Tokoh-tokoh Kedah dalam legenda dan sejarah : satu kajian perbandingan

Kedah merupakan negeri yang tertua di Malaysia dan mempunyai rangkaian sejarah yang agak panjang. Sejarah membuktikan bahawa Kedah pernah mengalami pelbagai perubahan budaya dan kepercayaan masyarakat. Pengaruh animisme, Hindu- Budha dan pengaruh Islam telah turut mempengaruhi masyarakat Kedah. Kedah juga telah dijajah oleh beberapa buah negara seperti Siam, Acheh dan Kerajaan Chola di India. Kesemua pengaruh ini telah mengwujudkan suatu sintesis Animisme, Hindu-Buddha dan Islam dalam masyarakat Melayu. Kedah juga sangat terkenal dengan beberapa orang tokoh legenda yang sentiasa menjadi pujaan masyarakat. Diantara mereka yang terkenal ialah Tok Syeikh Jarum, Mahsuri, Puteri Lindungan Bulan, Tunku Anom, Haji Mohd. Said Yan dan Panglima Nayan. Kedah is the oldest state in Malaysia, which reflects the longest network of history. History proof that Kedah has undergone a spectrum of various diverse cultural changes as well as societal belief. The strong animism of Hindu-Buddha as well as Islam have great influence on the people of Kedah. Kedah had also been invaded, conquered and ruled by various powerful countries of that era such as Siam, Acheh and the Chola dynasty from India. All these influences had shaped the thought and brought about the Hindu-Buddhist and Islamic synthesis in the Malay community. It is worth mentioning that Kedah is also well known for some of its distinct legendary personalities or heroes who are admired highly regarded by the community. Among the famous personalities are Tok Syeikh Jarum, Mahsuri, Puteri Lindungan Bulan, Tunku Anom, Haji Mohd. Said Yan dan Panglima Nayan

Basic fibroblast growth factor enhances the expansion and secretory profile of human placenta-derived mesenchymal stem cells

Introduction: Mesenchymal stem cells (MSCs) hold a great therapeutic potential for regenerative medicine and tissue engineering due to inherent immunomodulatory and reparative properties. Hence, it necessitates a readily available supplyof MSCs to meet the clinical demands adequately. Although, a human placenta can produce MSCs, the in vitro culture-mediated cellular senescence often affect the quality of cell product. Thus, the current study has explored the feasibility of basic fibroblast growth factor (bFGF) to enhance the growth of placenta-derived MSCs (PLC-MSCs). Methods: The basic fibroblast growth factor (bFGF) was supplemented to optimise the growth of MSCs. The effects of bFGF on morphology, growth kinetics and cytokine secretion of PLC-MSCs were assessed. Results: The bFGF supplementation increased the proliferation of PLC-MSCs in a dose-dependent manner and 40 ng/ml showed a high trophism effect on PLC-MSC’s growth. In the presence of bFGF, PLC-MSCs acquired a small and well-defined morphology that reflect an active proliferative status. BFGF has induced PLC-MSCs to achieve a shorter doubling time (45 hrs) as compared to the non-supplemented PLC-MSCs culture (81 hrs). Furthermore, bFGF impelled PLC-MSCs into cell cycle machinery where a substantial fraction of cells was driven to S and G2/M phases. Amongst, 36 screened cytokines, bFGF had only altered the secretion of IL-8, IL-6, TNFR1, MMP3 and VEGF. Conclusion: The present study showed that bFGF supplementation promotes the growth of PLC-MSCs without significantly deviating from the standard criteria of MSCs. Thus, bFGF could be considered as a potential mitogen to facilitate the large-scale production of PLC-MSCs

Immunosuppresive activity of human umbilical cord and placenta derived mesenchymal stem cells on lymphocyte proliferation

Current research in mesenchymal stem cells (MSC) concur its potential to be used in therapies to treat various inflammatory diseases and degenerative disorders. In the present study, human umbilical cord (UC) and placenta (PLC) derived MSC were generated and their immunosuppressive activity was assessed using human adaptive and innate lymphocytes. CD3/CD28 micro-beads activated T cells, pokeweed stimulated B cells and NK-92MI cell lines were cultured in the presence or absence of UC-MS and PLC-MSC. The proliferation and cell cycle status of responder cells was measured by tritiated thymidine assay and flow cytometer analysis respectively. Both, UC-MSC and PLC-MSC significantly exerted a significant dose dependent inhibition on lymphocytes proliferation. Further cell cycle analysis showed that T cells were arrested at G0 phase and NK-92MI cells were halted at G1 by preventing them transit from G1→ S phase (p<0.05). Transwell assay revealed that the immunosuppressive activity of MSC was mediated by a direct cell-to-cell contact than soluble factors (p<0.05). Although both UC and PLC derived MSC exerted a profound anti-proliferative activity on lymphocytes yet UC-MSC express the higher magnitude of immunosuppression in all tested assays

Profiling of Burkholderia cepacia Secretome at Mid-Logarithmic and Early-Stationary Phases of Growth

BACKGROUND: Burkholderia cepacia is a Gram-negative pathogen that causes serious respiratory infections in immunocompromised patients and individuals with cystic fibrosis. This bacterium is known to release extracellular proteins that may be involved in virulence. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, B. cepacia grown to mid-logarithmic and early-stationary phases were investigated on their ability to invade and survive intracellularly in A549 lung epithelial cells in order to discern the fate of these bacteria in the pathogenesis of B. cepacia lung infections in in vitro condition. The early-stationary phase B. cepacia was demonstrated to be more invasive than mid-logarithmic phase. In addition, culture supernatants of B. cepacia obtained from these phases of growth were also demonstrated to cause different cytotoxic potency on the A549 human lung epithelial cells. Profiling of the supernatants using the gel-based proteomics approach identified 43 proteins that were commonly released in both the growth phases and 40 proteins newly-released at the early-stationary phase. The latter proteins may account for the higher cytotoxic activity of the early-stationary culture supernatant compared to that obtained at the mid-logarithmic phase. Among the newly-released proteins in the early-stationary phase supernatant were flagellar hook-associated domain protein (FliD), flagellar hook-associated protein (FlgK), TonB-dependent siderophore (Fiu), Elongation factor G (FusA), phosphoglycerate kinase (Pgk) and sulfatase (AslA) which are known for their virulence. CONCLUSION/SIGNIFICANCE: Differences in the ability of B. cepacia to invade and survive intracellularly inside the epithelial cells at different phases of growth may improve our understanding of the varied disease progressions associated with B. cepacia infections. In addition, the identified culture supernatant proteins may be used as targets for the development of new strategies to control B. cepacia infection using agents that can block their release

Evaluation of metabolic and immunological changes in streptozotocin-nicotinamide induced diabetic rats

Type 2 diabetes is a chronic disease with growing public health concern globally. Finding remedies to assist this health issue requires recruiting appropriate animal model for experimental studies. This study was designated to evaluate metabolic and immunologic changes in streptozotocin-nicotinamide induced diabetic rats as a model of type 2 diabetes. Male rats were induced diabetes using nicotinamide (110 mg/kg) and streptozotocin (65 mg/kg). Following 42 days, biochemical and immunological tests showed that diabetic rats had higher levels of blood glucose, WBC, certain abnormalities in lipid profile and insufficient mitogenic responses of lymphocytes (p < 0.05). However, the status of the total antioxidant, inflammatory biomarkers and other parameters of full blood count (except HCT) were not significantly altered. Phenotyping assay indicated insignificant lymphocyte subtype imbalances excluding a significant rise in the level of CD4+CD25+ marker (p < 0.05). This model of diabetic animals may represent some but not all symptoms of human type 2 diabetes

The effect of human Mesenchymal stem cell on neutrophil oxidative burst

Objective: Mesenchymal stem cells (MSC) are multipotent, non-haematopoietic stem cells that are capable of differentiating into different varieties of mature cell types such as osteoblasts, chondrocytes, adipocytes. and myoblasts. There is abundant evidence showing that MSC not only affect the differentiation of haematopoietic progenitors, but also the function of mature cells like lymphocytes and neutrophils. However the effect of MSC on neutrophil function and its responses is not well studied. Therefore, this study was conducted to assess the effect of MSC on neutrophil nitric oxide production. Method: Neutrophils from heparanised venous blood were isolated using Ficoll-Hypaque density gradient centrifugation followed by Dextran sedimentation and red blood cell (RBC) lysis. Isolated neutrophils were on average of 97% purity as determined by morphologic analysis. MSC were generated from human bone marrow and characterised by immunophenotyping (monoclonal antibodies CD1O5, CD73 and CD34) using a flowcytometer. In order to test the effects of MSC on neutrophil function, isolated neutrophils were co-cultured in the presence or absence of MSC at different ratios for 24 and 48 hours. The amount of nitric oxide released was used as an indication of oxidative burst and measured using the Griess assay. Result: The results indicate that MSC neither elevate the NO level when cocultured with resting neutrophils nor alone. However MSC profoundly inhibit the secretion of nitric oxide in PMA stimulated neutrophils after 241w of incubation. Conclusion: MSC exert an immunomodulatory effect on neutrophil by suppressing neutrophil oxidative burst in vitro

Rosiglitazone diminishes the high-glucose-induced modulation of 5-fluorouracil cytotoxicity in colorectal cancer cells

Colorectal cancer (CRC) is the third most leading cause of morbidity and mortality throughout the world. 5- fluorouracil (5-FU), which is often administrated to disrupt carcinogenesis, was found to elevate blood glucose level among CRC patients. Thus, this study was conducted to evaluate the influence of rosiglitazone on antipro- liferative effect of 5-FU using cellular model. Two human colonic carcinoma cell lines (HCT 116 and HT 29) were cultured in the presence of 5-FU, rosiglitazone or in combination under normal and high glucose concentra- tion. The drug cytotoxicity was evaluated using the MTT assay whereas the assessment of cell cycle was carried out using the flow cytometry technique. Combination index (CI) method was used to determine the drug interac- tion between rosiglitazone and 5-FU. High glucose diminished the cytotoxic effect of 5-FU but at a high drug dosage, this effect could be overcome. Cell cycle analysis demonstrated that 5-FU and rosiglitazone caused G1- phase arrest and S-phase arrest, respectively. CI values indicated that rosiglitazone exerted synergistic effect on 5-FU regardless of glucose levels. This study is the first to demonstrate the influence of rosiglitazone on cytotox- lucose level. Rosiglitazone may be a promising drug for enhancing the effi- cacy of 5-FU in the treatment of CRC associated with hyperglycemia

Basic fibroblast growth factor modulates cell cycle of human umbilical cord-derived mesenchymal stem cells.

Background: Mesenchymal stem cells (MSC) have great potential in regenerative medicine, immunotherapy and gene therapy due to their unique properties of self-renewal, high plasticity, immune modulation and ease for genetic modification. However, production of MSC at sufficient clinical scale remains an issue as in vitro generation of MSC inadequately fulfils the demand with respect to patients. Objectives: This study has aimed to establish optimum conditions to generate and characterize MSC from human umbilical cord (UC-MSC). Materials and methods: To optimize MSC population growth, basic fibroblast growth factor (bFGF) was utilized in culture media. Effects of bFGF on expansion kinetics, cell cycle, survival of UC-MSC, cytokine secretion, expression of early stem-cell markers and immunomodulation were investigated. Results: bFGF supplementation profoundly enhanced UC-MSC proliferation by reducing population doubling time without altering immunophenotype and immunomodulatory function of UC-MSC. However, cell cycle studies revealed that bFGF drove the cells into the cell cycle, as a higher proportion of cells resided in S phase and progressed into M phase. Consistent with this, bFGF was shown to promote expression of cyclin D proteins and their relevant kinases to drive UC-MSC to transverse cell cycle check points, thus, committing the cells to DNA synthesis. Furthermore, supplementation with bFGF changed the cytokine profiles of the cells and reduced their apoptotic level. Conclusion: Our study showed that bFGF supplementation of UC-MSC culture enhanced the cells' growth kinetics without compromising their nature

Human mesenchymal stromal cells modulate T-cell immune response via transcriptomic regulation

Background aims: Mesenchymal stromal cells (MSCs) have been identified as pan-immunosuppressant in various in vitro and in vivo inflammatory models. Although the immunosuppressive activity of MSCs has been explored in various contexts, the precise molecular signaling pathways that govern inhibitory functions remain poorly elucidated. Methods: By using a microarray-based global gene expression profiling system, this study aimed to decipher the underlying molecular pathways that may mediate the immunosuppressive activity of umbilical cord–derived MSCs (UC-MSCs) on activated T cells. Results: In the presence of UC-MSCs, the proliferation of activated T cells was suppressed in a dose-depended manner by cell-to-cell contact mode via an active cell-cycle arrest at the G0/G1 phase of the cell cycle. The microarray analysis revealed that particularly, IFNG, CXCL9, IL2, IL2RA and CCND3 genes were down-regulated, whereas IL11, VSIG4, GFA1, TIMP3 and BBC3 genes were up-regulated by UC-MSCs. The dysregulated gene clusters associated with immune-response-related ontologies, namely, lymphocyte proliferation or activation, apoptosis and cell cycle, were further analyzed. Conclusions: Among the nine canonical pathways identified, three pathways (namely T-helper cell differentiation, cyclins and cell cycle regulation, and gap/tight junction signalling pathways) were highly enriched with these dysregulated genes. The pathways represent putative molecular pathways through which UC-MSCs elicit immunosuppressive activity toward activated T cells. This study provides a global snapshot of gene networks and pathways that contribute to the ability of UC-MSCs to suppress activated T cells