Recent studies suggest that reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) may exert beneficial effects on health. Therefore this study evaluated the effects of H2O2 and gamma-tocotrienol (GTT), an antioxidant, on D-[2-3H]Glucose uptake by myotubes compared to insulin. Results showed that H2O2 and insulin significantly increased D-[2-3H]Glucose uptake. This was associated with an increased in Vmax but Michaelis constant (Km) of the transport system remained unchanged indicating that an increase in amount, rather than affinity, of the glucose transporter was involved in the process. Western blot studies confirmed that H2O2 increased the expressions of insulin sensitive glucose transporter, GLUT4 and also hexokinase (an enzyme which phosphorylates glucose and indirectly stimulates glucose uptake by cells). H2O2 and insulin also stimulated increased in PPAR-γ and IRS-1, which are proteins of the insulin transduction pathway. The present data however showed that GTT did not exert any effect on glucose uptake. Thus, the study showed that H2O2 mimicked insulin action in stimulating glucose uptake in myotube cells by influencing the insulin signaling pathway.
Penanda kadar pusing ganti tulang (PPT) adalah berguna dalam penilaian status kesihatan tulang. Namun, pengaruh umur, kumpulan etnik dan antropometri badan terhadap aras PPT dalam kalangan lelaki masih belum jelas. Kajian ini bertujuan untuk menentukan pengaruh faktor-faktor tersebut terhadap aras PPT, iaitu aras osteokalsin (OC) dan telopeptida terminal-C kolagen jenis 1 (CTX-1) dalam kalangan lelaki Cina dan Melayu berumur 20 tahun dan ke atas (N = 407) di Lembah Klang. Subjek dikumpulkan melalui kaedah persampelan bertujuan. Ketinggian, berat badan dan indeks jisim badan subjek telah diukur. Darah mereka diambil pada waktu pagi untuk analisis aras OC dan CTX-1 serum dengan asai imunoserap terangkai enzim. Hasil kajian menunjukkan aras OC dan CTX-1 adalah lebih tinggi secara signifi kan dalam kalangan lelaki Melayu berbanding dengan lelaki Cina (p < 0.05). Aras OC dan CTX-1 adalah paling tinggi dalam kalangan lelaki berumur 20-29 tahun, dan kemudiannya menurun secara signifi kan berbanding dengan dekad sebelumnya dalam kalangan lelaki berumur 30-39 tahun (p < 0.005). Perbezaan aras kedua-dua PPT ini adalah tidak signifi kan di antara lelaki berusia 30-39 tahun dengan lelaki yang lebih tua (> 40 tahun dan ke atas) (p > 0.005). Aras OC berkorelasi secara signifi kan dan negatif dengan berat dan indeks jisim tubuh subjek dan korelasi ini adalah signifi kan untuk lelaki 20-39 tahun sahaja (p < 0.05). Aras CTX-1 tidak berkorelasi dengan antropometri badan subjek (p > 0.05). Secara kesimpulannya, aras PPT dalam kalangan lelaki di Malaysia boleh dipengaruhi oleh faktor umur, kumpulan etnik dan antropometri badan. Faktor-faktor ini seharusnya diambil kira dalam penilaian status kesihatan tulang lelaki berdasarkan aras PPT.
Tocopherols and tocotrienols have been shown in previous studies to protect neurons from oxidative injuries, especially from hydrogen peroxide (H2O2) and buthionine sulfoximine (BSO) induced oxidative stress. In this study, we compared two vitamin E isomers, γ-tocotrienol (GTT) and α-tocopherol (ATF) in their neuroprotective effects against H2O2-induced apoptosis in primary rat cortical neurons and human neuroblastoma cell line SH-SY5Y. Cytotoxicity screening of H2O2, GTT and ATF was done to determine the IC50 levels. To screen for neuroprotective effects, cortical neurons and SH-SY5Y cell cultures were pre-incubated with GTT or ATF, respectively at different concentrations for 1 hour before concurrent treatment of H2O2 at IC50. Results of these treatments were compared to cells treated with H2O2 only and control cells. Cytotoxicology screening showed that IC50 of H2O2 for cortical neuron is at 50 μM while SH-SY5Y have higher IC50 of 100 μM. GTT is cytotoxic to cortical neurons at ≥50 μM and SH-SY5Y at ≥100 μM while ATF did not show any toxicity within the range of concentration tested (1-750 μM). Results from neuroprotection screening showed that GTT and ATF were able to protect both cortical neurons and SH-SY5Y from H2O2-induced oxidative stress at concetration of ≤10 μM. Cellular uptake of GTT is higher in both cortical neurons and SH-SY5Y as compared to ATF when both cortical neuron and SH-SY5Y were incubated with 10 μM GTT or ATF, respectively for 24 hour. Although primary rat cortical neurons and human neuroblastoma SH-SY5Y were different culture system, the effects of GTT and ATF are similar in both H2O2 –induced culture which strongly suggest that both GTT and ATF act as free radical scavenger to exert their neuroprotective effects.
Coronary artery disease (CAD) predominantly manifests in older population above the age of 60 years old. The incidence
of CAD in younger individuals has been reported and is called premature CAD (pCAD). The prevalence for pCAD in
individuals below 45 years old is about 3-10% worldwide. Advances in risk prediction are of great importance as
absolute values of risk factors sometimes correlate poorly with individuals. The measurement of traditional risk factors
such as cholesterol level and blood pressure might be inadequate to predict risk for pCAD and therefore new biomarkers
are required. The introduction of omics technology offers insight into the mechanism and interactions involved during
disease progression and open the possibilities of discovering new biomarkers. Currently, new potential biomarkers for
pCAD have been explored such as homocysteine, apolipoproteins, microRNAs and single nucleotide polymorphisms. In
this review, we discussed the associated risk factors for pCAD, several reported and newly proposed biomarkers and
their potential to be used clinically.
ABSTRACT
Metabolic footprinting involves the determination of metabolites excreted or secreted by the cells.
This study aimed to identify the differential extracellular metabolites in colorectal cancer (CRC)
cells for the determination of molecular changes that occur as CRC progresses. CRC cells at
different stages ie; SW 1116 (stage A), HT 29 and SW 480 (stage B), HCT 15 and DLD-1 (stage
C), and HCT 116 (stage D) were grown in culture. The media in which the cells were grown are
subjected to metabolomics profiling using Liquid Chromatography Mass SpectrometryQuadrupole Time of Flight (LC/MS Q-TOF). Statistical and metabolic pathway analysis was
performed using Metaboanalyst software and identification of metabolites was determined by the
METLIN database. A total of 27 differential extracellular metabolites were identified in CRC cells
of different stages compared to stage A cells. Data from the Partial least squares-discriminant
analysis (PLS-DA) score plot shows a clear separation between CRC cells of different stages with
a few overlaps between stage B and C. Further analysis using variable importance in projection
(VIP) revealed 14 differential extracellular metabolites that were most significant in differentiating
CRC cells of the advanced stages from stage A which are 5-hydroxy-L-tryptophan,
indoleacetaldehyde, 4,5-dimethylthiazole, 8-oxodiacetoxyscirpenol, bisnorbiotin, 5-amino-6-
(5'phosphoribosylamino) uracil, glyceryl 5-hydroxydecanoate, sphinganine, 8,8-diethoxy-2,6-
dimethyl-2-octanol, l-cystine, thiamine acetic acid, phytosphingosine, PE
(20:4(5Z,8Z,11Z,14Z)/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), N-(2R-hydroxypentacosano-yl)-2Samino-1,3S,4R-octadecanetriol. The different expressions of metabolites may indicate altered
metabolic pathways in the more advanced CRC cells compared to stage A. This study highlights
the importance of conducting both metabolomics profiling of extracellular and intracellular to
generate a more complete understanding on the molecular changes that occur as CRC progresses
Childhood obesity is a global epidemic, which leads to the increasing number of studies on genetic locations associated with obesity-related traits. Polymorphisms of insulin (INS) gene have been shown to be associated with obesity-related phenotypes in Europeans; while insulin receptor (INSR) gene has been associated with energy regulation. Therefore, this study was conducted to investigate the association between the INS (rs689) and INSR (rs3745551) gene polymorphisms with childhood obesity risk in a Malay childhood population. Normal weight (538) and overweight or obese (557) children aged 6-12 years old were genotyped using semi-automated Sequenom iPLEX® Gold. Body mass index (BMI) was calculated from measured body weight and height. The rs689 (T/T: 0.006, A/T: 0.159 and A/A: 0.835) and rs3745551 (G/G: 0.054, A/G: 0.378 and A/A: 0.568) genotype distributions were consistent with Hardy Weinberg equilibrium. The T-minor allele frequency for rs689 was 8.6% and G-minor allele frequency for rs3745551 was 24.3%. Minor allele of INS gene polymorphisms significantly increased risk of obesity among Malay children (sex- and age-adjusted
OR=1.580; 95%CI: 1.134-2.201). However, INSR gene polymorphisms were not significantly associated with childhood obesity. In conclusion, the polymorphisms of INS gene, rather than INSR gene, were associated with childhood obesity in the Malay population.
Replicative senescence of human diploid fibroblasts (HDFs) occurs when cells lose their capacity to proliferate and enter a phase of irreversible growth arrest. Stress-induced premature senescence (SIPS) on the other hand is caused by subcytotoxic concentrations of various oxidants which trigger accelerated cellular senescence. In this study, a SIPS model was established by exposing human diploid fibroblasts (HDFs) to 20 μM H2O2 for 2 weeks. A proteomic comparison between young, senescent and SIPS cells was done using two dimensional gel electrophoresis (2DGE) to elucidate the changes in protein expression associated with cellular aging. Our analysis showed that 28 protein spots were differentially expressed in senescent cells whereas 10 protein spots were differentially expressed in SIPS as compared to young cells. Three similar protein spots were differentially expressed in both senescent and SIPS cells when compared to the young cells. These results indicate that a difference in protein expression exists between senescent cells and SIPS cells compared to young cells.
The aim of this study was to determine the relationships between ApoE genotypes and ‘behavioural and psychological symptoms of dementia’ (BPSD). A cross-sectional study was conducted on 46 outpatients with dementia (aged 60 and above) and their caregivers attending the psychogeriatric clinics at Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and Hospital Kuala Lumpur. Neuropsychiatric Inventory (NPI) was used for the assessment of BPSD. The patients’ blood samples were taken for Apolipoprotein genotyping after consented by the caregivers. There were more female (69.6%) and Chinese (50%) patients with a mean age of 73.7 years. ApoE ε3/ε3 was the most common ApoE allele (60.7%) and mostly found in Chinese patients. ApoE genotype was significantly associated with ethnicity (p=0.03) and marital status (p=0.01). Alzheimer disease was the most common subtype of dementia (41.3%) and the highest carrier of ApoE ε3/ε3 (30.4%). The ApoE ε4/ ε4 scored highest in BPSD median score 44 (17.5 to 90) but the relationships
between ApoE genotypes and subtypes of dementia or BPSD scores were not significant (p=0.20; p=0.64). Agitation was the most common symptom, with delusions showing the highest scores on the NPI with no significant association to ApoE 4 allele. In conclusion, there was no significant relationship between ApoE genotypes and severity or types of BPSD in dementia patients.
Chlorella vulgaris (ChV), sejenis alga hijau unisel telah dilaporkan mempunyai khasiat kesihatan pada penyakit tertentu termasuk kanser. Objektif utama kajian ialah untuk mengukur dan menilai kesan antioksidan dan antitumor ekstrak air panas ChV ke atas sel kanser hepar yang dijalankan secara in vivo dan in vitro. Asai DPPH yang dijalankan menunjukkan peratus pengautan ChV yang tinggi. Dalam kajian in vivo, tikus Wistar jantan (200-250 g) dibahagikan kepada lapan kumpulan: tikus kawalan (diet normal), tikus diaruh kanser hepar (diet kurang kolin + 0.1% etionin dalam air minuman) atau singkatannya CDE, tikus diberi rawatan ChV pada tiga dos berbeza (50, 150 dan 300 mg/kg berat badan) dan tikus CDE diberi rawatan ChV pada tiga dos berbeza. Sampel darah dan tisu diambil dari semua kumpulan tikus pada minggu 0, 4, 8 dan 12 untuk penentuan kadar proliferasi dan apoptosis sel untuk melihat kesan antitumor ChV. Peratus pembentukan nodul praneoplasia adalah tinggi pada tikus diaruh kanser hepar (CDE) tetapi ChV pada semua dos berjaya mengurangkannya. Pertambahan jumlah sel kanser semasa hepatokarsinogenesis ditunjukkan dengan peningkatan proliferasi hepatosit yang signifikan (p<0.05) pada tikus CDE berbanding kawalan tetapi ChV pada semua dos berjaya mengurangkan proliferasi secara signifikan (p<0.05). Peratus apoptosis sel didapati meningkat secara signifikan (p<0.05) pada tikus CDE, tetapi peningkatan yang lebih ketara berlaku pada tikus CDE diberi ChV (300 mg/kg berat badan). Dalam kajian in vitro pula, aktiviti antitumor ekstrak air panas ChV telah ditentukan dengan melihat perubahan dalam proliferasi dan apoptosis sel kanser hepar HepG2 yang dikultur di makmal. Ekstrak air panas ChV berjaya menurunkan kadar proliferasi sel HepG2 dengan signifikan secara berkadar terus dengan dos yang digunakan dengan nilai IC50 1.6 mg/ml. Hasil analisis TUNEL pula menunjukkan ekstrak air panas ChV berjaya mengaruh apoptosis dalam sel HepG2. Keputusan ini disokong oleh hasil pemblotan Western dengan peningkatan pengekspresan protein P53 dan protein proapoptosis BAX dan Kaspase-3. Daripada hasil-hasil kajian, dapatlah dicadangkan bahawa ChV berpotensi tinggi sebagai antioksidan serta berupaya memberi kesan antitumor kepada kanser hepar pada kajian in vivo dan in vitro.
Human skeletal muscle is a vital organ involved in movement and force generation. It suffers from deterioration in mass, strength, and regenerative capacity in sarcopenia. Skeletal muscle satellite cells are involved in the regeneration process in response to muscle loss. Tocotrienol, an isomer of vitamin E, was reported to have a protective effect on cellular aging. This research is aimed at determining the modulation of tocotrienol-rich fraction (TRF) on the gene expressions of stress-induced premature senescence (SIPS) human skeletal muscle myoblasts (CHQ5B). CHQ5B cells were divided into three groups, i.e., untreated young control, SIPS control (treated with 1 mM hydrogen peroxide), and TRF-posttreated groups (24 hours of 50 μg/mL TRF treatment after SIPS induction). The differential gene expressions were assessed using microarray, GSEA, and KEGG pathway analysis. Results showed that TRF treatment significantly regulated the gene expressions, i.e., p53 (RRM2B, SESN1), ErbB (EREG, SHC1, and SHC3), and FoxO (MSTN, SMAD3) signalling pathways in the SIPS myoblasts compared to the SIPS control group (p < 0.05). TRF treatment modulated the proliferation capacity of SIPS myoblasts through regulation of ErbB (upregulation of expression of EREG, SHC1, and SHC3) and FoxO (downregulation of expression of MSTN and SMAD3) and maintaining the renewal of satellite cells through p53 signalling (upregulation of RRM2B and SESN1), MRF, cell cycle, and Wnt signalling pathways.
Gestational Diabetes Mellitus (GDM) is associated with pregnancy complications, however its mechanism has not been fully understood. The aim of this study was to investigate the single nucleotide polymorphism (SNP) for identifying candidate genes involve in risk factors and complications of GDM. A total of 174 pregnant women with GDM and 114 healthy pregnant women were genotyped with 384 SNPs from 236 genes. The SNPs identified were rs10946398 (CDKAL1) in GDM risk factors; rs328 (LPL) and rs1042778 (OXTR) in complications of caesarean section; rs5404 (SLC2A2), rs5400 (SLC2A2) and rs13306465 (IRS1) for neonatal intensive care admission. Whereby SNPs rs12255372, rs7901695 and rs7903146 from TCF7L2 gene had six times higher risk (OR, 6.40-6.53) for T2DM at postpartum. In conclusion, although the above SNPs were identified with GDM risk factors and complications among pregnant Malaysian women with GDM, a larger study is needed to ascertain this candidate genes actual association.
Quantitative ultrasound (QUS) is a relatively easy, reliable, and safe method for bone status assessment, but reference data for Asian males remain scarce. Our study aimed to determine the values for one QUS parameter, the speed of sound (SOS) at the calcaneus, in Malaysian Chinese men and to determine the association between the SOS and several demographic characteristics, such as age, weight, height, and body mass index. Three hundred forty-eight Malaysian Chinese men aged 40 yr and older were recruited, and their calcaneal QUS value was determined using the CM-200 densitometer (Furuno Electric, Nishinomiya City, Japan). The results indicated a significant correlation between SOS and age, and multiple stepwise regression analysis indicated that age and height were important predictors of SOS. A significant reduction in SOS value was observed when men 60 yr and older were compared with men aged 40-49 yr. Compared with the reference data for Japanese males, Chinese men in Malaysia showed higher SOS values across all the age groups studied. In conclusion, there is an age-related decrease in SOS values in Malaysian Chinese men, and the SOS values established in this study can be used as a reference for future studies.