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International Journal of Biological... Jun 2024Inspired by the natural antimicrobial effect of the topographical features of insect wings, this study prepared urchin-like gold nanoparticles (UGNPs) and deposited them...
Inspired by the natural antimicrobial effect of the topographical features of insect wings, this study prepared urchin-like gold nanoparticles (UGNPs) and deposited them on poly(ε-caprolactone) (PCL)/chitosan (P/C) electrospun nanofiber film to strengthen antibacterial activities of this active packaging. Results showed that L-Dopa was a suitable reducing agent to prepare UGNPs, and the spine length of UGNPs increased from 21.23 to 35.83 nm as the molar ratio of L-Dopa:HAuCl increased from 1 to 3. As the nanofiber film was immersed in the nanoparticle solution for a longer time, the UGNP content in P/C nanofibers increased. As the spine length of UGNPs and depositing UGNP content increased, the inhibition rate against S. aureus and E. coli. of P/C nanofiber film increased. In addition, P/C nanofiber film deposited with UGNPs also exhibited good thermal stability, hydrophilicity, mechanical strength, and water vapor permeability, exhibiting its potential as an antibacterial active packaging.
PubMed: 38909730
DOI: 10.1016/j.ijbiomac.2024.133287 -
Scientific Reports Jun 2024Dopamine is one of the significant neurotransmitters and its monitoring in biological fluids is a critical issue in healthcare and modern biomedical technology. Here, we...
Dopamine is one of the significant neurotransmitters and its monitoring in biological fluids is a critical issue in healthcare and modern biomedical technology. Here, we have developed a dopamine biosensor based on surface plasmon resonance (SPR). For this purpose, the carboxymethyl dextran SPR chip was used as a surface to immobilize laccase as a bioaffinity recognition element. Data analysis exhibited that the acidic pH value is the optimal condition for dopamine interaction. Calculated kinetic affinity (K) (48,545 nM), obtained from a molecular docking study, showed strong association of dopamine with the active site of laccase. The biosensor exhibited a linearity from 0.01 to 189 μg/ml and a lower detection limit of 0.1 ng/ml (signal-to-noise ratio (S/N) = 3) that is significantly higher than the most direct dopamine detecting sensors reported so far. Experiments for specificity in the presence of compounds that can co-exist with dopamine detection such as ascorbic acid, urea and L-dopa showed no significant interference. The current dopamine biosensor with high sensitivity and specificity, represent a novel detection tool that offers a label-free, simple procedure and cost effective monitoring system.
Topics: Surface Plasmon Resonance; Dopamine; Biosensing Techniques; Molecular Docking Simulation; Laccase; Limit of Detection; Enzymes, Immobilized; Kinetics; Hydrogen-Ion Concentration; Dextrans
PubMed: 38906902
DOI: 10.1038/s41598-024-64796-w -
The Science of the Total Environment Jun 2024This paper investigates the potential of graphene-coated sand (GCS) as an advanced filtration medium for improving water quality and mitigating chemicals of emerging...
This paper investigates the potential of graphene-coated sand (GCS) as an advanced filtration medium for improving water quality and mitigating chemicals of emerging concern (CECs) in treated municipal wastewater, aiming to enhance water reuse. The study utilizes three types of sand (Ottawa, masonry, and concrete) coated with graphene to assess the impact of surface morphology, particle shape, and chemical composition on coating and filtration efficiency. Additionally, sand coated with graphene and activated graphene coated sand were both tested to understand the effect of coating and activation on the filtration process. The materials were characterized using digital microscopy, Raman spectroscopy, scanning electron microscopy (SEM), and X-ray diffraction analysis. The material's efficiency in removing turbidity, nutrients, chemical oxygen demand (COD), bacteria, and specific CECs (Aciclovir, Diatrizoic acid, Levodopa, Miconazole, Carbamazepine, Diphenhydramine, Irbesartan, Lidocaine, Losartan, and Sulfamethoxazole) was studied. Our findings indicate that GCS significantly improves water quality parameters, with notable efficiency in removing turbidity, COD (14.1 % and 69.1 % removal), and bacterial contaminants (64.9 % and 99.9 % removal). The study also highlights the material's capacity to remove challenging CECs like Sulfamethoxazole (up to 80 % removal) and Diphenhydramine (up to 90 % removal), showcasing its potential as a sustainable solution for water reuse applications. This research contributes to the field by providing a comprehensive evaluation of GCS in water treatment, suggesting its potential for removing CECs from treated municipal wastewater.
PubMed: 38906279
DOI: 10.1016/j.scitotenv.2024.174078 -
Journal of Parkinson's Disease Jun 2024The serotonin (5-HT) system can manipulate the processing of exogenous L-DOPA in the DA-denervated striatum, resulting in the modulation of L-DOPA-induced dyskinesia...
BACKGROUND
The serotonin (5-HT) system can manipulate the processing of exogenous L-DOPA in the DA-denervated striatum, resulting in the modulation of L-DOPA-induced dyskinesia (LID).
OBJECTIVE
To characterize the effects of the serotonin precursor 5-hydroxy-tryptophan (5-HTP) or the serotonin transporter (SERT) inhibitor, Citalopram on L-DOPA-induced behavior, neurochemical signals, and underlying protein expressions in an animal model of Parkinson's disease.
METHODS
MitoPark (MP) mice at 20 weeks of age, subjected to a 14-day administration of L-DOPA/Carbidopa, displayed dyskinesia, referred to as LID. Subsequent investigations explored the effects of 5-HT-modifying agents, such as 5-HTP and Citalopram, on abnormal involuntary movements (AIMs), locomotor activity, neurochemical signals, serotonin transporter activity, and protein expression in the DA-denervated striatum of LID MP mice.
RESULTS
5-HTP exhibited duration-dependent suppressive effects on developing and established LID, especially related to abnormal limb movements observed in L-DOPA-primed MP mice. However, Citalopram, predominantly suppressed abnormal axial movement induced by L-DOPA in LID MP mice. We demonstrated that 5-HTP could decrease L-DOPA-upregulation of DA turnover rates while concurrently upregulating 5-HT metabolism. Additionally, 5-HTP was shown to reduce the expressions of p-ERK and p-DARPP-32 in the striatum of LID MP mice. The effect of Citalopram in alleviating LID development may be attributed to downregulation of SERT activity in the dorsal striatum of LID MP mice.
CONCLUSIONS
While both single injection of 5-HTP and Citalopram effectively mitigated the development of LID, the difference in mitigation of AIM subtypes may be linked to the unique effects of these two serotonergic agents on L-DOPA-derived DA and 5-HT metabolism.
PubMed: 38905058
DOI: 10.3233/JPD-240080 -
Journal of Parkinson's Disease Jun 2024Levodopa is the gold standard of treatment in Parkinson's disease (PD). Its clinical effect changes as the disease progresses. Wearing off is a frequent first...
BACKGROUND
Levodopa is the gold standard of treatment in Parkinson's disease (PD). Its clinical effect changes as the disease progresses. Wearing off is a frequent first manifestation of motor fluctuations. Some patients with advanced PD report faster wearing off after physical exercise.
OBJECTIVE
The aim was to assess if pharmacokinetics of levodopa is influenced by physical exercise in patients with different disease advancement.
METHODS
22 patients with PD (12 untreated with levodopa and 10 with motor fluctuations) and 7 healthy controls (HC) were included. Plasma samples were collected at 9 fixed timepoints following administration of levodopa/benserazide 200/50 mg for two days: rest day and standardized physical exercise day. Clinical assessment with Unified Parkinson Disease Rating Scale part III (UPDRS III) was performed in fixed timepoints. Liquid chromatography-tandem mass spectrometry was used to measure levodopa concentrations.
RESULTS
No differences between the HC, levodopa naïve and advanced PD groups were observed regarding selected pharmacokinetic parameters. In advanced PD and HC no differences in pharmacokinetic parameters of levodopa with and without effort were observed. In levodopa naïve PD group higher mean residence time after rest than after exercise (168.9±48.3 min vs. 145.5±50.8 min; p = 0.026) was observed. In advanced PD group higher UPDRS III score (14.45±5.5 versus 20.9±6.1 points, p = 0.04) was observed after exercise.
CONCLUSIONS
The deterioration of motor status of advanced PD patients after physical effort is not reflected by changes in pharmacokinetics but rather mediated by central mechanisms.
PubMed: 38905055
DOI: 10.3233/JPD-230384 -
Journal of Neurology Jun 2024Following reports of low striatal dopamine content in Parkinson's disease, levodopa was shown to rapidly reverse hypokinesis, establishing the model of disease as one of...
Following reports of low striatal dopamine content in Parkinson's disease, levodopa was shown to rapidly reverse hypokinesis, establishing the model of disease as one of dopamine deficiency. Dopaminergic therapy became standard of care, yet it failed to reverse the disease, suggesting the understanding of disease was incomplete. The literature suggests the potential for toxicity of dopamine and its metabolites, perhaps more relevant given the recent evidence for elevated cytosolic dopamine levels in the dopaminergic neurons of people with Parkinson's. To understand the relevance of these data, multiple investigations are reviewed that tested dopamine reduction therapy as an alternative to dopaminergic agents. The data from use of an inhibitor of dopamine synthesis in experimental models suggest that such an approach could reverse disease pathology, which suggests that cytosolic dopamine excess is a primary driver of disease. These data support clinical investigation of dopamine reduction therapy for Parkinson's disease. Doing so will determine whether these experimental models are predictive and this treatment strategy is worth pursuing further. If clinical data are positive, it could warrant reconsideration of our disease model and treatment strategies, including a shift from dopaminergic to dopamine reduction treatment of the disease.
PubMed: 38904783
DOI: 10.1007/s00415-024-12526-7 -
European Thyroid Journal Jun 2024Correct diagnosis and prognostic evaluation of medullary thyroid cancer (MTC) are crucial for the therapy of MTC. The purpose of this study was to evaluate the...
OBJECTIVE
Correct diagnosis and prognostic evaluation of medullary thyroid cancer (MTC) are crucial for the therapy of MTC. The purpose of this study was to evaluate the diagnostic and prognostic value of [18F]F-DOPA PET/CT in patients with MTC.
METHODS
We reviewed MTC patients who underwent [18F]F-DOPA PET/CT from June 2008 to November 2023. Clinical characteristics, follow-up data, and the following [18F]F-DOPA PET/CT parameters were recorded: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumour volume (MTV), and SUVmean of multi-organs. The diagnostic value of PET/CT for detection of tumour lesions were calculated. Serum basal calcitonin (bCt) and stimulated calcitonin (sCt) were determined. Receiver operating characteristic (ROC), Kaplan-Meier and Cox regression analyses were performed.
RESULTS
109 patients (50 women, 59 men; average age, 55 ± 14 y) were included in the analysis. The patient-related sensitivity, specificity and accuracy of [18F]F-DOPA PET/CT were 95%, 93% and 94%, respectively. The lesion-related sensitivity, specificity and accuracy were 65%, 99% and 72%, respectively. The optimal cutoff values of bCt, sCt and CEA to obtain positive [18F]F-DOPA PET/CT results were 64 pg/mL, 1808 pg/mL and 4 µg/L, respectively. Patients with negative [18F]F-DOPA PET/CT had longer overall survival (OS) than patients with positive [18F]F-DOPA PET/CT results (P=0.017). Significant positive correlations were found between bCt, sCt and CEA with SUVmax, SUVmean and MTV of [18F]F-DOPA PET/CT (P<0.001). [18F]F-DOPA PET/CT results and MTV may be useful for evaluation of prognosis of patients with recurrent MTC (RMTC).
CONCLUSIONS
[18F]F-DOPA PET/CT had great value for diagnosis and prognostic assessment in patients with MTC. The DOPA PET/CT parameter SUVmean and MTV showed significant association to OS.
PubMed: 38900599
DOI: 10.1530/ETJ-24-0089 -
Naunyn-Schmiedeberg's Archives of... Jun 2024We have previously discovered that the selective activation of metabotropic glutamate type 2 receptors (mGluR) and concurrent stimulation of metabotropic glutamate types...
We have previously discovered that the selective activation of metabotropic glutamate type 2 receptors (mGluR) and concurrent stimulation of metabotropic glutamate types 2 and 3 receptors (mGluR) enhance the anti-parkinsonian action of L-3,4-dihydroxyphenylalanine (L-DOPA). Here, we sought to determine the effects of the mGluR orthosteric agonists LY-354,740 and LY-404,039, as well as the effects of the mGluR positive allosteric modulators LY-487,379 and CBiPES on the range of movement, bradykinesia, posture and alertness as adjuncts to L-DOPA. Ten 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmosets entered 4 experimental streams: L-DOPA + LY-354,740 (vehicle, 0.1, 0.3 and 1 mg/kg), L-DOPA + LY-404,039 (vehicle, 0.1, 1 and 10 mg/kg), L-DOPA + LY-487,379 (vehicle, 0.1, 1 and 10 mg/kg), L-DOPA + CBiPES (vehicle, 0.1, 1 and 10 mg/kg). For each molecule, treatments were randomised, and the range of movement, bradykinesia, posture and alertness were assessed by a blinded rater. None of the tested compounds significantly altered the global range of movement. LY-404,039 and CBiPES both reduced global bradykinesia, by up to 46% (both P < 0.05). LY-354,740, LY-404,039 and CBiPES each improved global posture by 35%, 44% and 39% (each P < 0.05), respectively. LY-404,039 and CBiPES both enhanced alertness by 54% (P < 0.05) and 79% (P < 0.01), respectively. LY-487,379 did not improve any of the parameters. Our results suggest that selective mGluR positive allosteric modulation and combined mGluR orthosteric stimulation might benefit bradykinesia, posture and alertness in PD when added to L-DOPA, which potentially represent novel therapeutic indications for molecules acting via these mechanisms.
PubMed: 38900249
DOI: 10.1007/s00210-024-03216-2 -
Movement Disorders Clinical Practice Jun 2024Dopaminergic responsiveness is a defining feature of Parkinson's disease (PD). However, there is limited information on how this evolves over time.
BACKGROUND
Dopaminergic responsiveness is a defining feature of Parkinson's disease (PD). However, there is limited information on how this evolves over time.
OBJECTIVES
To examine serial dopaminergic responses, if there are distinct patterns, and which factors predict these.
METHODS
We analyzed data from the Parkinson's Progression Markers Initiative on repeated dopaminergic challenge tests (≥24.5% defined as a definite response). Growth-mixture modeling evaluated for different response patterns and multinomial logistic regression tested for predictors of these clusters.
RESULTS
1525 dopaminergic challenge tests were performed in 336 patients. At enrolment, mean age was 61.2 years (SD 9.6), 66.4% were male and disease duration was 0.5 years (SD 0.5). 1 to 2 years after diagnosis, 48.0% of tests showed a definite response, but this proportion increased with longer disease duration (51.1-74.3%). We identified 3 response groups: "Striking" (n = 29, 8.7%); "Excellent" (n = 110; 32.7%) and "Modest" (n = 197, 58.6%). Significant differences were as follows: striking responders commenced treatment earlier (P = 0.02), were less likely to be on dopamine agonist monotherapy (P = 0.01), and had better cognition (P < 0.01) and activities of daily living (P = 0.01). Excellent responders had higher challenge doses (P = 0.03) and were more likely to be on combination therapy (P < 0.01).
CONCLUSION
Three distinct patterns of the dopaminergic response were observed. As the proportion of PD cases with definite dopa responsiveness increased over time, the initial treatment response may be an unreliable diagnostic aid.
PubMed: 38898616
DOI: 10.1002/mdc3.14139 -
Environmental Pollution (Barking, Essex... Jun 2024Parkinson's disease (PD) is one of the fastest-growing neurodegenerative diseases and has been linked to the exposure to numerous environmental neurotoxins. Although...
Parkinson's disease (PD) is one of the fastest-growing neurodegenerative diseases and has been linked to the exposure to numerous environmental neurotoxins. Although lead (Pb) exposure has been related to the development of PD, the molecular target of Pb to cause the onset of PD is insufficiently investigated. Herein, we explored the effects of Pb exposure on behavior, pathophysiology, and gene expression of wild-type (WT) fly (Drosophila melanogaster) by comparison with its PD model. After exposure to Pb, the WT flies showed PD-like locomotor impairments and selective loss of dopaminergic (DAergic) neurons, displaying similar phenotypes to fly PD model (PINK1). Transcriptomic analysis showed the similarity in gene expression profiles between Pb treatment WT flies and PINK1 mutant flies. Moreover, Pb exposure resulted in endogenous dopamine deficits in WT flies. Analyses of gene expression and enzyme activity confirmed that Pb exposure reduced tyrosine hydroxylase (TH) activity and led to failure of dopamine synthesis. Furthermore, molecular dynamics simulation confirmed that Pb was adsorbed by TH and subsequently inhibited the enzymatic activity. Exogenous injection of L-dopa and melatonin could partially rescue the pathological phenotypes of Pb-exposed flies and PD fly model. Antagonist injection of microRNA-133, which negatively regulated the expression of TH gene, ultimately rescued in the manifestation of PD phenotypes in flies. Involvement of TH overexpression mutants of fly strongly promoted the resistance to Pb exposure and rescued both behavior and the number of DAergic neurons. Therefore, our study elucidates the Pb molecular target in dopamine pathway and mechanism underlying the risks of Pb exposure on the occurrence of PD at environmentally-relevant concentrations.
PubMed: 38897282
DOI: 10.1016/j.envpol.2024.124383