Parkinson's disease tremor prediction using EEG data analysis-A preliminary and feasibility study.

PURPOSE: Tremor is one of the hallmarks of Parkinson's disease (PD) that does not respond effectively to conventional medications. In this regard, as a complementary solution, methods such as deep brain stimulation have been proposed. To apply the intervention with minimal side effects, it is necessary to predict tremor initiation. The purpose of the current study was to propose a novel methodology for predicting resting tremors using analysis of EEG time-series. METHODS: A modified algorithm for tremor onset detection from accelerometer data was proposed. Furthermore, a machine learning methodology for predicting PD hand tremors from EEG time-series was proposed. The most discriminative features extracted from EEG data based on statistical analyses and post-hoc tests were used to train the classifier for distinguishing pre-tremor conditions. RESULTS: Statistical analyses with post-hoc tests showed that features such as form factor and statistical features were the most discriminative features. Furthermore, limited numbers of EEG channels (F3, F7, P4, CP2, FC6, and C4) and EEG bands (Delta and Gamma) were sufficient for an accurate tremor prediction based on EEG data. Based on the selected feature set, a KNN classifier obtained the best pre-tremor prediction performance with an accuracy of 73.67%. CONCLUSION: This feasibility study was the first attempt to show the predicting ability of EEG time-series for PD hand tremor prediction. Considering the limitations of this study, future research with longer data, and different brain dynamics are needed for clinical applications.

Evaluation of Rosuvastatin Therapy on SIRT1 Gene Expression in Patients with Multiple Sclerosis: An Uncontrolled Clinical Trial.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease. Current medications have some limitations such as low efficacy and high side effects. In recent years, statins have been raised as potential therapeutics for MS treatment with minimal complications. In addition, patient monitoring using suitable molecular markers is necessary for treatment response evaluation. Objective: The aim of the present study was the evaluation of SIRT1 gene expression changes following rosuvastatin therapy in patients with MS. Methods: This before-after uncontrolled clinical trial study was performed on 25 patients with MS. Patients were treated with 20 mg rosuvastatin daily for 3 months. The Expanded Disability Status Scale (EDSS) was measured before and after statin therapy. Blood samples were taken from patients 2 times, before and after statin therapy, and centrifuged for white blood cell isolation. Total RNA was extracted using RNX-plus reagent, and complementary DNA was synthesized using Pars Tous cDNA Synthesis Kit. Real-time polymerase chain reaction was done using SYBR blue master mix and gene-specific primers in Roche light cycler. Patients' information was recorded using a checklist. Data analysis was performed using SPSS version 23 and Graph Pad version 9 software and P < 0.05 was considered a significant level. Results: SIRT1 was significantly upregulated in MS patients after statin therapy. Subsequently, EDSS of patients was decreased along with the increase in SIRT1 gene expression, although EDSS changes were not significant (P > 0.05). Pearson correlation test showed no significant relationship between EDSS and SIRT1 gene expression (P > 0.05). No significant relationship was observed between SIRT1 expression or EDSS levels with patients' age, sex, weight, height, and body mass index and administrated drugs (P > 0.05). Conclusions: SIRT1 potentially is a sensitive and reliable biomarker for patients with MS monitoring during statin therapy.

Evaluation of serum levels of asprosin and other metabolic profiles in patients with idiopathic tonic-clonic generalized epilepsy on treatment with valproic acid.

BACKGROUND: This cross-sectional research was undertaken to determine the serum levels of asprosin, a novel white adipose tissue-derived glucogenic adipokine, in epileptic patients on valproic acid treatment. METHODS: Sixty-six patients diagnosed with idiopathic tonic-clonic generalized epilepsy were divided into three groups: those treated with valproic acid (n = 22), those treated with lamotrigine (n = 22), and twenty-two newly diagnosed or untreated patients. A control group was twenty-two, healthy volunteers with a similar distribution of gender and age. Body mass index (BMI) and fasting serum levels of asprosin, glucose, glycohemoglobin (HbA1c), insulin, and lipid profile were measured for both patients and control groups. Additionally, homeostasis model assessment for insulin resistance (HOMA-IR) was also calculated for the investigated groups. RESULTS: The mean BMI values and fasting serum levels of glucose, HbA1c, insulin, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride were much higher in subjects treated with valproic acid than those in the other study groups. Furthermore, a higher number of participants in the valproic acid group fulfilled the insulin resistance criterion (defined as HOMA-IR > 2.5) compared with those in other study groups. The mean fasting serum asprosin concentration was also significantly higher in the valproic acid group than in other study groups. This was while the values of the study parameters were comparable in the healthy, un-treated, and lamotrigine groups. CONCLUSIONS: Our finding suggested that elevated asprosin level might be one of the pathological mechanisms involved in the development of obesity, insulin resistance, and metabolic disturbances related to valproic acid treatment.

Association study of promoter polymorphisms of interferon alpha and beta receptor subunit 1 (IFNAR1) gene and therapeutic response to interferon-beta in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease described by inflammatory neuronal losses and resultant failures. The disease could abate by interferon-beta (IFN-ß) therapy in MS patients. However, the drug response productivity is changeable between patients, and the accurate mechanism of action of the IFN-ß is not obvious. The present study aims to investigate the role of interferon alpha and beta receptor subunit 1 (IFNAR1) promoter polymorphisms towards IFN-ß treatment response in MS patients. METHODS: The subjects herein were separated into either responder (n = 57) or non-responder (n = 43) groups according to IFN-ß treatment and Expanded Disability Status Scale score. The Sanger sequencing method was used for genotyping. RESULTS: Among nearly 64 Single Nucleotide Polymorphisms (SNPs), we found a significant association between the rs2850015 polymorphism and the responders and non-responders to IFN-ß treatment in the recessive model of inheritance (P = 0.02). The results also revealed a significant change in the two groups of responders and non-responders to the treatment for rs36158718 as an Insertion/Deletion (INDEL) (P = 0.02). Moreover, bioinformatic analyses predicted a remarkable role for both rs2850015 and rs36158718 related to the changes of binding affinity of transcription factors and alterations in their alleles. CONCLUSION: The present study results suggest that the genetic heterogeneity in the promoter region of IFNAR1 could affect the response to IFN-ß. However, further studies with a larger sample size are needed to further demonstrate this relationship.

Association between methylene tetrahydrofolate reductase polymorphisms and risk of ischemic stroke.

Background: The methylene tetrahydrofolate reductase (MTHFR) is a folate-dependent enzyme which catalyzes the conversion of homocysteine to methionine. Two single nucleotide polymorphisms (SNPs) within this gene namely rs1801133 (C677T) and rs1801131 (A1298C) have been associated with elevated risk of ischemic stroke and total serum homocysteine in some populations.Aim: To assess associations between MTHFR SNPs and risk of ischemic stroke in Iranian population.Methods: In the current case-control study, we genotyped rs1801133 and rs1801131 SNPs in 318 Iranian patients with history of ischemic stroke and 400 age- and sex-matched controls using tetra-primer amplification refractory mutation system-polymerase chain reaction method.Results: The rs1801133 was significantly associated with risk of stroke in recessive model (OR (95% CI) = 1.89 (1.12-3.20), p = 0.03). The CT haplotype (rs1801131 and rs1801133, respectively) was significantly over-represented in patients compared with controls (OR (95% CI) = 1.71 (0.25-2.32), p = 0.002).Conclusion: Consequently, our data demonstrate contribution of MTHFR variants in risk of ischemic stroke in Iranian population.

Upregulation of VEGF-A and correlation between VEGF-A and FLT-1 expressions in Iranian multiple sclerosis patients.

Multiple sclerosis (MS) is among the most common diseases affecting brain and spinal cord. MS progression is characterized by breakdown of blood brain barrier which leads to increased vascular permeability and angiogenesis. Consequently, vascular endothelial growth factor A (VEGF) and its receptors are considered to be important components of MS progression. VEGFA and fms-related tyrosine kinase 1 (FLT1) play important roles in various aspects of MS. In this study, we investigated the relationship between these genes and MS. For this purpose, the expression levels of VEGFA and FLT1 were measured in the blood of 50 relapsing-remitting MS (RR-MS) patients and 50 healthy individuals using TaqMan quantitative real-time PCR. A significant upregulation of VEGFA expression was observed among MS patients compared with controls (p = 0.04). However, the difference in FLT1 gene expression between study groups was insignificant (p = 0.947). In addition, there was a significant positive correlation between VEGFA and FLT1 genes expressions (r = 0.769, p < 0.0001). In spite of the highly complex molecular mechanisms behind this, the findings imply participation of VEGFA in the pathogenesis of MS.

The effect of atorvastatin on the common carotid artery intima-media thickness in patients with ischemic stroke.

Occlusion of the initial segment of internal carotid artery is the most common reason for vascular events in the brain. The purpose of this study was to investigate the effect of one-year treatment with atorvastatin on intima-media thickness (IMT) of carotid arteries as a measure of atherosclerosis in stroke patients. In this prospective interventional study, 44 patients with ischemic stroke were investigated. Patients were treated with atorvastatin 40 mg once a day for one year. IMT of carotid arteries was measured by extracranial Doppler ultrasonography in the distal part of the common carotid artery at the beginning of the study, at 6 months and one year of treatment with atorvastatin. The IMT of both right and left carotid arteries decreased after 6- and 12-month atorvastatin treatment. Based on the results of this study, long-term administration of atorvastatin was associated with reduction in carotid artery IMT in patients with ischemic stroke. Such a decrease in IMT may prevent subsequent stroke or cardiovascular events in these patients.

Integrative analysis of OIP5-AS1/HUR1 to discover new potential biomarkers and therapeutic targets in multiple sclerosis.

Multiple sclerosis (MS) is a devastating autoimmune disease of the central nervous system associated with demyelination and axonal injury. This study was designed to find potential lncRNAs and their targets that are associated with the molecular basis of MS pathogenesis. In this study, peripheral blood samples were obtained from 50 relapsing-remitting MS (RR-MS) patients and 50 healthy controls. lncRNAs and their target were selected for validation using TaqMan Real-Time PCR. Interactions were studied based on approaches that used to investigation biological functions and signaling pathways affected by differentially expressed messenger RNAs (mRNAs). The results of this study indicate an increase in the expression of HUR1 (p = 0.0001), CPSF7 (p = 0.02), and reduction of CSTF2 expression (p = 0.04). Also, an increase in the expression of OIP5-AS1 (p = 0.01) was observed in men less than 30 years old. We performed a comparative analysis of the long noncoding RNAs (lncRNAs), and then we ranked them as candidate biomarkers according to a decreasing area under the receiver operating characteristic (ROC) curve (AUC) and plotted the results. Dysregulation of lncRNA expression has been linked to diseases. Further studies on the HUR1 gene can be used as diagnostic tools for the identification of high-risk individuals in families with a history of disease before, during, and even after treatment. Our data uncovered the expression profiles of lncRNAs and mRNAs in MS patients, which will help delineate the molecular mechanisms in MS pathogenesis. However, further studies need to determine the precise role of these genes in the pathological process in MS.

MALAT1 Genomic Variants and Risk of Multiple Sclerosis.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long noncoding RNA (lncRNA) with a possible role in the regulation of immune responses. A previous study has demonstrated down-regulation of this lncRNA in multiple sclerosis (MS) patients. In the current study, we genotyped two MALAT1 single nucleotide polymorphisms (SNPs) in 428 Iranian MS patients and 505 healthy subjects. The G allele of the rs619586 was significantly under-represented in MS patients compared with controls (OR (95% CI) = 0.65 (0.46-0.92), adjusted P value = 0.03). This SNP was associated with lower MS risk in dominant model (OR (95% CI) = 0.63 (0.43-0.91), adjusted P value = 0.03). The rs3200401 was not associated with MS risk in any inheritance model. Moreover, the A T haplotype (rs619586 and rs3200401, respectively) within MALAT1 was associated with MS risk. The current study provides additional evidences for contribution of MALAT1 in the pathogenesis of MS.

Expression analysis of long non-coding RNAs and their target genes in multiple sclerosis patients.

Multiple sclerosis (MS) is a progressive chronic autoimmune-mediated disease. Recently, long non-coding RNAs (lncRNAs) are characterized to participate in the adjustment of immune responses. Here, we evaluated the expression levels of GSTT1-AS1 and IFNG-AS1 lncRNAs and their targets (TNF and IFNG, respectively) in Iranian MS patients.In this case-control study, 50 relapsing-remitting MS patients and 50 healthy subjects were recruited. Expressions of GSTT1-AS1 and IFNG-AS1 lncRNAs, as well as TNF and IFNG genes, were assessed in their peripheral blood samples by SYBR Green-based Real-time quantitative PCR.Expression levels of GSTT1-AS1 and IFNG-AS1 lncRNAs were both significantly downregulated (p values 0.032 and 0.013, respectively). On the other hand, the expression of TNF and IFNG showed increased levels, however, did not reach statistical significance after our analysis (p > 0.05). Spearman correlation analysis showed that GSTT1-AS1 had a significant positive moderate correlation with IFNG-AS1 (r = 0.541, p < 0.0001), IFNG (r = 0.329, p = 0.001), and TNF (r = 0.204, p = 0.041). Also, IFNG-AS1 revealed the same correlation with IFNG (r = 0.475, p < 0.0001) as well as TNF (r = 0.399, p < 0.0001). Furthermore, GSTT1-AS1 (r = 0.313, p = 0.027) and (IFNG r = 0.478, p < 0.0001) demonstrated a significant positive correlation with age at onset.Briefly, the current study provided for the first time dysregulation of GSTT1-AS1 and IFNG-AS lncRNAs network in MS, which highlights the significant role of epigenetic pathways in this autoimmune disorder. Larger sample size and further investigation assays could shed light on the underlying mechanisms in this area of science.

Expression analysis of vitamin D receptor-associated lncRNAs in epileptic patients.

Vitamin D has been vastly acknowledged as a neuroactive steroid controlling neurodevelopment. As it exerts its functions through activation of vitamin D receptor (VDR), several studies have assessed the role of VDR in brain function. More recently, a number of long non-coding RNAs (lncRNAs) have been recognized that alter expression of VDR. In the current study, we evaluated expression of four VDR-related lncRNAs (LINC00511, LINC00346, SNHG6 and SNHG16) in peripheral blood of 40 epileptic patients and 39 healthy subjects using quantitative real time PCR method. The relative expression levels of SNHG16 and LINC00511 were higher in epileptic patients compared with healthy subjects. For SNHG16, the difference was only significant between male patients and male controls, while LINC00511 had the opposite pattern. The results of Quantile regression model showed significant associations between SNHG6 and SNHG16 expressions and gender (P values of 0.027 and 0.009 respectively). Significant correlations were detected between expression levels of SNHG6 and SNHG16 (r = 0.32, P = 0.004), SNHG6 and LINC00346 (r = 0.37, P = 0.001), SNHG16 and LINC00346 (r = 0.30, P = 0.007) as well as SNHG16 and LINC00511 (r = 0.29, P = 0.009). Expression of LINC00346 was inversely correlated with vitamin D levels only in male epileptic patients (r = -0.58, P = 0.011). Expression of SNHG6 was correlated with vitamin D levels in male controls but no other subgroups (r = 0.51, P = 0.044). Based on the results of ROC curve analysis, SNHG16 had the diagnostic power of 0.86 in male subjects. Taken together, the current study provides evidences for dys-regulation of VDR-related lncRNAs in epileptic patients. The clinical significance of these finding should be explored in future studies.

Expression analysis of cytokine coding genes in epileptic patients.

Epilepsy is a chronic disorder in which immune dysregulation is shown to be involved. Imbalances in the cytokine levels both in serum and brain tissue have been demonstrated in epileptic patients. In the present study, we assessed mRNA expression of TNF-α, TGF-ß, IFN-γ, CXCL8, IL-1ß, IL-2, 1L-4, IL-6, IL-17 and CXCL8 in blood samples of 40 epileptic patients compared with age- and sex-matched healthy controls by means of quantitative real time PCR. The relative levels of CXCL8 transcripts were significantly higher in total epileptic patients compared with healthy subjects (P = .023). Relative mRNA expression of IFN-γ was significantly higher in female patients compared with female healthy subject (P = .048). In addition, significant correlations have been found between the mRNA levels of mentioned cytokines. Such imbalance between expression of pro-inflammatory and anti-inflammatory cytokines might be implicated in the pathogenesis of epilepsy.

STAT5a and STAT6 gene expression levels in multiple sclerosis patients.

Multiple sclerosis (MS) is a complex inflammatory, autoimmune disease of the central nervous system (CNS). The disease pathogenesis is not well defined yet. Cytokines have an important role in inflammation as characteristic feature of the disease. Janus kinase/signal transducers and activators of transcriptions (JAK/STAT) family promote cytokine-mediated cell activation. Failure in the JAK/STAT signaling pathway is associated with the pathological outcome in MS. In this study, we compared the expression levels of STAT5a and STAT6 genes in the blood of 50 relapsing-remitting MS (RR-MS) patients and 50 healthy controls by Taqman Quantitative Real-Time PCR in patients and healthy control group. We found that STAT5a expression was significantly down-regulated (p = .049), whereas STAT6 gene expression was significantly up-regulated (p = .046) in MS patients compared with controls. Moreover, there was significant correlation between the STAT6 gene expression and Kurtzke Expanded Disability Status Scale (EDSS) criterion. However, no significant correlation was demonstrated between the expression of STAT5a gene and clinical findings. Furthermore, there was not significant correlation between expression levels of STAT5a and STAT6 genes. Our findings suggest that STAT5a and STAT6 dysregulation may have a critical role in modification of immune responses leading to imbalance between Th2- and Th1-related cytokines. However, the mechanisms underlying it still remain to be elucidated. Future studies are needed to explore the role of STAT5a and STAT6 as prognostic biomarkers in research, design of experimental therapies or clinical settings of the MS.

Cytokine profile in autistic patients.

The etiology of Autism Spectrum Disorders (ASDs) as severe neurodevelopmental ailments is not known. However, several evidences point to dysregulation of immune system as an underlying cause of ASD. In the present study we evaluated the mRNA expression levels of TNF-α, TGF-ß, IFN-γ, CXCL8, IL-1ß, IL-2, 1L-4, IL-6, IL-17 in whole blood samples of 30 ASD patients and 41 age and sex-matched healthy subjects with means of real-time PCR. TNF-α, IL-6 and IL-17 have been shown to be significantly up-regulated in ASD patients compared with healthy subjects (P < 0.0001, P = 0.001 and P < 0.0001 respectively). IL-2 has been shown to be significantly down-regulated in total ASD patients (P < 0.0001). No significant difference has been found in expression levels of other cytokines between patients and healthy subjects. The present study provides further evidences for dysregulation of immune response in ASD patients.

Expression analysis of GRIN2B, BDNF, and IL-1ß genes in the whole blood of epileptic patients.

Epilepsy is a brain disorder with a global prevalence of 1%. It has been attributed to genetics and environmental factors. Despite efforts to identify the molecular pathology of epilepsy, the underlying mechanism is not understood yet. This study was carried out to compare GRIN2B, BDNF, and IL-1ß gene expressions in 50 patients suffering from generalized epilepsy with tonic-colonic seizures and 50 age- and sex-matched healthy subjects using TaqMan Real-time PCR. Our results demonstrated significant upregulation of these genes in people with epilepsy compared with healthy subjects. We also found a positive correlation between GRIN2B and BDNF expression (r2=0.4619, p < 0.0001), BDNF and IL-1ß expression (r2 = 0.515, p < 0.0001), and GRIN2B and IL-1ß gene expressions (r2 = 0.666, p < 0.0001) which implies the possibility to estimate the expression level of these genes by assessment of expression of one of them. Considering the results of the previous animal studies which showed upregulation of these genes in brain tissues of epileptic animals, the expression levels of GRIN2B, BDNF, and IL-1ß in blood samples might be related to their expression in brain samples. Future studies are needed to assess the role of these genes in the pathogenesis of epilepsy and evaluate whether altered expression of these genes along with imaging methods can facilitate subtyping the epilepsy.

Expression analysis of beta-secretase 1 (BACE1) and its naturally occurring antisense (BACE1-AS) in blood of epileptic patients.

Beta-secretase 1 (BACE1) gene encodes a transmembrane protease from the peptidase A1 family of aspartic proteases whose role in the pathogenesis of Alzheimer's disease has been assessed. The enzymatic activity of BACE1 on several proteins implicated in epileptogenesis implies its role in the pathogenesis of epilepsy. In the present study, we assessed expression of BACE1 and its naturally occurring antisense (BACE1-AS) in peripheral blood of 40 epileptic patients and 40 age- and sex-matched healthy subjects. We did not detect either any difference in the expression of these genes between cases and controls or significant correlation between their expressions and participants' age. However, we demonstrated a significant correlation between expression levels of BACE1 and BACE1-AS which supports the previously suggested feed-forward mechanism of regulation between these two transcripts. Future studies in larger sample sizes are needed to elaborate the function of BACE1 in epilepsy.

Determination of cytokine levels in multiple sclerosis patients and their relevance with patients' response to Cinnovex.

Multiple sclerosis (MS) is a heterogeneous chronic immune-mediated disorder of the central nervous system (CNS) with several environmental and genetic factors participating in its development and disease course. Interferon (IFN)-ß therapy is considered as the first line treatment in this disorder. The present study enrolled 231 relapsing-remitting MS patients who were diagnosed as IFN-ß responders (n=146) and non-responders (n=85). Serum cytokine levels were analyzed by commercially available ELISA kits in distinct groups based on HLA-A, -B and -DRB1 alleles. IFN-γ levels were significantly higher in responders compared with non-responders, whereas IL-17A and IL-6 had the opposite trend. The levels of IL-10 and IL-4 were not significantly different between two groups. IFN-γ and IL-17A levels were associated with response to IFN-ß. Comparison of cytokine levels revealed higher IFN-γ levels in HLA-DRB1∗04 positive patients (n=72) compared with HLA-DRB1∗04 negative patients (n=159). In responder group, patients who were positive for HLA-DRB1∗15 had significantly higher levels of IL-6 compared to HLA-DRB1∗15 negative patients. IL-17A levels tend to be higher in responder patients who were positive for HLA-DRB1∗04 compared with those were negative for the same allele. This study suggests that the serum levels of pro- and anti-inflammatory cytokines are different among IFN-ß responders and non-responders. Future studies are needed to confirm their efficiency in determination of response to IFN-ß in MS patients.

Further Evidence of the Positive Influence of Repetitive Transcranial Magnetic Stimulation on Speech and Language in Patients with Aphasia after Stroke: Results from a Double-Blind Intervention with Sham Condition.

BACKGROUND: After a stroke, up to 20% of patients suffer from aphasia. The preferred treatment for stroke-related aphasia (SRA) is regular speech and language training (SLT). In the present study, we investigated to what extent adjuvant repetitive transcranial magnetic stimulation (rTMS) might enhance recovery. While there is growing evidence of the positive effect of adjuvant rTMS on aphasia, no study has yet been based on an Iranian sample. METHOD: A total of 12 patients (mean age: 55 years; right-handed; 7 women) underwent treatment for SRA 1 month after stroke. The standard treatment consisted of regular 45-min SLT sessions 5 times a week for 2 consecutive weeks. Additionally, patients were randomly assigned either to adjuvant rTMS (5 times a week for 30 min) or to a sham condition (5 times a week for 30 min). At baseline and after 2 weeks of intervention, the degree of aphasia was assessed with the Farsi version of the Western Aphasia Battery. rTMS was applied to the inferior posterior frontal gyrus of the right hemisphere. RESULTS: Speech and language improved over time, but more so in the rTMS than in the sham condition. Large effect sizes were observed for content, fluency, and the aphasia quotient; medium effect sizes were observed for command comprehension and repetition, while effect sizes were small for auditory comprehension and naming. CONCLUSIONS: Among patients with SRA, compared to a sham condition, adjuvant rTMS improved speech and language skills. The present results add to the accumulating evidence that rTMS as a neuromodulation technique has the capacity to enhance the effect of conventional SLT.

Phospholipase D1 expression analysis in relapsing-remitting multiple sclerosis patients.

Multiple sclerosis (MS) is a chronic disorder resulting from destruction of the myelin or insulating covers of neurons in the central nervous system (CNS). Several lines of evidence suggest a role for immune response in the occurrence and progression of this disorder. Several disease-modifying agents (DMA) including ß-interferons (IFNß) are being used in MS patients in order to stop the disease at the early inflammatory stage, postpone disease progression and diminish future disability. Phospholipase D1 (PLD1) is a critical enzyme responsible for the making lipid second messenger phosphatidic acid. It has an established function in regulation of immune response. In the present study we have evaluated PLD1 transcript levels and plasma concentrations in 78 relapsing-remitting MS (RRMS) patients as well as 78 normal age- and sex-matched healthy subjects using real-time quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Significant PLD1 down-regulation has been observed in total MS patients compared with controls (P < 0.001) as well as IFN-ß responders (P = 0.034) and non-responders (P < 0.001) compared with controls, respectively. However, a significant up-regulation has been detected in IFN-ß responders compared with non-responders (P = 0.047). In both males and females groups, significant down-regulations have been detected in patients compared with controls (P = 0.014 and P = 0.002, respectively). The same results have been detected in PLD1 plasma concentrations. In conclusion, PLD1 transcripts in blood and its plasma concentrations can be used as putative biomarkers for evaluation of therapeutic responses to IFN-ß in RRMS patients. However, this result should be validated in future studies.

BACE1 Inhibition Utilizing Organic Compounds Holds Promise as a Potential Treatment for Alzheimer's and Parkinson's Diseases.

Background: Neurological disorders like Alzheimer's disease (AD) and Parkinson's disease (PD) manifest through gradually deteriorating cognitive functions. An encouraging strategy for addressing these disorders involves the inhibition of precursor-cleaving enzyme 1 (BACE1). Objectives: In the current research, a virtual screening technique was employed to identify potential BACE1 inhibitors among selected herbal isolates. Methods: This study evaluated 79 flavonoids, anthraquinones (AQs), and cinnamic acid derivatives for their potential blood-brain barrier (BBB) permeability. Using the AutoDock 4.0 tool, molecular docking analysis was conducted to determine the binding affinity of BBB permeable compounds to the BACE1 active site. Molecular dynamics (MD) simulations were performed to assess the stability of the docked poses of the most potent inhibitors. The interactions between the most effective plant-based inhibitors and the residues within the BACE1 catalytic site were examined before and after MD simulations. Results: Ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine were among the highest-ranking BACE1 inhibitors, with inhibition constant values calculated in the nanomolar range. Furthermore, during 10 ns simulations, the docked poses of these ligands were observed to be stable. Conclusion: The findings propose that ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine might serve as potential choices for the treatment of AD and PD, laying the groundwork for the creation of innovative BACE1 inhibitors.