ABSTRACT
Alzheimer's disease is one of the causes associated with the early stages of dementia. Nowadays, the main treatment available is to inhibit the actions of the acetylcholinesterase (AChE) enzyme, which has been identified as responsible for the disease. In this study, computational methods were used to examine the structure and therapeutic ability of chemical compounds extracted from Millettia brandisiana natural products against AChE. This plant is commonly known as a traditional medicine in Vietnam and Thailand for the treatment of several diseases. Furthermore, machine learning helped us narrow down the choice of 85 substances for further studies by molecular docking and molecular dynamics simulations to gain deeper insights into the interactions between inhibitors and disease proteins. Of the five top-choice substances, γ-dimethylallyloxy-5,7,2,5-tetramethoxyisoflavone emerges as a promising substance due to its large free binding energy to AChE and the high thermodynamic stability of the resulting complex.
Subject(s)
Acetylcholinesterase , Cholinesterase Inhibitors , Millettia , Molecular Docking Simulation , Molecular Dynamics Simulation , Phytochemicals , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/isolation & purification , Acetylcholinesterase/metabolism , Acetylcholinesterase/chemistry , Millettia/chemistry , Phytochemicals/chemistry , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Humans , ThermodynamicsABSTRACT
OBJECTIVE: The purposes of the study was to evaluate for the functional improvement of outcomes of patients undergoing surgical management for tongue cancer at varying periods after surgery. DESIGN: Case series with intervention. PARTICIPANTS: Thirty consecutive patients, from 2011 to 2015, with carcinoma of the tongue undergoing surgical resection and reconstruction with a radial forearm free flap. MAIN MEASURES: The Speech Intelligibility Test (SIT) is used for objective evaluation of speech function. The 7-point ordinal scale Functional Oral Intake Score (FOIS) was used to estimate the swallowing function. RESULTS: The patients included were 25 men and 5 women with a mean age of 50.4â¯years (range - 27-65). All tumors were squamous cell carcinomas and all patients underwent a hemiglossectomy. There were two complete flap failures, with a resultant flap success rate of 93.3%. The initial mean speech intelligibility scores at 1-month increased from 72.3⯱â¯0.2 to 77.7⯱â¯8.9 at 6-months after surgery (pâ¯=â¯0.05). Similarly, the mean score of swallowing function improved from 6.1 at 1-month to 6.8 at 6-months after surgery (pâ¯=â¯0.05). CONCLUSION: Reconstruction of hemiglossectomy defects with a radial forearm free flap offers functional benefits in speech and deglutition that demonstrate progressive improvement when 1- and 6-month post-surgical assessments are compared.
