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  1. Fulltext A Review on the Effects of Bisphenol A and Its Derivatives on Skeletal Health
    Chin KY, Pang KL, Mark-Lee WF
    Int J Med Sci, 2018;15(10):1043-1050.
    PMID: 30013446 DOI: 10.7150/ijms.25634
    Bisphenol A (BPA) is an endocrine disruptor which can bind to the oestrogen receptor. It also possesses oestrogenic, antiandrogenic, inflammatory and oxidative properties. Since bone responds to changes in sex hormones, inflammatory and oxidative status, BPA exposure could influence bone health in humans. This review aimed to summarize the current evidence on the relationship between BPA and bone health derived from cellular, animal and human studies. Exposure to BPA (0.5-12.5 µM) decreased the proliferation of osteoblast and osteoclast precursor cells and induce their apoptosis. Bisphenol AF (10 nM) enhanced transforming growth factor beta signalling but bisphenol S (10 nM) inhibited Wnt signalling involved in osteoblast differentiation in vitro. In animals, BPA and its derivatives demonstrated distinct effects in different models. In prenatal/postnatal exposure, BPA increased femoral bone mineral content in male rats (at 25 ug/kg/day) but decreased femoral mechanical strength in female mice (at 10 µg/kg/day). In oestrogen deficiency models, BPA improved bone mineral density and microstructures in aromatase knockout mice (at very high dose, 0.1% or 1.0% w/w diet) but decreased trabecular density in ovariectomized rats (at 37 or 370 ug/kg/day). In contrast, bisphenol A diglycidyl ether (30 mg/kg/day i.p.) improved bone health in normal male and female rodents and decreased trabecular separation in ovariectomized rodents. Two cross-sectional studies have been performed to examine the relationship between BPA level and bone mineral density in humans but they yielded negligible association. As a conclusion, BPA and its derivatives could influence bone health and a possible gender effect was observed in animal studies. However, its effects in humans await verification from more comprehensive longitudinal studies in the future.
  2. Fulltext A comparative study on morphochemical properties and osteogenic cell differentiation within bone graft and coral graft culture systems
    Puvaneswary S, Balaji Raghavendran HR, Ibrahim NS, Murali MR, Merican AM, Kamarul T
    Int J Med Sci, 2013;10(12):1608-14.
    PMID: 24151432 DOI: 10.7150/ijms.6496
    The objective of this study was to compare the morphological and chemical composition of bone graft (BG) and coral graft (CG) as well as their osteogenic differentiation potential using rabbit mesenchymal stem cells (rMSCs) in vitro. SEM analysis of BG and CG revealed that the pores in these grafts were interconnected, and their micro-CT confirmed pore sizes in the range of 107-315 µm and 103-514 µm with a total porosity of 92% and 94%, respectively. EDS analysis indicated that the level of calcium in CG was relatively higher than that in BG. FTIR of BG and CG confirmed the presence of functional groups corresponding to carbonyl, aromatic, alkyl, and alkane groups. XRD results revealed that the phase content of the inorganic layer comprised highly crystalline form of calcium carbonate and carbon. Atomic force microscopy analysis showed CG had better surface roughness compared to BG. In addition, significantly higher levels of osteogenic differentiation markers, namely, alkaline phosphatase (ALP), Osteocalcin (OC) levels, and Osteonectin and Runx2, Integrin gene expression were detected in the CG cultures, when compared with those in the BG cultures. In conclusion, our results demonstrate that the osteogenic differentiation of rMSCs is relatively superior in coral graft than in bone graft culture system.
  3. Fulltext An Analysis of the Clinical and Radiological Prognostic Factors Affecting the Outcomes of Lumbar Intradiscal Biacuplasty
    Md MY, Md CG, Md CW, MSc YC, MSc HJ, Md IH, et al.
    Int J Med Sci, 2023;20(8):1115-1122.
    PMID: 37484806 DOI: 10.7150/ijms.85777
    Purpose: Intradiscal biacuplasty (IDB) has been proven to be effective for treating lumbar degenerative disc disease (DDD). However, there has not been a reported prognostic factor for IDB. The present study meticulously evaluates the general and radiographic features that may serve as markers for predicting the therapeutic outcome of IDB. Methods: A prospective case series study was conducted, following time-series analysis moving averages models, with forty-one patients suffering from chronic discogenic lower back pain for more than six months. These patients subsequently received lumbar cool radiofrequency IDB and were enrolled in the study. Thirty-seven patients completed follow-up questionnaires at 1, 3, 6, and 12 months. The surgical outcomes were reported using visual analogue scale (VAS), Oswestry disability index (ODI), and the consumption of nonsteroidal anti-inflammatory drugs (NSAID). Furthermore, a univariate analysis was performed to identify prognostic factors associated with pain relief from age, gender, body mass index (BMI), and pre-operative lumbar magnetic resonance imaging reading. Results: Significant reductions were found in estimated VAS and ODI at the post-operative period at 1, 3, 6, and 12 months (P < 0.001). The NSAID dosage was significantly decreased at 3-month and 1-year follow-up (P < 0.05). No procedure-related complications were detected. The prognosis of IDB was not related to disc height, Pfirrmann grading or Modic endplate change. However, disc extrusions were associated with promising outcomes (VAS improvement ≥ 50%) on pain relief (P < 0.05). Conclusion: IDB is a good alternative choice for treating lumbar DDD. Patients with a painful extrusion lumbar disc may gain some benefits after receiving IDB following a period of failed conservative treatment. These findings may also add some references for physicians in the decision making when treating lumbar DDD.
  4. Fulltext An Association Map on the Effect of Flavonoids on the Signaling Pathways in Colorectal Cancer
    Koosha S, Alshawsh MA, Looi CY, Seyedan A, Mohamed Z
    Int J Med Sci, 2016;13(5):374-85.
    PMID: 27226778 DOI: 10.7150/ijms.14485
    Colorectal cancer (CRC) is the third most common type of cancer in the world, causing thousands of deaths annually. Although chemotherapy is known to be an effective treatment to combat colon cancer, it produces severe side effects. Natural products, on the other hand, appear to generate fewer side effects than do chemotherapeutic drugs. Flavonoids are polyphenolic compounds found in various fruits and vegetables known to possess antioxidant activities, and the literature shows that several of these flavonoids have anti-CRC propertiesFlavonoids are classified into five main subclasses: flavonols, flavanones, flavones, flavan-3-ols, and flavanonols. Of these subclasses, the flavanonols have a minimum effect against CRC, whereas the flavones play an important role. The main targets for the inhibitory effect of flavonoids on CRC signaling pathways are caspase; nuclear factor kappa B; mitogen-activated protein kinase/p38; matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9; p53; β-catenin; cyclin-dependent kinase (CDK)2 and CDK4; and cyclins A, B, D, and E. In this review article, we summarize the in vitro and in vivo studies that have been performed since 2000 on the anti-CRC properties of flavonoids. We also describe the signaling pathways affected by flavonoids that have been found to be involved in CRC. Some flavonoids have the potential to be an effective alternative to chemotherapeutic drugs in the treatment of colon cancer; well-controlled clinical studies should, however, be conducted to support this proposal.
  5. Fulltext Bisphenol A, Dichlorodiphenyltrichloroethane (DDT) and Vinclozolin Affect ex-vivo Uterine Contraction in Rats via Uterotonin (Prostaglandin F2α, Acetylcholine and Oxytocin) Related Pathways
    Salleh N, Giribabu N, Feng AO, Myint K
    Int J Med Sci, 2015;12(11):914-25.
    PMID: 26640411 DOI: 10.7150/ijms.11957
    Bisphenol-A (BPA), dichrolodiphenyltrichloroethane (DDT) and vinclozolin were found able to induce abnormal uterine contraction. The mechanisms involved remains unclear. We hypothesized that the effect of these compounds were mediated via the uterotonin pathways. Therefore, in this study, effects of BPA, vinclozolin and DDT-only and in combination with uterotonins (PGF-2α, acetylcholine and oxytocin) on the force and pattern of uterine contraction were observed.
  6. Fulltext Calcaneal quantitative ultrasound as a determinant of bone health status: what properties of bone does it reflect?
    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.
  7. Fulltext Can Saliva Proteins Be Used to Predict the Onset of Acute Myocardial Infarction among High-Risk Patients?
    Rahim MA, Rahim ZH, Ahmad WA, Hashim OH
    Int J Med Sci, 2015;12(4):329-35.
    PMID: 25897294 DOI: 10.7150/ijms.11280
    Human saliva plays a pivotal role in digesting food and maintaining oral hygiene. The presence of electrolytes, mucus, glycoproteins, enzymes, antibacterial compounds, and gingival crevicular fluid in saliva ensures the optimum condition of oral cavity and general health condition. Saliva collection has been proven non-invasive, convenient, and inexpensive compared to conventional venipuncture procedure. These distinctive advantages provide a promising potential of saliva as a diagnostic fluid. Through comprehensive analysis, an array of salivary proteins and peptides may be beneficial as biomarkers in oral and systemic diseases. In this review, we discuss the utility of human salivary proteomes and tabulate the recent salivary biomarkers found in subjects with acute myocardial infarction as well as respective methods employed. In a clinical setting, since acute myocardial infarction contributes to large cases of mortality worldwide, an early intervention using these biomarkers will provide an effective solution to reduce global heart attack incidence particularly among its high-risk group of type-2 diabetes mellitus patients. The utility of salivary biomarkers will make the prediction of this cardiac event possible due to its reliability hence improve the quality of life of the patients. Current challenges in saliva collection are also addressed to improve the quality of saliva samples and produce robust biomarkers for future use in clinical applications.
  8. Fulltext Characterization and potential roles of bone marrow-derived stromal cells in cancer development and metastasis
    Kawai H, Tsujigiwa H, Siar CH, Nakano K, Takabatake K, Fujii M, et al.
    Int J Med Sci, 2018;15(12):1406-1414.
    PMID: 30275769 DOI: 10.7150/ijms.24370
    Background: The tumor microenvironment and its stromal cells play an important role in cancer development and metastasis. Bone marrow-derived cells (BMDCs), a rich source of hematopoietic and mesenchymal stem cells, putatively contribute to this tumoral stroma. However their characteristics and roles within the tumor microenvironment are unclear. In the present study, BMDCs in the tumor microenvironment were traced using the green fluorescent protein (GFP) bone marrow transplantation model. Methods: C57BL/6 mice were irradiated and rescued by bone marrow transplantation from GFP-transgenic mice. Lewis lung cancer cells were inoculated into the mice to generate subcutaneous allograft tumors or lung metastases. Confocal microscopy, immunohistochemistry for GFP, α-SMA, CD11b, CD31, CD34 and CD105, and double-fluorescent immunohistochemistry for GFP-CD11b, GFP-CD105 and GFP-CD31 were performed. Results: Round and dendritic-shaped GFP-positive mononuclear cells constituted a significant stromal subpopulation in primary tumor peripheral area (PA) and metastatic tumor area (MA) microenvironment, thus implicating an invasive and metastatic role for these cells. CD11b co-expression in GFP-positive cells suggests that round/dendritic cell subpopulations are possibly BM-derived macrophages. Identification of GFP-positive mononuclear infiltrates co-expressing CD31 suggests that these cells might be BM-derived angioblasts, whereas their non-reactivity for CD34, CD105 and α-SMA implies an altered vascular phenotype distinct from endothelial cells. Significant upregulation of GFP-positive, CD31-positive and GFP/CD31 double-positive cell densities positively correlated with PA and MA (P<0.05). Conclusion: Taken together, in vivo evidence of traceable GFP-positive BMDCs in primary and metastatic tumor microenvironment suggests that recruited BMDCs might partake in cancer invasion and metastasis, possess multilineage potency and promote angiogenesis.
  9. Fulltext Chlorophytum borivilianum root extract maintains near normal blood glucose, insulin and lipid profile levels and prevents oxidative stress in the pancreas of streptozotocin-induced adult male diabetic rats
    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
  10. Fulltext Clinical Significance of BCL2, C-MYC, and BCL6 Genetic Abnormalities, Epstein-Barr Virus Infection, CD5 Protein Expression, Germinal Center B Cell/Non-Germinal Center B-Cell Subtypes, Co-expression of MYC/BCL2 Proteins and Co-expression of MYC/BCL2/BCL6 Proteins in Diffuse Large B-Cell Lymphoma: A Clinical and Pathological Correlation Study of 120 Patients
    Ting CY, Chang KM, Kuan JW, Sathar J, Chew LP, Wong OJ, et al.
    Int J Med Sci, 2019;16(4):556-566.
    PMID: 31171907 DOI: 10.7150/ijms.27610
    Background: Clinical significance of germinal center B-cell (GCB) and non-GCB sub-categorization, expression of MYC, BCL2, BCL6, CD5 proteins and Epstein Barr virus encoded RNA (EBER) positivity in diffuse large B-cell lymphoma (DLBCL) remain controversial. Could these biomarkers accurately identify high risk DLBCL patients? Are MYC, BCL2 and BCL6 proteins expression feasible as baseline testing to predict c-Myc, BCL2 or BCL6 gene rearrangements? Aims: To investigate prognostic values of GCB/non-GCB sub-categorization, Double Protein Expression Lymphoma (DPL), Triple Protein Expression Lymphoma (TPL), positivity of CD5 protein and EBER in patients with DLBCL disease. To evaluate correlation between BCL2 , c-Myc and BCL6 gene rearrangements with BCL2, MYC and BCL6 proteins expression. Methods: Diagnostic tissue samples of 120 DLBCL patients between January 2012 to December 2013 from four major hospitals in Malaysia were selected. Samples were subjected to immunohistochemical staining, fluorescent in-situ hybridization (FISH) testing, and central pathological review. Pathological data were correlated with clinical characteristics and treatment outcome. Results: A total of 120 cases were analysed. Mean age of diagnosis was 54.1 years ± 14.6, 64 were males, 56 were females, mean follow up period was 25 months (ranged from 1 to 36 months). Of the 120 cases, 74.2% were non-GCB whereas 25.8% were GCB, 6.7% were EBER positive, 6.7% expressed CD5 protein, 13.3% were DPL and 40% were TPL. The prevalence of c-Myc, BCL2, BCL6 gene rearrangements were 5.8%, 5.8%, and 14.2%, respectively; and 1.6% were Double Hit Lymphoma (DHL). EBER positivity, DPL, TPL, c-Myc gene rearrangement, BCL2 gene rearrangement, extra copies of BCL2 gene and BCL6 gene rearrangement were associated with shorter median overall survival (P<0.05). IPI score was the significant determinants of median overall survival in DPL and TPL (P<0.05). CD5 protein expression and GCB/non-GCB sub-categorization did not affect treatment outcome (P>0.05). Overall, c-Myc, BCL2 and BCL6 gene rearrangements showed weak correlation with expression of MYC, BCL2 and BCL6 proteins (P>0.05). Fluorescent in situ hybridization is the preferred technique for prediction of treatment outcome in DLBCL patients. Conclusion:c-Myc, BCL2, and BCL6 gene rearrangements, EBER expression, DHL, TPL and IPI score are reliable risk stratification tools. MYC, BCL2 and BCL6 proteins expression are not applicable as baseline biomarkers to predict c-Myc, BCL2, and BCL6 gene rearrangements.
  11. Fulltext Collagen Triple Helix Repeat Containing-1 (CTHRC1) Expression in Oral Squamous Cell Carcinoma (OSCC): Prognostic Value and Clinico-Pathological Implications
    Lee CE, Vincent-Chong VK, Ramanathan A, Kallarakkal TG, Karen-Ng LP, Ghani WM, et al.
    Int J Med Sci, 2015;12(12):937-45.
    PMID: 26664254 DOI: 10.7150/ijms.11605
    Collagen Triple Helix Repeat Containing 1 (CTHRC1) is a protein often found to be over-expressed in various types of human cancers. However, correlation between CTHRC1 expression level with clinico-pathological characteristics and prognosis in oral cancer remains unclear. Therefore, this study aimed to determine mRNA and protein expression of CTHRC1 in oral squamous cell carcinoma (OSCC) and to evaluate the clinical and prognostic impact of CTHRC1 in OSCC.
  12. Correlations of HBV genotypes, mutations affecting HBeAg expression and HBeAg/ anti-HBe status in HBV carriers
    Lim CK, Tan JT, Khoo JB, Ravichandran A, Low HM, Chan YC, et al.
    Int J Med Sci, 2006;3(1):14-20.
    PMID: 16421626
    This study was carried out to determine the effects of hepatitis B virus genotypes, core promoter mutations (A1762G1764-->T1762A1764) as well as precore stop codon mutations (TGG-->TAG) on HBeAg expression and HBeAg/ anti-HBe status. Study was also performed on the effects of codon 15 variants (C1858/ T1858) on the predisposition of precore stop codon mutations (TGG-->TAG). A total of 77 sera samples were analyzed. Fifty one samples were successfully genotyped of which the predominant genotype was genotype B (29/ 51, 56.9 %), followed by genotype C (16/ 51, 31.4 %). Co-infections by genotypes B and C were observed in four samples (7.8 %). To a lesser degree, genotypes D and E (2.0 % each) were also observed. For core promoter mutations, the prevalence was 68.8 % (53/ 77) for A1762G1764 wild-type and 14.3 % (11/ 77) for T1762A1764 mutant while 9.1 % (7/ 77) was co-infected by both strains. The prevalence of codon 15 variants was found to be 42.9 % (33/ 77) for T1858 variant and 16.9 % (13/ 77) for C1858 variant. No TAG mutation was found. In our study, no associations were found between genotypes (B and C) and core promoter mutations as well as codon 15 variants. Also no correlation was observed between HBeAg/ anti-HBe status with genotypes (B and C) and core promoter mutations.
  13. Fulltext DNA methylation profiling revealed promoter hypermethylation-induced silencing of p16, DDAH2 and DUSP1 in primary oral squamous cell carcinoma
    Khor GH, Froemming GR, Zain RB, Abraham MT, Omar E, Tan SK, et al.
    Int J Med Sci, 2013;10(12):1727-39.
    PMID: 24155659 DOI: 10.7150/ijms.6884
    BACKGROUND: Hypermethylation in promoter regions of genes might lead to altered gene functions and result in malignant cellular transformation. Thus, biomarker identification for hypermethylated genes would be very useful for early diagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC). The objectives of this study were to screen and validate differentially hypermethylated genes in OSCC and correlate the hypermethylation-induced genes with demographic, clinocopathological characteristics and survival rate of OSCC.

    METHODS: DNA methylation profiling was utilized to screen the differentially hypermethylated genes in OSCC. Three selected differentially-hypermethylated genes of p16, DDAH2 and DUSP1 were further validated for methylation status and protein expression. The correlation between demographic, clinicopathological characteristics, and survival rate of OSCC patients with hypermethylation of p16, DDAH2 and DUSP1 genes were analysed in the study.

    RESULTS: Methylation profiling demonstrated 33 promoter hypermethylated genes in OSCC. The differentially-hypermethylated genes of p16, DDAH2 and DUSP1 revealed positivity of 78%, 80% and 88% in methylation-specific polymerase chain reaction and 24% and 22% of immunoreactivity in DDAH2 and DUSP1 genes, respectively. Promoter hypermethylation of p16 gene was found significantly associated with tumour site of buccal, gum, tongue and lip (P=0.001). In addition, DDAH2 methylation level was correlated significantly with patients' age (P=0.050). In this study, overall five-year survival rate was 38.1% for OSCC patients and was influenced by sex difference.

    CONCLUSIONS: The study has identified 33 promoter hypermethylated genes that were significantly silenced in OSCC, which might be involved in an important mechanism in oral carcinogenesis. Our approaches revealed signature candidates of differentially hypermethylated genes of DDAH2 and DUSP1 which can be further developed as potential biomarkers for OSCC as diagnostic, prognostic and therapeutic targets in the future.

  14. Fulltext Detection of Human Papillomavirus 16-Specific IgG and IgM Antibodies in Patient Sera: A Potential Indicator of Oral Squamous Cell Carcinoma Risk Factor
    Kerishnan JP, Gopinath SC, Kai SB, Tang TH, Ng HL, Rahman ZA, et al.
    Int J Med Sci, 2016;13(6):424-31.
    PMID: 27279791 DOI: 10.7150/ijms.14475
    The association between human papillomavirus type 16 (HPV16) and oral cancer has been widely reported. However, detecting anti-HPV antibodies in patient sera to determine risk for oral squamous cell carcinoma (OSCC) has not been well studied. In the present investigation, a total of 206 OSCC serum samples from the Malaysian Oral Cancer Database & Tissue Bank System, with 134 control serum samples, were analyzed by enzyme-linked immunosorbant assay (ELISA) to detect HPV16-specific IgG and IgM antibodies. In addition, nested PCR analysis using comprehensive consensus primers (PGMY09/11 and GP5(+)/6(+)) was used to confirm the presence of HPV. Furthermore, we have evaluated the association of various additional causal factors (e.g., smoking, alcohol consumption, and betel quid chewing) in HPV-infected OSCC patients. Statistical analysis of the Malaysian population indicated that OSCC was more prevalent in female Indian patients that practices betel quid chewing. ELISA revealed that HPV16 IgG, which demonstrates past exposure, could be detected in 197 (95.6%) OSCC patients and HPV16-specific IgM was found in a total of 42 (20.4%) OSCC patients, indicating current exposure. Taken together, our study suggest that HPV infection may play a significant role in OSCC (OR: 13.6; 95% CI: 3.89-47.51) and HPV16-specific IgG and IgM antibodies could represent a significant indicator of risk factors in OSCC patients.
  15. Fulltext Different isolation methods alter the gene expression profiling of adipose derived stem cells
    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.
  16. Fulltext Differential protein expression between chondrogenic differentiated MSCs, undifferentiated MSCs and adult chondrocytes derived from Oryctolagus cuniculus in vitro
    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. Fulltext Energy and nutritional composition of Tiger milk mushroom (Lignosus tigris Chon S. Tan) sclerotia and the antioxidant activity of its extracts
    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.
  18. Fulltext Enhanced Expression of Sodium Hydrogen Exchanger (NHE)-1, 2 and 4 in the Cervix of Ovariectomised Rats by Phytoestrogen Genistein
    Ismail N, Giribabu N, Muniandy S, Salleh N
    Int J Med Sci, 2015;12(6):468-77.
    PMID: 26078707 DOI: 10.7150/ijms.11210
    Restoring the pH of cervicovaginal fluid is important for the cervicovaginal health after menopause. Genistein, which is a widely consumed dietary health supplement to overcome the post-menopausal complications could help to restore the cervicovaginal fluid pH. We hypothesized that genistien effect involves changes in expression of NHE-1, 2 and 4 proteins and mRNAs in the cervix. This study investigated effect of genistein on NHE-1, 2 and 4 protein and mRNA expression in the cervix in order to elucidate the mechanisms underlying possible effect of this compound on cervicovaginal fluid pH after menopause.
  19. Fulltext Establishing an Animal Model of Secondary Osteoporosis by Using a Gonadotropin-releasing Hormone Agonist
    Mohamad NV, Che Zulkepli MAA, May Theseira K, Zulkifli N, Shahrom NQ, Ridzuan NAM, et al.
    Int J Med Sci, 2018;15(4):300-308.
    PMID: 29511366 DOI: 10.7150/ijms.22732
    Introduction: Orchidectomy is currently the preferred method to induce bone loss in preclinical male osteoporosis model. Gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer treatment can induce testosterone deficiency but its effects on bone in preclinical male osteoporosis model are less studied. Objective: This study aimed to evaluate the skeletal effect of buserelin (a GnRH agonist) in male rats and compare it with orchidectomy. Methods: Forty-six three-month-old male Sprague-Dawley rats were divided into three experimental arms. The baseline arm (n=6) was sacrificed at the onset of the study. In the buserelin arm, the rats received a daily subcutaneous injection of either normal saline (n=8), buserelin acetate at 25 µg/kg (n=8) or 75 µg/kg (n=8). In the orchidectomy arm, the rats were either sham-operated (n=8) or orchidectomized (n=8). All groups underwent in-vivo X-ray micro-computed tomography scanning at the left proximal tibia every month. Blood was collected at the beginning and the end of the study for testosterone level evaluation. The rats were euthanized after the three-month treatment. The femurs were harvested for biomechanical strength and bone calcium determination. Results: The results showed that buserelin at both doses caused a significant decline in testosterone level and deterioration in bone microstructure (p<0.05), but did not affect bone calcium content (p>0.05). Buserelin at 25 µg/kg decreased displacement and strain of the femur significantly (p<0.05). Similar changes were observed in the orchidectomized group compared to the sham-operated group but without any significant changes in biomechanical strength (p>0.05). Conclusion: Buserelin can induce testosterone deficiency and the associated deterioration of bone microarchitecture similar to orchidectomy in three months. However, it may require a longer time to show significant effects on bone strength and mineral content.
  20. Fulltext Evaluation of antiviral activities of four local Malaysian Phyllanthus species against herpes simplex viruses and possible antiviral target
    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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