Displaying publications 61 - 80 of 101 in total

Abstract:
Sort:
  1. Chin KY
    Drug Des Devel Ther, 2016;10:3029-3042.
    PMID: 27703331
    Osteoarthritis is a degenerative disease of the joint affecting aging populations worldwide. It has an underlying inflammatory cause, which contributes to the loss of chondrocytes, leading to diminished cartilage layer at the affected joints. Compounds with anti-inflammatory properties are potential treatment agents for osteoarthritis. Curcumin derived from Curcuma species is an anti-inflammatory compound as such. This review aims to summarize the antiosteoarthritic effects of curcumin derived from clinical and preclinical studies. Many clinical trials have been conducted to determine the effectiveness of curcumin in osteoarthritic patients. Extracts of Curcuma species, curcuminoids and enhanced curcumin, were used in these studies. Patients with osteoarthritis showed improvement in pain, physical function, and quality of life after taking curcumin. They also reported reduced concomitant usage of analgesics and side effects during treatment. In vitro studies demonstrated that curcumin could prevent the apoptosis of chondrocytes, suppress the release of proteoglycans and metal metalloproteases and expression of cyclooxygenase, prostaglandin E-2, and inflammatory cytokines in chondrocytes. These were achieved by blocking the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) system in the chondrocytes, by preventing the activation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, phosphorylation, and translocation of the p65 subunit of NF-κB complexes into the nucleus. In conclusion, curcumin is a potential candidate for the treatment of osteoarthritis. More well-planned randomized control trials and enhanced curcumin formulation are required to justify the use of curcumin in treating osteoarthritis.
    Matched MeSH terms: Chondrocytes/drug effects*; Chondrocytes/chemistry
  2. Samuel S, Ahmad RE, Ramasamy TS, Karunanithi P, Naveen SV, Kamarul T
    Platelets, 2019;30(1):66-74.
    PMID: 29090639 DOI: 10.1080/09537104.2017.1371287
    Platelet-rich concentrate (PRC), used in conjunction with other chondroinductive growth factors, have been shown to induce chondrogenesis of human mesenchymal stromal cells (hMSC) in pellet culture. However, pellet culture systems promote cell hypertrophy and the presence of other chondroinductive growth factors in the culture media used in previous studies obscures accurate determination of the effect of platelet itself in inducing chondrogenic differentiation. Hence, this study aimed to investigate the effect of PRC alone in enhancing the chondrogenic differentiation potential of human mesenchymal stromal cells (hMSC) encapsulated in three-dimensional alginate constructs. Cells encapsulated in alginate were cultured in serum-free medium supplemented with only 15% PRC. Scanning electron microscopy was used to determine the cell morphology. Chondrogenic molecular signature of hMSCs was determined by quantitative real-time PCR and verified at protein levels via immunohistochemistry and enzyme-linked immunosorbent assay. Results showed that the cells cultured in the presence of PRC for 24 days maintained a chondrocytic phenotype and demonstrated minimal upregulation of cartilaginous extracellular matrix (ECM) marker genes (SOX9, TNC, COL2, ACAN, COMP) and reduced expression of chondrocyte hypertrophy genes (Col X, Runx2) compared to the standard chondrogenic medium (p 
    Matched MeSH terms: Chondrocytes/metabolism*; Chondrocytes/pathology
  3. 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.
    Matched MeSH terms: Chondrocytes/drug effects*; Chondrocytes/metabolism*
  4. Hamid AA, Idrus RB, Saim AB, Sathappan S, Chua KH
    Clinics (Sao Paulo), 2012;67(2):99-106.
    PMID: 22358233
    OBJECTIVES: Understanding the changes in chondrogenic gene expression that are involved in the differentiation of human adipose-derived stem cells to chondrogenic cells is important prior to using this approach for cartilage repair. The aims of the study were to characterize human adipose-derived stem cells and to examine chondrogenic gene expression after one, two, and three weeks of induction.

    MATERIALS AND METHODS: Human adipose-derived stem cells at passage 4 were evaluated by flow cytometry to examine the expression of surface markers. These adipose-derived stem cells were tested for adipogenic and osteogenic differentiation capacity. Ribonucleic acid was extracted from the cells for quantitative polymerase chain reaction analysis to determine the expression levels of chondrogenic genes after chondrogenic induction.

    RESULTS: Human adipose-derived stem cells were strongly positive for the mesenchymal markers CD90, CD73, CD44, CD9, and histocompatibility antigen and successfully differentiated into adipogenic and osteogenic lineages. The human adipose-derived stem cells aggregated and formed a dense matrix after chondrogenic induction. The expression of chondrogenic genes (collagen type II, aggrecan core protein, collagen type XI, COMP, and ELASTIN) was significantly higher after the first week of induction. However, a significantly elevated expression of collagen type X was observed after three weeks of chondrogenic induction.

    CONCLUSION: Human adipose-derived stem cells retain stem cell characteristics after expansion in culture to passage 4 and serve as a feasible source of cells for cartilage regeneration. Chondrogenesis in human adipose-derived stem cells was most prominent after one week of chondrogenic induction.

    Matched MeSH terms: Chondrocytes/cytology; Chondrocytes/metabolism*
  5. Sulaiman SB, Idrus RBH, Hwei NM
    Polymers (Basel), 2020 Oct 19;12(10).
    PMID: 33086577 DOI: 10.3390/polym12102404
    The gelatin microsphere (GM) provides an attractive option for tissue engineering due to its versatility, as reported by various studies. This review presents the history, characteristics of, and the multiple approaches to, the production of GM, and in particular, the water in oil emulsification technique. Thereafter, the application of GM as a drug delivery system for cartilage diseases is introduced. The review then focusses on the emerging application of GM as a carrier for cells and biologics, and biologics delivery within a cartilage construct. The influence of GM on chondrocytes in terms of promoting chondrocyte proliferation and chondrogenic differentiation is highlighted. Furthermore, GM seeded with cells has been shown to have a high tendency to form aggregates; hence the concept of using GM seeded with cells as the building block for the formation of a complex tissue construct. Despite the advancement in GM research, some issues must still be addressed, particularly the improvement of GM's ability to home to defect sites. As such, the strategy of intraarticular injection of GM seeded with antibody-coated cells is proposed. By addressing this in future studies, a better-targeted delivery system, that would result in more effective intervention, can be achieved.
    Matched MeSH terms: Chondrocytes
  6. Sha'ban M, Ahmad Radzi MA
    Adv Exp Med Biol, 2020;1249:97-114.
    PMID: 32602093 DOI: 10.1007/978-981-15-3258-0_7
    Joint cartilage has been a significant focus on the field of tissue engineering and regenerative medicine (TERM) since its inception in the 1980s. Represented by only one cell type, cartilage has been a simple tissue that is thought to be straightforward to deal with. After three decades, engineering cartilage has proven to be anything but easy. With the demographic shift in the distribution of world population towards ageing, it is expected that there is a growing need for more effective options for joint restoration and repair. Despite the increasing understanding of the factors governing cartilage development, there is still a lot to do to bridge the gap from bench to bedside. Dedicated methods to regenerate reliable articular cartilage that would be equivalent to the original tissue are still lacking. The use of cells, scaffolds and signalling factors has always been central to the TERM. However, without denying the importance of cells and signalling factors, the question posed in this chapter is whether the answer would come from the methods to use or not to use scaffold for cartilage TERM. This paper presents some efforts in TERM area and proposes a solution that will transpire from the ongoing attempts to understand certain aspects of cartilage development, degeneration and regeneration. While an ideal formulation for cartilage regeneration has yet to be resolved, it is felt that scaffold is still needed for cartilage TERM for years to come.
    Matched MeSH terms: Chondrocytes
  7. Khairani Idah Mokhtar, Noraini Abu Bakar, Azrul Fazwan Kharuddin
    MyJurnal
    Runt-related transcription factor 2 (RUNX2) plays important roles in osteoblast
    differentiation, tooth development and chondrocyte maturation; hence its involvement in
    craniofacial development is paramount. Mutation in RUNX2 is implicated with cleidocranial
    dysplasia; a bone development disorder, while single nucleotide polymorphism (SNP) in RUNX2 is
    associated with Class II/2 malocclusion. This study aimed to determine RUNX2 SNP of DNA marker
    (rs6930053) in malocclusion patients from local population. (Copied from article).
    Matched MeSH terms: Chondrocytes
  8. Chin KY, Ima-Nirwana S
    Front Pharmacol, 2018;9:946.
    PMID: 30186176 DOI: 10.3389/fphar.2018.00946
    Osteoarthritis is a debilitating disease of the joint involving cartilage degeneration and chondrocytes apoptosis. Oxidative stress is one of the many proposed mechanisms underpinning joint degeneration in osteoarthritis. The current pharmacotherapies emphasize pain and symptomatic management of the patients but do not alter the biological processes underlying the cartilage degeneration. Vitamin E is a potential agent to prevent or treat osteoarthritis due to its antioxidant and anti-inflammatory effects. This review aims to summarize the current evidence on the relationship between vitamin E and osteoarthritis derived from preclinical and human studies. Cellular studies showed that vitamin E mitigated oxidative stress in cartilage explants or chondrocyte culture invoked by mechanical stress or free radicals. Animal studies suggested that vitamin E treatment prevented cartilage degeneration and improve oxidative status in animal models of osteoarthritis. Low circulating or synovial vitamin E was observed in human osteoarthritic patients compared to healthy controls. Observational studies also demonstrated that vitamin E was related to induction or progression of osteoarthritis in the general population. Vitamin E supplementation might improve the outcomes in patients with osteoarthritis, but negative results were also reported. Different isomers of vitamin E might possess distinct anti-osteoarthritic effects. As a conclusion, vitamin E may retard the progression of osteoarthritis by ameliorating oxidative stress and inflammation of the joint. Further studies are warranted to develop vitamin E as an anti-osteoarthritis agent to reduce the global burden of this disease.
    Matched MeSH terms: Chondrocytes
  9. Adila A Hamid, Satish Vaarman Jeyabalan, Aleza Omar, Nik Zattil Hanan Mohd Yasin, Wong TL, Liau LL, et al.
    Sains Malaysiana, 2018;47:2369-2379.
    Currently, fetal bovine serum (FBS) have been widely use in culture media to promote human cell proliferation. However,
    the usage of FBS for cell therapy in clinical application was associated with the risk of viral and prion transmission as
    well as immune rejection. To provide an option for this risk, this study was conducted to determine the effect of adipose
    derived stem cells (ADSCs) co-culture with chondrocyte in promoting cell proliferation and chondrogenesis toward
    FBS free condition. ADSCs co-cultured with chondrocyte at the ratio of 1:1, 2:1 and 1:2 were tested. Cell morphology
    changes, cell proliferation and gene expression level of stemness (Oct4, FGF-4, Nanog) and chondrogenic (Collagen
    Type II, ACP) were assessed. The results showed ADSCs in all co-culture groups changed morphology from fibroblastic
    spindle to polygonal shape which resembled chondrocytes. The morphological changes were accompanied with increased
    expression of chondrogenic genes; denoted chondrogenesis process. While maintaining expression of stemness genes
    indicated continuation of cell proliferation. From the three co-culture groups tested; ADSCs and chondrocytes (1:1 ratio)
    have been shown to exert better effects in promoting cell proliferation and chondrogenesis. In conclusion, ADSCs could
    replace FBS to grow sufficient number of chondrogenic cells to repair cartilage injury in the near future. Further in vivo
    study should be performed to test the effectiveness of this co-culture technique in cartilage injury repair.
    Matched MeSH terms: Chondrocytes
  10. Chin KY, Pang KL
    Nutrients, 2017 Sep 26;9(10).
    PMID: 28954409 DOI: 10.3390/nu9101060
    Osteoarthritis is a major cause of morbidity among the elderly worldwide. It is a disease characterized by localized inflammation of the joint and destruction of cartilage, leading to loss of function. Impaired chondrocyte repair mechanisms, due to inflammation, oxidative stress and autophagy, play important roles in the pathogenesis of osteoarthritis. Olive and its derivatives, which possess anti-inflammatory, antioxidant and autophagy-enhancing activities, are suitable candidates for therapeutic interventions for osteoarthritis. This review aimed to summarize the current evidence on the effects of olive and its derivatives, on osteoarthritis and chondrocytes. The literature on animal and human studies has demonstrated a beneficial effect of olive and its derivatives on the progression of osteoarthritis. In vitro studies have suggested that the augmentation of autophagy (though sirtuin-1) and suppression of inflammation by olive polyphenols could contribute to the chondroprotective effects of olive polyphenols. More research and well-planned clinical trials are required to justify the use of olive-based treatment in osteoarthritis.
    Matched MeSH terms: Chondrocytes/drug effects; Chondrocytes/metabolism; Chondrocytes/pathology
  11. Ariffin SMZ, Bennett D, Ferrell WR, Lockhart JC, Dunning L, Clements DN, et al.
    J Feline Med Surg, 2021 08;23(8):794-803.
    PMID: 33284033 DOI: 10.1177/1098612X20977796
    OBJECTIVES: The aim of this study was to determine the presence of protease-activated receptor 2 (PAR2) and matriptase proteins and quantify PAR2 and matriptase mRNA expression in the articular cartilage and synovial membrane of cats with and without osteoarthritis (OA).

    METHODS: A total of 28 articular cartilage samples from adult cats (14 OA and 14 normal), 10 synovial membranes from adult cats (five OA and five normal) and three cartilage samples from 9-week-old fetal cats were used. The presence of PAR2 and matriptase in the cartilage and synovial membrane of the adult samples was detected by immunohistochemical (IHC) staining, while real-time PCR was used for mRNA expression analyses in all samples.

    RESULTS: PAR2 was detected in all OA and normal articular cartilage and synovial membrane samples but confined to only a few superficial chondrocytes in the normal samples. Matriptase was only detected in OA articular cartilage and synovial membrane samples. PAR2 and matriptase mRNA expression were, however, detected in all cartilage and synovial membrane samples. PAR2 and matriptase mRNA expression levels in OA articular cartilage were five (P <0.001) and 3.3 (P <0.001) times higher than that of the healthy group, respectively. There was no significant difference (P = 0.05) in the OA synovial membrane PAR2 and matriptase mRNA expression compared with the normal samples.

    CONCLUSIONS AND RELEVANCE: Detection of PAR2 and matriptase proteins and gene expression in feline articular tissues is a novel and important finding, and supports the hypothesis that serine proteases are involved in the pathogenesis of feline OA. The consistent presence of PAR2 and matriptase protein in the cytoplasm of OA chondrocytes suggests a possible involvement of proteases in cartilage degradation. Further investigations into the PAR2 and matriptase pathobiology could enhance our understanding of the proteolytic cascades in feline OA, which might lead to the development of novel therapeutic strategies.

    Matched MeSH terms: Chondrocytes
  12. Tay LX, Ahmad RE, Dashtdar H, Tay KW, Masjuddin T, Ab-Rahim S, et al.
    Am J Sports Med, 2012 Jan;40(1):83-90.
    PMID: 21917609 DOI: 10.1177/0363546511420819
    Mesenchymal stem cells (MSCs) represent a promising alternative form of cell-based therapy for cartilage injury. However, the capacity of MSCs for chondrogenesis has not been fully explored. In particular, there is presently a lack of studies comparing the effectiveness of MSCs to conventional autologous chondrocyte (autoC) treatment for regeneration of full-thickness cartilage defects in vivo.
    Matched MeSH terms: Chondrocytes/transplantation*
  13. Munirah S, Ruszymah BH, Samsudin OC, Badrul AH, Azmi B, Aminuddin BS
    J Orthop Surg (Hong Kong), 2008 Aug;16(2):220-9.
    PMID: 18725677
    To evaluate the effect of autologous human serum (AHS) versus pooled human serum (PHS) versus foetal bovine serum (FBS) for growth of articular chondrocytes and formation of chondrocytefibrin constructs.
    Matched MeSH terms: Chondrocytes/physiology*
  14. Alfaqeh H, Norhamdan MY, Chua KH, Chen HC, Aminuddin BS, Ruszymah BH
    Med J Malaysia, 2008 Jul;63 Suppl A:37-8.
    PMID: 19024972
    This study was to determine if autologous bone marrow mesenchymal stem cells (BMSCs) cultured in chondrogenic medium could repair surgically induced osteoarthritis. Sheep BMSCs were cultured in medium containing 5ng/ml TGFbeta3 + 50ng/ml IGF-1 for three weeks. The cultured cells were then suspended at density of 2x10(6) cell/ml and injected intraarticularly into the osteoarthritic knee joint. After six weeks, the distal head of the femur and the proximal tibial plateau were removed and stained with H&E. The results indicated that knee joints treated with autologous BMSCs cultured in chondrogenic medium showed clear evidence of articular cartilage regeneration in comparison with other groups.
    Matched MeSH terms: Chondrocytes/transplantation*
  15. Chua KH, Aminuddin BS, Fuzina NH, Ruszymah BH
    Med J Malaysia, 2004 May;59 Suppl B:7-8.
    PMID: 15468792
    The regulation roles of insulin-like growth factor-1 (IGF-1) with basic fibroblast growth factor (bFGF) and transforming growth factor beta 2 (TGFbeta2) in human nasal septum chondrocytes monolayer culture and cartilage engineering was investigated in this study. The role of IGF-1 with bFGF and TGFbeta2 was investigated by measuring chondrocyte growth kinetic and collagen genes expression. IGF-1 together with bFGF and TGFbeta2 promote cartilage tissue engineering, increase type II collagen expression and enhance the histological features of engineered cartilage.
    Matched MeSH terms: Chondrocytes/cytology*
  16. Goh JC, Shao XX, Hutmacher D, Lee EH
    Med J Malaysia, 2004 May;59 Suppl B:17-8.
    PMID: 15468797
    Matched MeSH terms: Chondrocytes/cytology*
  17. Ude CC, Sulaiman SB, Min-Hwei N, Hui-Cheng C, Ahmad J, Yahaya NM, et al.
    PLoS One, 2014;9(6):e98770.
    PMID: 24911365 DOI: 10.1371/journal.pone.0098770
    In this study, Adipose stem cells (ADSC) and bone marrow stem cells (BMSC), multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model.
    Matched MeSH terms: Chondrocytes/cytology; Chondrocytes/metabolism
  18. Ishak MF, Chua KH, Asma A, Saim L, Aminuddin BS, Ruszymah BH, et al.
    Int J Pediatr Otorhinolaryngol, 2011 Jun;75(6):835-40.
    PMID: 21543123 DOI: 10.1016/j.ijporl.2011.03.021
    This study was aimed to see the difference between chondrocytes from normal cartilage compared to chondrocytes from microtic cartilage. Specific attentions were to characterize the growth of chondrocytes in terms of cell morphology, growth profile and RT-PCR analysis.
    Matched MeSH terms: Chondrocytes/cytology*; Chondrocytes/metabolism
  19. Munirah S, Samsudin OC, Aminuddin BS, Ruszymah BH
    Tissue Cell, 2010 Oct;42(5):282-92.
    PMID: 20810142 DOI: 10.1016/j.tice.2010.07.002
    Monolayer culture expansion remains as a fundamental step to acquire sufficient number of cells for 3D constructs formation. It has been well-documented that cell expansion is however accompanied by cellular dedifferentiation. In order to promote cell growth and circumvent cellular dedifferentiation, we evaluated the effects of Transforming Growth Factor Beta-2 (TGF-β2), Insulin-like Growth Factor-I (IGF-I) and basic Fibroblast Growth Factor (bFGF) combination on articular chondrocytes culture and 'chondrocytes-fibrin' construct formation. Chondrocytes were serially cultured in: (1) F12:DMEM+10% Foetal Bovine Serum (FBS) with growth factors (FD10GFs), (2) F12:DMEM+2%FBS with the growth factors (FD2GFs) and, (3) F12:DMEM+10%FBS without growth factors (FD) as control. Cultured chondrocytes were evaluated by means of growth kinetics parameters, cell cycle analysis, quantitative phenotypic expression of collagen type II, aggrecan core protein sox-9 and collagen type I and, immunochemistry technique. Harvested chondrocytes were incorporated with plasma-derived fibrin and were polymerized to form the 3D constructs and implanted subcutaneously at the dorsum of athymic nude mice for eight (8) weeks. Resulted constructs were assigned for gross inspections and microscopic evaluation using standard histochemicals staining, immunochemistry technique and, quantitative phenotypic expression of cartilage markers to reassure cartilaginous tissue formation. Growth kinetics performance of chondrocytes cultured in three (3) types of culture media from the most to least was in the following order: FD10GFs>FD2GFs>FD. Following growth kinetics analysis, we decided to use FD10GFs and FD (control) for further evaluation and 'chondrocytes-fibrin' constructs formation. Chondrocytes cultured in FD10GFs preserved the normal diploid state (2c) with no evidence of aneuploidy, haploidy or tetraploidy. Expression of cartilage-specific markers namely collagen type II, aggrecan core protein and sox-9 were significantly higher in FD10GFs when compared to control. After implantation, 'chondrocytes-fibrin' constructs exhibited firm, white, smooth and glistening cartilage-like properties. FD10GFs constructs formed better quality cartilage-like tissue than FD constructs in term of overall cartilaginous tissue formation, cells organization and extracellular matrix distribution in the specimens. Cartilaginous tissue formation was confirmed by the presence of lacunae and cartilage-isolated cells embedded within basophilic ground substance. Presence of proteoglycan was confirmed by positive Safranin O staining. Collagen type II exhibited immunopositivity at the pericellular and inter-territorial matrix area. Chondrogenic properties of the construct were further confirmed by the expression of genes encoding collagen type II, aggrecan core protein and sox9. In conclusion, FD10GFs promotes the proliferation of chondrocytes and formation of good quality 'chondrocytes-fibrin' constructs which may have potential use of matrix-induced cell implantation.
    Matched MeSH terms: Chondrocytes/cytology*; Chondrocytes/drug effects
  20. Chua KH, Lee TH, Nagandran K, Md Yahaya NH, Lee CT, Tjih ET, et al.
    PMID: 23339380 DOI: 10.1186/1472-6882-13-19
    Osteoarthritis (OA) is a degenerative joint disease that results in the destruction of cartilage. Edible Bird's Nest (EBN) extract contains important components, which can reduce the progression of osteoarthritis and helps in the regeneration of the cartilage. The present study aimed to investigate the effect of EBN extract on the catabolic and anabolic activities of the human articular chondrocytes (HACs) isolated from the knee joint of patients with OA.
    Matched MeSH terms: Chondrocytes/drug effects*; Chondrocytes/metabolism
Filters
Contact Us

Please provide feedback to Administrator ([email protected])

External Links