OBJECTIVE: The objective of this study is to search for more potent benzimidazole-based cholinesterase inhibitors, through the modification of the 1- and 2-positions of the benzimidazole core.
METHODS: Synthesis of compounds were carried out via a 4-step reaction scheme following a previously reported protocol. Structure-activity relationship of the compounds are established through in vitro cholinesterase assays and in silico docking studies. Furthermore, cytotoxicity and blood brain barrier (BBB) permeability of the compounds were also investigated.
RESULTS: Among the synthesised compounds, three of them (5IIa, 5IIb, and 5IIc) exhibited potent selective butyrylcholinesterase inhibition at low micromolar level. The compounds did not show any significant cytotoxicity when tested against a panel of human cell lines. Moreover, the most active compound, 5IIc, was highly permeable across the blood brain barrier.
CONCLUSION: In total 10 benzimidazole derivatives were synthesized and screened for their AChE and BuChE inhibitory activities. Lead compound 5Iic, represents a valuable compound for further development as potential AD therapeutics.
Objective: In this paper, we reported the identification of six differentially expressed proteins isolated from cancer cells, following exposure to the cytotoxic fern extracts.
Materials and Methods: The identities of these cancer proteins were determined by matrix-assisted laser desorption ionization time-of-flight protein sequencing.
Results: The cancer proteins were identified as follows: elongation factor 1-γ, glyceraldehydes-3-phosphate dehydrogenase, heat shock protein 90-β, heterogeneous nuclear ribonucleoprotein-A2/B1, truncated nucleolar phosphoprotein B23, and tubulin-β chain. To the best of our knowledge, this paper represents the first time these cancer proteins are being reported, following exposure to the aforementioned cytotoxic fern extracts.
Conclusion: It is hoped that further efforts in this direction could lead to the identification and development of target-specific chemotherapeutic agents.
SUMMARY: Cytotoxic fern extracts were tested in anti-cancer proteomic works.Six differentially-expressed cancer proteins were identified.Potential anti-cancer protein targets were reported. Abbreviations used: EF: Elongation factor; HRP: Horseradish peroxidase; HSP: Heat shock protein; MALDI: Matrix-assisted laser desorption/ionization.
RESULTS: Aqueous extracts of the leaves and rhizomes of Cyathea latebrosa, Dicranopteris curranii, Gleichenia truncata, and Phymatopteris triloba were analysed. P. triloba leaf extract had the highest contents of total flavonoids (118.6 mg/g dry matter), hydroxycinnamic acids (69.7 mg/g dry matter), and proanthocyanidins (29.4 mg/g dry matter). P. triloba leaf and rhizome extracts as well as G. truncata leaf extract inhibited the growth of both Gram-positive and Gram-negative bacteria. P. triloba leaf extract produced a minimum inhibitory concentration (MIC) value of 0.78 mg dry matter/mL when tested against Pseudomonas aeruginosa, which is 2.5-fold higher than that of ampicillin. Among all extracts, P. triloba leaf extract had the highest anti-glucosidase activity (EC50 = 56 μg dry matter/mL) and also the highest antioxidant potential based on DPPH radical scavenging and Ferric Reducing Antioxidant Power assays. Antioxidant activities of both the leaf and rhizome extracts correlated positively with total flavonoid and hydroxycinnamic acid contents (R(2) = 0.80-0.95). On the other hand, anti-glucosidase activity correlated with total proanthocyanidin contents in both the leaf and rhizome extracts (R(2) = 0.62-0.84).
CONCLUSIONS: In conclusion, highland ferns are potential sources of antibacterial agents, glucosidase inhibitors, and antioxidants.
METHODS: This study, which involved the caregivers of schizophrenia patients from a hospital in Kuala Lumpur, Malaysia, was comprised of three parts, namely in-depth interviews, a pilot study, and the validation of the developed questionnaire, known as Caregiver Cope (CgCopeTM).
RESULTS: Part A originally consisted of eight themes, and it was later modified to seven themes with four items each after discussions with some experts. Part B initially had 28 items derived from the seven themes in Part A, which were then reduced to six components after a factor analysis. Part C of the questionnaire consisted of 19 items, with six components (Distraction, Caring for patient, Venting, Religion, Recreation, and Social support) having a moderate to high reliability ranging from a Cronbach's alpha coefficient of 0.54 to 0.82. A factor analysis showed that the six factors of coping accounted for 62.36% of the total variance.
CONCLUSION: The CgCOPETM questionnaire is suitable for use among caregivers of schizophrenia patients. There is a need to further validate the instrument among caregivers of other patient populations.
METHODS: We assessed the use of composite outcomes in neonatal RCTs included in Cochrane Neonatal reviews published till November 2017. Two authors reviewed the components of the composite outcomes to compare their patient importance and computed the ratios of effect sizes and event rates between the components, with an a priori threshold of 1.5, indicating a substantial difference. Descriptive statistics were presented.
RESULTS: We extracted 7,766 outcomes in 2,134 RCTs in 312 systematic reviews. Among them, 55 composite outcomes (0.7%) were identified in 46 RCTs. The vast majority (92.7%) of composite outcomes had 2 components, with death being the most common component (included 51 times [92.7%]). The components in nearly three-quarters of the composite outcomes (n = 40 [72.7%]) had different patient importance, while the effect sizes and event rates differed substantially between the components in 27 (49.1%) and 35 (63.6%) outcomes, respectively, with up to 43-fold difference in the event rates observed.
CONCLUSIONS: The majority of composite outcomes in neonatal RCTs had different patient importance with contrasting effect sizes and event rates between the components. In patient communication, clinicians should highlight individual components, rather than the composites, with explanation on the relationship between the components, to avoid misleading impression on the effect of the intervention. Future trials should report the estimates of all individual components alongside the composite outcomes presented.
Results: 3,5-Dinitrosalicylic acid (DNS) method, FTIR, and GC-FID were employed to evaluate the reducing sugar concentration, functional groups of alcohol bonds and concentration of bioethanol, respectively. The two-way ANOVA results (p