Objectives Bone defect is serious condition that is usually caused by traffic accident. Chitosan is a polymer developed as a scaffold to treat bone defect. However, the mechanism by which chitosan can accelerate bone growth in defect area is still unclear. This study aims to identify proteins which are crucial to the osteogenic properties of chitosan monomer using an in silico study. Methods Molecular docking was carried out on chitosan monomer, which are d-glucosamine and glucosamine 6-phosphate units against bone morphogenetic protein 2 (BMP-2), fibronectin, fibroblast growth factor (Fgf), and phosphate transporter (PiT) using AutoDock Vina. Ligand preparation was carried out using Chem3D version 15.0.0.106, while protein preparation was performed using AutoDockTools version 1.5.6. Results The results showed that glucosamine 6-phosphate had the best binding affinity with fibronectin and PiT, which was −5.7 kcal mol−1 on both proteins, while d-glucosamine had the best binding affinity with PiT (−5.2 kcal mol−1). Conclusions This study suggests that the osteogenic properties of chitosan may be due to the presence of bonds between glucosamine units and fibronectin and/or PiT. However, in vitro studies need to be done to prove this.
BackgroundOsteoarthritis (OA) is a chronic degenerative joint disease, characterized by physiological disorders, such as cartilage degradation, bone remodeling, osteophyte formation, and joint inflammation, which results in pain. Several studies have reported problems with the use of pain medications in OA, such as the use of a combination of many drugs and their long-term use. Therefore, this study was designed to evaluate the use of pain medications in OA patients. The study focused on the analysis of effectiveness and drug related problems (DRPs) with the category of drug interactions and adverse drug events (ADEs) in knee OA patients in Orthopedic and Traumatology Clinic, Universitas Airlangga Teaching Hospital, Surabaya, Indonesia.MethodsThe study used a retrospective approach through tracking and recording of the medical data from the period of 1st January to 30th June, 2018. The potential of drug interactions was determined by analyzing data based on literature. The actual side effects of the drug were identified based on the patient’s medical record through clinical data, laboratory data, and therapeutic data received by the patient. The study involved 143 subjects who met the inclusion criteria of 871 visits to the hospital.ResultsThe results showed that women as much as 80.42% with an age distribution of at most 46–65 years are the most affected by OA cases. The predominant history of illness and comorbidities in OA patients was hypertension in 58.74% of patients. The use of analgesic meloxicam had a percentage of 26.06%, sodium diclofenac 20.21%, mefenamic acid 4.36% and paracetamol 4.25%. The effectiveness of the use of pain reliever was characterized by a decrease in VAS in each patient at the beginning and at the end of the study, where a decrease in pain intensity occurred in 79.72% of patients who received pain medications. Based on drug interactions, we were able to identify pharmacodynamic interactions of 43 events (4.94%) and onine events of pharmacokinetic interactions (1.03%), with a minor severity of 7 events (0.80%),44 moderate events (5.05%), and one major event (0.11%). Mostly identified side effects of the drugs were those due to the use of non-steroid anti inflammatory drugs, which occurred in 42 events (4.82%).ConclusionsIt can be concluded that OA therapy with a number of pain relievers shows an adequate therapeutic response with some side effects and interactions both pharmacokinetically and pharmacodynamically.
Objectives Nonalcoholic fatty liver disease (NAFLD) is exceptionally common around the world. The development of NAFLD is increasing rapidly in the world, along with changes in lifestyle. Excess lipid intake is one of the risk factors for NAFLD. The NAFLD model is induced by a high-fat diet contains SFA, MUFA, and ῳ-6 PUFA. This study aims to assess the effect of high-fat diet variation on liver histology in developing NAFLD models in mice. Methods Thirty-six male mice (Balb/c) were divided into six groups fed a high-fat diet containing beef tallow 60%, beef tallow 45%, vegetable ghee, animal ghee + corn oil, vegetable ghee + corn oil for 28 days and compared to a control group fed a chow diet. All of the mice were fed with a high-fat diet in the form of pellets ad libitum for 28 days. Bodyweight and food intake were measured every day. At the last day of treatment, animals were sacrificed and the Liver were taken for histological analysis. Results This study showed that NAFLD model development was achieved in all group mice fed a high-fat diet with different degrees of NAFLD. Beef tallow 60% had the worst liver histology. Conclusions Thus, based on this study, we found that high-fat diet variations influenced the development of NAFLD models in mice, particularly concerning liver histology.
Objectives Histamine N-methyltransferase (HNMT) is an enzyme that plays a crucial role in the inactivation of histamine in central nervous system, kidneys and bronchi. Inhibition of HNMT is known to have a potential role in treating attention-deficit hyperactivity disorder, memory impairment, mental illness and neurodegenerative illnesses. Therefore, to find potential compounds that could be developed as novel HNMT inhibitors, this study conducted an in silico study of the secondary metabolites of Nigella sativa L and Curcuma xanthorrhiza Roxb. Methods In this study, we conducted a molecular docking study of 36 secondary metabolites of N. sativa L and 26 secondary metabolites of C. xanthorrhiza Roxb using an in silico approach targeting HNMT protein (PDB ID: 2AOT) using AutoDockVina software. The prediction of ADMET characteristics was done using the pkCSM Online Tool. Results This study obtained one metabolite from N. sativa L (longifolene) and seven metabolites from C. xanthorrhiza Roxb {(+)-beta-atlantone, humulene epoxide, (−)-beta-curcumene, (E)-caryophyllene, germacrone, (R)-(−)-xanthorrhizol, and (−)-beta-caryophyllene epoxide} which were predicted to have potential to be developed as HNMT inhibitors. Conclusions This study found several secondary metabolites of N. sativa L and C. xanthorrhiza Roxb which had activity as HNMT inhibitors. This research can likewise be utilized as a basis for further research, both in vitro, in vivo, and clinical trials related to the development of secondary metabolites from N. sativa L and C. xanthorrhiza Roxb as novel HNMT inhibitor compounds.
Background: Nicotine, a psychoactive compound from the tobacco plant, produces a reward effect that potentially causes addiction. It is postulated that nicotine addiction occurs through increased reactive oxygen species production in nucleus accumbens, which causes damage to the endogenous antioxidant defense system resulting in an increased need for nicotine intake, which leads to addiction. The antioxidants, andrographolide and epigallocatechin gallate (EGCG), are expected as potential substances to decrease the risk of nicotine addiction. This study aimed to analyze the effect of andrographolide and EGCG on the risk of addiction induced by nicotine and cigarette smoke extract (CSE) in mice. Methods: Thirty-five Balb/c male mice, divided into seven groups, were used in this study. The administered drugs were normal saline 1.0 mL/kg BW as control group, nicotine 0.5 mg/kg BW, CSE 1.0 mg/kg BW, andrographolide 50 mg/kg BW, and EGCG 50 mg/kg BW as pre-treatment. Conditioned place preference (CPP) with a biased design method was used to evaluate the reward effects induced by nicotine and CSE. Several stages were carried out, namely pre-conditioning, conditioning, post-conditioning, extinction, and reinstatement tests. Results: Based on the CPP score, both nicotine (p<0.001) and CSE (p<0.001) groups increased the reward effect significantly compared to that of the normal saline group. The andrographolide + nicotine (p<0.001) and EGCG + nicotine (p<0.001) groups decreased the reward effect significantly compared to that of the nicotine group without pharmacological treatment. Similarly, the andrographolide + CSE (p<0.001) and EGCG + CSE (p<0.01) groups decreased the reward effect significantly compared to that of the CSE group without pharmacological treatment. Conclusions: Andrographolide and EGCG lower the risk of addiction induced by nicotine and CSE.
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