Displaying publications 1 - 20 of 32 in total

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  1. Moving beyond nanotechnology to uncover a glimmer of hope in diabetes medicine: Effective nanoparticle-based therapeutic strategies for the management and treatment of diabetic foot ulcers
    Hosseinzadeh A, Zamani A, Johari HG, Vaez A, Golchin A, Tayebi L, et al.
    Cell Biochem Funct, 2023 Jul;41(5):517-541.
    PMID: 37282756 DOI: 10.1002/cbf.3816
    Hyperglycemia, a distinguishing feature of diabetes mellitus that might cause a diabetic foot ulcer (DFU), is an endocrine disorder that affects an extremely high percentage of people. Having a comprehensive understanding of the molecular mechanisms underlying the pathophysiology of diabetic wound healing can help researchers and developers design effective therapeutic strategies to treat the wound healing process in diabetes patients. Using nanoscaffolds and nanotherapeutics with dimensions ranging from 1 to 100 nm represents a state-of-the-art and viable therapeutic strategy for accelerating the wound healing process in diabetic patients, particularly those with DFU. Nanoparticles can interact with biological constituents and infiltrate wound sites owing to their reduced diameter and enhanced surface area. Furthermore, it is noteworthy that they promote the processes of vascularization, cellular proliferation, cell signaling, cell-to-cell interactions, and the formation of biomolecules that are essential for effective wound healing. Nanomaterials possess the ability to effectively transport and deliver various pharmacological agents, such as nucleic acids, growth factors, antioxidants, and antibiotics, to specific tissues, where they can be continuously released and affect the wound healing process in DFU. The present article elucidates the ongoing endeavors in the field of nanoparticle-mediated therapies for the management of DFU.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins
  2. Fulltext Unravelling the role of HAS2, GREM1, and PTGS2 gene expression in cumulus cells: implications for human oocyte development competency - a systematic review and integrated bioinformatic analysis
    Faizal AM, Elias MH, Jin NM, Abu MA, Syafruddin SE, Zainuddin AA, et al.
    Front Endocrinol (Lausanne), 2024;15:1274376.
    PMID: 38524634 DOI: 10.3389/fendo.2024.1274376
    The leading indicator for successful outcomes in in-vitro fertilization (IVF) is the quality of gametes in oocytes and sperm. Thus, advanced research aims to highlight the parameter in assessing these qualities - DNA fragmentation in sperm and oocyte development capacity (ODC) via evaluation of microenvironments involving its maturation process. Regarding oocytes, most evidence reveals the role of cumulus cells as non-invasive methods in assessing their development competency, mainly via gene expression evaluation. Our review aims to consolidate the evidence of GDF-9 derivatives, the HAS2, GREM1, and PTGS2 gene expression in cumulus cells used as ODC markers in relevant publications and tailored to current IVF outcomes. In addition to that, we also added the bioinformatic analysis in our review to strengthen the evidence aiming for a better understanding of the pathways and cluster of the genes of interest - HAS2, GREM1, and PTGS2 in cumulus cell level. Otherwise, the current non-invasive method can be used in exploring various causes of infertility that may affect these gene expressions at the cumulus cell level. Nevertheless, this method can also be used in assessing the ODC in various cohorts of women or as an improvement of markers following targeted tools or procedures by evaluating the advancement of these gene expressions following the targeted intervention.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/genetics; Intercellular Signaling Peptides and Proteins/metabolism
  3. Fulltext Potential treatment of squamous cell carcinoma by targeting heparin-binding protein 17/fibroblast growth factor-binding protein 1 with vitamin D3 or eldecalcitol
    Shintani T, Higaki M, Rosli SNZ, Okamoto T
    In Vitro Cell Dev Biol Anim, 2024 Jun;60(6):583-589.
    PMID: 38713345 DOI: 10.1007/s11626-024-00913-3
    Heparin-binding protein 17 (HBp17), first purified in 1991 from the conditioned medium of the human A431 squamous cell carcinoma (SCC) cell line, was later renamed fibroblast growth factor-binding protein 1 (FGFBP-1). HBp17/FGFBP-1 is specifically expressed and secreted by epithelial cells, and it reversibly binds to fibroblast growth factor (FGF)-1 and FGF-2, as well as FGFs-7, -10, and -22, indicating a crucial involvement in the transportation and function of these FGFs. Our laboratory has investigated and reported several studies to elucidate the function of HBp17/FGFBP-1 in SCC cells and its potential as a molecular therapeutic target. HBp17/FGFBP-1 transgene exoression in A431-4 cells, a clonal subline of A431 that lacks tumorigenicity and does not express HBp17/FGFBP-1, demonstrated a significantly enhanced proliferation in vitro compared with A431-4 cells, and it acquired tumorigenicity in the subcutis of nude mice. Knockout (KO) of the HBp17/FGFBP-1 by genome editing significantly suppressed tumor growth, cell motility, and tumorigenicity compared with control cells. A comprehensive analysis of expressed molecules in both cell types revealed that molecules that promote epithelial cell differentiation were highly expressed in HBp17/FGFBP-1 KO cells. Additionally, we reported that 1α,25(OH)2D3 or eldecalcitol (ED-71), which is an analog of 1α,25(OH)2D3, suppresses HBp17/FGFBP-1 expression and tumor growth in vitro and in vivo by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway. Here, we discuss the prospects of molecular targeted therapy targeting HBp17/FGFBP-1 with 1α,25(OH)2D3 or ED71 in SCC and oral SCC.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/genetics; Intercellular Signaling Peptides and Proteins/metabolism
  4. Fulltext Removal of failed dental implant with application of concentrated growth factor (CGF): a case report
    Nurul Ain Mohamed Yusof, Mohd Salman Masri, Erni Noor
    Compendium of Oral Science, 2018;5(1):46-53.
    MyJurnal
    Introduction: High survival rates of dental implants were commonly reported even after 10 years of follow up. Nevertheless, complications and failure may occur and the implant would need to be removed. In recent years, the use of autogenous blood products in dental surgery has increased due to its ability to aid the healing of the soft and hard tissues. Clinical case: The case demonstrated the utilisation of concentrated growth factor (CGF) from the patient’s blood for healing following conservative removal of a failed dental implant. Subsequently, the patient showed satisfactory recovery without any infections and clinical complaints. Conclusion: This explantation procedure, together with the use of CGF, may prevent the normal bone resorption and accelerate soft tissue healing. As it is biological in nature having originated from the patient’s blood, it is more readily accepted by the tissues and the risk of infection is low.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins
  5. Fulltext Adipose-derived stem cells in tissue engineering: laboratory to bedside
    Halim, A.S., Mohaini, M., L, Chin Keong
    JUMMEC, 2013;16(2):1-10.
    MyJurnal
    Human adipose tissue has been recognized as an alternative source of adult stem cells. The abundance and ease of harvest of adipose tissue has made it suitable for use in regenerative medicine and tissue engineering. Adipose-derived stem cells isolated from human adipose tissue are able to differentiate into several mesenchymal lineages and secrete growth factors that exhibit therapeutic potential. Protein profiles have been established using various isolation methods, which has expanded researchers’ understanding of adipose-derived stem cells in clinical applications. This review highlights the properties, isolation methods, immunophenotype and clinical applications of adipose-derived stem cells.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins
  6. Fulltext Lyophilised Platelet-Rich Fibrin: Physical and Biological Characterisation
    Ngah NA, Dias GJ, Tong DC, Mohd Noor SNF, Ratnayake J, Cooper PR, et al.
    Molecules, 2021 Nov 25;26(23).
    PMID: 34885714 DOI: 10.3390/molecules26237131
    BACKGROUND: Platelet-rich fibrin (PRF) has gained popularity in craniofacial surgery, as it provides an excellent reservoir of autologous growth factors (GFs) that are essential for bone regeneration. However, the low elastic modulus, short-term clinical application, poor storage potential and limitations in emergency therapy use restrict its more widespread clinical application. This study fabricates lyophilised PRF (Ly-PRF), evaluates its physical and biological properties, and explores its application for craniofacial tissue engineering purposes.

    MATERIAL AND METHODS: A lyophilisation method was applied, and the outcome was evaluated and compared with traditionally prepared PRF. We investigated how lyophilisation affected PRF's physical characteristics and biological properties by determining: (1) the physical and morphological architecture of Ly-PRF using SEM, and (2) the kinetic release of PDGF-AB using ELISA.

    RESULTS: Ly-PRF exhibited a dense and homogeneous interconnected 3D fibrin network. Moreover, clusters of morphologically consistent cells of platelets and leukocytes were apparent within Ly-PRF, along with evidence of PDGF-AB release in accordance with previously reports.

    CONCLUSIONS: The protocol established in this study for Ly-PRF preparation demonstrated versatility, and provides a biomaterial with growth factor release for potential use as a craniofacial bioscaffold.

    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism; Intercellular Signaling Peptides and Proteins/therapeutic use; Intercellular Signaling Peptides and Proteins/chemistry*
  7. Inducible transgene expression in undifferentiated mouse embryonic stem cells and embryoid bodies
    Nordin N, Nathan S, Li M, Mason JO
    Med J Malaysia, 2008 Jul;63 Suppl A:59-60.
    PMID: 19024983
    Obtaining pure population of neural cells from embryonic stem (ES) cells remains a challenge as little is known about the genes that govern embryonic stem cell differentiation. Using mouse ES cells, we aim to uncover the mechanisms that regulate neural differentiation of ES cells by focusing on roles played by Wnt family genes. Combining two techniques, Cre/loxP-based genetic recombination and ligand-dependent activation of Cre, we have generated transgenic ES cell lines that allow for the temporal control of expression and activity of Wnt gene (Wnt1-Ha) and Wnt antagonist (Dkk1). The ability of these cell lines in inducing the expression of transgene in undifferentiated ES cells and, more importantly, in differentiated derivatives of ES cells in vitro is evaluated.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/genetics
  8. Fulltext Effect of Growth Factor Supplementation on the Hair Cell Specific Markers of Cells Harvested from Basilar Membrane
    Ubaidah MA, Chua KH, Ami M, Zainal A, Saim A, Saim L, et al.
    J Int Adv Otol, 2015 Apr;11(1):23-9.
    PMID: 26223713 DOI: 10.5152/iao.2015.539
    Loss of auditory hair cells is a major cause of deafness. The presence of auditory progenitor cells in the inner ear raises the hope for mammalian inner ear cell regeneration. In this study, we aimed to investigate the effect of growth factor supplementations, namely a combination of epidermal growth factor (EGF), insulin-like growth factor (IGF), and beta (β)-fibroblast growth factor (βFGF), on the expression of hair cell-specific markers by cells harvested from the cochlear membrane. This would provide an insight into the capability of these cells to differentiate into hair cells.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/pharmacology*
  9. Fulltext The efficiency of cell sorting and harvesting methods for In vitro expansion of human umbilical cord blood derived CD34+ hematopoietic stem cells
    Borojerdi, Mohadese Hashem, Maqbool, Maryam, Zuraidah Yusoff, Vidyadaran, Sharmili, Hwa, Ling King, George, Elizabeth, et al.
    Malaysian Journal of Medicine and Health Sciences, 2015;11(2):21-28.
    MyJurnal
    Introduction: During the last three decades hematopoietic stem cell transplantation (HSCT) has become a well-established treatment for many hematologic malignancies. The most important limitation for HSC transplantation is the low number of hematopoietic stem cells (HSC) that can lead to delayed engraftment or graft failures. Numerous attempts have been made to improve in vitro HSC expansion via optimization of various methods such as isolation techniques, supplementing with growth factors, utilizing stromal cells as feeder layer and other culture conditions. Objective: This project is aimed to decipher the efficiency of an isolation technique and retrieval of culture expanded HSC from feeder layer using two different harvesting methods. Materials and Methods: Hematopoietic stem cells from human umbilical cord blood were isolated via MACS mediated CD34+ double sorting. Then, the cells were cultured onto MSC feeder layer for 3 and 5 days. Culture expanded cells were harvested using two different harvesting method namely cell aspiration and trypsinization methods. Hematopoietic stem cell expansion index were calculated based on harvesting methods for each time point. Results: The numbers of HSC isolated from human umbilical cord blood were 1.64 x 106 and 1.20 x106 cells at single and double sortings respectively. Although the number of sorted cells diminished at the second sorting yet the yield of CD34+ purity has increased from 43.73% at single sorting to 81.40% at double sorting. Employing the trypsinization method, the HSC harvested from feeder layer showed a significant increase in expansion index (EI) as compared to the cell aspiration harvesting method (p≤ 0.05). However, the purity of CD34+ HSC was found higher when the cells were harvested using aspiration method (82.43%) as compared to the trypsinization method (74.13%). Conclusion: A pure population of CD34+ HSC can be retrieved when the cells were double sorted using MACS and expanded in culture after being harvested using cell aspiration method.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins
  10. Fulltext Cytotoxicity effect of oil palm (Elaeis guineensis) kernel protein hydrolysates
    Chang, S.K., Hamajima, H., Amin, I., Yanagita, T., Mohd. Esa, N., Baharuldin, M.T.H.
    International Food Research Journal, 2014;21(3):909-914.
    MyJurnal
    This study was conducted to ascertain the cytotoxicity effect of oil palm (Elaeis guineensis) kernel protein hydrolysates (OPKHs) produced from its protein isolate. A modified microplate titer WST-1 [2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium] assay was used to investigate the cytotoxicity of hydrolysates produced from protease and pepsin-pancreatin hydrolysis at various concentrations (0.1, 1, 10, 100 μg/ml and 1 mg/ml) using HepG2 cell model. Additionally, peptide stimulation test using OPKHs at 1 mg/ml was carried out to investigate whether OPKHs could serve as growth factor for HepG2 cells other than affecting its viability. As a result, oleic acid appeared to normalize the WST-1 readings of HepG2 cells treated with both hydrolysates at 1 mg/ml. The presence of amino acids in OPKHs could stimulate the growth and prolongs the viability of HepG2 cells. Both OPKHs were non-cytotoxic to HepG2 cells at all tested concentrations even at high concentrations. This study indicated that pepsin-pancreatin and protease hydrolysates produced from oil palm kernel protein were non-cytotoxic on HepG2 cells.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins
  11. Brain endothelial cells increase the proliferation of Plasmodium falciparum through production of soluble factors
    Khaw LT, Ball HJ, Mitchell AJ, Grau GE, Stocker R, Golenser J, et al.
    Exp Parasitol, 2014 Oct;145:34-41.
    PMID: 25045850 DOI: 10.1016/j.exppara.2014.07.002
    We here describe the novel finding that brain endothelial cells in vitro can stimulate the growth of Plasmodium falciparum through the production of low molecular weight growth factors. By using a conditioned medium approach, we show that the brain endothelial cells continued to release these factors over time. If this mirrors the in vivo situation, these growth factors potentially would provide an advantage, in terms of enhanced growth, for sequestered parasitised red blood cells in the brain microvasculature. We observed this phenomenon with brain endothelial cells from several sources as well as a second P. falciparum strain. The characteristics of the growth factors included: <3 kDa molecular weight, heat stable, and in part chloroform soluble. Future efforts should be directed at identifying these growth factors, since blocking their production or actions might be of benefit for reducing parasite load and, hence, malaria pathology.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism*
  12. Solubilized antigen of Blastocystis hominis facilitates the growth of human colorectal cancer cells, HCT116
    Chandramathi S, Suresh K, Kuppusamy UR
    Parasitol Res, 2010 Mar;106(4):941-5.
    PMID: 20165878 DOI: 10.1007/s00436-010-1764-7
    Blastocystis hominis is one of the most common intestinal protozoan parasites in humans, and reports have shown that blastocystosis is coupled with intestinal disorders. In the past, researchers have developed an in vitro model using B. hominis culture filtrates to investigate its ability in triggering inflammatory cytokine responses and transcription factors in human colonic epithelial cells. Studies have also correlated the inflammation by parasitic infection with cancer. The present study provides evidence of the parasite facilitating cancer cell growth through observing the cytopathic effect, cellular immunomodulation, and apoptotic responses of B. hominis, especially in malignancy. Here we investigated the effect of solubilized antigen from B. hominis on cell viability, using peripheral blood mononuclear cells (PBMCs) and human colorectal carcinoma cells (HCT116). The gene expressions of cytokines namely interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha, interferon gamma, nuclear factor kappa light-chain enhancer of activated B cells (a gene transcription factor), and proapoptotic genes namely protein 53 and cathepsin B were also studied. Results exhibited favor the fact that antigen from B. hominis, at a certain concentration, could facilitate the growth of HCT116 while having the ability to downregulate immune cell responses (PBMCs). Therefore, there is a vital need to screen colorectal cancer patients for B. hominis infection as it possesses the ability to enhance the tumor growth.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/pharmacology*
  13. Fulltext Early clearance of Chikungunya virus in children is associated with a strong innate immune response
    Simarmata D, Ng DC, Kam YW, Lee B, Sum MS, Her Z, et al.
    Sci Rep, 2016 05 16;6:26097.
    PMID: 27180811 DOI: 10.1038/srep26097
    Chikungunya fever (CHIKF) is a global infectious disease which can affect a wide range of age groups. The pathological and immunological response upon Chikungunya virus (CHIKV) infection have been reported over the last few years. However, the clinical profile and immune response upon CHIKV infection in children remain largely unknown. In this study, we analyzed the clinical and immunological response, focusing on the cytokine/chemokine profile in a CHIKV-infected pediatric cohort from Sarawak, Malaysia. Unique immune mediators triggered upon CHIKV infection were identified through meta-analysis of the immune signatures between this pediatric group and cohorts from previous outbreaks. The data generated from this study revealed that a broad spectrum of cytokines/chemokines is up-regulated in a sub-group of virus-infected children stratified according to their viremic status during hospitalization. Furthermore, different immune mediator profiles (the levels of pro-inflammatory cytokines, chemokines and growth and other factors) were observed between children and adults. This study gives an important insight to understand the immune response of CHIKV infection in children and would aid in the development of better prognostics and clinical management for children.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  14. Microenvironmental factors involved in human amnion mesenchymal stem cells fate decisions
    Syva SH, Ampon K, Lasimbang H, Fatimah SS
    J Tissue Eng Regen Med, 2017 02;11(2):311-320.
    PMID: 26073746 DOI: 10.1002/term.2043
    Human amnion mesenchymal stem cells (HAMCs) show great differentiation and proliferation potential and also other remarkable features that could serve as an outstanding alternative source of stem cells in regenerative medicine. Recent reports have demonstrated various kinds of effective artificial niche that mimic the microenvironment of different types of stem cell to maintain and control their fate and function. The components of the stem cell microenvironment consist mainly of soluble and insoluble factors responsible for regulating stem cell differentiation and self-renewal. Extensive studies have been made on regulating HAMCs differentiation into specific phenotypes; however, the understanding of relevant factors in directing stem cell fate decisions in HAMCs remain underexplored. In this review, we have therefore identified soluble and insoluble factors, including mechanical stimuli and cues from the other supporting cells that are involved in directing HAMCs fate decisions. In order to strengthen the significance of understanding on the relevant factors involved in stem cell fate decisions, recent technologies developed to specifically mimic the microenvironments of specific cell lineages are also reviewed. Copyright © 2015 John Wiley & Sons, Ltd.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  15. Effect of gamma radiation on the expression of mRNA growth factors in glycerol cryopreserved human amniotic membrane
    Yatim RM, Kannan TP, Ab Hamid SS
    Cell Tissue Bank, 2016 Dec;17(4):643-651.
    PMID: 27535136
    Human amniotic membrane (HAM) due to its high biocompatibility, low immunogenicity, anti-microbial, anti-viral properties as well as the presence of growth factors has been used in various clinical applications. The growth factors play an important role in wound healing. The current study aimed to explore the effect of 15 kGy gamma radiation dose on selected growth factors and receptors mRNA present in HAM. Eight growth factors, namely, EGF, HGF, KGF, TGF-α, TGF-β1, TGF-β2, TGF-β3 and bFGF and two growth factor receptors, HGFR and KGFR were evaluated in this study. The total RNA was extracted and converted to complimentary DNA using commercial kits. Subsequently, the mRNA expressions of these growth factors were evaluated using real-time PCR and the results were statistically analyzed using REST-MCS software. This study confirmed the presence of these mRNA growth factors and receptors in fresh, glycerol cryopreserved and irradiated glycerol cryopreserved HAM. In glycerol cryopreserved HAM, the results showed up-regulation of HGF and bFGF and down-regulation of EGF, HGFR, KGF, KGFR, TGF-α, TGF-β1, TGF-β2 and TGF-β3 relative to the fresh HAM which acted as the control, whereas in irradiated glycerol cryopreserved HAM, the results showed up-regulation of EGF, HGF, KGF, KGFR, TGF-β1, TGF-β2 and TGF-β3 and down-regulation of HGFR, TGF-α and bFGF relative to the glycerol cryopreserved HAM which acted as the control. However, these mRNA expressions did not show any statistical significant difference compared to the control groups. This study concluded that a dose of 15 kGy of gamma radiation did not affect the mRNA expression for the growth factors' and receptors' in the glycerol cryopreserved HAM.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/genetics*
  16. Fulltext Prostate Cancer and Bone Metastases: The Underlying Mechanisms
    Wong SK, Mohamad NV, Giaze TR, Chin KY, Mohamed N, Ima-Nirwana S
    Int J Mol Sci, 2019 May 27;20(10).
    PMID: 31137764 DOI: 10.3390/ijms20102587
    Patients with advanced prostate cancer often develop bone metastases, leading to bone pain, skeletal fracture, and increased mortality. Bone provides a hospitable microenvironment to tumor cells. The disease manifestation is driven by the interaction between invading tumor cells, bone-forming osteoblasts, and bone-resorbing osteoclasts. The increased level of osteoclast-activating factor (parathyroid hormone-related peptide, PTHrP) is believed to induce bone resorption by upregulating receptor activator of nuclear factor-kappa B ligand (RANKL) and the release of various growth factors into the bone microenvironment to enhance cancer cell growth. However, the underlying molecular mechanisms remain poorly understood. This review outlines the possible molecular mechanisms involved in governing bone metastases driven by prostate cancer, which further provide the basis in searching for new molecular targets for the development of potential therapy.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  17. Notch4 overexpression in ameloblastoma correlates with the solid/multicystic phenotype
    Siar CH, Nagatsuka H, Chuah KS, Rivera RS, Nakano K, Ng KH, et al.
    Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2010 Aug;110(2):224-33.
    PMID: 20659700 DOI: 10.1016/j.tripleo.2010.03.009
    Notch signaling has been implicated in cell fate decisions during odontogenesis and tumorigenesis of some odontogenic neoplasms; however, its role in solid/multicystic (SA), unicystic (UA), and recurrent (RA) ameloblastoma remains unclear. The aim of this study was to determine Notch receptor and ligand expressions in these subtypes and to speculate on their significance.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/biosynthesis*; Intercellular Signaling Peptides and Proteins/genetics
  18. Endogenous and induced angiogenic characteristics of human chorion-derived stem cells
    Nur Fariha MM, Chua KH, Tan GC, Lim YH, Hayati AR
    Cell Biol Int, 2012;36(12):1145-53.
    PMID: 22957758 DOI: 10.1042/CBI20120044
    Cell-based therapy using stem cells has emerged as one of the pro-angiogenic methods to enhance blood vessel growth and sprouting in ischaemic conditions. This study investigated the endogenous and induced angiogenic characteristics of hCDSC (human chorion-derived stem cell) using QPCR (quantitative PCR) method, immunocytochemistry and fibrin-matrigel migration assay. The results showed that cultured hCDSC endogenously expressed angiogenic-endogenic-associated genes (VEGF, bFGF, PGF, HGF, Ang-1, PECAM-1, eNOS, Ve-cad, CD34, VEGFR-2 and vWF), with significant increase in mRNA levels of PGF, HGF, Ang-1, eNOS, VEGFR-2 and vWF following induction by bFGF (basic fibroblast growth factor) and VEGF (vascular endothelial growth factor). These enhanced angiogenic properties suggest that induced hCDSC provides a stronger angiogenic effect for the treatment of ischaemia. After angiogenic induction, hCDSC showed no reduction in the expression of the stemness genes, but had significantly higher levels of mRNA of Oct-4, Nanog (3), FZD9, ABCG-2 and BST-1. The induced cells were positive for PECAM-1 (platelet/endothelial cell adhesion molecule 1) and vWF (von Willebrand factor) with immunocytochemistry staining. hCDSC also showed endothelial migration behaviour when cultured in fibrin-matrigel construct and were capable of forming vessels in vivo after implanting into nude mice. These data suggest that hCDSC could be the cells of choice in the cell-based therapy for pro-angiogenic purpose.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/analysis; Intercellular Signaling Peptides and Proteins/genetics*
  19. Fulltext IGF-1 enhances cell proliferation and survival during early differentiation of mesenchymal stem cells to neural progenitor-like cells
    Huat TJ, Khan AA, Pati S, Mustafa Z, Abdullah JM, Jaafar H
    BMC Neurosci, 2014;15:91.
    PMID: 25047045 DOI: 10.1186/1471-2202-15-91
    There has been increasing interest recently in the plasticity of mesenchymal stem cells (MSCs) and their potential to differentiate into neural lineages. To unravel the roles and effects of different growth factors in the differentiation of MSCs into neural lineages, we have differentiated MSCs into neural lineages using different combinations of growth factors. Based on previous studies of the roles of insulin-like growth factor 1 (IGF-1) in neural stem cell isolation in the laboratory, we hypothesized that IGF-1 can enhance proliferation and reduce apoptosis in neural progenitor-like cells (NPCs) during differentiation of MSCs into NCPs.We induced MSCs differentiation under four different combinations of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, (C) EGF + bFGF + LIF, (D) EGF + bFGF + BDNF, and (E) without growth factors, as a negative control. The neurospheres formed were characterized by immunofluorescence staining against nestin, and the expression was measured by flow cytometry. Cell proliferation and apoptosis were also studied by MTS and Annexin V assay, respectively, at three different time intervals (24 hr, 3 days, and 5 days). The neurospheres formed in the four groups were then terminally differentiated into neuron and glial cells.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/metabolism
  20. Silencing of PROS1 induces apoptosis and inhibits migration and invasion of glioblastoma multiforme cells
    Che Mat MF, Abdul Murad NA, Ibrahim K, Mohd Mokhtar N, Wan Ngah WZ, Harun R, et al.
    Int J Oncol, 2016 Dec;49(6):2359-2366.
    PMID: 27840905 DOI: 10.3892/ijo.2016.3755
    Glioblastoma multiforme (GBM) is an aggressive brain tumor and most patients have poor prognosis. Despite many advances in research, there has been no significant improvement in the patient survival rate. New molecular therapies are being studied and RNA interference (RNAi) therapy is one of the promising approaches to improve prognosis and increase survival in patients with GBM. We performed a meta‑analysis of five different microarray datasets and identified 460 significantly upregulated genes in GBM. Loss‑of‑function screening of these upregulated genes using LN18 cells was performed to identify the significant target genes for glioma. Further investigations were performed using siRNA in LN18 cells and various functional assays were carried out on the selected candidate gene to understand further its role in GBM. We identified PROS1 as a candidate gene for GBM from the meta‑analysis and RNAi screening. Knockdown of PROS1 in LN18 cells significantly induced apoptosis compared to siPROS1‑untreated cells (p<0.05). Migration in cells treated with siPROS1 was reduced significantly (p<0.05) and this was confirmed with wound-healing assay. PROS1 knockdown showed substantial reduction in cell invasion up to 82% (p<0.01). In addition, inhibition of PROS1 leads to decrease in cellular proliferation by 18%. Knockdown of PROS1 in LN18 cells caused activation of both of the extrinsic and intrinsic apoptotic pathways. It caused major upregulation of FasL which is important for death receptor signaling activation and also downregulation of GAS6 and other members of TAM family of receptors. PROS1 may play an important role in the development of GBM through cellular proliferation, migration and invasion as well as apoptosis. Targeting PROS1 in GBM could be a novel therapeutic strategy in GBM treatment.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/biosynthesis
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