Displaying publications 41 - 60 of 73 in total

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  1. Huang CJ, Nguyen PN, Choo KB, Sugii S, Wee K, Cheong SK, et al.
    Int J Med Sci, 2014;11(8):824-33.
    PMID: 24936146 DOI: 10.7150/ijms.8358
    A miRNA precursor generally gives rise to one major miRNA species derived from the 5' arm, and are called miRNA-5p. However, more recent studies have shown co-expression of miRNA-5p and -3p, albeit in different concentrations, in cancer cells targeting different sets of transcripts. Co-expression and regulation of the -5p and -3p miRNA species in stem cells, particularly in the reprogramming process, have not been studied.
  2. Choong PF, Teh HX, Teoh HK, Ong HK, Choo KB, Sugii S, et al.
    Int J Med Sci, 2014;11(11):1154-60.
    PMID: 25170299 DOI: 10.7150/ijms.8281
    Four osteosarcoma cell lines, Saos-2, MG-63, G-292 and U-2 OS, were reprogrammed to pluripotent state using Yamanaka factors retroviral transduction method. Embryonic stem cell (ESC)-like clusters started to appear between 15 to 20 days post transduction. Morphology of the colonies resembled that of ESC colonies with defined border and tightly-packed cells. The reprogrammed sarcomas expressed alkaline phosphatase and pluripotency markers, OCT4, SSEA4, TRA-1-60 and TRA-1-81, as in ESC up to Passage 15. All reprogrammed sarcomas could form embryoid body-like spheres when cultured in suspension in a low attachment dish for up to 10 days. Further testing on the directed differentiation capacity of the reprogrammed sarcomas showed all four reprogrammed sarcoma lines could differentiate into adipocytes while reprogrammed Saos-2-REP, MG-63-REP and G-292-REP could differentiate into osteocytes. Among the 4 osteosarcoma cell lines, U-2 OS reported the highest transduction efficiency but recorded the lowest reprogramming stability under long term culture. Thus, there may be intrinsic differences governing the variable responses of osteosarcoma cell lines towards reprogramming and long term culture effect of the reprogrammed cells. This is a first report to associate intrinsic factors in different osteosarcoma cell lines with variable reprogramming responses and effects on the reprogrammed cells after prolonged culture.
  3. Choo KB, Tai L, Hymavathee KS, Wong CY, Nguyen PN, Huang CJ, et al.
    Int J Med Sci, 2014;11(11):1201-7.
    PMID: 25249788 DOI: 10.7150/ijms.8356
    On in vitro expansion for therapeutic purposes, the regenerative potentials of mesenchymal stem cells (MSCs) decline and rapidly enter pre-mature senescence probably involving oxidative stress. To develop strategies to prevent or slow down the decline of regenerative potentials in MSC culture, it is important to first address damages caused by oxidative stress-induced premature senescence (OSIPS). However, most existing OSIPS study models involve either long-term culture to achieve growth arrest or immediate growth arrest post oxidative agent treatment and are unsuitable for post-induction studies.
  4. Giribabu N, Kumar KE, Rekha SS, Muniandy S, Salleh N
    Int J Med Sci, 2014;11(11):1172-84.
    PMID: 25249786 DOI: 10.7150/ijms.9056
    The effect of C. borivilianum root on blood glucose, glycated hemoglobin (HbAIc), insulin and lipid profile levels in diabetes mellitus are not fully understood. This study therefore investigated the effect of C. borivilianum root on the above parameters and oxidative stress of the pancreas in diabetes.
    METHODS: C. borivilianum root aqueous extract (250 and 500 mg/kg/day) was administered to streptozotocin (STZ)-induced male diabetic rats for 28 days. Body weight, blood glucose, HbA1c, insulin, lipid profile levels and glucose homeostasis indices were determined. Histopathological changes and oxidative stress parameters i.e. lipid peroxidation (LPO) and antioxidant enzymes activity levels of the pancreas were investigated.
    RESULTS: C. borivilianum root extract treatment to diabetic rats maintained near normal body weight, blood glucose, HbA1c, lipid profile and insulin levels with higher HOMA-β cell functioning index, number of Islets/pancreas, number of β-cells/Islets however with lower HOMA-insulin resistance (IR) index as compared to non-treated diabetic rats. Negative correlations between serum insulin and blood glucose, HbA1c, triglyceride (TG) and total cholesterol (TC) levels were observed. C. borivilianum root extract administration prevented the increase in lipid peroxidation and the decrease in activity levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) with mild histopathological changes in the pancreas of diabetic rats.
    CONCLUSIONS: C. borivilianum root maintains near normal levels of these metabolites and prevented oxidative stress-induced damage to the pancreas in diabetes.
    KEYWORDS: Chlorophytum borivilianum; diabetes; glucose; lipid profile; oxidative stress.; pancreas
  5. Rothan HA, Djordjevic I, Bahrani H, Paydar M, Ibrahim F, Abd Rahmanh N, et al.
    Int J Med Sci, 2014;11(10):1029-38.
    PMID: 25136258 DOI: 10.7150/ijms.8895
    Platelet rich plasma clot- releasate (PRCR) shows significant influence on tissue regeneration in clinical trials. Although, the mechanism of PRCR effect on fibroblast differentiation has been studied on 2D culture system, a detailed investigation is needed to establish the role of PRCR in cell seeded in 3D scaffolds. Therefore, a study was conducted to evaluate the influence of PRCR in fibroblasts (DFB) differentiation and extracellular matrix formation on both 3D and 2D culture systems. Cell viability was measured using MTT assay and DFB differentiation was evaluated by determining the expression levels of nucleostamin and alpha smooth muscle actin (α-SMA), using indirect immunostaining and Western blotting. The expression levels of extracellular matrix genes (collagen-I, collagen-III, fibronectin and laminin) and focal adhesion formation gene (integrin beta-1) were measured using Real-time PCR. The PRCR at 10% showed significant effect on cells viability compared with 5% and 20% in both culture environments. The decrease in the expression levels of nucleostamin and the increase in α-SMA signify the DFB differentiation to myofibroblast-like cells that was prominently greater in 3D compared to 2D culture. In 3D culture systems, the total collage production, expression levels of the extracellular matrix gene and the focal adhesion gene were increased significantly compared to 2D culture. In conclusion, 3D culture environments enhances the proliferative and differentiation effects of PRCR on DFB, thereby potentially increases the efficacy of DFB for future tissue engineering clinical application.
  6. Chin KY, Ima-Nirwana S, Mohamed IN, Aminuddin A, Johari MH, Ngah WZ
    Int J Med Sci, 2014;11(4):349-55.
    PMID: 24578612 DOI: 10.7150/ijms.7104
    Alteration in lipid profile is a common observation in patients with thyroid dysfunction, but the current knowledge on the relationship between lipids and thyroid hormone levels in euthyroid state is insufficient. The current study aimed to determine the association between thyroid hormones and thyroid-stimulating hormone (TSH) with lipid profile in a euthyroid male population.
  7. Firoozinia M, Zareian Jahromi M, Moghadamtousi SZ, Nikzad S, Abdul Kadir H
    Int J Med Sci, 2014;11(6):620-5.
    PMID: 24782652 DOI: 10.7150/ijms.8251
    A family of PI3Ks is the lipid kinases, which enhance intracellular pools of phosphatidyl inositol 3,4,5-tri-phosphate (PIP3) through phosphorylating its precursor. Amplifications and deletions of genes, as well as somatic missense of the PIK3CA gene have been described in many human cancer varieties, including of the brain, colon, liver, lung and stomach. Immunohistochemistry and Real-time quantitative PCR tests were used to determine the PIK3CA gene amplification (gene copy number) and to detect protein expression, respectively. The results obtained were analysed and the ratio of PIK3CA to β-actin gene copy number was calculated. Positive gene amplification of PIK3CA was appointed as a copy number of ≥4. Also, PI3K p110α protein expression was scored from 0 to 3+ and the scores of 2+ and 3+ were considered as positive for PI3K p110α protein expression. We studied 50 breast carcinoma samples for PI3K p110α protein expression and PIK3CA gene copy numbers. In general, 36 out of 50 (72%) breast carcinoma samples showed a significant increase in PIK3CA gene amplification. 12 out of 50 (24%) showed positive staining, and 38 out of 50 (76%) showed negative staining for PI3K p110α expression. We have identified no significant relationship between PIK3CA amplification, race (p= 0.630) and histological type (p=0. 731) in breast carcinoma, but correlation of PIK3CA amplification and age showed a significant relationship (p=0. 003) between them. No significant relationship has been identified in correlation of PI3K p110α protein expression compared to age (p=0. 284), race (p=0. 546) and histological type (p=0. 285). Amplification of PIK3CA was frequent in breast carcinoma and occurs in stages of breast carcinoma. Our result shows that there is a relationship between gene amplification and age in breast carcinoma. We suggest that PIK3CA is significant in breast tumorigenesis serve as a prevalent mechanism contributes to the oncogenic activation pathway of PIK3CA in breast cancer.
  8. Yap HY, Aziz AA, Fung SY, Ng ST, Tan CS, Tan NH
    Int J Med Sci, 2014;11(6):602-7.
    PMID: 24782649 DOI: 10.7150/ijms.8341
    The Lignosus is a genus of fungi that have useful medicinal properties. In Southeast Asia, three species of Lignosus (locally known collectively as Tiger milk mushrooms) have been reported including L. tigris, L. rhinocerotis, and L. cameronensis. All three have been used as important medicinal mushrooms by the natives of Peninsular Malaysia. In this work, the nutritional composition and antioxidant activities of the wild type and a cultivated strain of L. tigris sclerotial extracts were investigated. The sclerotia are rich in carbohydrates with moderate amount of protein and low fat content. Free radical scavenging activities of L. tigris sclerotial extracts correlate with their phenolic content, which ranges from 6.25 to 45.42 mg GAE/g extract. The FRAP values ranged from 0.002 to 0.041 mmol/min/g extract, while the DPPH(•), ABTS(•+), and superoxide anion (SOA) scavenging activities ranged from 0.18 to 2.53, 0.01 to 0.36, and -4.53 to 10.05 mmol Trolox equivalents/g extract, respectively. L. tigris cultivar shows good prospect to be developed into functional food due to its good nutritional value and potent SOA scavenging activity.
  9. Lee ML, Fung SY, Chung I, Pailoor J, Cheah SH, Tan NH
    Int J Med Sci, 2014;11(6):593-601.
    PMID: 24782648 DOI: 10.7150/ijms.8096
    King cobra (Ophiophagus hannah) venom L-amino acid oxidase (OH-LAAO), a heat stable enzyme, has been shown to exhibit very potent anti-proliferative activity against human breast and lung tumorigenic cells but not in their non-tumorigenic counterparts. We further examine its in vitro and in vivo anti-tumor activity in a human prostate adenocarcinoma (PC-3) model. OH-LAAO demonstrated potent cytotoxicity against PC-3 cells with IC50 of 0.05 µg/mL after 72 h incubation in vitro. It induced apoptosis as evidenced with an increase in caspase-3/7 cleavages and an increase in annexin V-stained cells. To examine its in vivo anti-tumor activity, we treated PC-3 tumor xenograft implanted subcutaneously in immunodeficient NU/NU (nude) mice with 1 µg/g OH-LAAO given intraperitoneally (i.p.). After 8 weeks of treatment, OH-LAAO treated PC-3 tumors were markedly inhibited, when compared to the control group (P <0.05). TUNEL staining analysis on the tumor sections showed a significantly increase of apoptotic cells in the LAAO-treated animals. Histological examinations of the vital organs in these two groups showed no significant differences with normal tissues, indicating no obvious tissue damage. The treatment also did not cause any significant changes on the body weight of the mice during the duration of the study. These observations suggest that OH-LAAO cytotoxic effects may be specific to tumor xenografts and less to normal organs. Given its potent anti-tumor activities shown in vitro as well as in vivo, the king cobra venom LAAO can potentially be developed to treat prostate cancer and other solid tumors.
  10. Tang YQ, Jaganath IB, Manikam R, Sekaran SD
    Int J Med Sci, 2014;11(6):564-77.
    PMID: 24782645 DOI: 10.7150/ijms.7704
    Melanoma is the most fatal form of skin cancer. Different signalling pathways and proteins will be differentially expressed to pace with the tumour growth. Thus, these signalling molecules and proteins are become potential targets to halt the progression of cancer. The present works were attempted to investigate the underlying molecular mechanisms of anticancer effects of Phyllanthus (P.amarus, P.niruri, P.urinaria and P.watsonii) on skin melanoma, MeWo cells.
  11. AbuBakar S, Shu MH, Johari J, Wong PF
    Int J Med Sci, 2014;11(6):538-44.
    PMID: 24782642 DOI: 10.7150/ijms.7896
    Alteration in the endothelium leading to increased vascular permeability contributes to plasma leakage seen in dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). An earlier study showed that senescent endothelial cells (ECs) altered the ECs permeability. Here we investigated the susceptibility of senescing human umbilical vein endothelial cells (HUVECs) to dengue virus infection and determined if dengue virus infection induces HUVECs senescence. Our results suggest that DENV type-2 (DENV-2) foci forming unit (FFU) and extracellular virus RNA copy number were reduced by at least 35% and 85% in infection of the intermediate young and early senescent HUVECs, respectively, in comparison to infection of young HUVECs. No to low infectivity was recovered from infection of late senescent HUVECs. DENV infection also increases the percentage of HUVECs expressing senescence-associated (SA)-β-gal, cells arrested at the G2/M phase or 4N DNA content stage and cells with enlarged morphology, indicative of senescing cells. Alteration of HUVECs morphology was recorded using impedance-based real-time cell analysis system following DENV-2 infection. These results suggest that senescing HUVECs do not support DENV infection and DENV infection induces HUVECs senescence. The finding highlights the possible role of induction of senescence in DENV infection of the endothelial cells.
  12. Gnanasegaran N, Govindasamy V, Musa S, Kasim NH
    Int J Med Sci, 2014;11(4):391-403.
    PMID: 24669199 DOI: 10.7150/ijms.7697
    Human adipose stem cells (ASCs) has been in the limelight since its discovery as a suitable source of mesenchymal stem cells (MSCs) in regenerative medicine. Currently, two major techniques are used to isolate ASCs, namely liposuction and tissue biopsy. These two methods are relatively risk-free but the question as to which method could give a more efficient output remains unclear. Thus, this study was carried out to compare and contrast the output generated in regards to growth kinetics, differentiation capabilities in vitro, and gene expression profiling. It was found that ASCs from both isolation methods were comparable in terms of growth kinetics and tri-lineage differentiation. Furthermore, ASCs from both populations were reported as CD44(+), CD73(+), CD90(+), CD166(+), CD34(-), CD45(-) and HLA-DR(-). However, in regards to gene expression, a group of overlapping genes as well as distinct genes were observed. Distinct gene expressions indicated that ASCs (liposuction) has endoderm lineage propensity whereas ASCs (biopsy) has a tendency towards mesoderm/ectoderm lineage. This information suggests involvement in different functional activity in accordance to isolation method. In conclusion, future studies to better understand these gene functions should be carried out in order to contribute in the applicability of each respective cells in regenerative therapy.
  13. Shamshirband S, Hessam S, Javidnia H, Amiribesheli M, Vahdat S, Petković D, et al.
    Int J Med Sci, 2014;11(5):508-14.
    PMID: 24688316 DOI: 10.7150/ijms.8249
    There is a high risk of tuberculosis (TB) disease diagnosis among conventional methods.
  14. Chin KY, Ima-Nirwana S, Mohamed IN, Ahmad F, Ramli ES, Aminuddin A, et al.
    Int J Med Sci, 2014;11(2):151-7.
    PMID: 24465160 DOI: 10.7150/ijms.7152
    Recent studies revealed a possible reciprocal relationship between the skeletal system and obesity and lipid metabolism, mediated by osteocalcin, an osteoblast-specific protein. This study aimed to validate the relationship between serum osteocalcin and indices of obesity and lipid parameters in a group of Malaysian men.
  15. Naveen SV, Ahmad RE, Hui WJ, Suhaeb AM, Murali MR, Shanmugam R, et al.
    Int J Med Sci, 2014;11(1):97-105.
    PMID: 24396291 DOI: 10.7150/ijms.6964
    Monosodium -iodoacetate (MIA)-induced animal model of osteoarthritis (OA) is under-utilised despite having many inherent advantages. At present, there is lack of studies that directly compare the degenerative changes induced by MIA with the surgical osteoarthritis induction method and human osteoarthritis, which would further verify a greater use of this model. Therefore, we compared the histological, biochemical and biomechanical characteristics in rat model using MIA against the anterior cruciate ligament transection (ACLT) and human cartilage with clinically established osteoarthritis. The right knees of Sprague-Dawley rats were subjected to either MIA or ACLT (n=18 in each group). Six rats were used as controls. Human cartilage samples were collected and compared from patients clinically diagnosed with (n=7) and without osteoarthritis (n=3). Histological, biochemical (Glycosaminoglycans/total protein) and biomechanical (cartilage stiffness) evaluations were performed at the end of the 1(st) and 2(nd) week after OA induction. For human samples, evaluations were performed at the time of sampling. Histopathological changes in the MIA group were comparable to that observed in the ACLT group and human OA. The Mankin scores of the 3 groups were comparable (MIA: 11.5 ± 1.0; ACLT: 10.1 ± 1.1; human OA: 13.2 ± 0.8). Comparable reduction in Glycosaminoglycan/total protein content in the intervention groups were observed (MIA: 7 ± 0.6; ACLT: 6.6 ± 0.5; human OA: 3.1 ± 0.7). Cartilage stiffness score were 24.2 ± 15.3 Mpa for MIA, 25.3 ± 4.8 for ACLT and 0.5 ± 0.0 Mpa for human OA. The MIA model produces comparable degenerative changes to ACLT and human OA with the advantage of being rapid, minimally invasive and reproducible. Therefore, wider utilisation of MIA as animal translational OA model should perhaps be advocated.
  16. Tay LX, Lim CK, Mansor A, Kamarul T
    Int J Med Sci, 2014;11(1):24-33.
    PMID: 24396283 DOI: 10.7150/ijms.7244
    This preliminary study aims to determine the differentially expressed proteins from chondrogenic differentiated multipotent stromal cells (cMSCs) in comparison to undifferentiated multipotent stromal cells (MSCs) and adult chondrocytes (ACs).
  17. Teh CS, Chua KH, Thong KL
    Int J Med Sci, 2014;11(7):732-41.
    PMID: 24904229 DOI: 10.7150/ijms.7768
    The incidence of enteric fever caused by Salmonella enterica serovar Paratyphi A (S. Paratyphi A) is increasing in many parts of the world. Although there is no major outbreak of paratyphoid fever in recent years, S. Paratyphi A infection still remains a public health problem in many tropical countries. Therefore, surveillance studies play an important role in monitoring infections and the emergence of multidrug resistance, especially in endemic countries such as India, Nepal, Pakistan and China. In China, enteric fever was caused predominantly by S. Paratyphi A rather than by Salmonella enterica serovar Typhi (S. Typhi). Sometimes, S. Paratyphi A infection can evolve into a carrier state which increases the risk of transmission for travellers. Hence, paratyphoid fever is usually classified as a "travel-associated" disease. To date, diagnosis of paratyphoid fever based on the clinical presentation is not satisfactory as it resembles other febrile illnesses, and could not be distinguished from S. Typhi infection. With the availability of Whole Genome Sequencing technology, the genomes of S. Paratyphi A could be studied in-depth and more specific targets for detection will be revealed. Hence, detection of S. Paratyphi A with Polymerase Chain Reaction (PCR) method appears to be a more reliable approach compared to the Widal test. On the other hand, due to increasing incidence of S. Paratyphi A infections worldwide, the need to produce a paratyphoid vaccine is essential and urgent. Hence various vaccine projects that involve clinical trials have been carried out. Overall, this review provides the insights of S. Paratyphi A, including the bacteriology, epidemiology, management and antibiotic susceptibility, diagnoses and vaccine development.
  18. Dehghan F, Muniandy S, Yusof A, Salleh N
    Int J Med Sci, 2014;11(2):180-91.
    PMID: 24465164 DOI: 10.7150/ijms.6283
    The incidence of non-contact knee injury was found higher in female than in male and is related to the phases of the menstrual cycle. This raised the possibility that female sex-steroids are involved in the mechanism underlying this injury via affecting the expression of the receptors for relaxin, a peptide hormone known to modulate ligament laxity. Therefore, this study aims to investigate the effect of sex-steroids on relaxin receptor isoforms (RXFP1 & RXFP2) expression in the ligaments and tendons of the knee.

    METHODS: Ovariectomized adult female WKY rats were treated with different doses of estrogen (0.2, 2, 20 μg/kg), progesterone (4mg) and testosterone (125 & 250μg/kg) for three consecutive days. At the end of the treatment, the animals were sacrificed and the patellar tendon and lateral collateral ligament were harvested for mRNA and protein expression analyses by Real Time PCR and Western blotting respectively.

    RESULTS: RXFP1, the main isoform expressed in these knee structures and RXFP2 showed a dose-dependent increase in expression with estrogen. Progesterone treatment resulted in an increase while testosterone caused a dose-dependent decrease in the mRNA and protein expression of both relaxin receptor isoforms.

    DISCUSSION: Progesterone and high dose estrogen up-regulate while testosterone down-regulates RXFP1 and RXFP2 expression in the patellar tendon and lateral collateral ligament of rat's knee.

    CONCLUSION: Relaxin receptor isoforms up-regulation by progesterone and high dose estrogen could provide the basis for the reported increase in knee laxity while down-regulation of these receptor isoforms by testosterone could explain low incidence of non-contact knee injury in male.

  19. Chin KY, Ima-Nirwana S
    Int J Med Sci, 2013;10(12):1778-83.
    PMID: 24273451 DOI: 10.7150/ijms.6765
    Quantitative ultrasound (QUS) has emerged as a convenient and popular screening tool for osteoporosis. This review aimed to provide basic information on the principle of QUS measurement and discuss the properties of bone reflected by QUS indices. QUS employed high frequency sound waves generated by the device to determine bone health status in humans. In vitro studies showed that QUS indices were significantly associated with bone mineral density (BMD), bone microarchitecture and mechanical parameters. In humans, QUS indices were found to be associated with BMD as well. In addition, QUS could discriminate subjects with and without fracture history and predict risk for future fracture. In conclusion, QUS is able to reflect bone quality and should be used in the screening of osteoporosis, especially in developing countries where dual-X-ray absorptiometry devices are less accessible to the general population.
  20. Tan WC, Jaganath IB, Manikam R, Sekaran SD
    Int J Med Sci, 2013;10(13):1817-29.
    PMID: 24324358 DOI: 10.7150/ijms.6902
    Nucleoside analogues such as acyclovir are effective antiviral drugs against herpes simplex virus infections since its introduction. However, with the emergence of acyclovir-resistant HSV strains particularly in immunocompromised patients, there is a need to develop an alternative antiherpetic drug and plants could be the potential lead. In this study, the antiviral activity of the aqueous extract of four Phyllanthus species were evaluated against herpes simplex virus type-1 (HSV-1) and HSV-2 in Vero cells by quantitative PCR. The protein expressions of untreated and treated infected Vero cells were studied by 2D-gel electrophoresis and Western blot. This is the first study that reported the antiviral activity of P. watsonii. P. urinaria was shown to demonstrate the strongest antiviral activity against HSV-1 and HSV-2, with SI >33.6. Time-of-addition studies suggested that the extract may act against the early infection stage and the replication stage. Protein expression studies indicated that cellular proteins that are involved in maintaining cytoskeletal structure could be potential target for development of antiviral drugs. Preliminary findings indicated that P. urinaria demonstrated potent inhibitory activity against HSV. Hence, further studies such as in vivo evaluation are required for the development of effective antiherpetic drug.
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