Displaying publications 61 - 80 of 145 in total

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  1. Hossain MM, Mukheem A, Kamarul T
    Life Sci, 2015 Aug 15;135:55-67.
    PMID: 25818192 DOI: 10.1016/j.lfs.2015.03.010
    Hypoadiponectinemia is characterized by low plasma adiponectin levels that can be caused by genetic factors, such as single nucleotide polymorphisms (SNPs) and mutations in the adiponectin gene or by visceral fat deposition/obesity. Reports have suggested that hypoadiponectinemia is associated with dyslipidemia, hypertension, hyperuricemia, metabolic syndrome, atherosclerosis, type 2 diabetes mellitus and various cardiovascular diseases. Previous studies have highlighted several potential strategies to up-regulate adiponectin secretion and function, including visceral fat reduction through diet therapy and exercise, administration of exogenous adiponectin, treatment with peroxisome proliferator-activating receptor gamma (PPARγ) agonists (e.g., thiazolidinediones (TZDs)) and ligands (e.g., bezafibrate and fenofibrate) or the blocking of the renin-angiotensin system. Likewise, the up-regulation of the expression and stimulation of adiponectin receptors by using adiponectin receptor agonists would be an effective method to treat obesity-related conditions. Notably, adiponectin is an abundantly expressed bioactive protein that also exhibits a wide spectrum of biological properties, such as insulin-sensitizing, anti-diabetic, anti-inflammatory and anti-atherosclerotic activities. Although targeting adiponectin and its receptors has been useful for treating diabetes and other metabolic-related diseases in experimental studies, current drug development based on adiponectin/adiponectin receptors for clinical applications is scarce, and there is a lack of available clinical trial data. This comprehensive review discusses the strategies that are presently being pursued to harness the potential of adiponectin up-regulation. In addition, we examined the current status of drug development and its potential for clinical applications.
  2. 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.

  3. Fallahiarezoodar A, Abdul Kadir MR, Alizadeh M, Naveen SV, Kamarul T
    Knee Surg Sports Traumatol Arthrosc, 2014 Dec;22(12):3019-27.
    PMID: 25149643 DOI: 10.1007/s00167-014-3227-7
    PURPOSE: Reproducing the femoral rollback through specially designed mechanism in knee implants is required to achieve full knee function in total knee arthroplasty. Most contemporary implants use cam/post mechanism to replace the function of Posterior Cruciate Ligament. This study was aimed to determine the most appropriate cam and post designs to produce normal femoral rollback of the knee.

    METHODS: Three different cams (triangle, ellipse, and circle) and three different posts (straight, convex, concave) geometries were considered in this study and were analysed using kinematic analyses. Femoral rollback did not occur until reaching 50° of knee flexion. Beyond this angle, two of the nine combinations demonstrate poor knee flexion and were eliminated from the study.

    RESULTS: The combination of circle cam with concave post, straight post and convex post showed 15.6, 15.9 and 16.1 mm posterior translation of the femur, respectively. The use of ellipse cam with convex post and straight post demonstrated a 15.3 and 14.9 mm femoral rollback, whilst the combination of triangle cam with convex post and straight post showed 16.1 and 15.8 mm femoral rollback, respectively.

    CONCLUSION: The present study demonstrates that the use of circle cam and convex post created the best femoral rollback effect which in turn produces the highest amount of knee flexion. The findings of the study suggest that if the design is applied for knee implants, superior knee flexion may be possible for future patients.

    LEVEL OF EVIDENCE: IV.

  4. Samsudin EZ, Kamarul T
    Knee Surg Sports Traumatol Arthrosc, 2016 Dec;24(12):3912-3926.
    PMID: 26003481
    PURPOSE: This paper aims to review the current evidence for autologous chondrocyte implantation (ACI) generations relative to other treatment modalities, different cell delivery methods and different cell source application.

    METHODS: Literature search was performed to identify all level I and II studies reporting the clinical and structural outcome of any ACI generation in human knees using the following medical electronic databases: PubMed, EMBASE, Cochrane Library, CINAHL, SPORTDiscus and NICE healthcare database. The level of evidence, sample size calculation and risk of bias were determined for all included studies to enable quality assessment.

    RESULTS: Twenty studies were included in the analysis, reporting on a total of 1094 patients. Of the 20 studies, 13 compared ACI with other treatment modalities, seven compared different ACI cell delivery methods, and one compared different cell source for implantation. Studies included were heterogeneous in baseline design, preventing meta-analysis. Data showed a trend towards similar outcomes when comparing ACI generations with other repair techniques and when comparing different cell delivery methods and cell source selection. Majority of the studies (80 %) were level II evidence, and overall the quality of studies can be rated as average to low, with the absence of power analysis in 65 % studies.

    CONCLUSION: At present, there are insufficient data to conclude any superiority of ACI techniques. Considering its two-stage operation and cost, it may be appropriate to reserve ACI for patients with larger defects or those who have had inadequate response to other repair procedures until hard evidence enables specific clinical recommendations be made.

    LEVEL OF EVIDENCE: II.

  5. 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.

  6. Fatihhi SJ, Rabiatul AA, Harun MN, Kadir MR, Kamarul T, Syahrom A
    J Mech Behav Biomed Mater, 2016 Feb;54:21-32.
    PMID: 26410762 DOI: 10.1016/j.jmbbm.2015.09.006
    The present study reports the effects of combined torsional and compressive cyclic loading on trabecular bone in order to mimic true physiological conditions and thereby provides improved data that represents clinical and real life conditions. However, only compressive behaviour is evaluated in most previous studies of bone mechanics. From the monotonic evaluation, it is observed that lower stress is needed for the onset of microcrack in the sample under torsional loading, compared to the stress needed in compression. Trabecular bone samples were subjected to a combination of torsion and compression fatigue at different stress levels during which they were compared to compressive axial fatigue. The stress levels were determined by considering the monotonic strength at 25-50% for both compressive and shear stresses. Significant decrease in fatigue lifetime is observed in between samples of pure compression fatigue and those with superpositioned torsional loading (p<0.05). The reduction in fatigue lifetime became more evident at a high torsional stress level. In this case, the failure of the sample is said to be 'torsional dominant'. Fatigue behaviour of bovine trabecular bone begins with plastic deformation, followed by strain accumulation and modulus reduction. As the strain rate increases, more energy dissipates and the sample finally failed. Further, the analysis of fractograph revealed something on the trabeculae by bending in sample with superpositioned torsional loading. In conclusion, torsional loading decreases the quality of the trabecular properties in terms of stiffness, life and structural integrity. It is hoped that results from this study will improve the understanding of the behaviour of trabecular bone under combined fatigue and help to develop future assessments of trabecular failure.
  7. Hosseinzadeh A, Bahrampour Juybari K, Kamarul T, Sharifi AM
    J Physiol Biochem, 2019 Jun;75(2):153-162.
    PMID: 30796627 DOI: 10.1007/s13105-019-00666-8
    The high glucose concentration is able to disturb chondrocyte homeostasis and contribute to OA pathogenesis. This study was designed to investigate the protective effects of atorvastatin (ATO) on high glucose (HG)-mediated oxidative stress and mitochondrial apoptosis in C28I2 human chondrocytes. The protective effect of ATO (0.01 and 0.1 μM) on HG (75 mM)-induced oxidative stress and apoptosis was evaluated in C28I2 cells. The effects of ATO on HG-induced intracellular ROS production and lipid peroxidation were detected and the protein expression levels of Bax, Bcl-2, caspase-3, total and phosphorylated JNK and P38 MAPKs were analyzed by Western blotting. The mRNA expression levels of antioxidant enzymes including heme oxygenase-1, NAD(P)H quinine oxidoreductase, glutathione S-transferase-P1, catalase, superoxide dismutase-1, glutathione peroxidase-1, -3, -4 were evaluated by reverse transcription-polymerase chain reaction. Pretreatment with ATO remarkably increased the gene expression levels of antioxidant enzymes and reduced HG-induced elevation of ROS, lipid peroxidation, Bax/Bcl-2 ratio, caspase-3 activation, and JNK and P38 phosphorylation. Atorvastatin could considerably reduce HG-induced oxidative stress and mitochondrial apoptosis through increasing the expression of antioxidant enzymes. Atorvastatin may be considered as a promising agent to prevent high glucose-induced cartilage degradation in OA patients.
  8. 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 ​

  9. Kamarul T, Selvaratnam L, Masjuddin T, Ab-Rahim S, Ng C, Chan KY, et al.
    J Orthop Surg (Hong Kong), 2008 Aug;16(2):230-6.
    PMID: 18725678
    To compare the efficacy of autologous chondrocyte transplantation (ACT) versus non-operative measures for cartilage repair in rabbits.
  10. Kamarul T, Ahmad TS, Loh WY
    J Orthop Surg (Hong Kong), 2006 Aug;14(2):172-7.
    PMID: 16914783
    To measure the hand grip strength of Malaysians aged 18 to 65 years.
  11. Kamarul T, Mansor A, Robson N, Albusaidi SH, Suhaeb AM, Samsudin EZ
    J Orthop Surg (Hong Kong), 2018 1 13;26(1):2309499017749983.
    PMID: 29320962 DOI: 10.1177/2309499017749983
    PURPOSE: Worldwide advances in microsurgery have made salvaging of amputated hand via replantation and revascularization common procedures. The present study examines the outcome of these procedures in a tertiary hospital in Malaysia.

    METHODS: Patients with hand amputation who underwent replantation or revascularization from 2005 to 2012 were identified and reviewed for patient characteristics, amputation characteristics and survival rates. Successfully treated patients were interviewed to assess the functional outcome using Quick Disability of the Arm, Shoulder and Hand (Quick-DASH) questionnaire and Michigan Hand Outcome Questionnaire (MHQ). Statistical analysis was performed to evaluate outcome and elicit predictive factors.

    RESULTS: Fifty-five patients were enrolled: 37 (67.3%) underwent replantation and 18 (32.7%) underwent revascularization. The overall success rate of 78% ( n = 43) was within the range of previously reported data (61.6% to 96.0%). Ischaemic time <6 h provided significantly better survival rates ( p < 0.05). Functional outcomes were successfully assessed in 34 patients (79%), at a mean follow-up of 40 months (range 11-93 months). The overall Quick-DASH and MHQ scores were 42.82 ± 23.69 and 60.94 ± 12.82, respectively. No previous reports of functional outcome were available for comparison. Both Quick-DASH ( p = 0.001) and MHQ scores ( p < 0.001) were significantly higher for finger injuries, followed by thumb, wrist and palm injuries.

    CONCLUSION: Ischaemic time and level of injury are important predictors of success rate of replantation and revascularization of amputated upper limb appendages.

  12. Dashtdar H, Rothan HA, Tay T, Ahmad RE, Ali R, Tay LX, et al.
    J Orthop Res, 2011 Sep;29(9):1336-42.
    PMID: 21445989 DOI: 10.1002/jor.21413
    Chondrogenic differentiated mesenchymal stem cells (CMSCs) have been shown to produce superior chondrogenic expression markers in vitro. However, the use of these cells in vivo has not been fully explored. In this study, in vivo assessment of cartilage repair potential between allogenic-derived chondrogenic pre-differentiated mesenchymal stem cells and undifferentiated MSCs (MSCs) were compared. Bilateral full thickness cartilage defects were created on the medial femoral condyles of 12 rabbits (n = 12). Rabbits were divided into two groups. In one group, the defects in the right knees were repaired using alginate encapsulated MSCs while in the second group, CMSCs were used. The animals were sacrificed and the repaired and control knees were assessed at 3 and 6 months after implantation. Quantitative analysis was performed by measuring the Glycosaminoglycans (GAGs)/total protein content. The mean Brittberg score was higher in the transplanted knees as compared to the untreated knee at 6 months (p  0.05). This study demonstrates that the use of either MSC or CMSC produced superior healing when compared to cartilage defects that were untreated. However, both cells produced comparable treatment outcomes.
  13. 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.
  14. Chong PP, Selvaratnam L, Abbas AA, Kamarul T
    J Orthop Res, 2012 Apr;30(4):634-42.
    PMID: 21922534 DOI: 10.1002/jor.21556
    The use of mesenchymal stem cells (MSCs) for cartilage repair has generated much interest owing to their multipotentiality. However, their significant presence in peripheral blood (PB) has been a matter of much debate. The objectives of this study are to isolate and characterize MSCs derived from PB and, compare their chondrogenic potential to MSC derived from bone marrow (BM). PB and BM derived MSCs from 20 patients were isolated and characterized. From 2 ml of PB and BM, 5.4 ± 0.6 million and 10.5 ± 0.8 million adherent cells, respectively, were obtained by cell cultures at passage 2. Both PB and BM derived MSCs were able to undergo tri-lineage differentiation and showed negative expression of CD34 and CD45, but positively expressed CD105, CD166, and CD29. Qualitative and quantitative examinations on the chondrogenic potential of PB and BM derived MSCs expressed similar cartilage specific gene (COMP) and proteoglycan levels, respectively. Furthermore, the s-GAG levels expressed by chondrogenic MSCs in cultures were similar to that of native chondrocytes. In conclusion, this study demonstrates that MSCs from PB maintain similar characteristics and have similar chondrogenic differentiation potential to those derived from BM, while producing comparable s-GAG expressions to chondrocytes.
  15. Lee SY, Wee AS, Lim CK, Abbas AA, Selvaratnam L, Merican AM, et al.
    J Mater Sci Mater Med, 2013 Jun;24(6):1561-70.
    PMID: 23512151 DOI: 10.1007/s10856-013-4907-4
    This study aims to pre-assess the in vitro and in vivo biocompatibility of poly(vinyl alcohol)-carboxylmethyl-chitosan-poly(ethylene glycol) (PCP) scaffold. PCP was lyophilised to create supermacroporous structures. 3-(4, 5-dimethyl-thiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and immunohistochemistry (IHC) were used to evaluate the effectiveness of PCP scaffolds for chondrocytes attachment and proliferation. The ultrastructural was assessed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Extracellular matrix (ECM) formation was evaluated using collagen type-II staining, glycosaminoglycan (GAG) and collagen assays. Histological analysis was conducted on 3-week implanted Sprague-Dawley rats. The MTT, IHC, SEM and TEM analyses confirm that PCP scaffolds promoted cell attachment and proliferation in vitro. The chondrocyte-PCP constructs secreted GAG and collagen type-II, both increased significantly from day-14 to day-28 (P 
  16. 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.
  17. Pourshahrestani S, Zeimaran E, Adib Kadri N, Gargiulo N, Samuel S, Naveen SV, et al.
    J Mater Chem B, 2016 Jan 07;4(1):71-86.
    PMID: 32262810 DOI: 10.1039/c5tb02062j
    Haemorrhage remains the leading cause of potentially survivable death in both military and civilian populations. Although a large variety of hemostatic agents have been developed, many of them have an inadequate capacity to induce hemostasis and are not effective in killing bacteria. In recent years, mesoporous bioactive glasses (MBGs) were found to be effective in inducing hemostasis. However, the materials may not be considered as ideal hemostats since they do not offer antimicrobial activity. The gallium ion (Ga+3) not only exhibits antibacterial properties but also accelerates the blood coagulation cascade. The aim of this study was to develop MBGs containing various concentrations of Ga2O3 (1, 2 & 3 mol%) via the evaporation-induced self-assembly (EISA) process and investigate whether the addition of Ga3+ would induce both hemostatic and antibacterial effects. The results indicated that the incorporation of lower Ga2O3 content (1 mol%) into the MBG system improved structural properties including the specific surface area, mesopore size and pore volume as well as the release of silicon and calcium ions. The bioactive glass was found to stimulate blood coagulation, platelet adhesion and thrombus generation and exerted an antibacterial effect against both Escherichia coli and Staphylococcus aureus. Likewise, Ga-doped MBGs showed excellent cytocompatibility even after 3 days, with the 1% Ga2O3-containing MBG attaining the best biocompatibility that render them safe hemostatic agents for stopping bleeding. This study demonstrated that the lowest Ga2O3-substituted MBG can be a potent candidate for controlling haemorrhage and wound infection.
  18. Zahari SN, Latif MJA, Rahim NRA, Kadir MRA, Kamarul T
    J Healthc Eng, 2017;2017:9618940.
    PMID: 29065672 DOI: 10.1155/2017/9618940
    The present study was conducted to examine the effects of body weight on intradiscal pressure (IDP) and annulus stress of intervertebral discs at lumbar spine. Three-dimensional finite element model of osseoligamentous lumbar spine was developed subjected to follower load of 500 N, 800 N, and 1200 N which represent the loads for individuals who are normal and overweight with the pure moments at 7.5 Nm in flexion and extension motions. It was observed that the maximum IDP was 1.26 MPa at L1-L2 vertebral segment. However, the highest increment of IDP was found at L4-L5 segment where the IDP was increased to 30% in flexion and it was more severe at extension motion reaching to 80%. Furthermore, the maximum annulus stress also occurred at the L1-L2 segment with 3.9 MPa in extension motion. However, the highest increment was also found at L4-L5 where the annulus stress increased to 17% in extension motion. Based on these results, the increase of physiological loading could be an important factor to the increment of intradiscal pressure and annulus fibrosis stress at all intervertebral discs at the lumbar spine which may lead to early intervertebral disc damage.
  19. Tajali R, Eidi A, Tafti HA, Pazouki A, Kamarul T, Sharifi AM
    J Diabetes Metab Disord, 2023 Dec;22(2):1039-1052.
    PMID: 37975135 DOI: 10.1007/s40200-023-01280-8
    OBJECTIVES: Diabetes mellitus (DM) is a complex metabolic disease that results from impaired insulin secreting pancreatic β-cells or insulin resistance. Although available medications help control the disease, patients suffer from its complications. Therefore, finding effective therapeutic approaches to treat DM is a priority. Adipose Derived Stem Cells (ADSCs) based therapy is a promising strategy in various regenerative medicine applications, but its systematic translational use is still somewhat out of reach. This review is aimed at clarifying achievements as well as challenges facing the application of ADSCs for the treatment of DM, with a special focus on the mechanisms involved.

    METHODS: Literature searches were carried out on "Scopus", "PubMed" and "Google Scholar" up to September 2022 to find relevant articles in the English language for the scope of this review.

    RESULTS: Recent evidence showed a significant role of ADSC therapies in DM by ameliorating insulin resistance and hyperglycemia, regulating hepatic glucose metabolism, promoting β cell function and regeneration, and functioning as a gene delivery tool. In addition, ADSCs could improve diabetic wound healing by promoting collagen deposition, inhibiting inflammation, and enhancing angiogenesis.

    CONCLUSION: Overall, this literature review revealed the great clinical implications of ADSCs for translating into the clinical setting for the treatment of diabetes. However, further large-scale and controlled studies are needed to overcome challenges and confirm the safety and optimal therapeutic scheme before daily clinical application.

    SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-023-01280-8.

  20. Hosseinzadeh A, Jafari D, Kamarul T, Bagheri A, Sharifi AM
    J Cell Biochem, 2017 Jul;118(7):1879-1888.
    PMID: 28169456 DOI: 10.1002/jcb.25907
    The protective effects and mechanisms of DADS on IL-1β-mediated oxidative stress and mitochondrial apoptosis were investigated in C28I2 human chondrocytes. The effect of various concentrations of DADS (1, 5 10, 25, 50, and 100 μM) on C28I2 cell viability was evaluated in different times (2, 4, 8, 16, and 24 h) to obtain the non-cytotoxic concentrations of drug by MTT-assay. The protective effect of non-toxic concentrations of DADS on experimentally induced oxidative stress and apoptosis by IL-1β in C28I2 was evaluated. The effects of DADS on IL-1β-induced intracellular ROS production and lipid peroxidation were detected and the proteins expression of Nrf2, Bax, Bcl-2, caspase-3, total and phosphorylated JNK, and P38 MAPKs were analyzed by Western blotting. The mRNA expression of detoxifying phase II/antioxidant enzymes including heme oxygenase-1, NAD(P)H quinine oxidoreductase, glutathione S-transferase-P1, catalase, superoxide dismutase-1, glutathione peroxidase-1, -3, -4 were evaluated by reverse transcription-polymerase chain reaction. DADS in 1, 5, 10, and 25 μM concentrations had no cytotoxic effect after 24 h. Pretreatment with DADS remarkably increased Nrf2 nuclear translocation as well as the genes expression of detoxifying phase II/antioxidant enzymes and reduced IL-1β-induced elevation of ROS, lipid peroxidation, Bax/Bcl-2 ratio, caspase-3 activation, and JNK and P38 phosphorylation. DADS could considerably reduce IL-1β-induced oxidative stress and consequent mitochondrial apoptosis, as the major mechanisms of chondrocyte cell death in an experimental model of osteoarthritis. It may be considered as natural product in protecting OA-induced cartilage damage in clinical setting. J. Cell. Biochem. 118: 1879-1888, 2017. © 2017 Wiley Periodicals, Inc.
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