OBJECTIVE: The current study aimed to model and verify the anti-Smo activity of berberine and its derivatives using a novel automated script.
METHOD: Based on the patented inventions filed on ADMET modelling until 2016, which also predicts ADMET parameters and binding efficiency indices for all molecules, a script was developed to run automated molecular docking for a large number of small molecules.
RESULTS: Berberine was found to interact with Lys395 of Smo receptor via hydrogen bonding and cation-π interactions. In addition, π-π interactions between berberine aromatic rings and two aromatic residues in the Smo transmembrane domain, Tyr394 and Phe484, were noted. Binding efficiency indices using an in silico approach to plot the Smo-specific binding potency of each ligand was performed. The mRNA level of Gli1 was studied as the outcome of Hh signalling pathway to show the effect of berberine on hedgehog signalling.
CONCLUSION: This study predicted the role of berberine as an inhibitor of Smo receptor, suggesting its effectiveness in hedgehog signalling during cancer treatment.
METHODS: The correlation of these variants to the plasma BDNF level among Malaysian MDD patients was assessed. A total of 300 cases and 300 matched controls recruited from four public hospitals within the Klang Valley of Selangor State, Malaysia and matched for age, sex and ethnicity were screened for BDNF rs6265, rs1048218 and rs1048220 using high resolution melting (HRM).
FINDINGS: BDNF rs1048218 and BDNF rs1048220 were monomorphic and were excluded from further analysis. The distribution of the alleles and genotypes for BDNF rs6265 was in Hardy-Weinberg equilibrium for the controls (p = 0.13) but was in Hardy Weinberg disequilibrium for the cases (p = 0.011). Findings from this study indicated that having BDNF rs6265 in the Malaysian population increase the odds of developing MDD by 2.05 folds (95% CI = 1.48-3.65). Plasma from 206 cases and 206 controls were randomly selected to measure the BDNF level using enzyme-linked immunosorbent assay (ELISA). A significant decrease in the plasma BDNF level of the cases as compared to controls (p<0.0001) was observed. However, there was no evidence of the effect of the rs6265 genotypes on the BDNF level indicating a possible role of other factors in modulating the BDNF level that warrants further investigation.
CONCLUSION: The study indicated that having the BDNF rs6265 allele (A) increase the risk of developing MDD in the Malaysian population suggesting a possible role of BDNF in the etiology of the disorder.
RESULTS: Assessment of the motor performance showed that, the forelimb grip strength was significantly (P<0.0001) greater in the WT mice compared to Ts1Cje mice regardless of gender. The average survival time of the WT mice during the hanging wire test was significantly (P<0.0001) greater compared to the Ts1Cje mice. Also, the WT mice performed significantly (P<0.05) better than the Ts1Cje mice in the latency to maintain a coordinated motor movement against the rotating rod. Adult Ts1Cje mice exhibited significantly (P<0.001) lower nerve conduction velocity compared with their aged matched WT mice. Further analysis showed a significantly (P<0.001) higher population of type I fibres in WT compared to Ts1Cje mice. Also, there was significantly (P<0.01) higher population of COX deficient fibres in Ts1Cje mice. Expression of Myf5 was significantly (P<0.05) reduced in triceps of Ts1Cje mice while MyoD expression was significantly (P<0.05) increased in quadriceps of Ts1Cje mice.
CONCLUSION: Ts1Cje mice exhibited weaker muscle strength. The lower population of the type I fibres and higher population of COX deficient fibres in Ts1Cje mice may contribute to the muscle weakness seen in this mouse model for DS.
METHODS: Molecular docking and molecular dynamics simulations were used for EGFR, p38, ERK1/2, and AKT. The effects of berberine and lapatinib on MAPK and PI3K pathways in MDA-MB231 and MCF-7 cells were evaluated using immunoflorescence assays, and the amounts of phosphorylated kinases were compared to total kinases after treating with different concentrations of berberine.
RESULTS: Simulations showed berberine accurately interacted with EGFR, AKT, P38, and ERK1/2 active sites in silico (scores = -7.57 to -7.92 Kcal/mol) and decreased the levels of active forms of corresponding enzymes in both cell lines; however, berberine binding to p38 showed less stability. Cytotoxicity analysis indicated that MDA-MB231 cells were resistant to berberine compared to MCF-7 cells [72 h IC50 = 50 versus 15 μM, respectively). Also, lapatinib strongly activated AKT but suppressed EGFR in MDA-MB231 cells. The activity of EGFR, AKT, P38, and ERK1/2 were affected by berberine; however, berberine dramatically reduced EGFR and AKT phosphorylation.
CONCLUSION: By way of its multikinase inhibitory effects, berberine might be a useful replacement for lapatinib, an EGFR inhibitor which can cause acquired drug resistance in patients.
SUBJECTS/METHODS: Vitamin D intake from both food and supplement of 217 pregnant women was assessed using a validated food frequency questionnaire. Hypothetical effect of expanded supplementation and food fortifications strategies were modelled using the consumption data.
RESULTS: The results revealed that more than half (67.7%) of pregnant women had inadequate vitamin D intake (RNI < 15 µg/day). The modelling results demonstrated the potential of universal provision of 10 µg/day of multivitamins supplements in increasing vitamin D intake. Moreover, mandatory fortification of both milk and malted drink at single level of 5 µg/serving would lead to increase in vitamin D intake of Malaysians, particularly pregnant women.
CONCLUSIONS: The outcome of this study can be used as a reference for public health professionals to re-evaluate the existing Malaysian food fortification policies and supplementation recommendation for vitamin D for pregnant women.