Multi-population Black Hole Algorithm for the problem of data clustering.

The retrieval of important information from a dataset requires applying a special data mining technique known as data clustering (DC). DC classifies similar objects into a groups of similar characteristics. Clustering involves grouping the data around k-cluster centres that typically are selected randomly. Recently, the issues behind DC have called for a search for an alternative solution. Recently, a nature-based optimization algorithm named Black Hole Algorithm (BHA) was developed to address the several well-known optimization problems. The BHA is a metaheuristic (population-based) that mimics the event around the natural phenomena of black holes, whereby an individual star represents the potential solutions revolving around the solution space. The original BHA algorithm showed better performance compared to other algorithms when applied to a benchmark dataset, despite its poor exploration capability. Hence, this paper presents a multi-population version of BHA as a generalization of the BHA called MBHA wherein the performance of the algorithm is not dependent on the best-found solution but a set of generated best solutions. The method formulated was subjected to testing using a set of nine widespread and popular benchmark test functions. The ensuing experimental outcomes indicated the highly precise results generated by the method compared to BHA and comparable algorithms in the study, as well as excellent robustness. Furthermore, the proposed MBHA achieved a high rate of convergence on six real datasets (collected from the UCL machine learning lab), making it suitable for DC problems. Lastly, the evaluations conclusively indicated the appropriateness of the proposed algorithm to resolve DC issues.

Docetaxel-Loaded Poly(3HB-co-4HB) Biodegradable Nanoparticles: Impact of Copolymer Composition.

Polyhydroxyalkanoate (PHA) copolymers show a relatively higher in vivo degradation rate compared to other PHAs, thus, they receive a great deal of attention for a wide range of medical applications. Nanoparticles (NPs) loaded with poorly water-soluble anticancer drug docetaxel (DCX) were produced using poly(3-hydroxybutyrate-co-4-hydroxybutyrate), P(3HB-co-4HB), copolymers biosynthesised from Cupriavidus malaysiensis USMAA1020 isolated from the Malaysian environment. Three copolymers with different molar proportions of 4-hydroxybutirate (4HB) were used: 16% (PHB16), 30% (PHB30) and 70% (PHB70) 4HB-containing P(3HB-co-4HB). Blank and DCX-loaded nanoparticles were then characterized for their size and size distribution, surface charge, encapsulation efficiency and drug release. Preformulation studies showed that an optimised formulation could be achieved through the emulsification/solvent evaporation method using PHB70 with the addition of 1.0% PVA, as stabilizer and 0.03% VitE-TPGS, as surfactant. DCX-loaded PHB70 nanoparticles (DCX-PHB70) gave the desired particle size distribution in terms of average particle size around 150 nm and narrow particle size distribution (polydispersity index (PDI) below 0.100). The encapsulation efficiency result showed that at 30% w/w drug-to-polymer ratio: DCX- PHB16 NPs were able to encapsulate up to 42% of DCX; DCX-PHB30 NPs encapsulated up to 46% of DCX and DCX-PHB70 NPs encapsulated up to 50% of DCX within the nanoparticle system. Approximately 60% of DCX was released from the DCX-PHB70 NPs within 7 days for 5%, 10% and 20% of drug-to-polymer ratio while for the 30% and 40% drug-to-polymer ratios, an almost complete drug release (98%) after 7 days of incubation was observed.

Dengue protease inhibition activity of selected Malaysian medicinal herbs.

Dengue fever is one of major health problem around the world including Malaysia. It is caused by the arthropode-borne flavivirus and transmitted by the bite of the Aedes aegypti or Aedes albopictus mosquito infected with one of the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, or DENV-4). In this study, a screening exercise of various Malaysian medicinal plants showed that the extracts of Lawsonia inermis, Dryobalanops aromatica, Punica granatum, Zizyphus jujuba Lam. and Zingiber zerumbet exhibited potent inhibitory activity against NS2B-NS3 serine protease. The methanol extracts of Dryobalanops aromatica showed inhibition of 99.70 % at concentration of 200 µg/mL with IC50 value of 0.30 ± 0.16 µg/mL.

Dengue protease inhibition activity of selected Malaysian medicinal herbs

@#Dengue fever is one of major health problem around the world including Malaysia. It is caused by the arthropode-borne flavivirus and transmitted by the bite of the Aedes aegypti or Aedes albopictus mosquito infected with one of the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, or DENV-4). In this study, a screening exercise of various Malaysian medicinal plants showed that the extracts of Lawsonia inermis, Dryobalanops aromatica, Punica granatum, Zizyphus jujuba Lam. and Zingiber zerumbet exhibited potent inhibitory activity against NS2B-NS3 serine protease. The methanol extracts of Dryobalanops aromatica showed inhibition of 99.70 % at concentration of 200 μg/mL with IC50 value of 0.30 ± 0.16 μg/mL.

Prenylated xanthones from mangosteen as promising cholinesterase inhibitors and their molecular docking studies.

Garcinia mangostana is a well-known tropical plant found mostly in South East Asia. The present study investigated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of G. mangostana extract and its chemical constituents using Ellman's colorimetric method. Cholinesterase inhibitory-guided approach led to identification of six bioactive prenylated xanthones showing moderate to potent cholinesterases inhibition with IC50 values of lower than 20.5 µM. The most potent inhibitor of AChE was garcinone C while γ-mangostin was the most potent inhibitor of BChE with IC50 values of 1.24 and 1.78 µM, respectively. Among the xanthones, mangostanol, 3-isomangostin, garcinone C and α-mangostin are AChE selective inhibitors, 8-deoxygartanin is a BChE selective inhibitor while γ-mangostin is a dual inhibitor. Preliminary structure-activity relationship suggests the importance of the C-8 prenyl and C-7 hydroxy groups for good AChE and BChE inhibitory activities. The enzyme kinetic studies indicate that both α-mangostin and garcinone C are mixed-mode inhibitors, while γ-mangostin is a non-competitive inhibitor of AChE. In contrast, both γ-mangostin and garcinone C are uncompetitive inhibitors, while α-mangostin is a mixed-mode inhibitor of BChE. Molecular docking studies revealed that α-mangostin, γ-mangostin and garcinone C interacts differently with the five important regions of AChE and BChE. The nature of protein-ligand interactions is mainly hydrophobic and hydrogen bonding. These bioactive prenylated xanthones are worthy for further investigations.

Refinement of a low-resolution crystal structure to better understand erythromycin interactions on large ribosomal subunit.

Macrolides are a group of diverse class of naturally occurring and synthetic antibiotics made of macrocyclic-lactone ring carrying one or more sugar moieties linked to various atoms of the lactone ring. These macrolides selectively bind to a single high affinity site on the prokaryotic 50S ribosomal subunit, making them highly effective towards a wide range of bacterial pathogens. The understanding of binding between macrolides and ribosome serves a good basis in elucidating how they work at the molecular level and these findings would be important in rational drug design. Here, we report refinement of reconstructed PDB structure of erythromycin-ribosome system using molecular dynamics (MD) simulation. Interesting findings were observed in this refinement stage that could improve the understanding of the binding of erythromycin A (ERYA) onto the 50S subunit. The results showed ERYA was highly hydrated and water molecules were found to be important in bridging hydrogen bond at the binding pocket during the simulation time. ERYA binding to ribosome was also strengthened by hydrogen bond network and hydrophobic interactions between the antibiotic and the ribosome. Our MD simulation also demonstrated direct interaction of ERYA with Domains II, V and with C1773 (U1782EC), a residue in Domain IV that has yet been described of its role in ERYA binding. It is hoped that this refinement will serve as a starting model for a further enhancement of our understanding towards the binding of ERYA to ribosome.

Chemical reactivity as a tool to study carcinogenicity: reaction between estradiol and estrone 3,4-quinones ultimate carcinogens and guanine.

In this article we study the chemical reactions between guanine and two ultimate carcinogens, the 3,4-quinone forms of the estrogens estrone (E1) and estradiol (E2). DNA was truncated to guanine, i.e. no deoxyribose moiety was included. Due to a complex reaction that involves proton transfer via water molecules we applied linear free energy relationships rather than computation of the transition state and activation energies. The minima corresponding to reactants and products were obtained on the B3LYP/6-31G(d) level. The effects of hydration were considered using the solvent reaction field of Tomasi and co-workers and the Langevin dipoles model of Florian and Warshel. No significant difference in reaction free energy for the reaction involving estrone and estradiol metabolites was found, despite the fact that for the two substances different carcinogenic activities were reported. Differences in carcinogenicity may be therefore attributed to other types of interactions or reactions such as (i) specific interactions of the carbonyl or hydroxyl group with DNA giving rise to different activation free energies for the reactions, (ii) the reaction of depurination and subsequent effects on the DNA, (iii) enzymatic or nonenzymatic oxidation steps (P450, aromatase, peroxidases, O2) and detoxification reactions (catechol-O-methyl transferase, S-transferase), or (iv) binding of the hormone to its nuclear receptors.

Carboprost trometamol in the management of the third stage of labor.

OBJECTIVE: To compare carboprost trometamol with methylergometrine in managing the third stage of labor. METHOD: One hundred and fifty parturient women were randomly assigned to use carboprost trometamol or methylergometrine immediately after delivery. RESULT: Both the duration of the third stage and the mean blood loss were significantly less in the carboprost group than the methergine group (P < 0.001). CONCLUSION: Carboprost trometamol is a more potent uterotonic drug than methylergometrine. Reducing blood loss in parturient women is very important especially in cases where there is the likelihood of anemia.