRD and the reclassification of this variant as pathogenic. SRD patients manifest a broad constellation of symptoms, albeit well-managed using low-dose L-dopa/carbidopa. This study highlights the value of genetic testing in expediting early diagnosis and intervention to mitigate the onset of this disorder. Full article

Background: Sensors for continuous glucose monitoring (CGM) are now commonly used by people with type 1 and type 2 diabetes. However, the response of these devices to potentially interfering nutritional, pharmaceutical, or endogenous substances is barely explored. We previously developed an in vitro test method for continuous and dynamic CGM interference testing and herein explore the sensitivity of the Abbott Libre2 (L2) and Dexcom G6 (G6) sensors to a panel of 68 individual substances. Methods: In each interference experiment, L2 and G6 sensors were exposed in triplicate to substance gradients from zero to supraphysiological concentrations at a stable glucose concentration of 200 mg/dL. YSI Stat 2300 Plus was used as the glucose reference method. Interference was presumed if the CGM sensors showed a mean bias of at least ±10% from baseline with a tested substance at any given substance concentration. Results: Both L2 and G6 sensors showed interference with the following substances: dithiothreitol (maximal bias from baseline: L2/G6: +46%/−18%), galactose (>+100%/+17%), mannose (>+100%/+20%), and N-acetyl-cysteine (+11%/+18%). The following substances were found to interfere with L2 sensors only: ascorbic acid (+48%), ibuprofen (+14%), icodextrin (+10%), methyldopa (+16%), red wine (+12%), and xylose (>+100%). On the other hand, the following substances were found to interfere with G6 sensors only: acetaminophen (>+100%), ethyl alcohol (+12%), gentisic acid (+18%), hydroxyurea (>+100%), l-cysteine (−25%), l-Dopa (+11%), and uric acid (+33%). Additionally, G6 sensors could subsequently not be calibrated for use after exposure to dithiothreitol, gentisic acid, l-cysteine, and mesalazine (sensor fouling). Conclusions: Our standardized dynamic interference testing protocol identified several nutritional, pharmaceutical and endogenous substances that substantially influenced L2 and G6 sensor signals. Clinical trials are now necessary to investigate whether our findings are of relevance during routine care. Full article

Background/Objectives: Determining whether 3,4-dihydroxy-6-[¹⁸F]fluoro-L-phenylalanine positron emission tomography/computed tomography ([¹⁸F]F-DOPA PET/CT) data indicate brain metastasis progression (MP) or brain radionecrosis (RN) is challenging. The aim of this study was to present a method usable in the clinical setting without dedicated software that relies on less than five minutes of SiPM PET/CT data collected immediately after [¹⁸F]F-DOPA injection. Methods: We prospectively enrolled 15 patients with 19 lesions. Each acquisition was conducted in list mode (LM) for 25 min using a four-ring SiPM PET/CT system. We reconstructed three volumes from the LM file: acquisition duration of 120 s (V120), 270 s (V270), and 10 min for the standard clinical volume (Vclin). We measured each lesion’s maximum voxel activity (LS_max) and the corresponding mean activity with its standard deviation (CL_mean, CL_sd). We then calculated the LS_max/CL_mean ratio and the coefficient of variation (COV), defined as 100 × (CL_sd/CL_mean). Results: Lesions were classified as RN (n = 7) and MP (n = 12). For all volumes, LS_max/CL_mean differed significantly. The COV parameter exhibited significant differences in all comparisons except for V120 vs. V270. The best diagnostic performances were observed for V120 and V270, with an accuracy of 94.7%. The AUC values were 97.6% in both cases. Conclusions: A simple, static [¹⁸F]F-DOPA PET/CT acquisition, starting 1.5 min after injection and lasting less than five minutes, permitted reaching excellent diagnostic performance (100% sensitivity, 91.7% specificity, and 97.6% AUC) in discriminating between RN and MP. Full article

3,4-Dihydroxy-L-phenylalanine (DOPA) is a promising noncanonical amino acid (ncAA) that introduces novel catechol chemical features into proteins, expanding their functional potential. However, the most common approach to incorporating ncAAs into proteins relies on stop codon suppression, which is often limited by the competition of endogenous translational termination machinery. Here, we employed a special in vitro protein expression system that facilitates the efficiency of DOPA incorporation into proteins by removing essential Class I peptide release factors through targeted degradation. In the absence of both RF1 and RF2, we successfully demonstrated DOPA incorporation at all three stop codons (TAG, TAA, and TGA). By optimizing the concentration of engineered DOPA-specific aminoacyl-tRNA synthetase (DOPARS), DOPA, and DNA template, we achieved a synthesis yield of 2.24 µg of sfGFP with 100% DOPA incorporation in a 20 μL reaction system. DOPARS exhibited a dissociation constant (Kd) of 11.7 μM for DOPA but showed no detectable binding to its native counterpart, tyrosine. Additionally, DOPA was successfully incorporated into a reverse transcriptase, which interfered with its activity. This system demonstrates a fast and efficient approach for precise DOPA incorporation into proteins, paving the way for advanced protein engineering applications. Full article