Inhibitory effects of ß-asarone on lncRNA BACE1-mediated induction of autophagy in a model of Alzheimer's disease.

The primary aim of this study was to examine the correlation between the formation of Aß plaques and autophagy, which is regulated by ß-asarone and the lncRNA BACE1-AS. Additionally, the study sought to explore potential targets of the drug in inhibiting the deposition of toxic AD-related proteins and restoring impaired mitochondrial and autophagic functions. SHY5Y cells were utilized to construct a stable Alzheimer's disease (AD) model, followed by the utilization of interference and overexpression lentiviruses targeting BACE1-AS to establish a cell model. The cells were categorized into five groups, including a normal group, siRNA/BACE1 group, and ß-asarone group. The fluorescence quantitative PCR technique was employed to assess the disparity in BACE1 mRNA expression, while changes in immunofluorescence (IF) were observed to determine the stable interference titre and action time of the lentiviruses. Additionally, western blotting (WB) and fluorescence quantitative PCR were employed to evaluate the expression of proteins and mRNAs associated with AD and autophagy. The findings demonstrated a significant elevation in BACE1 expression levels in brain tissue among individuals with AD compared to those without the condition. Moreover, the results indicated that the introduction of ß-asarone led to an increase in the expression of the BACE1-AS gene in the cell group transfected with plasmid H12732. Furthermore, it was observed that ß-asarone enhanced the expression levels of shRNA and BACE1 after 72 h. In contrast, ß-asarone suppressed the expression of PS1, Aß, BACE1, APP, and p62, while promoting the expression of syn, LC3 I/II, and Beclin-1. Based on these findings, it can be concluded that ß-Asarone exerts a comprehensive influence on the expression of proteins associated with AD and synaptic function. ß-Asarone exhibits the potential to mitigate Aß deposition by impeding the expression of lncBACE1, thereby facilitating autophagy through the suppression of BACE1's inhibitory impact on autophagy. This complements the self-enhancing effect of autophagy.

A study on the effects of the Qihuang Needle therapy on patients with Parkinson's disease.

Objective: This study aimed to evaluate the effectiveness of the Qihuang Needle (QHN) in treating Parkinson's disease (PD). Design setting and participants: The trial was an 8-week randomized clinical trial (4 weeks of treatment followed by 4 weeks of follow-up) conducted from January 2021 to July 2022 in outpatient settings at three clinical sites in Guangzhou, China. Thirty-four participants with PD were diagnosed based on the diagnostic criteria formulated by the brain bank of the British Parkinson's Disease Society in 1992. Interventions: Patients in the treatment and control groups received six sessions within 4 weeks of the QHN therapy or the sham acupuncture therapy (two times per week for the first two consecutive weeks and one time per week for the following two consecutive weeks). Main outcomes and measures: The primary outcome measure was the change in the Parkinson's Disease Rating Scale-Part III Motor Examination (UPDRS III) between baseline and 8 weeks after treatments. Secondary outcome measures were the Non-Motor Symptoms Scale for Parkinson's Disease (NMSS) and Parkinson's Disease Daily Quality of Life-39 (PDQ-39). Real-time shear wave elastography (SWE) was assessed for each patient at baseline and during the 4-week period as the third outcome measure. Results: A more significant reduction of UPDRS III score, PDQ-39, NMSS, and SWE was observed in the QHN group than in the sham acupuncture group. Conclusions: The QHN therapy consistently demonstrated superiority and produced clinically meaningful benefits in reducing motor and non-motor symptoms, as well as significantly improving muscle stiffness, in patients with PD.

Stability and bioactivity studies on dipeptidyl peptidase IV resistant glucogan-like peptide-1 analogues.

Glucagon-like peptide-1 (GLP-1) was once considered as an ideal anti-diabetic candidate for its important role in maintaining glucose homeostasis through the regulation of islet hormone secretion, as well as hepatic and gastric function. However, the major therapeutic obstacle for using native GLP-1 as a therapeutic agent is its very short half-life primarily due to their degradation by the enzyme dipeptidyl peptidase IV (DPP-IV). In this study, GLP-1 analogues with modifications in amino acid site 8, 22 and 23 were synthesized using solid phase peptide synthesis. Resistance of these analogues to DPP-IV cleavage was investigated in vitro by incubation of the peptides with DPP-IV or human plasma. Glucoregulating efficacy of the analogues was evaluated in normal Kunming mice using intraperitoneal glucose tolerance model. Glucose lowering effect of combination therapy (analogue plus Vildagliptin) has also been studied. In vitro studies showed that the modified analogues were much more stable than native GLP-1 (nearly 100% of the peptide keep intact after 4 h incubation). In vivo biological activity evaluation revealed that His8-EEE (the most potent GLP-1 analogues in this study) exhibited significantly improved glycemic control potency (approximately 4.1-fold over saline and 2.5-fold over GLP-1) and longer time of active duration (at least 5 h). Combination therapy also showed the trend of its superiority over mono-therapy. Modified analogues showed increased potency and biological half-time compared with the native GLP-1, which may help to understand the structure-activity relationship of GLP-1 analogues.