Induction of Apoptosis by 2', 3’-Epoxyisocapnolactone and 8-Hydroxyisocapnolactone-2', 3’- Diol Isolated from Micromelum Minutum in Human T-Lymphocyte Leukemia Cem-Ss Cells

2',3'-epoxyisocapnolactone and 8-hydroxyisocapnolactone-2',3'-diol are two bioactive compounds isolated from the leaves of Mzcromelum minutum. The cytotoxic effect of the compounds was tested on a variety of human cell lines respectively using MTT assay. They were found to be most sensitive against human T-lymphoblastic leukemia cells (CEM-SS). The inhibition effect of 2',3'-epoxyisocapnolactone and 8- hydroxyisocapnolactone-2',3'-diol at 50% of cell population (ICso) was found to be 4.6 pg/ml (13.5 pM) and 3 pdml (7.8 pM) on CEM-SS cells, respectively. Besides that, the inhibitor effect of the compounds on other human cells were found to be 13.4 pdml(39.2 pM) and 9.0 pdml(23.9 pM) on cervical carcinoma cells (HeLa), 14.2 pg/ml (41.5 pM) and 7.7 pdml (20.5 pM) on colon adenocarcinoma cells (HT29), 7.4 pg/ml (21.6 pM) and 5.9 pdml (1 5.7 pM) on hepatocarcinoma cells (HepG2), 6.5 pglml (19.0 pM) and 7.1 pg/ml(18.9 pM) on transform liver cells (Chang). For comparative purposes, the ICW of several clinical cytotoxic drugs against CEM-SS cells were determined. The inhibitor effect of the compounds were more significant compared with methotrexate [ICm = >30 pg/ml (66.1 pM)], cytosine arabinoside [IC5o = >30 pg/ml (123.5 pM)] and colchicines [IC50 = 8 pglml (20.1 pM)] The compounds also shown near similar ICso concentration as compare with cis-diamine dichloroplatinum [IC50 = 3 pg/ml (10.1 pM)], vinorelbine [IC50 = 3 pg/ml (3.9 pM)] and doxorubicin [IC5o = 2.4 pg/ml (4.1 pM)]. Furthermore, from proliferation assay study, the compounds were significantly inhibiting the proliferation of cells at ICso value. From the morphological observation and agarose gel electrophoresis, apoptosis of the compounds on CEM-SS cells was determined. By using phase contrast, fluorescence and electron microcopies, observation on morphological alterations indicating apoptosis was evaluated. From DNA fragmentation, Acridine orange and Propidium iodide staining and DNA content analyses, the compounds were confirmed to have ability in promoting apoptosis. However, the percentage of apoptosis induced is low and the event is time-dependent. At high concentration of 10 pg/m, 2',3'- epoxyisocapnolactone and 8-hydroxyisocapnolactone-2',3'-diol induced necrosis. Furthermore, 8-hydroxyisocapnolactone-2',3'-diol also exhibited better cytotoxicity compared to 2',3'-epoxyisocapnolactone. The induction time for apoptosis by 8- hydroxyisocapnolactone-2',3'-diol in CEM-SS is earlier than 2',3'-epoxyisocapnolactone, which is 4 hours and 12 hours after treatment. Based on the results obtained, 2',3'- epoxyisocapnolactone and 8-hydroxyisocapnolactone-2',3'-diol are able to induced apoptosis

Effect on kacip fatimah (labisia pumila) water extract on mamographic density- a pilot study

Introduction Kacip Fatimah is a traditional herb that contains phytoestrogen and is commonly used by the Malay population in Malaysia to treat various gynecological illnesses. It is also used as an alternative to hormone replacement therapy due to its estrogenic effect. Postmenopausal hormone use is associated with increase in mammographic density and mammographic density is an independent risk factor for breast cancer. Objective Our purpose was to evaluate the effect of Kacip Fatimah (Labisia pumila) water extract on mammographic density in postmenopausal women. Material and Method A prospective, randomized, double-blind placebo-controlled pilot study was conducted. A total of 69 postmenopausal women were equally randomized to receive Kacip Fatimah water extract 140 mg/day, 280 mg/day, 560 mg/day or placebo. Mammograms were performed at baseline and after 6 months of treatment. Mammographic density was evaluated according to percentage scale, BIRAD classification and computer assisted measurement of breast density. Result The categorical assessments showed that there was no significant shift in categorical classification as assessed by BIRAD and percentage categories in either control or treatment groups. There was slight increase in breast density as assessed by computer assisted method although the increases were not statistically significant. The increases in breast density over pretreatment baseline were 0.2 °/o, 0.1 %, 1.5 % and 0.6 % for placebo, 140 mg group, 280 mg group and 560 mg group, respectively. These values were not significantly different from one another. This small increase in breast density might be due to the fact that phytoestrogen is a weak estrogen. Conclusion Kacip Fatimah extract given over a period of 6 months did not significantly affect mammographic density

Improved dielectric performance of barium strontium titanate multilayered capacitor by means of pulsed laser deposition and slow injection sol-gel methods

A Pt/BST/NiFe/Cu multilayered capacitor was fabricated incorporating a polycrystalline Ba0.5Sr0.5TiO3 (BST) film deposited using the pulsed laser deposition technique. Qualitative X-ray diffraction analysis confirmed a perovskite structure for the deposited BST dielectric films which were fired at various temperatures. No intermediate phase was discernable with a post-annealing temperature of 750°C and highly crystallized thin film was obtained at a post-annealing temperature of 800°C. The fabricated capacitor with a BST film thickness of 665 nm exhibited respectable electrical performance with a dielectric constant, k of 657 and a dielectric loss, tan δ = 0.0137 at room temperature at an applied frequency of 1 MHz. The recorded charge storage density and leakage current density were 4.6 μC cm-2 and 33 nA cm-2, respectively, with ±5 V bias

Biological activity of palladium(II) and platinum(II) complexes of the acetone Schiff bases of S-methyl- and S-benzyldithiocarbazate and the X-ray crystal structure of the [Pd(asme)2] (asme=anionic form of the acetone Schiff base of S-methyldithiocarbazate) complex

Palladium(II) and platinum(II) complexes of general empirical formula, [M(NS)2] (NS=uninegatively charged acetone Schiff bases of S-methyl- and S-benzyldithiocarbazate; M=PtII and PdII) have been prepared and characterized by a variety of physicochemical techniques. Based on conductance, IR and electronic spectral evidence, a square-planar structure is assigned to these complexes. The crystal and molecular structure of the [Pd(asme)2] complex (asme=anionic form of the acetone Schiff base of S-methyldithiocarbazate) has been determined by X-ray diffraction. The complex has a distorted cis-square planar structure with the ligands coordinated to the palladium(II) ions as uninegatively charged bidentate NS chelating agents via the azomethine nitrogen and the mercaptide sulfur atoms. The distortion from a regular square-planar geometry is attributed to the restricted bite angles of the ligands. Antimicrobial tests indicate that the Schiff bases exhibit strong activities against the pathogenic bacteria, Bacillus subtilis (mutant defective DNA repair), methicillin-resistant Staphylococcus aureus, B. subtilis (wild type) and Pseudomonas aeruginosa and the fungi, Candida albicans (CA), Candida lypotica (2075), Saccharomyces cerevisiae (20341) and Aspergillus ochraceous (398)—the activities exhibited by these compounds being greater than that of the standard antibacterial and antifungal drugs, streptomycin and nystatin, respectively. The palladium(II) and platinum(II) complexes are inactive against most of these organisms but, the microbe, Pseudomonas aeruginosa shows strong sensitivity to the platinum(II) complexes. Screening of the compounds for their cytotoxicities against T-lymphoblastic leukemia cancer cells has shown that the acetone Schiff base of S-methyldithiocarbazate (Hasme) exhibits a very weak activity, whereas the S-benzyl derivative (Hasbz) is inactive. However, the palladium(II) complexes exhibit strong cytotoxicities against this cancer; their activities being more than that of the standard anticancer drug, tamoxifen. The [Pt(asme)2] complex exhibits a very weak cytotoxicity, whereas [Pt(asbz)2] is inactive against leukemic cells

Jerantinine A induces tumor-specific cell death through modulation of splicing factor 3b subunit 1 (SF3B1)

Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents. Jerantinine A (JA) is a novel indole alkaloid which displays potent anti-proliferative activities against human cancer cell lines by inhibiting tubulin polymerization and inducing G2/M cell cycle arrest. Using a combined pooled-genome wide shRNA library screen and global proteomic profiling, we showed that JA targets the spliceosome by up-regulating SF3B1 and SF3B3 protein in breast cancer cells. Notably, JA induced significant tumor-specific cell death and a significant increase in unspliced pre-mRNAs. In contrast, depletion of endogenous SF3B1 abrogated the apoptotic effects, but not the G2/M cell cycle arrest induced by JA. Further analyses showed that JA stabilizes endogenous SF3B1 protein in breast cancer cells and induced dissociation of the protein from the nucleosome complex. Together, these results demonstrate that JA exerts its antitumor activity by targeting SF3B1 and SF3B3 in addition to its reported targeting of tubulin polymerization

Cyclic Tetrapyrrolic Photosensitisers from the leaves of Phaeanthus ophthalmicus

<p>Abstract</p> <p>Background</p> <p>Twenty-seven extracts from 26 plants were identified as photo-cytotoxic in the course of our bioassay guided screening program for photosensitisers from 128 extracts prepared from 64 terrestrial plants in two different collection sites in Malaysia - Royal Belum Forest Reserve in the State of Perak and Gunung Nuang in the State of Selangor. One of the photo-cytotoxic extracts from the leaves of <it>Phaeanthus ophtalmicus </it>was further investigated.</p> <p>Results</p> <p>The ethanolic extract of the leaves from <it>Phaeanthus ophtalmicus </it>was able to reduce the <it>in vitro </it>viability of leukaemic HL60 cells to < 50% when exposed to 9.6 J/cm²of a broad spectrum light at a concentration of 20 μg/mL. Dereplication of the photo-cytotoxic fractions from <it>P. ophthalmicus </it>extracts based on TLC R_fvalues and HPLC co-injection of reference tetrapyrrolic compounds enabled quick identification of known photosensitisers, pheophorbide-<it>a</it>, pheophorbide-<it>a </it>methyl ester, 13²-hydroxypheophorbide-<it>a </it>methyl ester, pheophytin-<it>a </it>and 15¹-hydroxypurpurin 7-lactone dimethyl ester. In addition, compound <b>1 </b>which was not previously isolated as a natural product was also identified as 7-formyl-15¹-hydroxypurpurin-7-lactone methyl ester using standard spectroscopic techniques.</p> <p>Conclusions</p> <p>Our results suggest that the main photosensitisers in plants are based on the cyclic tetrapyrrole structure and photosensitisers with other structures, if present, are present in very minor amounts or are not as active as those with the cyclic tetrapyrrole structure.</p

Towards fast and scalable detection of attack clones in Android applications

The mobile operating system Android gains popularity among smartphone users as they gradually integrate their lifestyle with apps that provide services for their convenience which includes entering sensitive information such as bank account numbers, credit card numbers, and passwords into the apps. As such, Android is also gaining popularity in becoming the target for malicious attacks to steal such information. Despite studies and researches on methods to increase detection of malware components in suspected apps, malware are evolving and becoming more elusive to such methods. The purpose of this project is to look at existing techniques which summarize and identify malware apps with accuracy and scalability. We will also be looking at Software Architecture Recovery techniques used to accurately identify and decouple modules in a mobile application. By decoupling the modules in the app, the components can be differentiated into ad libraries and malware parts of the app. An approach which integrates existing techniques to build a system is proposed in this project. The existing techniques include generating centroids, which are representatives of methods in a class program, and using Application Similarity Degree to compare the degree of similarity between two apps. There is also Module Decoupling which decouples an app into clusters of modules which are highly similar. Soot, a third party library which provides intermediate representation of Java class files in Jimple and has the capability to perform static program analysis on programs, is used extensively in implementing the existing techniques discussed. After evaluating the system with valid tests from six different malware families and dataset of 212 ad libraries and 2468 variants of malware, the system was able to accurately identify most of the malware and ad library components from within the test apps. There were some errors which indicates that the system requires some fine-tuning such as the means of calculating the self-similarity for Affinity Propagation clustering.Bachelor of Engineering (Computer Science