Microglial activation and polarization play a central role in poststroke inflammation and neuronal damage. Modulating microglial polarization from pro-inflammatory to anti-inflammatory phenotype is a promising therapeutic strategy for the treatment of cerebral ischemia. Polyphyllin I (PPI), a steroidal saponin, shows multiple bioactivities in various diseases, but the potential function of PPI in cerebral ischemia is not elucidated yet. In our study, the influence of PPI on cerebral ischemia–reperfusion injury was evaluated. Mouse middle cerebral artery occlusion (MCAO) model and oxygen–glucose deprivation and reoxygenation (OGD/R) model were constructed to mimic cerebral ischemia–reperfusion injury in vivo and in vitro. TTC staining, TUNEL staining, RT-qPCR, ELISA, flow cytometry, western blot, immunofluorescence, hanging wire test, rotarod test and foot-fault test, open-field test and Morris water maze test were performed in our study. We found that PPI alleviated cerebral ischemia–reperfusion injury and neuroinflammation, and improved functional recovery of mice after MCAO. PPI modulated microglial polarization towards anti-inflammatory M2 phenotype in MCAO mice in vivo and post OGD/R in vitro. Besides, PPI promoted autophagy via suppressing Akt/mTOR signaling in microglia, while inhibition of autophagy abrogated the effect of PPI on M2 microglial polarization after OGD/R. Furthermore, PPI facilitated autophagy-mediated ROS clearance to inhibit NLRP3 inflammasome activation in microglia, and NLRP3 inflammasome reactivation by nigericin abolished the effect of PPI on M2 microglia polarization. In conclusion, PPI alleviated post-stroke neuroinflammation and tissue damage via increasing autophagy-mediated M2 microglial polarization. Our data suggested that PPI had potential for ischemic stroke treatment.

Purpose. To clarify the relationship between certain genotypes or alleles of the APOE gene and the onset risk of Parkinson’s disease dementia (PDD). Methods. The PubMed, Cochrane, Embase, CBM, CNKI, and Wanfang databases were searched to identify all case-control studies and cohort studies published before October 30, 2017, that investigated the association between the APOE gene and the onset of PDD. Manual information retrieval was also performed. All studies that met the quality requirements were included in a meta-analysis performed using RevMan 5.3 software. Results. The meta-analysis included 17 studies, with a total of 820 patients in the PDD group and 1,922 in the non-PDD group. The influence of the APOE gene on PDD onset was analyzed from three aspects: five genotypes vs. ε3/3, ε2+/ε4+ vs. ε3/3, and ε4+ vs. ε4−. The risk factors for PDD may include the genotypes ε3/4 (OR 1.47, 95% CI 1.14–1.89) and ε4/4 (OR 2.93, 95% CI 1.20–7.14). In patients with PDD, there was no significant difference in the distribution of ε2+ vs. ε3/3 (OR 1.35, 95% CI 0.97–1.87, P=0.07). The risk of PDD was 1.61 times greater in ε4+ compared with ε3/3 (OR 1.61, 95% CI 1.24–2.08, P=0.0003). As the results indicated that ε2+ did not play a role as a risk factor or a protective factor, we divided the population into ε4+ and ε4− for the meta-analysis and found that, among patients with Parkinson’s disease, the dementia risk of those with ε4+ was 1.72 times greater than that of those with ε4− (OR 1.72, 95% CI 1.41–2.10, P<0.00001). Subgroup analysis in accordance with different geographical regions revealed that ε4+ was a risk factor for PDD in people from all regions. Conclusions. Among the APOE genotypes, ε2+ is neither a risk factor nor a protective factor for PDD, while ε4+ is a risk factor for PDD. The present results are applicable to Asian, European, and American patients with Parkinson’s disease. Regarding the single APOE genotypes, ε3/4 and ε4/4 may be risk factors for PDD; however, further studies with large sample sizes are needed to verify this.

Purpose. This study aimed to explore new core genes related to the occurrence of Parkinsons disease (PD) and core genes that can lead to the progression of PD. Methods. The expression profile data of GSE42966, which contained six substantia nigra tissues isolated from normal individuals and nine substantia nigra tissues isolated from patients with PD, were obtained from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified, followed by functional enrichment analysis and protein-protein interaction (PPI) network construction. We then identified 10 hub genes and analyzed their expression in different Braak stages. Results. A total of 773 DEGs were identified that were significantly enriched in metabolic pathways. Ten hub genes were identified through the PPI network, namely, GNG3, MAPK1, FPR1, ATP5B, GNG2, PRKACA, HRAS, HSPA8, PSAP, and GABBR2. The expression of HRAS was different in patients with PD with Braak stages 3 and 4. Conclusion. These 10 hub genes and the metabolic pathways they are enriched in may be involved in the pathogenesis of PD. HRAS may have potential value in predicting the progression of PD.

Dysferlin myopathy is an autosomal recessive hereditary muscular dystrophy due to deficiency of dysferlin caused by alteration of the DYSF gene; Limb-girdle muscular dystrophy type 2B (LGMD2B) is the most common in Its clinical phenotypes. However, LGMD2B is rarely seen in clinical cases and may initially present as weakness of proximalpelvis muscles and muscles in the posterior compartments of thighs,which will then cause difficulty in running and limping during walking. Laboratory tests at an early stage of the disease often indicate an increased level of serum creatine kinase (CK). Moreover, polymyositis (PM) is manifested as symmetrical proximal muscle weakness of the four limbs, accompanied by an increased level of serum CK. Thus, both are very difficult to identify in clinical practice. A 25-year-old woman was admitted to our department as the limb weakness progressively worsened. She began to experience proximal muscle weakness of both lower limbs without obvious inducement, which markedly increased when she climbed the stairs or stood up after squatting. Then her symptoms worsened, with difficulty in proximal and distal lifting of the lower extremities. Through combined immunohistochemistry and Western-blot analysis, The patient was diagnosed with LGMD2B. There were symptomatic treatments such as coenzyme Q10. After symptomatic treatments, the patient's symptoms were obviously relieved, and the CK level decreased. Through this case, we found that combined application of immunohistochemistry and Western-blot analysis is helpful in early diagnosis of LGMD2B, and a new site of frame-shift mutation in the patient's DYSF gene was found.

This study aimed to explore the N6-methyladenosine (m6A) modification genes involved in the pathogenesis of Parkinsons disease (PD) through data analysis of the two data sets GSE120306 and GSE22491 in the GEO database and further explore its influence on cell phenotype in PD. We analyzed the differentially expressed genes and function enrichment analysis of the two sets of data and found that the expression of the m6A-modification gene HNRNPC was significantly downregulated in the PD group, and it played an important role in DNA metabolism, RNA metabolism, and RNA processing and may be involved in PD. Then, we constructed the HNRNPC differential expression cell line to study the role of this gene in the pathogenesis of PD. The results showed that overexpression of HNRNPC can promote the proliferation of PC12 cells, inhibit their apoptosis, and inhibit the expression of inflammatory factors IFN-β, IL-6, and TNF-α, suggesting that HNRNPC may cause PD by inhibiting the proliferation of dopaminergic nerve cells, promoting their apoptosis, and causing immune inflammation. Our study also has certain limitations. For example, the data of the experimental group and the validation group come from different cell types, and the data of the experimental group involve individuals with G2019S LRRK2 mutations. In addition, due to the low expression of HNRNPC in PC12 cells, we used the method of overexpressing this gene to study its function. All these factors may cause our conclusions to be biased. Therefore, more research is still needed to corroborate it in the future.