In this study, a series of novel ferulic and caffeic acid dimers was designed and synthesised, and their multifunctional properties against Alzheimer's disease (AD) were evaluated. Results showed that our multifunctional strategy was great supported by enhancing the inhibition of Aβ self-induced aggregation. Moreover, 7b also had potent protective effects against glutamate-induced cell death without significant cell toxicity in mouse hippocampal neuronal HT22 cells and 10c effectively scavenged diphenylpicrylhydrazyl free radicals. Collectively, these data strongly encourage further optimisation of 7b as a new hit to develop multifunctional agents for the treatment of AD.
Background: Irritable bowel syndrome is a chronic functional gastrointestinal disease, of which diarrheapredominant irritable bowel syndrome (IBS-D) is a common subtype. In China, acupoint application therapy is currently widely used as an effective complementary therapy for IBS-D. In the clinical management of IBS-D, acupoint application is usually combined with other therapies, including acupuncture, moxibustion, and Chinese herbal and Western medicine. However, at present, evidence regarding the most effective options for treating IBS-D is insufficient. Therefore, this protocol proposes a systematic review and network meta-analysis for evaluating the effectiveness of acupoint application and its combination therapies in treating IBS-D, and for identifying the acupoint application-related treatments with the highest probability of being the best intervention.Methods: Six English electronic databases (PubMed, Ovid MEDLINE, Scopus, Web of Science, the Cochrane Library, and EMBASE), four Chinese electronic databases [China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (CQVIP), WanFang, and SinoMed), and one Japanese medical database (Citation Information by National Institute of Informatics (CiNii)] will be searched for eligible randomized controlled trials from their inception to June 1, 2022. The efficacy and safety of acupoint application therapy and its combination therapies for patients with IBS-D will be evaluated. The STATA 14.0 (StataCorp, USA) software package will be used for the meta-analysis.A Bayesian NMA will be performed using R (version 4.0.2) and Aggregate Data Drug Information System (ADDIS, version 1.16.8) software packages. Bias risk will be assessed using the Cochrane Collaboration's risk of bias tool; specifically, publication bias will be evaluated using Egger's test and funnel plots. The rank probabilities of various outcomes for each intervention will be calculated, clustered, and ranked using the cumulative ranking curve method. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method will be employed to assess the certainty of evidence for NMA outcomes.Discussion: This study will aim to determine the clinical efficacy of acupoint application therapy and its combined therapy in the treatment of IBS-D and provide an evidence-based foundation for identifying the best acupoint application program.
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