Displaying publications 1 - 20 of 145 in total

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  1. Ab-Rahim S, Selvaratnam L, Kamarul T
    Cell Biol Int, 2008 Jul;32(7):841-7.
    PMID: 18479947 DOI: 10.1016/j.cellbi.2008.03.016
    Articular cartilage extracellular matrix (ECM) plays a crucial role in regulating chondrocyte functions via cell-matrix interaction, cytoskeletal organization and integrin-mediated signaling. Factors such as interleukins, basic fibroblast growth factor (bFGF), bone morphogenic proteins (BMPs) and insulin-like growth factor (IGF) have been shown to modulate the synthesis of extracellular matrix in vitro. However, the effects of TGF-beta1 and beta-estradiol in ECM regulation require further investigation, although there have been suggestions that these factors do play a positive role. To establish the role of these factors on chondrocytes derived from articular joints, a study was conducted to investigate the effects of TGF-beta1 and beta-estradiol on glycosaminoglycan secretion and type II collagen distribution (two major component of cartilage ECM in vivo). Thus, chondrocyte cultures initiated from rabbit articular cartilage were treated with 10ng/ml of TGF-beta1, 10nM of beta-estradiol or with a combination of both factors. Sulphated glycosaminoglycan (GAG) and type II collagen levels were then measured in both these culture systems. The results revealed that the synthesis of GAG and type II collagen was shown to be enhanced in the TGF-beta1 treated cultures. This increase was also noted when TGF-beta1 and beta-estradiol were both used as culture supplements. However, beta-estradiol alone did not appear to affect GAG or type II collagen deposition. There was also no difference between the amount of collagen type II and GAG being expressed when chondrocyte cultures were treated with TGF-beta1 when compared with cultures treated with combined factors. From this, we conclude that although TGF-beta1 appears to stimulate chondrocyte ECM synthesis, beta-estradiol fails to produce similar effects. The findings of this study confirm that contrary to previous claims, beta-estradiol has little or no effect on chondrocyte ECM synthesis. Furthermore, the use of TGF-beta1 may be useful in future studies looking into biological mechanisms by which ECM synthesis in chondrocyte cultures can be augmented, particularly for clinical application.
  2. Ab-Rahim S, Selvaratnam L, Raghavendran HR, Kamarul T
    Mol Cell Biochem, 2013 Apr;376(1-2):11-20.
    PMID: 23238871 DOI: 10.1007/s11010-012-1543-0
    Tissue engineering approaches often require expansion of cell numbers in vitro to accelerate tissue regenerative processes. Although several studies have used this technique for therapeutic purposes, a major concern involving the use of isolated chondrocyte culture is the reduction of extracellular matrix (ECM) protein expressed due to the transfer of cells from the normal physiological milieu to the artificial 2D environment provided by the cell culture flasks. To overcome this issue, the use of alginate hydrogel beads as a substrate in chondrocyte cultures has been suggested. However, the resultant characteristics of cells embedded in this bead is elusive. To elucidate this, a study using chondrocytes isolated from rabbit knee articular cartilage expanded in vitro as monolayer and chondrocyte-alginate constructs was conducted. Immunohistochemical evaluation and ECM distribution was examined with or without transforming growth factor (TGF-β1) supplement to determine the ability of cells to express major chondrogenic proteins in these environments. Histological examination followed by transmission electron microscopy and scanning electron microscopy was performed to determine the morphology and the ultrastructural characteristics of these cells. Results demonstrated a significant increase in glycosaminoglycan/mg protein levels in chondrocyte cultures grown in alginate construct than in monolayer cultures. In addition, an abundance of ECM protein distribution surrounding chondrocytes cultured in alginate hydrogel was observed. In conclusion, the current study demonstrates that the use of alginate hydrogel beads in chondrocyte cultures with or without TGF-β1 supplement provided superior ECM expression than monolayer cultures.
  3. Abbas AA, Mohamad JA, Lydia AL, Selvaratnam L, Razif A, Ab-Rahim S, et al.
    JUMMEC, 2014;17(1):8-13.
    MyJurnal
    Autologous chondrocyte implantation (ACI) is a widely accepted procedure for the treatment of large, fullthickness chondral defects involving various joints, but its use in developing countries is limited because of high cost and failure rates due to limited resources and support systems. Five patients (age
  4. Afshar R, Fong TS, Latifi MH, Kanthan SR, Kamarul T
    J Hand Surg Eur Vol, 2012 Jun;37(5):396-401.
    PMID: 22019989 DOI: 10.1177/1753193411424557
    The use of bicortical screws to fix metacarpal fractures has been suggested to provide no added biomechanical advantage over unicortical screw fixation. However, this was only demonstrated in static loading regimes, which may not be representative of biological conditions. The present study was done to determine whether similar outcomes are obtained when cyclic loading is applied. Transverse midshaft osteotomies were created in 20 metacarpals harvested from three cadavers. Fractures were stabilised using 2.0 mm mini fragment plates fixed with either bicortical or unicortical screw fixation. These fixations were tested to failure with a three-point bending cyclic loading protocol using an electromechanical microtester and a 1 kN load cell. The mean load to failure was 370 N (SD 116) for unicortical fixation and 450 N (SD 135) for bicortical fixation. Significant differences between these two constructs were observed. A biomechanical advantage was found when using bicortical screws in metacarpal fracture plating.
  5. Ahrend MD, Noser H, Shanmugam R, Burr F, Kamer L, Kamarul T, et al.
    J Orthop Translat, 2020 Jan;20:100-106.
    PMID: 31908940 DOI: 10.1016/j.jot.2019.10.004
    Background/Objective: Artificial bone models (ABMs) are used in orthopaedics for research of biomechanics, development of implants and educational purposes. Most of the commercially available ABMs approximate the morphology of Europeans, but they may not depict the Asian anatomy. Therefore, our aim was to develop the first Asian ABM of the pelvis and compare it with the existing pelvic ABM (Synbone®; Caucasian male).

    Methods: One hundred clinical computed tomography (CTs) of adult pelvises (male n ​= ​50, female n ​= ​50) of Malay, Chinese and Indian descent were acquired. CTs were segmented and defined landmarks were placed. Three 3D statistical pelvic model and mean models (overall, male, female) were generated. Anatomical variations were analysed using principal component analysis. To measure gender-related differences and differences to the existing ABM, distances between the anterior superior iliac spines (ASIS), the anterior inferior iliac spines (AIIS), the promontory and the symphysis (conjugate vera, CV) as well as the ischial spines (diameter transversa, DT) were quantified.

    Results: Principal component analysis displayed large variability regarding the pelvic shape and size. Female and male statistical models were similar in ASIS (225 ​± ​20; 227 ​± ​13 ​mm; P ​= ​0.4153) and AIIS (185 ​± ​11; 187 ​± ​10 ​mm; P ​= ​0.3982) and differed in CV (116 ​± ​10; 105 ​± ​10 ​mm; P ​

  6. Aizah N, Chong PP, Kamarul T
    Cartilage, 2021 12;13(2_suppl):1322S-1333S.
    PMID: 31569963 DOI: 10.1177/1947603519878479
    OBJECTIVE: Advances in research have shown that the subchondral bone plays an important role in the propagation of cartilage loss and progression of osteoarthritis (OA), but whether the subchondral bone changes precede or lead to articular cartilage loss remains debatable. In order to elucidate the subchondral bone and cartilage changes that occur in early OA, an experiment using anterior cruciate ligament transection (ACLT) induced posttraumatic OA model of the rat knee was conducted.

    DESIGN: Forty-two Sprague Dawley rats were divided into 2 groups: the ACLT group and the nonoperated control group. Surgery was conducted on the ACLT group, and subsequently rats from both groups were sacrificed at 1, 2, and 3 weeks postsurgery. Subchondral bone was evaluated using a high-resolution peripheral quantitative computed tomography scanner, while cartilage was histologically evaluated and scored.

    RESULTS: A significant reduction in the subchondral trabecular bone thickness and spacing was found as early as 1 week postsurgery in ACLT rats compared with the nonoperated control. This was subsequently followed by a reduction in bone mineral density and bone fractional volume at week 2, and finally a decrease in the trabecular number at week 3. These changes occurred together with cartilage degeneration as reflected by an increasing Mankin score over all 3 weeks.

    CONCLUSIONS: Significant changes in subchondral bone occur very early in OA concurrent with surface articular cartilage degenerative change suggest that factors affecting bone remodeling and resorption together with cartilage matrix degradation occur very early in the disease.

  7. Ali NM, Akhtar MN, Ky H, Lim KL, Abu N, Zareen S, et al.
    Drug Des Devel Ther, 2016;10:1897-907.
    PMID: 27358555 DOI: 10.2147/DDDT.S102164
    Known as naturally occurring biologically active compounds, flavokawain A and B are the leading chalcones that possess anticancer properties. Another flavokawain derivative, (E)-1-(2'-Hydroxy-4',6'-dimethoxyphenyl)-3-(4-methylthio)phenyl)prop-2-ene-1-one (FLS) was characterized with (1)H-nuclear magnetic resonance, electron-impact mas spectrometry, infrared spectroscopy, and ultraviolet ((1)H NMR, EI-MS, IR, and UV) spectroscopic techniques. FLS cytotoxic efficacy against human cancer cells (MCF-7, MDA-MB-231, and MCF-10A) resulted in the reduction of IC50 values in a time- and dose-dependent mode with high specificity on MCF-7 (IC50 of 36 μM at 48 hours) against normal breast cell MCF-10A (no IC50 detected up to 180 μM at 72 hours). Light, scanning electron, and fluorescent microscopic analysis of MCF-7 cells treated with 36 μM of FLS displayed cell shrinkage, apoptotic body, and DNA fragmentation. Additionally, induction of G2/M cell arrest within 24 hours and apoptosis at subsequent time points was discovered via flow cytometry analysis. The roles of PLK-1, Wee-1, and phosphorylation of CDC-2 in G2/M arrest and proapoptotic factors (Bax, caspase 9, and p53) in promotion of apoptosis of FLS against MCF-7 cells were discovered using fluorometric, quantitative real-time polymerase chain reaction, and Western blot analysis. Interestingly, the presence of SCH3 (thiomethyl group) on ring B structure contributed to the selective cytotoxicity against MCF-7 cells compared to other chalcones, flavokawain A and B. Overall, our data suggest potential therapeutic value for flavokawain derivative FLS to be further developed as a new anticancer drug.
  8. Alias R, Mahmoodian R, Genasan K, Vellasamy KM, Hamdi Abd Shukor M, Kamarul T
    Mater Sci Eng C Mater Biol Appl, 2020 Feb;107:110304.
    PMID: 31761210 DOI: 10.1016/j.msec.2019.110304
    Surgical site infection associated with surgical instruments has always been a factor in delaying post-operative recovery of patients. The evolution in surface modification of surgical instruments can be a potential choice to overcome the nosocomial infection mainly caused by bacterial populations such as Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. A study was, therefore, conducted characterising the morphology, hydrophobicity, adhesion strength, phase, Nano-hardness, surface chemistry, antimicrobial and biocompatibility of SS 316L steel deposited with a Nano-composite layer of Silver (Ag) and Tantalum oxide (Ta2O5) using physical vapour deposition magnetron sputtering. The adhesion strength of Ag/AgTa2O5 coating on SS 316L and treated at 250-850 °C of thermal treatment was evaluated using micro-scratch. The Ag/Ag-Ta2O5-400 °C was shown a 154% improvement in adhesion strength on SS 316L when compared with as-sputtered layer or Ag/Ag-Ta2O5-250, 550, 700 and 850 °C. The FESEM, XPS, and XRD indicated the segregation of Ag on the surface of SS 316L after the crystallization. Wettability and Nano-indentation tests demonstrated an increase in hydrophobicity (77.3 ± 0.3°) and Nano-hardness (1.12 ± 0.43 GPa) when compared with as-sputtered layer, after the 400 °C of thermal treatment. The antibacterial performance on Ag/Ag-Ta2O5-400 °C indicated a significant zone of inhibition to Staphylococcus aureus (A-axis: 16.33 ± 0.58 mm; B-axis: 25.67 ± 0.58 mm, p 
  9. Alizadeh M, Kadir MR, Fadhli MM, Fallahiarezoodar A, Azmi B, Murali MR, et al.
    J Orthop Res, 2013 Sep;31(9):1447-54.
    PMID: 23640802 DOI: 10.1002/jor.22376
    Posterior instrumentation is a common fixation method used to treat thoracolumbar burst fractures. However, the role of different cross-link configurations in improving fixation stability in these fractures has not been established. A 3D finite element model of T11-L3 was used to investigate the biomechanical behavior of short (2 level) and long (4 level) segmental spine pedicle screw fixation with various cross-links to treat a hypothetical L1 vertebra burst fracture. Three types of cross-link configurations with an applied moment of 7.5 Nm and 200 N axial force were evaluated. The long construct was stiffer than the short construct irrespective of whether the cross-links were used (p < 0.05). The short constructs showed no significant differences between the cross-link configurations. The XL cross-link provided the highest stiffness and was 14.9% stiffer than the one without a cross-link. The long construct resulted in reduced stress to the adjacent vertebral bodies and screw necks, with 66.7% reduction in bending stress on L2 when the XL cross-link was used. Thus, the stability for L1 burst fracture fixation was best achieved by using long segmental posterior instrumentation constructs and an XL cross-link configuration. Cross-links did not improved stability when a short structure was used.
  10. Almasi D, Iqbal N, Sadeghi M, Sudin I, Abdul Kadir MR, Kamarul T
    Int J Biomater, 2016;2016:8202653.
    PMID: 27127513 DOI: 10.1155/2016/8202653
    There is an increased interest in the use of polyether ether ketone (PEEK) for orthopedic and dental implant applications due to its elastic modulus close to that of bone, biocompatibility, and its radiolucent properties. However, PEEK is still categorized as bioinert due to its low integration with surrounding tissues. Many studies have reported on methods to increase the bioactivity of PEEK, but there is still one-preparation method for preparing bioactive PEEK implant where the produced implant with desirable mechanical and bioactivity properties is required. The aim of this review is to present the progress of the preparation methods for improvement of the bioactivity of PEEK and to discuss the strengths and weaknesses of the existing methods.
  11. Almasi D, Izman S, Sadeghi M, Iqbal N, Roozbahani F, Krishnamurithy G, et al.
    Int J Biomater, 2015;2015:475435.
    PMID: 25838826 DOI: 10.1155/2015/475435
    Polyether ether ketone (PEEK) is considered the best alternative material for titanium for spinal fusion cage implants due to its low elasticity modulus and radiolucent property. The main problem of PEEK is its bioinert properties. Coating with hydroxyapatite (HA) showed very good improvement in bioactivity of the PEEK implants. However the existing methods for deposition of HA have some disadvantages and damage the PEEK substrate. In our previous study a new method for deposition of HA on PEEK was presented. In this study cell proliferation of mesenchymal stem cell and apatite formation in simulated body fluid (SBF) tests were conducted to probe the effect of this new method in improvement of the bioactivity of PEEK. The mesenchymal stem cell proliferation result showed better cells proliferation on the treated layer in comparison with untreated PEEK. The apatite formation results showed the growth of the HA on the treated PEEK but there was not any sight of the growth of HA on the untreated PEEK even after 2 weeks. The results showed the new method of the HA deposition improved the bioactivity of the treated PEEK in comparison with the bare PEEK.
  12. Azura L, Ahmad TS, Kamarul T
    Med J Malaysia, 2006 Dec;61 Suppl B:51-4.
    PMID: 17600993
    We report a case of scapholunate dissociation which was initially missed and presented late. A modification of Blatt dorsal capsulodesis performed using dorsal intercarpal ligament (DICL) and extra tunnel appears not only to add to dorsal stability but also address the volar problem as well. This modification may be a better alternative to the current technique of using a single flap.
  13. Bahrampour Juybari K, Kamarul T, Najafi M, Jafari D, Sharifi AM
    Cell Tissue Res, 2018 08;373(2):407-419.
    PMID: 29582166 DOI: 10.1007/s00441-018-2825-y
    Strategies based on mesenchymal stem cell (MSC) therapy for restoring injured articular cartilage are not effective enough in osteoarthritis (OA). Due to the enhanced inflammation and oxidative stress in OA microenvironment, differentiation of MSCs into chondrocytes would be impaired. This study aims to explore the effects of diallyl disulfide (DADS) on IL-1β-mediated inflammation and oxidative stress in human adipose derived mesenchymal stem cells (hADSCs) during chondrogenesis. MTT assay was employed to examine the effects of various concentrations of DADS on the viability of hADSCs at different time scales to obtain non-cytotoxic concentration range of DADS. The effects of DADS on IL-1β-induced intracellular ROS generation and lipid peroxidation were evaluated in hADSCs. Western blotting was used to analyze the protein expression levels of IκBα (np), IκBα (p), NF-κB (np) and NF-κB (p). Furthermore, the gene expression levels of antioxidant enzymes in hADSCs and chondrogenic markers at days 7, 14 and 21 of differentiation were measured using qRT-PCR. The results showed that addition of DADS significantly enhanced the mRNA expression levels of antioxidant enzymes as well as reduced ROS elevation, lipid peroxidation, IκBα activation and NF-κB nuclear translocation in hADSCs treated with IL-1β. In addition, DADS could significantly increase the expression levels of IL-1β-induced impaired chondrogenic marker genes in differentiated hADSCs. Treatment with DADS may provide an effective approach to prevent the pro-inflammatory cytokines and oxidative stress as catabolic causes of chondrocyte cell death and enhance the protective anabolic effects by promoting chondrogenesis associated gene expressions in hADSCs exposed to OA condition.
  14. Baig S, Seevasant I, Mohamad J, Mukheem A, Huri HZ, Kamarul T
    Cell Death Dis, 2016;7:e2058.
    PMID: 26775709 DOI: 10.1038/cddis.2015.275
    Underneath the intricacy of every cancer lies mysterious events that impel the tumour cell and its posterity into abnormal growth and tissue invasion. Oncogenic mutations disturb the regulatory circuits responsible for the governance of versatile cellular functions, permitting tumour cells to endure deregulated proliferation, resist to proapoptotic insults, invade and erode normal tissues and above all escape apoptosis. This disruption of apoptosis has been highly implicated in various malignancies and has been exploited as an anticancer strategy. Owing to the fact that apoptosis causes minimal inflammation and damage to the tissue, apoptotic cell death-based therapy has been the centre of attraction for the development of anticancer drugs. Increased understanding of the molecular pathways underlying apoptosis has enabled scientists to establish unique approaches targeting apoptosis pathways in cancer therapeutics. In this review, we reconnoitre the two major pathways (intrinsic and extrinsic) targeted cancer therapeutics, steering toward chief modulators of these pathways, such as B-cell lymphoma 2 protein family members (pro- and antiapoptotic), inhibitor of apoptosis proteins, and the foremost thespian of extrinsic pathway regulator, tumour necrosis factor-related apoptosis-inducing agent. Together, we also will have a look from clinical perspective to address the agents (drugs) and therapeutic strategies adopted to target these specific proteins/pathways that have entered clinical trials.
  15. Baig S, Azizan AHS, Raghavendran HRB, Natarajan E, Naveen S, Murali MR, et al.
    Stem Cells Int, 2019;2019:5142518.
    PMID: 30956670 DOI: 10.1155/2019/5142518
    We have determined the protective effects of Thymus serpyllum (TS) extract and nanoparticle-loaded TS on hydrogen peroxide-induced cell death of mesenchymal stromal cells (MSCs) in vitro. Gas chromatography-mass spectroscopy confirmed the spectrum of active components in the extract. Out of the three different extracts, the hexane extract showed significant free radical scavenging activity. Treatment of MSCs with H2O2 (hydrogen peroxide) significantly increased intracellular cell death; however, pretreatment with TS extract and nanoparticle-loaded TS (200 μg/ml) suppressed H2O2-induced elevation of Cyt-c and MMP13 and increased the survival rates of MSCs. H2O2-induced (0.1 mM) changes in cytokines were attenuated in the extract and nanoparticles by pretreatment and cotreatment at two time points (p < 0.05). H2O2 increased cell apoptosis. In contrast, treatment with nanoparticle-loaded TS suppressed the percentage of apoptosis considerably (p < 0.05). Therefore, TS may be considered as a potential candidate for enhancing the effectiveness of MSC transplantation in cell therapy.
  16. Bajuri MN, Abdul Kadir MR, Murali MR, Kamarul T
    Med Biol Eng Comput, 2013 Feb;51(1-2):175-86.
    PMID: 23124814 DOI: 10.1007/s11517-012-0982-9
    The total replacement of wrists affected by rheumatoid arthritis (RA) has had mixed outcomes in terms of failure rates. This study was therefore conducted to analyse the biomechanics of wrist arthroplasty using recently reported implants that have shown encouraging results with the aim of providing some insights for the future development of wrist implants. A model of a healthy wrist was developed using computed tomography images from a healthy volunteer. An RA model was simulated based on all ten general characteristics of the disease. The ReMotion ™ total wrist system was then modelled to simulate total wrist arthroplasty (TWA). Finite element analysis was performed with loads simulating the static hand grip action. The results show that the RA model produced distorted patterns of stress distribution with tenfold higher contact pressure than the healthy model. For the TWA model, contact pressure was found to be approximately fivefold lower than the RA model. Compared to the healthy model, significant improvements were observed for the TWA model with minor variations in the stress distribution. In conclusion, the modelled TWA reduced contact pressure between bones but did not restore the stress distribution to the normal healthy condition.
  17. Bajuri MN, Kadir MR, Raman MM, Kamarul T
    Med Eng Phys, 2012 Nov;34(9):1294-302.
    PMID: 22277308 DOI: 10.1016/j.medengphy.2011.12.020
    Understanding the pathomechanics involved in rheumatoid arthritis (RA) of the wrist provides valuable information, which will invariably allow various therapeutic possibilities to be explored. The computational modelling of this disease permits the appropriate simulation to be conducted seamlessly. A study that underpins the fundamental concept that produces the biomechanical changes in a rheumatoid wrist was thus conducted through the use of finite element method. The RA model was constructed from computed tomography datasets, taking into account three major characteristics: synovial proliferation, cartilage destruction and ligamentous laxity. As control, a healthy wrist joint model was developed in parallel and compared. Cartilage was modelled based on the shape of the articulation while the ligaments were modelled with linear spring elements. A load-controlled analysis was performed simulating physiological hand grip loading conditions. The results demonstrated that the diseased model produced abnormal wrist extension and stress distribution as compared to the healthy wrist model. Due to the weakening of the ligaments, destruction of the cartilage and lower bone density, the altered biomechanical stresses were particularly evident at the radioscaphoid and capitolunate articulations which correlate to clinical findings. These results demonstrate the robust finding of the developed RA wrist model, which accurately predicted the pathological process.
  18. Balaji Raghavendran HR, Puvaneswary S, Talebian S, Murali MR, Raman Murali M, Naveen SV, et al.
    PLoS One, 2014;9(8):e104389.
    PMID: 25140798 DOI: 10.1371/journal.pone.0104389
    A comparative study on the in vitro osteogenic potential of electrospun poly-L-lactide/hydroxyapatite/collagen (PLLA/HA/Col, PLLA/HA, and PLLA/Col) scaffolds was conducted. The morphology, chemical composition, and surface roughness of the fibrous scaffolds were examined. Furthermore, cell attachment, distribution, morphology, mineralization, extracellular matrix protein localization, and gene expression of human mesenchymal stromal cells (hMSCs) differentiated on the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA were also analyzed. The electrospun scaffolds with a diameter of 200-950 nm demonstrated well-formed interconnected fibrous network structure, which supported the growth of hMSCs. When compared with PLLA/H%A and PLLA/Col scaffolds, PLLA/Col/HA scaffolds presented a higher density of viable cells and significant upregulation of genes associated with osteogenic lineage, which were achieved without the use of specific medium or growth factors. These results were supported by the elevated levels of calcium, osteocalcin, and mineralization (P<0.05) observed at different time points (0, 7, 14, and 21 days). Furthermore, electron microscopic observations and fibronectin localization revealed that PLLA/Col/HA scaffolds exhibited superior osteoinductivity, when compared with PLLA/Col or PLLA/HA scaffolds. These findings indicated that the fibrous structure and synergistic action of Col and nano-HA with high-molecular-weight PLLA played a vital role in inducing osteogenic differentiation of hMSCs. The data obtained in this study demonstrated that the developed fibrous PLLA/Col/HA biocomposite scaffold may be supportive for stem cell based therapies for bone repair, when compared with the other two scaffolds.
  19. Barathan M, Gopal K, Mohamed R, Ellegård R, Saeidi A, Vadivelu J, et al.
    Apoptosis, 2015 Apr;20(4):466-80.
    PMID: 25577277 DOI: 10.1007/s10495-014-1084-y
    Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using a commercial QuantiGenePlex(®) 2.0 assay, we determined the spontaneous expression profile of 80 different pro- and anti-apoptotic genes in persistent HCV disease. Onset of spontaneous apoptosis significantly correlated with the up-regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160. Besides, spontaneous differential surface protein expression suggestive of T cell inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4 on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14, Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1, Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our observation suggests the spontaneous onset of apoptosis signaling and T cell exhaustion in chronic HCV disease.
  20. Boo L, Selvaratnam L, Tai CC, Ahmad TS, Kamarul T
    J Mater Sci Mater Med, 2011 May;22(5):1343-56.
    PMID: 21461701 DOI: 10.1007/s10856-011-4294-7
    The use of mesenchymal stem cells (MSCs) in tissue repair and regeneration despite their multipotentiality has been limited by their cell source quantity and decelerating proliferative yield efficiency. A study was thus undertaken to determine the feasibility of using microcarrier beads in spinner flask cultures for MSCs expansion and compared to that of conventional monolayer cultures and static microcarrier cultures. Isolation and characterization of bone marrow derived MSCs were conducted from six adult New Zealand white rabbits. Analysis of cell morphology on microcarriers and culture plates at different time points (D0, D3, D10, D14) during cell culture were performed using scanning electron microscopy and bright field microscopy. Cell proliferation rates and cell number were measured over a period of 14 days, respectively followed by post-expansion characterization. MTT proliferation assay demonstrated a 3.20 fold increase in cell proliferation rates in MSCs cultured on microcarriers in spinner flask as compared to monolayer cultures (p < 0.05). Cell counts at day 14 were higher in those seeded on stirred microcarrier cultures (6.24 ± 0.0420 cells/ml) × 10(5) as compared to monolayer cultures (0.22 ± 0.004 cells/ml) × 10(5) and static microcarrier cultures (0.20 ± 0.002 cells/ml) × 10(5). Scanning electron microscopy demonstrated an increase in cell colonization of the cells on the microcarriers in stirred cultures. Bead-expanded MSCs were successfully differentiated into osteogenic and chondrogenic lineages. This system offers an improved and efficient alternative for culturing MSCs with preservation to their phenotype and multipotentiality.
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