CircDLGAP4 overexpression ameliorates neuronal injury in Parkinson's disease by binding to EIF4A3 and increasing HMGA2 expression.

Parkinson's disease (PD) is a prevalent neurodegenerative disease, and its prevalence increases steadily with age. Circular RNAs (circRNAs) are involved in various neurodegenerative diseases. Here, we aimed to explore the role of circRNA DLG-associated protein 4 (circDLGAP4) in 1-methyl-4-phenylpyridinium ion (MPP+ )-induced neuronal injury in PD. SH-SY5Y cells were treated with MPP+ to establish PD cell models. The levels of circDLGAP4 and high mobility group AT-hook 2 (HMGA2) in SH-SY5Y cells were detected. SH-SY5Y cell viability and apoptosis were detected. The levels of inflammatory damage (IL-1ß, IL-6, TNF-α) and oxidative stress (reactive oxygen species, lactate dehydrogenase, superoxide dismutase, and malondialdehyde)-related factors were measured. The binding of eukaryotic initiation factor 4A3 (EIF4A3) to circDLGAP4 and HMGA2 was analyzed using RNA pull-down or RNA immunoprecipitation. The stability of HMGA2 was detected after actinomycin D treatment, and its effects on neuronal injury were tested. CircDLGAP4 expression was decreased in MPP+ -induced SH-SY5Y cells. CircDLGAP4 upregulation restored cell activity, decreased apoptosis, and reduced inflammatory damage and oxidative stress in PD cell models. CircDLGAP4 bound to EIF4A3 to increase HMGA2 expression and stability. Silencing HMGA2 attenuated the protective effect of circDLGAP4 overexpression. Overall, circDLGAP4 upregulated HMGA2 by recruiting EIF4A3, thus increasing the mRNA stability of HMGA2 and alleviating neuronal injury in PD.

Hsa_circ_0054220 Upregulates HMGA1 by the Competitive RNA Pattern to Promote Neural Impairment in MPTP Model of Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease. Circular RNAs (circRNAs) have been confirmed to regulate neurodegenerative diseases. This study was aimed to explore hsa_circ_0054220 functions in PD. MPP-stimulated SH-SY5Y cells were established as the PD cell model. PD mouse model was established by MPTP. Gene expression in cells and tissues was tested by RT-qPCR. Cell viability and apoptosis were evaluated through CCK-8 and TUNEL assays. The interactions of RNAs were determined by RNA pull-down assay, RIP assay, and luciferase reporter assay. Circ_0054220 expressed at a high level in MPP-treated SH-SY5Y cells. Circ_0054220 inhibition promoted viability and suppressed apoptosis in MPP-stimulated cells. Furthermore, we found that circ_0054220 can competitively bind to miR-145 and miR-625 to upregulate high mobility group A1 (HMGA1) expression. HMGA1 was positively regulated by circ_0054220 and overexpressed in MPP-treated cells as well as the striatum (STR), substantia nigra pars compacta (SNpc), and serum of MPTP-induced mouse model of PD. HMGA1 overexpression counteracted the function of circ_0054220 silencing on cell apoptosis. Furthermore, HMGA1 inhibition notably alleviated motor dysfunction and increased the quantity of neurons in mice resembling PD. Circ_0054220 upregulates HMGA1 by the competitive endogenous RNAs (ceRNA) pattern to promote neural impairment in PD.

Association of 'Klotho' gene polymorphism with cerebral infarction.

Background: We aimed to investigate the expression of Klotho gene in peripheral blood of patients with cerebral infarction (CI) and the association of its polymorphisms with the occurrence of CI. Methods: A total of 60 CI patients (CI group) and 20 healthy people receiving physical examination (control group) were enrolled as the research subjects. The expression of Klotho gene in CI group and control group was determined using enzyme-linked immunosorbent assay kit. Single nucleotide polymorphisms (rs192031, rs200131 and rs102312) in the promoter region of the Klotho gene were typed via conformational difference gel electrophoresis. Besides, whether the distribution frequencies of Klotho genotypes conformed to Hardy-Weinberg equilibrium was evaluated by chi-square test. Meanwhile, the associations of Klotho alleles and gene polymorphisms with CI occurrence were analyzed. Results: The protein expression level of Klotho in the peripheral blood was remarkably lower in patients in CI group than that in control group (P<0.05).HardyWeinberg equilibrium analysis revealed that Klotho gene polymorphisms (rs192031, rs200131 and rs102312) conformed to the genetic equilibrium distribution (P>0.05). Gene-based association analysis manifested that only rs192031 polymorphism and alleles were correlated with CI occurrence (P<0.05). Systolic blood pressure and highdensity lipoprotein cholesterol were notably higher in CI patients with TT genotype of Klotho gene polymorphism rs192031 than those in control group (P<0.05). Furthermore, there were no associations of rs200131 and rs102312 polymorphisms and alleles with the occurrence of CI (P>0.05). Conclusions: The expression level of Klotho is evidently reduced in the peripheral blood of CI patients. Rs192031 in the promoter region of the Klotho gene is associated with the occurrence of CI, while rs200131 and rs102312 have no relations with CI.

Guillain-Barré syndrome following bacterial meningitis: a case report and literature review.

BACKGROUND: We reported a case of an adult that presented Guillain-Barré syndrome (GBS) after bacterial meningitis which was secondary to chronic suppurative otitis media (CSOM). To our knowledge, this is the first case involving an adult presenting with GBS following bacterial meningitis. CASE PRESENTATION: A 46-year man with type 2 diabetes and otitis media (OM) suffered with fever, headache, and vomiting for 6 days. The patient's neck stiffness was obvious and the Kernig and Brudzinski signs were produced. The result of cerebrospinal fluid (CSF) analysis and cytological examination of the CSF supported the diagnose of bacterial meningitis. On day 17 the patient felt numbness in both hands and feet, which gradually progressed to weakness of the limbs. Bladder dysfunction occurred, which required catheterization. The patient showed a tetraparesis with emphasis on the legs. The deep tendon reflexes of limbs were absent. The patient had peripheral hypalgesia and deep sensory dysfunction. The symptoms were possibly a result of GBS. Nerve conduction study showed that the F wave latency of the upper and lower limbs was prolonged, particularly the lower limbs. 8 days later the repeated nerve conduction study showed a low compound muscle action potential (3.3 mV) with a normal distal motor latency (14.2 ms) and a low motor nerve conduction velocity (34.3 m/s) in the tibial nerve. The patient still required assistance when walking 3 months after onset. CONCLUSIONS: GBS following bacterial meningitis is rare and limbs weakness in patients with bacterial meningitis was usually considered because of weakness. This case should serve as a reminder for clinical doctors that when a patient with bacterial meningitis complains about limbs numbness or weakness, GBS should be considered, especially when the patient had diabetes mellitus (DM) history.

[Analysis of the related risk factors of diabetic peripheral neuropathy].

OBJECTIVE: To explore the risk factors of diabetic peripheral neuropathy (DPN) and the relationship between DPN and diabetic retinopathy (DR). METHODS: The data of the in-patients with type 2 diabetes mellitus (T2 DM) were retrospectively studied. A total of 200 T2 DM patients were divided into DPN group (n = 136) and non-DPN group (n = 64) according to peripheral neuropathy. The basic clinical data and the incidence rate of DR were compared between two groups. Logistic regression analysis was used to study the risk factors of DPN. RESULTS: The course of disease, the level of BMI, glycosylated hemoglobin (HbA1c), 2 hour postprandial blood glucose (2 hPG), 2 hour glucose C peptide (2 hC-P) and the incidence rate of the DR were significantly different between two groups (P < 0.01). Logistic regression analysis showed that significant differences were observed in T2 DM complicated by DR (P = 0.023), the course of disease (P = 0.008), the level of HbA1c (P = 0.006), BMI (P = 0.000) and 2 hC-P (P = 0.065). CONCLUSION: Diabetic retinopathy, the course of disease, the level of BMI,HbA1c and 2 hC-P are the risk factors for type 2 diabetic peripheral neuropathy. Diabetic peripheral neuropathy is positive correlated with diabetic retinopathy.

[An EMD based epileptic spike detection method].

The automatic spike detection in EEG is significant in both diagnosing illness and alleviating the heavy labour force of the doctor. This paper proposes a new EMD based method to complete spike detection. It decomposes a signal into a few intrinsic mode functions (IMF), and then applies the nonlinear energy operator (NEO) to the first IMF to complete the automatic detection. Sufficient results are obtained by applying this method to the spike detection of the simulation signal and the real epileptic EEG signal.

[An EMD based time-frequency distribution and its application in EEG analysis].

Hilbert-Huang transform (HHT) is a new time-frequency analytic method to analyze the nonlinear and the non-stationary signals. The key step of this method is the empirical mode decomposition (EMD), with which any complicated signal can be decomposed into a finite and small number of intrinsic mode functions (IMF). In this paper, a new EMD based method for suppressing the cross-term of Wigner-Ville distribution (WVD) is developed and is applied to analyze the epileptic EEG signals. The simulation data and analysis results show that the new method suppresses the cross-term of the WVD effectively with an excellent resolution.

[Extraction of epileptic spike waves in EEG with B-spline wavelet].

The automatic detection of EEG spikes is important both in diagnosis and alleviating the hart work of doctors. This paper uses B-spline wavelet which does well in detecting break point to detect spike of epilepsy. Through experiment, the validity of the method is proved.