Clinical Characteristics of Multiple Sclerosis Patients Complicated by Disabilities and Analysis of Risk Factors Related to Disease Progression.

Objective: To analyze the clinical characteristics of multiple sclerosis (MS) patients complicated by disabilities in China, and to discuss the related factors of disease progression. Methods: Ninety-three MS patients presented to our hospital between March 2017 and December 2019 were selected as the research participants to conduct a retrospective analysis. Demographic information, onset time, onset age, clinical symptoms, MS types, and Expanded Disability Status Scale (EDSS) score were collected from all patients, and preliminary observation was made on MS cases in China. Subsequently, patients were grouped according to their sex, onset age and MS types to observe the differences in clinical characteristics of MS under different conditions. Finally, Logistic analysis was conducted to analyze the related factors affecting disease progression in MS patients. Results: MS was likely to occur in all age groups, among which the 30-40 age group had a slightly higher predilection. Women were more predisposed to MS, with motor symptoms as the major clinical presentations. The number of patients with sensory symptoms and the frequency of episodes in the past year were higher in female patients than in male patients (P < .05). Clinical isolated syndrome (CIS) patients had lower baseline ESDD than relapsing remitting MS (RRMS) patients (P < .05). According to Logistic regression analysis, baseline ESDD score and the frequency of episodes in the past year were independent risk factors affecting MS progression (P < .05). Conclusions: The clinical characteristics of MS in the Chinese population are basically similar to those in foreign countries, but RRMS accounts for a relatively low proportion. The ESDD score and the frequency of episodes in the past year are independent risk factors for MS progression.

CYP metabolic pathway related gene polymorphism increases the risk of embolic and atherothrombotic stroke and vulnerable carotid plaque in southeast China.

OBJECTIVE: To investigate the association of CYP metabolic pathway-related genetic polymorphisms with the susceptibility to ischemic stroke and stability of carotid plaque in southeast China. METHODS: We consecutively enrolled 294 acute ischemic stroke patients with carotid plaque and 282 controls from Wenling First People's Hospital. The patients were divided into the carotid vulnerable plaque group and stable plaque group according to the results of carotid B-mode ultrasonography. Polymorphisms of CYP3A5 (G6986A, rs776746), CYP2C9*2 (C430T, rs1799853), CYP2C9*3 (A1075C, rs1057910), and EPHX2 (G860A, rs751141) were determined using polymerase chain reaction and mass spectrometry analysis. RESULTS: EPHX2 GG may reduce the susceptibility to ischemic stroke (OR = 0.520, 95% CI: 0.288 ∼ 0.940, P = 0.030) and AA+AG may increase the risk for ischemic stroke (OR = 1.748, 95% CI: 1.001 ∼ 3.052, P = 0.050). The distribution of CYP3A5 genotypes showed significant differences between the vulnerable plaque and stable plaque groups (P = 0.026). Multivariate logistic regression analysis found that CYP3A5 GG could reduce the risk of vulnerable plaques (OR = 0.405, 95% CI: 0.178 ∼ 0.920, P = 0.031). CONCLUSION: EPHX2 G860A polymorphism may reduce the stroke susceptibility, while other SNPs of CYP genes are not associated with ischemic stroke in southeast China. Furthermore CYP3A5 polymorphism was related with carotid plaque instability.

Citronellol Prevents 6-OHDA-Induced Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis in Parkinson Disease Model of SH-SY5Y Cells via Modulating ROS-NO, MAPK/ERK, and PI3K/Akt Signaling Pathways.

Parkinson disease is a neurodegenerative disorder distinguished by dopaminergic shortage in the striatum and the accumulation of α-synuclein neuronal aggregates in the brains of patients. Since, there is no accurate treatment available for Parkinson disease, researches are designed to alleviate the pathognomonic symptoms such as neuroinflammation, oxidative stress, mitochondrial dysfunction, and apoptosis. Accordingly, a number of compounds have been reported to inhibit these pathognomonic symptoms. In this study, we have assessed the neuroprotective potential of citronellol against 6-OHDA-induced neurotoxicity in SH-SY5Y cells. The results found that citronellol treatment effectively hindered the cell death caused by 6-OHDA and thereby maintaining the cell viability in SH-SY5Y cells at 50 µg/mL concentration. As expected, the citronellol treatment significantly reduced the 6-OHDA-induced secretion of inflammatory factors (IL-1ß, IL-6, and TNF-α), which was obtained through ELISA technique. Similarly, citronellol hindered the 6-OHDA-induced oxidative stress by lowering the intracellular ROS and NO level and MDA leakage along with increased expression of SOD level in SH-SY5Y cells. The JC-1 staining showed that 6-OHDA increased the number of green fluorescent dots with ruptured mitochondrial membrane potential, while citronellol increased the amount of red fluorescent, showing the rescue potential against the 6-OHDA-induced mitochondrial dysfunction. Furthermore, citronellol hampered the 6-OHDA-induced apoptosis via the suppression of Bcl-2/Bax pathway. The western blotting results hypothesized that citronellol rescued SH-SY5Y cells from 6-OHDA-induced neurotoxicity via modulating ROS-NO, MAPK/ERK, and PI3K/Akt signaling pathways. However, further clinical trials are required to verify the anti-Parkinson efficacy.

Cerebrospinal Fluid Extracellular Vesicles with Distinct Properties in Autoimmune Encephalitis and Herpes Simplex Encephalitis.

Encephalitis mediated by autoantibodies against neuronal antigens and herpes simplex encephalitis (HSE) are seemingly separate causes of encephalopathy in adults. Autoimmune encephalitis (AE) is autoimmune in origin, and herpes simplex encephalitis is infectious. The purpose of this study was to examine the role of cerebrospinal fluid (CSF) exosomes from patients with antibody-positive AE and HSE. Towards this, exosomes were isolated from CSF from 13 patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, 11 patients with anti-gamma-aminobutyric acid-B (GABAB) receptor encephalitis, 9 patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis, and 8 patients with anti-contactin-associated protein-like 2 (CASPR2) encephalitis, and 12 control individuals negative of antibodies against neuronal autoantigens. There were ten miRNAs highly expressed in patients with anti-NMDAR encephalitis compared to those in control subjects. Eight miRNAs were found to be lower expressed in anti-NMDAR encephalitis CSF-derived exosomes. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched by AE differential expressed exosomic miRNAs demonstrated that AE-related exosomic miRNAs may participate as a feedback regulation in cancer development. In addition, the exosome concentration in CSF of 9 HSE patients was significantly higher compared to those from 9 HSV( -) patients. This observation was consistent with the results that exosome concentration was found to be higher in the animal model which was inoculated intranasally with HSV-1 compared to controls. Furthermore, western blot demonstrated that the subunits of NMDAR, GABABR, and AMPAR were detected highly expressed in exosomes derived from sera of HSV-1-treated animal model compared to controls. More importantly, exosomes isolated from CSF of HSE patients contained higher expression levels of two miRNAs encoded by HSV, miR-H2-3p, and miR-H4-3p compared to those from HSV( -) patients. In summary, HSV may trigger brain autoimmunity in HSE by presentation of surface autoantigens via exosomes.