A gain of function p53 gene mutant promotes growth suppression in human liver cancer cells

Primary liver cancer is one of the most common cancer in the world with highest cancer mortality rate. The most common type of primary liver cancer is hepatocellular carcinoma (HCC). There are many risk factors for liver cancer and currently available treatments for HCC are largely inadequate. Gene mutation and dysfunction of p53 are common and is recognized as an important molecular event in hepatocarcinogenesis. Therefore, replacement of the aberrant p53 gene is an attractive approach in the treatment of HCC providing an alternative treatment for primary HCC. In this study, we assessed whether the transfection with wild-type p53 gene is able to restore the pro-apoptotic effects and evaluate the feasibility of gene therapy in fixing a faulty p53 molecule. We established a non-viral cationic lipid-based p53 gene delivery into two human HCC cell lines namely HLF and PLC/PRF/5 cells. Both cell lines have mutations in the p53 gene. We compared the results with the normal liver cell line, WRL68, that constitutively expresses the wild-type p53 gene. In this study, the introduction of wild-type p53 gene into HLF and PLC/PRF/5 cells resulted in an increased of p53 gene expression, protein expression and cells growth inhibition shown in MTS reduction cell viability assay, FITC-Annexin V and PI apoptosis assay, western blot and caspase activity assay. In summary, the study provides a promising therapeutic approach for p53 gene delivery into HCC patients. The p53 gene delivery can be instituted together with chemotherapy as a combination treatment to induce apoptosis

Screening for HLA-B*1502 Polymorphism in Febrile Seizure Predicted Lead to Epilepsy

Mutation in neuronal sodium channel -1-subunit gene (SCN1A) and neuronal sodium channel -1-subunit gene (SCN1B) has been linked with forms of generalized epilepsy with febrile seizure plus (GEFS+) and epileptic infantile syndrome like severe myoclonic epilepsy of infancy (SMEI) (Mulley et al., 2005; Scheffer et al., 2007). Since this idiopathic epilepsy typically begins with prolonged febrile seizures (FS) in the first year of life, therefore febrile seizure patient with mutation in SCN1A has a high risk to develop epilepsy on their later life (Dube et al., 2009). Carbamazepine (CBZ) has been known as the most common anti-epileptic drug which can cause Steven-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients with HLA-B*1502 polymorphism. Since the Javanese population have 16,67% of these allele, studying the presence of these allele in patients predicted epilepsy is important. Furthermore, this study was intended to develop a PCR-based diagnostic protocol to screen HLA-B*1502 polymorphism in epileptic patients to prevent SJS/TEN by carbamazepine. Focusing on epileptic predicted patients, HLA-B*1502 genotyping by sequence specific primer (SSP)-PCR was performed on 31 repeated FS patients with mutation in SCN1A and SCN1A/SCN1B gene. The result show that the HLA-B*1502 polymorphism was detected in 14 (45,2%) individuals including 8 cases related to mutation SCN1A gene and 6 to SCN1A/SCN1B gene. It illustrates that HLA-B*1502 allele is frequent in these patients. It can thus be suggested that detection of this allele should be done before epilepsy treatment. Later, patients with this allele should avoid CBZ to prevent SJS/TEN during drug administration

Blood lead concentrations and the Neuropsychology scores of pregnant women in Klang Valley Malaysia

Pregnant women with high blood lead posed high risk to their fetus as placental transfer can occurs to the fetus. The objective of this study was to identify the relationship between blood lead and the neuropsychological score of women who were in their 3rd trimester of pregnancy. These respondents were undergoing a routine antenatal checkup at a teaching hospital located in Klang Valley areas. Blood lead concentrations were analyzed using graphite furnace Atomic Absorption Spectrophotometer (AAS). The neuropsychological scores were measured with WHO Neurobehavioral Core Test battery (NCTB). The test consists of 7 items, which made up of the Digit Symbol, Trail Making, Digit Span, Benton Visual Retention Test, Pursuit Aiming, Santa Ana Manual Dexterity, Reaction Time and Movement Time tests. The mean blood lead was 7.78±4.77 µg/dL. The mean score for the total NCTB test was 50.00±5.24. Statistical analysis showed blood lead concentrations were inversely correlated with the total NCTB score (r= –0.462, p≤0.01). The correlation was about 21.3%. The General Linear Model (GLM) showed that age (β= –0.15, p=0.017), weight (β=2.67, p=0.05) and height (β=–1.97, p=0.05) also influence the total neuropsychological scores. In conclusion, blood lead reduces the total neuropsychological scores. The scores for each of the 7 items were inversely and significantly correlated with blood lead concentrations except for the Trail Making and Santa Ana Manual Dexterity tests

Assessing the Nutritional Status of Children with Leukemia from Hospitals in Kuala Lumpur

A cross-sectional study was carried out to evaluate the nutritional status of 51 subjects with leukemia aged 4 to 12 years from the Haematology & Oncology Paediatric Ward, Universiti Kebangsaan Malaysia Medical Centre (PPUKM) and the Paediatric Institute of Kuala Lumpur. Nutritional status was assessed using anthropometric measurements, biochemical and haematological parameters. Subjects comprised 32 (62.7%) males and 19 (27.3%) females. Most of the subjects (41.2%) were in the age group of 4 to 6 years. More than half of the children were Malays (70.6%) followed by Indians (15.7%) and Chinese (13.7%). The subjects were diagnosed as acute lymphoblastic leukemia (ALL) (84.3%) followed by acute myelogenous leukemia (AML) (13.7%) and chronic myelogenous leukemia (CML) (2.0%) respectively. Most of the children were in remission status (54.9%). Underweight (<-2 SD for weight-for-age) was observed in 37.3% of the children while 17.6% of them were stunted (<-2 SD for height-for-age), and sign(s) of malnutrition (<-2 SD) for mid upper arm circumference (MUAC)-for-age was observed in 15.7% of the subjects. Approximately 20.0% of the subjects were in the severe malnutrition category with respect to low serum albumin levels (<3.5g/dl). All subjects had hemoglobin levels of less than the normal range. While the results indicated no significant differences in the nutritional status of subjects with leukemia at different stages of treatment, it was observed that the prevalence of malnutrition was higher in children with newly diagnosed leukemia. Thus, the nutritional status of children with leukemia should be monitored closely as there is a likelihood of deterioration owing to the disease

NFIX as a Master Regulator for Lung Cancer Progression

About 40% of lung cancer cases globally are diagnosed at the advanced stage. Lung cancer has a high mortality and overall survival in stage I disease is only 70%. This study was aimed at finding a candidate of transcription regulator that initiates the mechanism for metastasis by integrating computational and functional studies. The genes involved in lung cancer were retrieved using in silico software. 10 kb promoter sequences upstream were scanned for the master regulator. Transient transfection of shRNA NFIXs were conducted against A549 and NCI-H1299 cell lines. qRT-PCR and functional assays for cell proliferation, migration and invasion were carried out to validate the involvement of NFIX in metastasis. Genome-wide gene expression microarray using a HumanHT-12v4.0 Expression BeadChip Kit was performed to identify differentially expressed genes and construct a new regulatory network. The in silico analysis identified NFIX as a master regulator and is strongly associated with 17 genes involved in the migration and invasion pathways including IL6ST, TIMP1 and ITGB1. Silencing of NFIX showed reduced expression of IL6ST, TIMP1 and ITGB1 as well as the cellular proliferation, migration and invasion processes. The data was integrated with the in silico analyses to find the differentially expressed genes. Microarray analysis showed that 18 genes were expressed differentially in both cell lines after statistical analyses integration between t-test, LIMMA and ANOVA with Benjamini-Hochberg adjustment at p-value &lt; 0.05. A transcriptional regulatory network was created using all 18 genes, the existing regulated genes including the new genes PTCH1, NFAT5 and GGCX that were found highly associated with NFIX, the master regulator of metastasis. This study suggests that NFIX is a promising target for therapeutic intervention that is expected to inhibit metastatic recurrence and improve survival rate

Marketing in Malaysian Technology Firms

Today’s world technology recognizes Internet and World Wide Web as two of the main communication mediums in technology firms. modern technology and social networking turn out to be a part of a large number of people’s lives. technology firms are challenged with this fast-moving social network in organization that encourage viral marketing too. There has been little study about the effect of viral marketing towards technology firms. This paper aims to explore the factors that influence the effectiveness of viral marketing, determine the most influential factor and identify the impacts of onlinecontents that influence the effectiveness of viral marketing. a quantitative method was used and 384 respondents from Southern Region Malaysia participated in the survey. The results showed that all the motivational factors like playfulness, community-driven, perceived ease of use, and perceived usefulness had significant impact on the viral marketing in the Malaysian technology firms. Two other factors like critical mass and peer pressure were found to be insignificant in this study. The findings may contribute to the judgement on Malaysian technology firms about viral marketing that blend firm skills, knowledge and technical leadership roles to manage emerging technologies, develop innovative solutions and complex firm’s problems

METABOLITES PROFILE OF COLORECTAL CANCER CELLS AT DIFFERENT STAGES

Objective: The aim of this study is to characterize the metabolite profiles of colorectal cancer (CRC) cells of different stages of the disease to understandthe pathophysiological changes that may help to identify prevention strategies as well as the sites for potential therapeutic drug actions.Methods: Six CRC cell lines of different stages (classified using the Dukes classification) were used, and they are SW 1116 (stage A), HT 29 and SW480 (stage B), HCT 15 and DLD-1 (stage C), and HCT 116 (stage D). Metabolites were extracted using methanol and water, and metabolic profiling wasperformed using liquid chromatography-mass spectrometry. Mass profiler professional software was used for statistical analysis.Results: There were 111,096 compounds detected across the samples, and 24 metabolites were identified to be significantly different betweenthe CRC stages. Most notably, there were eight metabolites that were significantly upregulated in the more advanced stages (B, C, and D) comparedwith Stage A. These metabolites include flavin mononucleotide, l-methionine, muricatacin, amillaripin, 2-methylbutyroylcarnitine, lumichrome,hexadeconoic acid, and lysoPE (0:0/16:0).Conclusion: This study showed that the expressions of metabolites at different stages of CRC were different, which represent the metabolic changesoccurring as CRC advances. The knowledge may help identify biomarkers for the staging of CRC, which could improve its prognosis as well as providea basis for the development of therapeutic interventions

Regulatory Non-coding RNAs Network in Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) spectrum comprises simple steatosis and non-alcoholic steatohepatitis (NASH) that can lead to fibrosis and cirrhosis. The patients usually have no history of excessive alcohol consumption and other etiologies that can cause fatty liver. Understanding of the pathophysiology of NAFLD has revealed that non-coding RNAs (ncRNAs) play significant roles in modulating the disease susceptibility, pathogenesis and progression. Currently, the ncRNAs are grouped according to their sizes and their regulatory or housekeeping functions. Each of these ncRNAs has a wide range of involvement in the regulation of the genes and biological pathways. Here, we briefly review the current literature the regulatory ncRNAs in NAFLD pathogenesis and progression, mainly the microRNAs, long non-coding RNAs and circular RNAs. We also discuss the co-regulatory functions and interactions between these ncRNAs in modulating the disease pathogenesis. Elucidation of ncRNAs in NAFLD may facilitate the identification of early diagnostic biomarkers and development of therapeutic strategies for NAFLD

Pembangunan usahawan di sektor perikanan Malaysia

Pada masa kini, dasar baru kerajaan telah menekankan semula kepentingan sektorn pertanian sebagai penggerak pembangunan ekonomi negara seiring dengan sektor perindustrian dan sektor perkhidmatan.Salah satu sub-sektor yang penting dalam sektor pertanian adalah bidang perikanan.Bagi merealisasikan matlamat tersebut, penglibatan pihak yang terlibat dengan pembangunan sektor perikanan, seperti Lembaga Kemajuan Ikan Malaysia (LKIM) dan Persatuan-persatuan Nelayan (PN) adalah penting.Kajian ini bertujuan mengkaji secara umum keberkesanan PN dalam bidang keusahawanan.Di samping itu kajian secara khususnya mengenalpasti faktor-faktor yang mempengaruhi sikap kecenderungan keusahawanan di kalangan Ahli Lembaga Pengarah (ALP) Persatuan-persatuan nelayan kawasan (PNK), negeri (PNN) dan pusat (NEKMAT).Kajian ini cuba menganalisis keberkesanan program Pembangunan Usahawan yang dijalankan oleh PNK, PNN dan NEKMAT dan mengenalpasti peluang-peluang perniagaan yang dijalankan di peringkat kebangsaan dan antarabangsa bagi produk perikanan terutama sekali dalam aktiviti-aktiviti perniagaan yang dijalankan pada masa kini.Pengumpulan data bagi kajian ini adalah melalui pengedaran borang soalselidik kepada 280 orang Ahli lembaga Pengarah Persatuan Nelayan yang di pilih secara rawak mudah dan temubual mendalam (in-depth interview) di beberapa buah PNK, PNN dan NEKMAT.Penganalisaan data dibuat dengan menggunakan analisis deskriptif, ujian-t, ANOVA, MANOVA, Diskriminan serta kajian kes.Analisis deskriptif digunakan bagi mendapatkan kekerapan, peratusan dan min responden, manakala ujian-T dan ANOVA digunakan untuk melihat perbezaan min berdasarkan sikap kecenderungan keusahawanan di kalangan Ahli Lembaga Pengarah PNK,PNN dan NEKMAT.Ujian MANOVA dan analisis Diskriminan digunakan bagi mengkaji pengelasan Pengurus dan Bukan Pengurus (Pengerusi dan Ahli-ahli Lembaga Pengarah) PNK, PNN dan NEKMAT terhadap sikap kecenderungan keusahawanan.Kajian kes pula di gunakan bagi melihat kekuatan, kelemahan, peluang dan ancaman yang terdapat di PNK yang dikenalpasti sebagai persatuan nelayan yang daif, kurang maju dan maju.Hasil kajian mendapati terdapat empat faktor ia itu pendapatan, jawatan, kursus keusahawanan dan status PN mempengaruhi sikap kecenderungan keusahawanan di kalangan ALP PN.Terdapat perbezaan yang signifikan di antara Pengurus dan Bukan Pengurus (Pengerusi dan Ahli Lembaga Pengarah) terhadap sikap kecenderungan keusahawanan dengan nilai 65% ketepatan dalam meramalkan keahlian kumpulan berdasarkan klasifikasi koefisien fungsian.Kajian kes mendapati kebanyakan PN masih bergantung kepada perniagaan tradisi seperti jualan minyak diesel, pemasaran ikan, jualan air batu dan medan ikan bakar.Penglibatan PN dalam aktiviti perniagaan lain masih boleh diperkembangkan sekiranya aktiviti kesedaran perniagaan lain boleh disebarkan kepada ALP dan ahli PN.Beberapa cadangan di syorkan oleh ahli-ahli penyelidik bagi program pembangunan usahawan yang sesuai dan lebih baik yang boleh dijalankan oleh PN

Blood Lead Concentrations and The Neuropsychology Scores of Pregnant Women in Klang Valley, Malaysia

Pregnant women with high blood lead posed high risk to their fetus as placental transfer can occurs to the fetus. The objective of this study was to identify the relationship between blood lead and the neuropsychological score of women who were in their 3rd trimester of pregnancy. These respondents were undergoing a routine antenatal checkup at a teaching hospital located in Klang Valley areas. Blood lead concentrations were analyzed using graphite furnace Atomic Absorption Spectrophotometer (AAS). The neuropsychological scores were measured with WHO Neurobehavioral Core Test battery (NCTB). The test consists of 7 items, which made up of the Digit Symbol, Trail Making, Digit Span, Benton Visual Retention Test, Pursuit Aiming, Santa Ana Manual Dexterity, Reaction Time and Movement Time tests. The mean blood lead was 7.78±4.77 µg/dL. The mean score for the total NCTB test was 50.00±5.24. Statistical analysis showed blood lead concentrations were inversely correlated with the total NCTB score (r= –0.462, p≤0.01). The correlation was about 21.3%. The General Linear Model (GLM) showed that age (β= –0.15, p=0.017), weight (β=2.67, p=0.05) and height (β=–1.97, p=0.05) also influence the total neuropsychological scores. In conclusion, blood lead reduces the total neuropsychological scores. The scores for each of the 7 items were inversely and significantly correlated with blood lead concentrations except for the Trail Making and Santa Ana Manual Dexterity tests