Displaying publications 1 - 20 of 28 in total

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  1. Genetically modified mesenchymal stem/stromal cells transfected with adiponectin gene can stably secrete adiponectin
    Hossain MM, Murali MR, Kamarul T
    Life Sci, 2017 Aug 01;182:50-56.
    PMID: 28606849 DOI: 10.1016/j.lfs.2017.06.007
    AIMS: Mesenchymal stem/stromal cells (MSCs) hold promises for the treatment of diverse diseases and regeneration of injured tissues. Genetic modification of MSCs through gene delivery might enhance their therapeutic potential. Adiponectin has been appeared as a potential biomarker for predicting various diseases. Plasma adiponectin levels are negatively correlated with various metabolic and vascular diseases and supplementation of exogenous adiponectin ameliorates the diseases. This study aims to develop adiponectin secreting genetically modified MSCs (GM-MSCs) as a potent strategic tool to complement endogenous adiponectin for the treatment of adiponectin deficiency diseases.

    MAIN METHODS: Human bone marrow derived MSCs were isolated, expanded in vitro and transfected with adiponectin gene containing plasmid vector. Total RNA was extracted and cDNA was prepared by reverse transcription polymerase chain reaction (RT-PCR). The expression of adiponectin gene and protein in GM-MSCs was analyzed by PCR and Western blotting respectively. The secretion of adiponectin protein from GM-MSCs was analyzed by enzyme-linked immunosorbent assay.

    KEY FINDINGS: The expression of adiponectin gene and plasmid DNA was detected in GM-MSCs but not in control group of MSCs. Adiponectin gene expression was detected in GM-MSCs at 2, 7, 14, 21 and 28days after transfection. Western blotting analysis revealed the expression of adiponectin protein only in GM-MSCs. The GM-MSCs stably secreted adiponectin protein into culture media at least for 4weeks.

    SIGNIFICANCE: GM-MSCs express and secret adiponectin protein. Therefore, these adiponectin secreting GM-MSCs could be instrumental for the supplementation of adiponectin in the treatment of adiponectin deficiency related diseases.

  2. Biomechanical analysis of the wrist arthroplasty in rheumatoid arthritis: a finite element analysis
    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.
  3. Coadministration of alloxan and nicotinamide in rats produces biochemical changes in blood and pathological alterations comparable to the changes in type II diabetes mellitus
    Vattam KK, Raghavendran H, Murali MR, Savatey H, Kamarul T
    Hum Exp Toxicol, 2016 Aug;35(8):893-901.
    PMID: 26429928 DOI: 10.1177/0960327115608246
    In the present study, thirty six male Sprague Dawley rats were randomly divided into six groups and were injected with varying doses of alloxan (Ax) and nicotinamide (NA). The serum levels of glucose, insulin, and adiponectin were measured weekly up to 4 weeks.
  4. Fulltext Current knowledge on alleviating Helicobacter pylori infections through the use of some commonly known natural products: bench to bedside
    Murali MR, Naveen SV, Son CG, Raghavendran HRB
    Integr Med Res, 2014 Sep;3(3):111-118.
    PMID: 28664086 DOI: 10.1016/j.imr.2014.04.001
    Helicobacter pylori, a spiral-shaped Gram-negative bacterium, has been classified as a class I carcinogen by the World Health Organization and recognized as the causative agent for peptic ulcers, duodenal ulcer, gastritis, mucosa-associated lymphoid tissue lymphomas, and gastric cancer. Owing to their alarming rate of drug resistance, eradication of H. pylori remains a global challenge. Triple therapy consisting of a proton pump inhibitor, clarithromycin, and either amoxicillin or metronidazole, is generally the recommended standard for the treatment of H. pylori infection. Complementary and alternative medicines have a long history in the treatment of gastrointestinal ailments and various compounds has been tested for anti-H. pylori activity both in vitro and in vivo; however, their successful use in human clinical trials is sporadic. Hence, the aim of this review is to analyze the role of some well-known natural products that have been tested in clinical trials in preventing, altering, or treating H. pylori infections. Whereas some in vitro and in vivo studies in the literature have demonstrated the successful use of a few potential natural products for the treatment of H. pylori-related infections, others indicate a need to consider natural products, with or without triple therapy, as a useful alternative in treating H. pylori-related infections. Thus, the reported mechanisms include killing of H. pylori urease inhibition, induction of bacterial cell damage, and immunomodulatory effect on the host immune system. Furthermore, both in vitro and in vivo studies have demonstrated the successful use of some potential natural products for the treatment of H. pylori-related infections. Nevertheless, the routine prescription of potential complementary and alternative medicines continues to be restrained, and evidence on the safety and efficacy of the active compounds remains a subject of ongoing debate.
  5. Finite element analysis of three commonly used external fixation devices for treating Type III pilon fractures
    Ramlee MH, Kadir MR, Murali MR, Kamarul T
    Med Eng Phys, 2014 Oct;36(10):1322-30.
    PMID: 25127377 DOI: 10.1016/j.medengphy.2014.05.015
    Pilon fractures are commonly caused by high energy trauma and can result in long-term immobilization of patients. The use of an external fixator i.e. the (1) Delta, (2) Mitkovic or (3) Unilateral frame for treating type III pilon fractures is generally recommended by many experts owing to the stability provided by these constructs. This allows this type of fracture to heal quickly whilst permitting early mobilization. However, the stability of one fixator over the other has not been previously demonstrated. This study was conducted to determine the biomechanical stability of these external fixators in type III pilon fractures using finite element modelling. Three-dimensional models of the tibia, fibula, talus, calcaneus, navicular, cuboid, three cuneiforms and five metatarsal bones were reconstructed from previously obtained CT datasets. Bones were assigned with isotropic material properties, while the cartilage was assigned as hyperelastic springs with Mooney-Rivlin properties. Axial loads of 350 N and 70 N were applied at the tibia to simulate the stance and the swing phase of a gait cycle. To prevent rigid body motion, the calcaneus and metatarsals were fixed distally in all degrees of freedom. The results indicate that the model with the Delta frame produced the lowest relative micromovement (0.03 mm) compared to the Mitkovic (0.05 mm) and Unilateral (0.42 mm) fixators during the stance phase. The highest stress concentrations were found at the pin of the Unilateral external fixator (509.2 MPa) compared to the Mitkovic (286.0 MPa) and the Delta (266.7 MPa) frames. In conclusion, the Delta external fixator was found to be the most stable external fixator for treating type III pilon fractures.
  6. Biomechanical evaluation of two commonly used external fixators in the treatment of open subtalar dislocation--a finite element analysis
    Ramlee MH, Kadir MR, Murali MR, Kamarul T
    Med Eng Phys, 2014 Oct;36(10):1358-66.
    PMID: 25092623 DOI: 10.1016/j.medengphy.2014.07.001
    Subtalar dislocation is a rare injury caused by high-energy trauma. Current treatment strategies include leg casts, internal fixation and external fixation. Among these, external fixators are the most commonly used as this method is believed to provide better stabilization. However, the biomechanical stability provided by these fixators has not been demonstrated. This biomechanical study compares two commonly used external fixators, i.e. Mitkovic and Delta. CT imaging data were used to reconstruct three-dimensional models of the tibia, fibula, talus, calcaneus, navicular, cuboid, three cuneiforms and five metatarsal bones. The 3D models of the bones and cartilages were then converted into four-noded linear tetrahedral elements, whilst the ligaments were modelled with linear spring elements. Bones and cartilage were idealized as homogeneous, isotropic and linear. To simulate loading during walking, axial loading (70 N during the swing and 350 N during the stance phase) was applied at the end of diaphyseal tibia. The results demonstrate that the Mitkovic fixator produced greater displacement (peak 3.0mm and 15.6mm) compared to the Delta fixator (peak 0.8mm and 3.9 mm), in both the swing and stance phase, respectively. This study demonstrates that the Delta external fixator provides superior stability over the Mitkovic fixator. The Delta fixator may be more effective in treating subtalar dislocation.
  7. Synergistic interaction of platelet derived growth factor (PDGF) with the surface of PLLA/Col/HA and PLLA/HA scaffolds produces rapid osteogenic differentiation
    Raghavendran HR, Mohan S, Genasan K, Murali MR, Naveen SV, Talebian S, et al.
    Colloids Surf B Biointerfaces, 2016 Mar 1;139:68-78.
    PMID: 26700235 DOI: 10.1016/j.colsurfb.2015.11.053
    Scaffolds with structural features similar to the extracellular matrix stimulate rapid osteogenic differentiation in favorable microenvironment and with growth factor supplementation. In this study, the osteogenic potential of electrospun poly-l-lactide/hydroxyapatite/collagen (PLLA/Col/HA, PLLA/HA and PLLA/Col) scaffolds were tested in vitro with the supplementation of platelet derived growth factor-BB (PDGF-BB). Cell attachment and topography, mineralization, extracellular matrix protein localization, and gene expression of the human mesenchymal stromal cells were compared between the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA. The levels of osteocalcin, calcium, and mineralization were significantly greater in the PLLA/Col/HA and PLLA/HA compared with PLLA/Col. High expression of fibronectin, intracellular adhesion molecule, cadherin, and collagen 1 (Col1) suggests that PLLA/Col/HA and PLLA/HA scaffolds had superior osteoinductivity than PLLA/Col. Additionally, osteopontin, osteocalcin, osterix, Runt-related transcription factor 2 (Runx2), and bone morphogenic protein (BMP2) expression were higher in PLLA/Col/HA and PLLA/HA compared with PLLA/Col. In comparison with PLLA/Col, the PLLA/Col/HA and PLLA/HA scaffolds presented a significant upregulation of the genes Runx2, Col 1, Integrin, osteonectin (ON), bone gamma-carboxyglutamic acid-containing protein (BGALP), osteopontin (OPN), and BMP2. The upregulation of these genes was further increased with PDGF-BB supplementation. These results show that PDGF-BB acts synergistically with PLLA/Col/HA and PLLA/HA to enhance the osteogenic differentiation potential. Therefore, this combination can be used for the rapid expansion of bone marrow stromal cells into bone-forming cells for tissue engineering.
  8. Fulltext Platelet rich concentrate promotes early cellular proliferation and multiple lineage differentiation of human mesenchymal stromal cells in vitro
    Shani S, Ahmad RE, Naveen SV, Murali MR, Puvanan K, Abbas AA, et al.
    ScientificWorldJournal, 2014;2014:845293.
    PMID: 25436230 DOI: 10.1155/2014/845293
    Platelet rich concentrate (PRC) is a natural adjuvant that aids in human mesenchymal stromal cell (hMSC) proliferation in vitro; however, its role requires further exploration. This study was conducted to determine the optimal concentration of PRC required for achieving the maximal proliferation, and the need for activating the platelets to achieve this effect, and if PRC could independently induce early differentiation of hMSC. The gene expression of markers for osteocytes (ALP, RUNX2), chondrocytes (SOX9, COL2A1), and adipocytes (PPAR-γ) was determined at each time point in hMSC treated with 15% activated and nonactivated PRC since maximal proliferative effect was achieved at this concentration. The isolated PRC had approximately fourfold higher platelet count than whole blood. There was no significant difference in hMSC proliferation between the activated and nonactivated PRC. Only RUNX2 and SOX9 genes were upregulated throughout the 8 days. However, protein expression study showed formation of oil globules from day 4, significant increase in ALP at days 6 and 8 (P ≤ 0.05), and increased glycosaminoglycan levels at all time points (P < 0.05), suggesting the early differentiation of hMSC into osteogenic and adipogenic lineages. This study demonstrates that the use of PRC increased hMSC proliferation and induced early differentiation of hMSC into multiple mesenchymal lineages, without preactivation or addition of differentiation medium.
  9. Fulltext Histology, glycosaminoglycan level and cartilage stiffness in monoiodoacetate-induced osteoarthritis: comparative analysis with anterior cruciate ligament transection in rat model and human osteoarthritis
    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.
  10. 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.
  11. Fulltext Incorporation of Fucoidan in β-Tricalcium phosphate-Chitosan scaffold prompts the differentiation of human bone marrow stromal cells into osteogenic lineage
    Puvaneswary S, Raghavendran HB, Talebian S, Murali MR, A Mahmod S, Singh S, et al.
    Sci Rep, 2016;6:24202.
    PMID: 27068453 DOI: 10.1038/srep24202
    In our previous study, we reported the fabrication and characterization of a novel tricalcium phosphate-fucoidan-chitosan (TCP-Fu-Ch) biocomposite scaffold. However, the previous report did not show whether the biocomposite scaffold can exhibit osteogenic differentiation of human bone marrow stromal cells in osteogenic media and normal media supplemented with platelet-derived growth factor (PDGF-BB). On day 15, the release of osteocalcin, was significant in the TCP-Fu-Ch scaffold, when compared with that in the TCP-Ch scaffold, and the level of release was approximately 8 and 6 ng/ml in osteogenic and normal media supplemented with PDGF-BB, respectively. Scanning electron microscopy of the TCP-Fu-Ch scaffold demonstrated mineralization and apatite layer formation on day 14, while the addition of PDGF-BB also improved the osteogenic differentiation of the scaffold. An array of gene expression analysis demonstrated that TCP-Fu-Ch scaffold cultured in osteogenic and normal media supplemented with PDGF-BB showed significant improvement in the expression of collagen 1, Runt-related transcription factor 2, osteonectin, bone gamma-carboxyglutamate protein, alkaline phosphatase, and PPA2, but a decline in the expression of integrin. Altogether, the present study demonstrated that fucoidan-incorporated TCP-Ch scaffold could be used in the differentiation of bone marrow stromal cells and can be a potential candidate for the treatment of bone-related ailments through tissue engineering technology.
  12. Fulltext Ultra-structural changes and expression of chondrogenic and hypertrophic genes during chondrogenic differentiation of mesenchymal stromal cells in alginate beads
    Dashtdar H, Murali MR, Selvaratnam L, Balaji Raghavendran H, Suhaeb AM, Ahmad TS, et al.
    PeerJ, 2016;4:e1650.
    PMID: 26966647 DOI: 10.7717/peerj.1650
    Chondrogenic differentiation of mesenchymal stromal cells (MSCs) in the form of pellet culture and encapsulation in alginate beads has been widely used as conventional model for in vitro chondrogenesis. However, comparative characterization between differentiation, hypertrophic markers, cell adhesion molecule and ultrastructural changes during alginate and pellet culture has not been described. Hence, the present study was conducted comparing MSCs cultured in pellet and alginate beads with monolayer culture. qPCR was performed to assess the expression of chondrogenic, hypertrophic, and cell adhesion molecule genes, whereas transmission electron microscopy (TEM) was used to assess the ultrastructural changes. In addition, immunocytochemistry for Collagen type II and aggrecan and glycosaminoglycan (GAG) analysis were performed. Our results indicate that pellet and alginate bead cultures were necessary for chondrogenic differentiation of MSC. It also indicates that cultures using alginate bead demonstrated significantly higher (p < 0.05) chondrogenic but lower hypertrophic (p < 0.05) gene expressions as compared with pellet cultures. N-cadherin and N-CAM1 expression were up-regulated in second and third weeks of culture and were comparable between the alginate bead and pellet culture groups, respectively. TEM images demonstrated ultrastructural changes resembling cell death in pellet cultures. Our results indicate that using alginate beads, MSCs express higher chondrogenic but lower hypertrophic gene expression. Enhanced production of extracellular matrix and cell adhesion molecules was also observed in this group. These findings suggest that alginate bead culture may serve as a superior chondrogenic model, whereas pellet culture is more appropriate as a hypertrophic model of chondrogenesis.
  13. Fulltext The effect of strontium ranelate on the healing of a fractured ulna with bone gap in rabbit
    Ibrahim MR, Singh S, Merican AM, Raghavendran HR, Murali MR, Naveen SV, et al.
    BMC Vet Res, 2016 Jun 16;12(1):112.
    PMID: 27307015 DOI: 10.1186/s12917-016-0724-6
    Fracture healing in bone gap is one of the major challenges encountered in Orthopedic Surgery. At present, the treatment includes bone graft, employing either internal or external fixation which has a significant impact on the patient, family and even society. New drugs are emerging in the markets such as anabolic bone-forming agents including teriparatide and strontium ranelate to stimulate bone growth. Based on the mechanism of their actions, we embarked on a study on the healing of a fractured ulna with bone gap in a rabbit model. We segregated ten rabbits into two groups: five rabbits in the test group and five rabbits in the control group. We created a 5 mm bone gap in the ulna bone, removing the periosteum as well. Rabbits in the test group received 450 mg/kg of strontium ranelate via oral administration, daily, for six weeks. The x-rays, CT scans and blood tests were performed every two weeks. At the end of six weeks, the rabbits were sacrificed, and the radius and ulna bones harvested for histopathological examination.
  14. Three dimensional alginate-fucoidan composite hydrogel augments the chondrogenic differentiation of mesenchymal stromal cells
    Karunanithi P, Murali MR, Samuel S, Raghavendran HRB, Abbas AA, Kamarul T
    Carbohydr Polym, 2016 08 20;147:294-303.
    PMID: 27178935 DOI: 10.1016/j.carbpol.2016.03.102
    Presence of sulfated polysaccharides like heparan sulphate has often been implicated in the regulation of chondrogenesis. However, recently there has been a plethora of interest in the use of non-animal extracted analogs of heparan sulphate. Here we remodeled alginate (1.5%) by incorporating fucoidan (0.5%), a natural sulphated polysaccharide extracted from seaweeds to form a composite hydrogel (Al-Fu), capable of enhancing chondrogenesis of human mesenchymal stromal cells (hMSCs). We confirmed the efficiency of fucoidan incorporation by FTIR and EDX analysis. Further, its ability to support hMSC attachment and chondrogenic differentiation was confirmed by SEM, biochemical glycosaminoglycan quantification, real-time quantitative PCR and immunocytochemical analyses of chondrogenic markers Sox-9, Collagen II, Aggrecan and COMP. Effect of Al-Fu hydrogel on hMSC hypertrophy was also confirmed by the downregulation of hypertrophic genes Collagen X and Runx2. This composite scaffold can hence be used as a cartilage biomimetic biomaterial to drive hMSC chondrogenesis and for other cartilage repair based therapies.
  15. Proliferation and osteogenic differentiation of mesenchymal stromal cells in a novel porous hydroxyapatite scaffold
    Krishnamurithy G, Murali MR, Hamdi M, Abbas AA, Raghavendran HB, Kamarul T
    Regen Med, 2015;10(5):579-90.
    PMID: 26237702 DOI: 10.2217/rme.15.27
    To compare the effect of bovine bone derived porous hydroxyapatite (BDHA) scaffold on proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hMSCs) compared with commercial hydroxyapatite (CHA) scaffold.
  16. Fulltext The use of X-shaped cross-link in posterior spinal constructs improves stability in thoracolumbar burst fracture: a finite element analysis
    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.
  17. Differential cytotoxic activity of Quercetin on colonic cancer cells depends on ROS generation through COX-2 expression
    Raja SB, Rajendiran V, Kasinathan NK, P A, Venkatabalasubramanian S, Murali MR, et al.
    Food Chem Toxicol, 2017 Aug;106(Pt A):92-106.
    PMID: 28479391 DOI: 10.1016/j.fct.2017.05.006
    Quercetin is a bioactive compound with anti-inflammatory, antioxidant and anticancer properties. This study exemplifies the differential cytotoxic activity of Quercetin on two human colonic cancer cell lines, HT29 and HCT15. IC50 of Quercetin for HT29 and HCT15 cells were 42.5 μM and 77.4 μM, respectively. Activation of caspase-3, increased level of cytosolic cytochrome c, decreased levels of pAkt, pGSK-3β and cyclin D1 in 40 μM Quercetin treated HT29 cells alone. Though, nuclear translocation of NFkB was increased in 40 μM Quercetin treated HT29 and HCT15 cells, over expression of COX-2 was observed in 40 μM Quercetin treated HT29 cells, whereas, Quercetin treated HCT15 cells did not expressed COX-2. Increased generation of reactive oxygen species (ROS) was observed only in Quercetin treated HT29 cells, which is due to over expression of COX-2, as COX-2 silencing inhibited Quercetin induced apoptosis and ROS generation. Insilico analysis provided evidence that Quercetin could partially inhibit COX-2 enzyme by binding to subunit A which has peroxidase activity and serves as source of ROS. However, Quercetin showed minimal effect on normal intestinal epithelial cells i,e IEC-6. To conclude, differential sensitivity of two cancer cells, HT29 and HCT15, to Quercetin depends on COX-2 dependent ROS generation that induces apoptosis and inhibits cell survival.
  18. Fulltext Mechanical Strain-Mediated Tenogenic Differentiation of Mesenchymal Stromal Cells Is Regulated through Epithelial Sodium Channels
    Nam HY, Murali MR, Ahmad RE, Pingguan-Murphy B, Raghavendran HRB, Kamarul T
    Stem Cells Int, 2020;2020:5385960.
    PMID: 32908542 DOI: 10.1155/2020/5385960
    It has been suggested that mechanical strain may elicit cell differentiation in adult somatic cells through activation of epithelial sodium channels (ENaC). However, such phenomenon has not been previously demonstrated in mesenchymal stromal cells (MSCs). The present study was thus conducted to investigate the role of ENaC in human bone marrow-derived MSCs (hMSCs) tenogenic differentiation during uniaxial tensile loading. Passaged-2 hMSCs were seeded onto silicone chambers coated with collagen I and subjected to stretching at 1 Hz frequency and 8% strain for 6, 24, 48, and 72 hours. Analyses at these time points included cell morphology and alignment observation, immunocytochemistry and immunofluorescence staining (collagen I, collagen III, fibronectin, and N-cadherin), and gene expression (ENaC subunits, and tenogenic markers). Unstrained cells at similar time points served as the control group. To demonstrate the involvement of ENaC in the differentiation process, an ENaC blocker (benzamil) was used and the results were compared to the noninhibited hMSCs. ENaC subunits' (α, β, γ, and δ) expression was observed in hMSCs, although only α subunit was significantly increased during stretching. An increase in tenogenic genes' (collagen1, collagen3, decorin, tenascin-c, scleraxis, and tenomodulin) and proteins' (collagen I, collagen III, fibronectin, and N-cadherin) expression suggests that hMSCs underwent tenogenic differentiation when subjected to uniaxial loading. Inhibition of ENaC function resulted in decreased expression of these markers, thereby suggesting that ENaC plays a vital role in tenogenic differentiation of hMSCs during mechanical loading.
  19. In-vitro bioactivity, biocompatibility and dissolution studies of diopside prepared from biowaste by using sol-gel combustion method
    Choudhary R, Vecstaudza J, Krishnamurithy G, Raghavendran HRB, Murali MR, Kamarul T, et al.
    Mater Sci Eng C Mater Biol Appl, 2016 Nov 01;68:89-100.
    PMID: 27524000 DOI: 10.1016/j.msec.2016.04.110
    Diopside was synthesized from biowaste (Eggshell) by sol-gel combustion method at low calcination temperature and the influence of two different fuels (urea, l-alanine) on the phase formation temperature, physical and biological properties of the resultant diopside was studied. The synthesized materials were characterized by heating microscopy, FTIR, XRD, BET, SEM and EDAX techniques. BET analysis reveals particles were of submicron size with porosity in the nanometer range. Bone-like apatite deposition ability of diopside scaffolds was examined under static and circulation mode of SBF (Simulated Body Fluid). It was noticed that diopside has the capability to deposit HAP (hydroxyapatite) within the early stages of immersion. ICP-OES analysis indicates release of Ca, Mg, Si ions and removal of P ions from the SBF, but in different quantities from diopside scaffolds. Cytocompatability studies on human bone marrow stromal cells (hBMSCs) revealed good cellular attachment on the surface of diopside scaffolds and formation of extracellular matrix (ECM). This study suggests that the usage of eggshell biowaste as calcium source provides an effective substitute for synthetic starting materials to fabricate bioproducts for biomedical applications.
  20. PVA-chitosan composite hydrogel versus alginate beads as a potential mesenchymal stem cell carrier for the treatment of focal cartilage defects
    Dashtdar H, Murali MR, Abbas AA, Suhaeb AM, Selvaratnam L, Tay LX, et al.
    Knee Surg Sports Traumatol Arthrosc, 2015 May;23(5):1368-1377.
    PMID: 24146054 DOI: 10.1007/s00167-013-2723-5
    PURPOSE: To investigate whether mesenchymal stem cells (MSCs) seeded in novel polyvinyl alcohol (PVA)-chitosan composite hydrogel can provide comparable or even further improve cartilage repair outcomes as compared to previously established alginate-transplanted models.

    METHODS: Medial femoral condyle defect was created in both knees of twenty-four mature New Zealand white rabbits, and the animals were divided into four groups containing six animals each. After 3 weeks, the right knees were transplanted with PVA-chitosan-MSC, PVA-chitosan scaffold alone, alginate-MSC construct or alginate alone. The left knee was kept as untreated control. Animals were killed at the end of 6 months after transplantation, and the cartilage repair was assessed through Brittberg morphological score, histological grading by O'Driscoll score and quantitative glycosaminoglycan analysis.

    RESULTS: Morphological and histological analyses showed significant (p < 0.05) tissue repair when treated with PVA-chitosan-MSC or alginate MSC as compared to the scaffold only and untreated control. In addition, safranin O staining and the glycosaminoglycan (GAG) content were significantly higher (p < 0.05) in MSC treatment groups than in scaffold-only or untreated control group. No significant difference was observed between the PVA-chitosan-MSC- and alginate-MSC-treated groups.

    CONCLUSION: PVA-chitosan hydrogel seeded with mesenchymal stem cells provides comparable treatment outcomes to that of previously established alginate-MSC construct implantation. This study supports the potential use of PVA-chitosan hydrogel seeded with MSCs for clinical use in cartilage repair such as traumatic injuries.

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