Mehrdokht Mazdeh

Background. Neurological disorders like Alzheimers disease (AD) and Parkinsons 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 bloodbrain 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 10ns 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.

Background and aims: Guillain-Barré syndrome (GBS) has several types, some of which damage myelin and some others cause axonal damage. Detecting the type of GBS is important in determining the type of treatment and its prognosis. This study was conducted to investigate the epidemiological characteristics of GBS and its variants in patients referred to Sina hospital in Hamadan, Iran, in 2018. Methods: In this cross-sectional study, 51 patients who were admitted to Sina hospital and diagnosed with GBS in 2018 were examined. Demographic data, GBS type, disease outcomes, and pre-clinical and clinical findings of patients were collected. Data were then analyzed using the Stata software version 12, and P value<0.05 was considered statistically significant. Results: Of the 51 investigated patients, 34 (66.66%) were male. The most common variant type was acute inflammatory demyelinating polyneuropathy (AIDP) with 27.45% of cases followed by acute motor axonal neuropathy (AMAN) with 19.61% of cases. Further, the highest average hospitalization days (11.1±11.7 days) were for chronic inflammatory demyelinating polyneuropathy (CIDP) patients, while the lowest (6.85±1.91 days) was for AIDP patients (P<0.001). All CIDP cases occurred in spring, and 71.43% of AIDP cases occurred in summer. Moreover, all 7 cases with acute motor and sensory axonal neuropathy (AMSAN) syndrome and the only case with the miller-fisher syndrome (MFS) occurred in fall (P<0.001). Conclusion: According to the results of this study, most variants of GBS in Hamadan province were AIDP in demyelinating form and AMAN variant in the axonal deterioration form. However, studies with a larger sample size are recommended in the west of Iran to better understand the epidemiology and to ensure common types of GBS.

Background. This study was undertaken to evaluate the influence of oral Acetyl‐L‐carnitine (ALC) in patients with acute ischemic stroke. Methods. Sixty‐nine cases with acute ischemic stroke with the onset of symptoms less than 24 hours not candidates for reperfusion therapy were randomly assigned to either the ALC group (1000 mg three times per day for three consecutive days) or the matching placebo group. The study outcomes based on intention‐to‐treat criteria included the change in the modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) score from baseline to day 90, as well as the change in serum levels of the inflammatory and oxidative stress biomarkers over the 3‐day treatment protocol. Results. The NIHSS score and mRS score on day 90 were improved by 5.82 and 0.94 scores, respectively, in the ALC‐treated group compared to 2.83 and 0.11 scores, respectively, in the placebo‐treated group, which demonstrated the superiority of ALC relative to placebo. By using the multivariable analysis after adjusting for other variables in the model, compared to the group treated with placebo, patients in the ALC group had lower NIHSS score (β: ‐2.40, 95% CI: ‐0.69, ‐4.10 (p = 0.007)) and mRS score (β: ‐1.18, 95% CI: ‐0.52, ‐1.84 (p = 0.001)) 90 days after the intervention. The percentage of patients with a favourable functional outcome at day 90, defined as mRS scores of 0 or 1, was significantly higher in the ALC group in comparison to the placebo group (52.9% versus 28.6%). Further, over the 3‐day treatment protocol, in the patients receiving ALC, the serum levels of proinflammatory biomarkers, including soluble intercellular adhesion molecule‐1 (sICAM‐1), interleukin 6 (IL‐6), tumor necrosis factor‐alpha (TNF‐α), and neuron‐specific enolase (NSE), showed a significant decrease, while the serum levels of antioxidant biomarkers, including glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (TAC), as well as the total L‐carnitine’s level showed a significant increase compared to those in patients receiving placebo indicating significant alteration. Conclusions. Although preliminary, these results suggested that ALC administration during the acute phase of ischemic stroke might be helpful in improving functional and neurological outcomes that are probably linked to its anti‐inflammatory and antioxidant properties. Trial Registration. This trial is registered with IRCT20150629022965N17 at Iranian Registry of Clinical Trials (registration date: 25/07/2018).

Objectives: It seems that psycho-physical factors of stroke patients undergoing Transcranial direct current stimulation (tDCS) treatment can affect implicit motor learning process in patient with stroke. The aim of this study was to determine the effects and adverse effects of tDCS on motor learning process in chronic unilateral stroke patients. Methods & Materials: This crossover, sham-controlled, randomized, blinded study was conducted in 2020 on 12 patients with chronic unilateral stroke (Mean±SD age, 60.33±1.87 years), (The Mean±SD time elapsed since the onset of the disease, 1.96±1.36 years) referred to Mobasher Kashani clinic in Hamadan, Iran who were selected using a convenience sampling technique. Patients were randomly divided in to 2 groups: experimental (dual tDCS+SRTT) (n=6) and sham (sham tDCS+SRTT) (n=6) groups. After 3 weeks of washing out period, patients in each group were treated in other brain stimulation group again. Data were collected using the record of reaction time and error of sequenced blocks by related software. Also, adverse effects of tDCS, pain or discomfort, attention and fatigue of patients were assessed by visual analogue scale (VAS) questionnaire. The data were analyzed using linear mixed effects. Results: Data analysis showed a considerable improvement in implicit motor learning in both brain stimulation groups. The most reported sensations were itching and tingling, which continued during all stimulation sessions. The pain or discomfort of the patients was negligible during the intervention sessions. Moreover, the type of brain stimulation, the time and their interaction had no significant effect on the fatigue, attention and pain of the patients (P>0.05). Conclusion: Dual-tDCS technique does not cause serious adverse effects in patients with stroke. It can be used as an effective and useful therapeutic strategy for increase in implicit motor learning in chronic stroke patients.

Background: Myasthenia gravis (MG) is an autoimmune disease that leads to fatigue and weakness after voluntary activities. If early diagnosed, MG can be treated, and a person’s performance and quality of life can be greatly improved as well. Materials and Methods: The study population of the present cross-sectional study included 80 patients with MG referring to Sina (Farshchian) hospital in Hamadan, Iran. The inclusion criterion included complete medical files. Finally, the variables were investigated using the chi-square test and two-sample t test by SPSS, version 16. Results: The mean (standard deviation) of the patients’ age was 45.6 ± 15.8 years and most patients (55.5%) were females and 72.5% of them were married. In addition, weakness, lethargy, and premature fatigue were the most common symptoms (47.5%) in patients while unsteady gait was the lowest prevalent symptom (11.3%). There was no significant relationship between gender and the incidence of symptoms in patients (P>0.05). However, a significant relationship was found between patients’ age with the shortness of breath and unsteady gait (P<0.05). Eventually, most women, especially married and elderly ones, contracted the disease. Conclusion: In general, there is a proper treatment for MG considering its early diagnosis. Accordingly, it is recommended that the level of awareness should be increased about the disease and provide appropriate medical and therapeutic facilities in this regard.

Background and Objective: This study investigated the difference between patients with mild cognitive impairment and healthy controls using Optical Coherence Tomography (OCT) regarding Retinal Nerve Fiber Layer (RNFL) thickness. Materials and Methods: In total, 20 patients with mild cognitive impairment and 20 healthy controls were subjected to neurological examination in ...

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS), in which axonal damage is a deteriorative factor. Brain-Derived Neurotrophic Factor (BDNF) is described as a neuronal-survival gene, also capable of exerting pleiotropic effects on the immune cells. Here, we aimed to investigate expression levels of BDNF and its antisense RNA, BDNF-AS, in Iranian MS patients. Our case-control study was based on collecting 50 whole blood samples of relapsing-remitting MS patients and 50 healthy controls. Then, expression analysis of BDNF and BDNF-AS was performed by Real-time quantitative PCR. We found a strong and positive correlation between BDNF and BDNF-AS in MS patients. This is while no significant difference in BDNF and BDNF-AS expression levels was seen between MS patients and controls (p>0.05). A significant and strong positive correlation was found between the expression levels of BDNF-AS and BDNF (r=0.785, p<0.0001). Further, significant positive moderate correlations of BDNF and BDNF-AS with other lncRNAs (GSTT1-AS1 and IFNG-AS1) and genes (TNF and IFNG) were revealed (p0.05). BDNF and BDNF-AS expression levels revealed insignificant discrepancies in patients and controls. We found a strong and positive correlation between BDNF and BDNF-AS in MS patients, which is, based on previous studies, a quit novel finding and can be further discussed by future works to unravel its possible application in MS. We suggest evaluation of different leukocytes subsets separately along with large cohort studies comprising a higher number of individuals from different ages to unravel the effects of other possible aspects.

Background: Multiple sclerosis (MS) is a chronic disease characterized by demyelination, glial activation and axonal degeneration in the central nervous system. At the present, there is no certain remedy for this disease. However, available therapies often attenuate disease progress.Methods: This study aims at identification of the effect of fingolimod on expanded disability status scale (EDSS) score and number of relapses in relapsing‐remitting MS (RRMS) patients in comparison with IFNβ. In the present 12‐month non‐randomized clinical trial, 55 RRMS patients aged between 18 and 45 with EDSS scores between 0 and 5.5 were divided into two groups. Twenty‐five patients received 0.5 mg oral fingolimod once a day for 12 months and 30 patients were under treatment with IFNβ. EDSS scores and number of relapses were recorded for all study participants monthly.Results: No significant difference was found in age and sex of patients recruited in two study groups. EDSS score was significantly lower in treatment group in month 10, 11 and 12 after treatment compared with control group (p values of 0.004, 0.006 and 0.007 respectively).Conclusion: Treated patients experienced no relapse during the study period. Fingolimod is effective in reduction of EDSS score and number of relapses in Iranian MS patients.