Proteomic Profile of Saliva in Parkinson's Disease Patients: A Proof of Concept Study.
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SUBMITTER: Figura M
PROVIDER: S-EPMC8158489 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe discovery of abnormal synchronization of neuronal activity in the basal ganglia in Parkinson's disease (PD) has prompted the development of novel neuromodulation paradigms. Coordinated reset neuromodulation intends to specifically counteract excessive synchronization and to induce cumulative unlearning of pathological synaptic connectivity and neuronal synchrony.MethodsIn this prospective case series, six PD patients were evaluated before and after coordinated reset neuromodulation according to a standardized protocol that included both electrophysiological recordings and clinical assessments.ResultsCoordinated reset neuromodulation of the subthalamic nucleus (STN) applied to six PD patients in an externalized setting during three stimulation days induced a significant and cumulative reduction of beta band activity that correlated with a significant improvement of motor function.ConclusionsThese results highlight the potential effects of coordinated reset neuromodulation of the STN in PD patients and encourage further development of this approach as an alternative to conventional high-frequency deep brain stimulation in PD.
| S-EPMC4282372 | biostudies-literature
Project description:BackgroundParkinson's disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons.ObjectiveTo assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT).MethodsTwelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12 weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14 weeks before commencing the same treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4 weeks of treatment, after 12 weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%.ResultsMeasures of mobility, cognition, dynamic balance and fine motor skill were significantly improved (p < 0.05) with PBM treatment for 12 weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed.ConclusionsPBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted.Trial registrationAustralian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018.
| S-EPMC8249215 | biostudies-literature
Project description:Genome wide DNA methylation profiling of saliva samples in Parkinson's disease (PD) patients and PD-free controls. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles. Samples included 128 PD patients and 131 controls with saliva DNA.
2018-03-02 | GSE111223 | GEO
Project description:Today, novel candidate therapeutics are identified in an environment which is intrinsically different from the clinical context in which they are ultimately evaluated. We present a strategy that allows biological relevance to be assessed in the early stages of drug discovery. Using molecular phenotyping and an in vitro model of diabetic cardiomyopathy, we show that by quantifying pathway reporter gene expression, molecular phenotyping can cluster compounds based on pathway profiles and dissect associations between pathway activities and disease phenotypes simultaneously. Molecular phenotyping identified a class of calcium-signaling modulators that can reverse disease-regulated pathways and phenotypes, which was validated by structurally distinct compounds of relevant classes. The technique was applicable to compounds with a range of binding specificities and detected false-positive hits missed by classical phenotypic assays. Our results advocate application of molecular phenotyping in drug discovery, promoting biological relevance as a key selection criterion early in the drug development cascade.
2017-05-24 | GSE89972 | GEO
Project description:Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Lewy pathology involves numerous organs. Submandibular glands are affected in about 75% of in vivo cases, with higher rates of positive findings in post-mortem histopathological studies. Salivary microbiome composi-tion in PD patients is also different than in healthy patients. Therefore, we hypothesize that saliva may serve as a potential source of biomarkers of Parkinson’s disease. To evaluate and compare the salivary proteome of PD patients and healthy controls (HC). Salivary samples from 39 subjects (24 PD patients mean age 61.6 8.2 and 15 HC mean age 60.96.7) were used. Saliva was collected 30 minutes after rinsing mouth with tap water, in the morning hours, using RNA-Pro-Sal kits. Samples were immediately frozen at -80oC after collection. Label-free LC-MS/MS mass spectrometry was performed to comprehensively characterize the proteome of the saliva. IPA analysis of upstream inhibitors was performed. A total of 530 proteins and peptides were identified. We observed significantly lower concentrations of S100-A16, ARP2/3 and VPS4B in PD group vs controls. Additional IPA analysis indicated PD98059 to be most significantly activated and beta-estradiol most significantly inhibited upstream regulators. Conclusions: Very limited data on the salivary proteome of PD subjects is available. The results of our analysis indicate that the salivary proteome of PD patients might be different than that of healthy controls. We observed significantly lower concentrations of proteins involved in inflammatory processes, exosome formation and adipose tissue formation among others. Upstream regulator analysis indicated several proteins previously associated with neurodegeneration to drive the differential protein expression in saliva. The main limitations of the study are variability of expression of proteins between subjects in the two groups and variations caused by external factors.
2022-10-14 | PXD023489 | Pride
Project description:Despite the benefits of balance exercise in clinical populations, balance training programs tend to be poorly described, which in turn makes it difficult to evaluate important training components and compare between programs. However, the use of wearable sensors may have the potential to monitor certain elements of balance training. Therefore, this study aimed to investigate the feasibility of using wearable sensors to provide objective indicators of the levels and progression of training activity during gait-related balance exercise in individuals with Parkinson's disease.Ten individuals with Parkinson's disease participated in 10 weeks of group training (three sessions/week) addressing highly-challenging balance exercises. The training program was designed to be progressive by gradually increasing the amount of gait-related balance exercise exercises (e.g. walking) and time spent dual-tasking throughout the intervention period. Accelerometers (Actigraph GT3X+) were used to measure volume (number of steps/session) and intensity (time spent walking >1.0 m/s) of dynamic training activity. Training activity was also expressed in relation to the participants' total daily volume of physical activity prior to the training period (i.e. number of steps during training/the number of steps per day). Feasibility encompassed the adequacy of data sampling, the output of accelerometer data and the participants' perception of the level of difficulty of training.Training activity data were successfully obtained in 98% of the training sessions (n?=?256) and data sampling did not interfere with training. Reflecting the progressive features of this intervention, training activity increased throughout the program, and corresponded to a high level of the participants' daily activity (28-43%). In line with the accelerometer data, a majority of the participants (n?=?8) perceived the training as challenging.The findings of this proof-of-concept study support the feasibility of applying wearable sensors in clinical settings to gain objective informative measures of gait-related balance exercise in individuals with Parkinson's disease. Still, this activity monitoring approach needs to be further validated in other populations and programs including gait-related balance exercises.NCT01417598 , 15th August 2011.
| S-EPMC5282864 | biostudies-literature
Project description:BackgroundSolriamfetol is approved (US and EU) for excessive daytime sleepiness (EDS) in narcolepsy and obstructive sleep apnea.ObjectivesEvaluate solriamfetol safety/efficacy for EDS in Parkinson's disease (PD).MethodsPhase 2, double-blind, 4-week, crossover trial: adults with PD and EDS were randomized to sequence A (placebo, solriamfetol 75, 150, 300 mg/d), B (solriamfetol 75, 150, 300 mg/d, placebo), or C (placebo). Outcomes (safety/tolerability [primary]; Epworth Sleepiness Scale [ESS]; Maintenance of Wakefulness Test [MWT]) were assessed weekly. P values are nominal.ResultsCommon adverse events (n = 66): nausea (10.7%), dizziness (7.1%), dry mouth (7.1%), headache (7.1%), anxiety (5.4%), constipation (5.4%), dyspepsia (5.4%). ESS decreased both placebo (-4.78) and solriamfetol (-4.82 to -5.72; P > 0.05). MWT improved dose-dependently with solriamfetol, increasing by 5.05 minutes with 300 mg relative to placebo (P = 0.0098).ConclusionsSafety/tolerability was consistent with solriamfetol's known profile. There were no significant improvements on ESS; MWT results suggest possible benefit with solriamfetol in PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
| S-EPMC8596433 | biostudies-literature
Project description:BackgroundAlthough total plasma lipoproteome consists of proteins that have shown promises as biomarkers that can identify Alzheimer's disease (AD), effect sizes are modest. The objective of this study is to provide initial proof-of-concept that the plasma lipoproteome more likely differ between AD cases and controls when measured in individual plasma lipoprotein fractions than when measured as total in immunodepleted plasma.MethodsWe first developed a targeted proteomics method based on selected reaction monitoring (SRM) and liquid chromatography and tandem mass spectrometry for measurement of 120 tryptic peptides from 79 proteins that are commonly present in plasma lipoproteins. Then in a proof-of concept case-control study of 5 AD cases and 5 sex- and age-matched controls, we applied the targeted proteomic method and performed relatively quantification of 120 tryptic peptides in plasma lipoprotein fractions (fractionated by sequential gradient ultracentrifugation) and in immunodepleted plasma (of albumin and IgG). Unadjusted p values from two-sample t-tests and overall fold change was used to evaluate a peptide relative difference between AD cases and controls, with lower p values (<?0.05) or greater fold differences (>?1.05 or?<?0.95) suggestive of greater peptide/protein differences.ResultsWithin-day and between-days technical precisions (mean %CV [SD] of all SRM transitions) of the targeted proteomic method were 3.95% (2.65) and 9.31% (5.59), respectively. Between-days technical precisions (mean % CV [SD]) of the entire plasma lipoproteomic workflow including plasma lipoprotein fractionation was 27.90% (14.61). Ten tryptic peptides that belonged to 5 proteins in plasma lipoproteins had unadjusted p values?<?0.05, compared to no peptides in immunodepleted plasma. Furthermore, 27, 32, 17, and 20 tryptic peptides in VLDL, IDL, LDL and HDL, demonstrated overall peptide fold differences?>?1.05 or?<?0.95, compared to only 6 tryptic peptides in immunodepleted plasma. The overall comparisons, therefore, suggested greater peptide/protein differences in plasma lipoproteome when measured in individual plasma lipoproteins than as total in immunodepleted plasma. Specifically, protein complement C3's peptide IHWESASLLR, had unadjusted p values of 0.00007, 0.00012, and 0.0006 and overall 1.25, 1.17, 1.14-fold changes in VLDL, IDL, and LDL, respectively. After positive False Discovery Rate (pFDR) adjustment, the complement C3 peptide IHWESASLLR in VLDL remained statistically different (adjusted p value?<?0.05).DiscussionThe findings may warrant future studies to investigate plasma lipoproteome when measured in individual plasma lipoprotein fractions for AD diagnosis.
| S-EPMC6147047 | biostudies-literature
Project description:Peripheral blood mononuclear cell (PBMC) gene expression profiling is a low-invasive tool used in human diet intervention studies. In dogs this technique has been used to investigate disease states but not to examine the effect of diet. We tested the hypothesis that diet alters dog systemic immune cell gene expression profiles by comparing PBMC gene expression in dogs fed either a premium kibbled diet or a raw red meat diet for 9 weeks. Our results showed that diet shifted the dogs’ PBMC gene expression profile and these alterations corresponded with changes in plasma IgA levels. This illustrates that PBMC microarrays are a useful tool that may be applied to study the long-term effects of diet on health outcomes for the dog.
2017-09-07 | GSE103529 | GEO
Project description:In this proof-of-concept study, spatial transcriptomics combined with public single-cell RNA sequencing data were used to explore the potential of this technology to study kidney allograft rejection. We aimed to map gene expression patterns within diverse pathological states by examining biopsies classified across non-rejection, T cell-mediated acute rejection, and interstitial fibrosis and tubular atrophy (IFTA). Our results revealed distinct immune cell signatures, including those of T and B lymphocytes, monocytes, mast cells, and plasma cells, and their spatial organization within the renal interstitium. We also mapped chemokine receptors and ligands to study immune-cell migration and recruitment. Finally, our analysis demonstrated differential spatial enrichment of transcription signatures associated with kidney allograft rejection across various biopsy regions. Interstitium regions displayed higher enrichment scores for rejection-associated gene expression patterns than did tubular areas, which had negative scores. This implies that these signatures are primarily driven by processes unfolding in the renal interstitium. Overall, this study highlights the value of spatial transcriptomics for revealing cellular heterogeneity and immune signatures in renal transplant biopsies, and demonstrates its potential for studying the molecular and cellular mechanisms associated with rejection. However, certain limitations must be borne in mind regarding the development and future applications of this technology.
2024-05-02 | GSE245870 | GEO