Displaying publications 621 - 640 of 3311 in total

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  1. Aerosol-based airway epithelial cell delivery improves airway regeneration and repair
    Kardia E, Ch'ng ES, Yahaya BH
    J Tissue Eng Regen Med, 2018 02;12(2):e995-e1007.
    PMID: 28105760 DOI: 10.1002/term.2421
    Aerosol-based cell therapy has emerged as a novel and promising therapeutic strategy for treating lung diseases. The goal of this study was to determine the safety and efficacy of aerosol-based airway epithelial cell (AEC) delivery in the setting of acute lung injury induced by tracheal brushing in rabbit. Twenty-four hours following injury, exogenous rabbit AECs were labelled with bromodeoxyuridine and aerosolized using the MicroSprayer® Aerosolizer into the injured airway. Histopathological assessments of the injury in the trachea and lungs were quantitatively scored (1 and 5 days after cell delivery). The aerosol-based AEC delivery appeared to be a safe procedure, as cellular rejection and complications in the liver and spleen were not detected. Airway injury initiated by tracheal brushing resulted in disruption of the tracheal epithelium as well as morphological damage in the lungs that is consistent with acute lung injury. Lung injury scores were reduced following 5 days after AEC delivery (AEC-treated, 0.25  ±  0.06 vs. untreated, 0.53  ±  0.05, P  
    Matched MeSH terms: Epithelial Cells/cytology; Epithelial Cells/transplantation*
  2. Fulltext Cudraflavone C Induces Tumor-Specific Apoptosis in Colorectal Cancer Cells through Inhibition of the Phosphoinositide 3-Kinase (PI3K)-AKT Pathway
    Soo HC, Chung FF, Lim KH, Yap VA, Bradshaw TD, Hii LW, et al.
    PLoS One, 2017;12(1):e0170551.
    PMID: 28107519 DOI: 10.1371/journal.pone.0170551
    Cudraflavone C (Cud C) is a naturally-occurring flavonol with reported anti-proliferative activities. However, the mechanisms by which Cud C induced cytotoxicity have yet to be fully elucidated. Here, we investigated the effects of Cud C on cell proliferation, caspase activation andapoptosis induction in colorectal cancer cells (CRC). We show that Cud C inhibits cell proliferation in KM12, Caco-2, HT29, HCC2998, HCT116 and SW48 CRC but not in the non-transformed colorectal epithelial cells, CCD CoN 841. Cud C induces tumor-selective apoptosis via mitochondrial depolarization and activation of the intrinsic caspase pathway. Gene expression profiling by microarray analyses revealed that tumor suppressor genes EGR1, HUWE1 and SMG1 were significantly up-regulated while oncogenes such as MYB1, CCNB1 and GPX2 were down-regulated following treatment with Cud C. Further analyses using Connectivity Map revealed that Cud C induced a gene signature highly similar to that of protein synthesis inhibitors and phosphoinositide 3-kinase (PI3K)-AKT inhibitors, suggesting that Cud C might inhibit PI3K-AKT signaling. A luminescent cell free PI3K lipid kinase assay revealed that Cud C significantly inhibited p110β/p85α PI3K activity, followed by p120γ, p110δ/p85α, and p110α/p85α PI3K activities. The inhibition by Cud C on p110β/p85α PI3K activity was comparable to LY-294002, a known PI3K inhibitor. Cud C also inhibited phosphorylation of AKT independent of NFκB activity in CRC cells, while ectopic expression of myristoylated AKT completely abrogated the anti-proliferative effects, and apoptosis induced by Cud C in CRC. These findings demonstrate that Cud C induces tumor-selective cytotoxicity by targeting the PI3K-AKT pathway. These findings provide novel insights into the mechanism of action of Cud C, and indicate that Cud C further development of Cud C derivatives as potential therapeutic agents is warranted.
    Matched MeSH terms: Caco-2 Cells; HT29 Cells; HCT116 Cells
  3. Development of multisubstituted hydroxyapatite nanopowders as biomedical materials for bone tissue engineering applications
    Baba Ismail YM, Wimpenny I, Bretcanu O, Dalgarno K, El Haj AJ
    J Biomed Mater Res A, 2017 Jun;105(6):1775-1785.
    PMID: 28198131 DOI: 10.1002/jbm.a.36038
    Ionic substitutions have been proposed as a tool to control the functional behavior of synthetic hydroxyapatite (HA), particularly for Bone Tissue Engineering applications. The effect of simultaneous substitution of different levels of carbonate (CO3) and silicon (Si) ions in the HA lattice was investigated. Furthermore, human bone marrow-derived mesenchymal stem cells (hMSCs) were cultured on multi-substituted HA (SiCHA) to determine if biomimetic chemical compositions were osteoconductive. Of the four different compositions investigates, SiCHA-1 (0.58 wt % Si) and SiCHA-2 (0.45 wt % Si) showed missing bands for CO3and Si using FTIR analysis, indicating competition for occupation of the phosphate site in the HA lattice; 500°C was considered the most favorable calcination temperature as: (i) the powders produced possessed a similar amount of CO3(2-8 wt %) and Si (<1.0 wt %) as present in native bone; and (ii) there was a minimal loss of CO3and Si from the HA structure to the surroundings during calcination. Higher Si content in SiCHA-1 led to lower cell viability and at most hindered proliferation, but no toxicity effect occurred. While, lower Si content in SiCHA-2 showed the highest ALP/DNA ratio after 21 days culture with hMSCs, indicating that the powder may stimulate osteogenic behavior to a greater extent than other powders. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1775-1785, 2017.
    Matched MeSH terms: Cells, Cultured; Mesenchymal Stromal Cells/cytology
  4. Fulltext Tropomyosin Receptor Kinase C Targeted Delivery of a Peptidomimetic Ligand-Photosensitizer Conjugate Induces Antitumor Immune Responses Following Photodynamic Therapy
    Kue CS, Kamkaew A, Voon SH, Kiew LV, Chung LY, Burgess K, et al.
    Sci Rep, 2016 11 17;6:37209.
    PMID: 27853305 DOI: 10.1038/srep37209
    Tropomyosin receptor kinase C (TrkC) targeted ligand-photosensitizer construct, IYIY-diiodo-boron-dipyrromethene (IYIY-I2-BODIPY) and its scrambled counterpart YIYI-I2-BODIPY have been prepared. IYIY-I2-BODIPY binds TrkC similar to neurotrophin-3 (NT-3), and NT-3 has been reported to modulate immune responses. Moreover, it could be shown that photodynamic therapy (PDT) elevates antitumor immune responses. This prompted us to investigate the immunological impacts mediated by IYIY-I2-BODIPY in pre- and post-PDT conditions. We demonstrated that IYIY-I2-BODIPY (strong response) and YIYI-I2-BODIPY (weak response) at 10 mg/kg, but not I2-BODIPY control, increased the levels of IL-2, IL-4, IL-6 and IL-17, but decreased the levels of systemic immunoregulatory mediators TGF-β, myeloid-derived suppressor cells and regulatory T-cells. Only IYIY-I2-BODIPY enhanced the IFN-γ+ and IL-17+ T-lymphocytes, and delayed tumor growth (~20% smaller size) in mice when administrated daily for 5 days. All those effects were observed without irradiation; when irradiated (520 nm, 100 J/cm2, 160 mW/cm2) to produce PDT effects (drug-light interval 1 h), IYIY-I2-BODIPY induced stronger responses. Moreover, photoirradiated IYIY-I2-BODIPY treated mice had high levels of effector T-cells compared to controls. Adoptive transfer of immune cells from IYIY-I2-BODIPY-treated survivor mice that were photoirradiated gave significantly delayed tumor growth (~40-50% smaller size) in recipient mice. IYIY-I2-BODIPY alone and in combination with PDT modulates the immune response in such a way that tumor growth is suppressed. Unlike immunosuppressive conventional chemotherapy, IYIY-I2-BODIPY can act as an immune-stimulatory chemotherapeutic agent with potential applications in clinical cancer treatment.
    Matched MeSH terms: Th17 Cells/immunology*; Th17 Cells/pathology
  5. Interleukin-17A promotes osteogenic differentiation by increasing OPG/RANKL ratio in stem cells from human exfoliated deciduous teeth (SHED)
    Sebastian AA, Kannan TP, Norazmi MN, Nurul AA
    J Tissue Eng Regen Med, 2018 08;12(8):1856-1866.
    PMID: 29774992 DOI: 10.1002/term.2706
    Stem cells derived from human exfoliated deciduous teeth (SHED) represent a promising cell source for bone tissue regeneration. This study evaluated the effects of interleukin-17A (IL-17A) on the osteogenic differentiation of SHED. SHED were cultured in complete alpha minimum essential medium supplemented with osteoinducing reagents and treated with recombinant IL-17A. The cells were quantitatively analysed for proliferative activity by MTS assay, cell markers expression, and apoptotic activity by flow cytometry. For osteogenic differentiation, alkaline phosphatase (ALP) activity was quantified; mineralization assays were carried out using von Kossa and Alizarin red, and expression of osteogenic markers were analysed by real-time polymerase chain reaction and Western blot. The results showed that treatment with IL-17A increased proliferative activity in a dose-dependent manner, but reduced the expression of stem cell markers (c-Myc and Nanog) as the days progressed. IL-17A induced osteogenic differentiation in SHED as evidenced by high ALP activity, increased matrix mineralization, and upregulation of the mRNA expression of the osteogenic markers ALP, alpha 1 type 1 collagen (Col1A1), runt-related transcription factor 2 (RUNX2), osteopontin (OPN), osteocalcin (OCN), and osteoprotegerin (OPG) but downregulation of receptor activator of nuclear factor κB ligand (RANKL) as well as altering the OPG/RANKL ratio. Findings from our study indicate that IL-17A enhances proliferation and osteogenic differentiation of SHED by regulating OPG/RANKL mechanism thus suggests therapeutic potential of IL-17A in bone regeneration.
    Matched MeSH terms: Stem Cells/cytology; Stem Cells/metabolism*
  6. Interferon-γ induces biphasic changes in caldesmon localization as well as adherens junction organization and expression in HUVECs
    Ng CT, Fong LY, Yong YK, Hakim MN, Ahmad Z
    Cytokine, 2018 11;111:541-550.
    PMID: 29909980 DOI: 10.1016/j.cyto.2018.06.010
    Endothelial barrier dysfunction leads to increased endothelial permeability and is an early step in the development of vascular inflammatory diseases such as atherosclerosis. Interferon-γ (IFN-γ), a proinflammatory cytokine, is known to cause increased endothelial permeability. However, the mechanisms by which IFN-γ disrupts the endothelial barrier have not been clarified. This study aimed to investigate how IFN-γ impairs the endothelial barrier integrity by specifically examining the roles of caldesmon, adherens junctions (AJs) and p38 mitogen-activated protein (MAP) kinase in IFN-γ-induced endothelial barrier dysfunction. IFN-γ exhibited a biphasic effect on caldesmon localization and both the structural organization and protein expression of AJs. In the early phase (4-8 h), IFN-γ induced the formation of peripheral caldesmon bands and discontinuous AJs, while AJ protein expression was unchanged. Interestingly, IFN-γ also stimulated caldesmon phosphorylation, resulting in actin dissociation from caldesmon at 8 h. Conversely, changes seen in the late phase (16-24 h) included cytoplasmic caldesmon dispersal, AJ linearization and junctional area reduction, which were associated with reduced membrane, cytoskeletal and total AJ protein expression. In addition, IFN-γ enhanced myosin binding to caldesmon at 12 h and persisted up to 24 h. Furthermore, inhibition of p38 MAP kinase by SB203580 did not reverse either the early or late phase changes observed. These data suggest that IFN-γ may activate signaling molecules other than p38 MAP kinase. In conclusion, our findings enhance the current understanding of how IFN-γ disrupts endothelial barrier function and reveal potential therapeutic targets, such as caldesmon and AJs, for the treatment of IFN-γ-associated vascular inflammatory diseases.
    Matched MeSH terms: Endothelial Cells/metabolism; Human Umbilical Vein Endothelial Cells
  7. Rate and extent of mitragynine and 7-hydroxymitragynine blood-brain barrier transport and their intra-brain distribution: the missing link in pharmacodynamic studies
    Yusof SR, Mohd Uzid M, Teh EH, Hanapi NA, Mohideen M, Mohamad Arshad AS, et al.
    Addict Biol, 2019 09;24(5):935-945.
    PMID: 30088322 DOI: 10.1111/adb.12661
    Mitragyna speciosa is reported to be beneficial for the management of chronic pain and opioid withdrawal in the evolving opioid epidemic. Data on the blood-brain barrier (BBB) transport of mitragynine and 7-hydroxymitragynine, the active compounds of the plant, are still lacking and inconclusive. Here, we present for the first time the rate and the extent of mitragynine and 7-hydroxymitragynine transport across the BBB, with an investigation of their post-BBB intra-brain distribution. We utilized an in vitro BBB model to study the rate of BBB permeation of the compounds and their interaction with efflux transporter P-glycoprotein (P-gp). Mitragynine showed higher apical-to-basolateral (A-B, i.e. blood-to-brain side) permeability than 7-hydroxymitragynine. 7-Hydroxymitragynine showed a tendency to efflux, with efflux ratio (B-A/A-B) of 1.39. Both were found to inhibit the P-gp and are also subject to efflux by the P-gp. Assessment of the extent of BBB transport in vivo in rats from unbound brain to plasma concentration ratios (Kp,uu,brain ) revealed extensive efflux of both compounds, with less than 10 percent of unbound mitragynine and 7-hydroxymitragynine in plasma crossing the BBB. By contrast, the extent of intra-brain distribution was significantly different, with mitragynine having 18-fold higher brain tissue uptake in brain slice assay compared with 7-hydroxymitragynine. Mitragynine showed a moderate capacity to accumulate inside brain parenchymal cells, while 7-hydroxymitragynine showed restricted cellular barrier transport. The presented findings from this systematic investigation of brain pharmacokinetics of mitragynine and 7-hydroxymitragynine are essential for design and interpretation of in vivo experiments aiming to establish exposure-response relationship.
    Matched MeSH terms: Cells, Cultured; Endothelial Cells/physiology
  8. Structural and bone marrow stem cell biocompatibility studies of hydrogel synthesized via chemo-enzymatic route
    Latfi ASA, Pramanik S, Poon CT, Gumel AM, Lai KW, Annuar MSM, et al.
    J Biomater Appl, 2019 01;33(6):854-865.
    PMID: 30458659 DOI: 10.1177/0885328218812490
    Natural biopolymers have many attractive medical applications; however, complications due to fibrosis caused a reduction in diffusion and dispersal of nutrients and waste products. Consequently, severe immunocompatibility problems and poor mechanical and degradation properties in synthetic polymers ensue. Hence, the present study investigates a novel hydrogel material synthesized from caprolactone, ethylene glycol, ethylenediamine, polyethylene glycol, ammonium persulfate, and tetramethylethylenediamine via chemo-enzymatic route. Spectroscopic analyses indicated the formation of polyurea and polyhydroxyurethane as the primary building block of the hydrogel starting material. Biocompatibility studies showed positive observation in biosafety test using direct contact cytotoxicity assay in addition to active cellular growth on the hydrogel scaffold based on fluorescence observation. The synthesized hydrogel also exhibited (self)fluorescence properties under specific wavelength excitation. Hence, synthesized hydrogel could be a potential candidate for medical imaging as well as tissue engineering applications as a tissue expander, coating material, biosensor, and drug delivery system.
    Matched MeSH terms: Cells, Cultured; Mesenchymal Stromal Cells/cytology*
  9. Fulltext Human Wharton's Jelly-Derived Mesenchymal Stem Cells Minimally Improve the Growth Kinetics and Cardiomyocyte Differentiation of Aged Murine Cardiac c-kit Cells in In Vitro without Rejuvenating Effect
    Ng WH, Yong YK, Ramasamy R, Ngalim SH, Lim V, Shaharuddin B, et al.
    Int J Mol Sci, 2019 Nov 06;20(22).
    PMID: 31698679 DOI: 10.3390/ijms20225519
    Cardiac c-kit cells show promise in regenerating an injured heart. While heart disease commonly affects elderly patients, it is unclear if autologous cardiac c-kit cells are functionally competent and applicable to these patients. This study characterised cardiac c-kit cells (CCs) from aged mice and studied the effects of human Wharton's Jelly-derived mesenchymal stem cells (MSCs) on the growth kinetics and cardiac differentiation of aged CCs in vitro. CCs were isolated from 4-week- and 18-month-old C57/BL6N mice and were directly co-cultured with MSCs or separated by transwell insert. Clonogenically expanded aged CCs showed comparable telomere length to young CCs. However, these cells showed lower Gata4, Nkx2.5, and Sox2 gene expressions, with changes of 2.4, 3767.0, and 4.9 folds, respectively. Direct co-culture of both cells increased aged CC migration, which repopulated 54.6 ± 4.4% of the gap area as compared to aged CCs with MSCs in transwell (42.9 ± 2.6%) and CCs without MSCs (44.7 ± 2.5%). Both direct and transwell co-culture improved proliferation in aged CCs by 15.0% and 16.4%, respectively, as traced using carboxyfluorescein succinimidyl ester (CFSE) for three days. These data suggest that MSCs can improve the growth kinetics of aged CCs. CCs retaining intact telomere are present in old hearts and could be obtained based on their self-renewing capability. Although these aged CCs with reduced growth kinetics are improved by MSCs via cell-cell contact, the effect is minimal.
    Matched MeSH terms: Clone Cells; Mesenchymal Stromal Cells/cytology*
  10. Magnoflorine Enhances LPS-Activated Pro-Inflammatory Responses via MyD88-Dependent Pathways in U937 Macrophages
    Haque MA, Jantan I, Harikrishnan H, Abdul Wahab SM
    Planta Med, 2018 Nov;84(17):1255-1264.
    PMID: 29906814 DOI: 10.1055/a-0637-9936
    Magnoflorine, a major bioactive metabolite isolated from Tinospora crispa, has been reported for its diverse biochemical and pharmacological properties. However, there is little report on its underlying mechanisms of action on immune responses, particularly on macrophage activation. In this study, we aimed to investigate the effects of magnoflorine, isolated from T. crispa on the pro-inflammatory mediators generation induced by LPS and the concomitant NF-κB, MAPKs, and PI3K-Akt signaling pathways in U937 macrophages. Differentiated U937 macrophages were treated with magnoflorine and the release of pro-inflammatory mediators was evaluated through ELISA, while the relative mRNA expression of the respective mediators was quantified through qRT-PCR. Correspondingly, western blotting was executed to observe the modulatory effects of magnoflorine on the expression of various markers related to NF-κB, MAPK and PI3K-Akt signaling activation in LPS-primed U937 macrophages. Magnoflorine significantly enhanced the upregulation of TNF-α, IL-1β, and PGE2 production as well as COX-2 protein expression. Successively, magnoflorine prompted the mRNA transcription level of these pro-inflammatory mediators. Magnoflorine enhanced the NF-κB activation by prompting p65, IκBα, and IKKα/β phosphorylation as well as IκBα degradation. Besides, magnoflorine treatments concentration-dependently augmented the phosphorylation of JNK, ERK, and p38 MAPKs as well as Akt. The immunoaugmenting effects were further confirmed by investigating the effects of magnoflorine on specific inhibitors, where the treatment with specific inhibitors of NF-κB, MAPKs, and PI3K-Akt proficiently blocked the magnoflorine-triggered TNF-α release and COX-2 expression. Magnoflorine furthermore enhanced the MyD88 and TLR4 upregulation. The results suggest that magnoflorine has high potential on augmenting immune responses.
    Matched MeSH terms: U937 Cells/drug effects*; U937 Cells/physiology
  11. An immunohistochemical study of CD1a and CD83-positive infiltrating dendritic cell density in cervical neoplasia
    Hayati AR, Zulkarnaen M
    Int J Gynecol Pathol, 2007 Jan;26(1):83-8.
    PMID: 17197902
    Cervical carcinoma is the second leading cancer in women in Malaysia, after breast cancer. Human papillomavirus (HPV) has been implicated in the development of dysplasia or cervical intraepithelial neoplasia and progression to squamous cell carcinoma. Because of the confinement of the human papillomavirus infection within the epithelial layer, the presence of dentritic cells or Langerhans cells in epithelial layer of the ectocervix is paramount in producing immune response. The mature dentritic cells express CD83 and high CD40/80/86, whereas the immature cells express CD1a and low CD40/80/86. By identifying CD1a and CD83, theoretically, both immature and mature dentritic cell populations can be studied. In view of the facts, we investigated the infiltrating cell density of mature and immature dentritic cells in cervical neoplasia.
    Matched MeSH terms: Dendritic Cells/cytology*; Dendritic Cells/immunology
  12. Fulltext Escherichia coli K1 utilizes host macropinocytic pathways for invasion of brain microvascular endothelial cells
    Loh LN, McCarthy EMC, Narang P, Khan NA, Ward TH
    Traffic, 2017 11;18(11):733-746.
    PMID: 28799243 DOI: 10.1111/tra.12508
    Eukaryotic cells utilize multiple endocytic pathways for specific uptake of ligands or molecules, and these pathways are commonly hijacked by pathogens to enable host cell invasion. Escherichia coli K1, a pathogenic bacterium that causes neonatal meningitis, invades the endothelium of the blood-brain barrier, but the entry route remains unclear. Here, we demonstrate that the bacteria trigger an actin-mediated uptake route, stimulating fluid phase uptake, membrane ruffling and macropinocytosis. The route of uptake requires intact lipid rafts as shown by cholesterol depletion. Using a variety of perturbants we demonstrate that small Rho GTPases and their downstream effectors have a significant effect on bacterial invasion. Furthermore, clathrin-mediated endocytosis appears to play an indirect role in E. coli K1 uptake. The data suggest that the bacteria effect a complex interplay between the Rho GTPases to increase their chances of uptake by macropinocytosis into human brain microvascular endothelial cells.
    Matched MeSH terms: Endothelial Cells/metabolism; Endothelial Cells/microbiology*
  13. Fulltext Real-time acquisition of transendothelial electrical resistance in an all-human, in vitro, 3-dimensional, blood-brain barrier model exemplifies tight-junction integrity
    Maherally Z, Fillmore HL, Tan SL, Tan SF, Jassam SA, Quack FI, et al.
    FASEB J, 2018 01;32(1):168-182.
    PMID: 28883042 DOI: 10.1096/fj.201700162R
    The blood-brain barrier (BBB) consists of endothelial cells, astrocytes, and pericytes embedded in basal lamina (BL). Most in vitro models use nonhuman, monolayer cultures for therapeutic-delivery studies, relying on transendothelial electrical resistance (TEER) measurements without other tight-junction (TJ) formation parameters. We aimed to develop reliable, reproducible, in vitro 3-dimensional (3D) models incorporating relevant human, in vivo cell types and BL proteins. The 3D BBB models were constructed with human brain endothelial cells, human astrocytes, and human brain pericytes in mono-, co-, and tricultures. TEER was measured in 3D models using a volt/ohmmeter and cellZscope. Influence of BL proteins-laminin, fibronectin, collagen type IV, agrin, and perlecan-on adhesion and TEER was assessed using an electric cell-substrate impedance-sensing system. TJ protein expression was assessed by Western blotting (WB) and immunocytochemistry (ICC). Perlecan (10 µg/ml) evoked unreportedly high, in vitro TEER values (1200 Ω) and the strongest adhesion. Coculturing endothelial cells with astrocytes yielded the greatest resistance over time. ICC and WB results correlated with resistance levels, with evidence of prominent occludin expression in cocultures. BL proteins exerted differential effects on TEER, whereas astrocytes in contact yielded higher TEER values and TJ expression.-Maherally, Z., Fillmore, H. L., Tan, S. L., Tan, S. F., Jassam, S. A., Quack, F. I., Hatherell, K. E., Pilkington, G. J. Real-time acquisition of transendothelial electrical resistance in an all-human, in vitro, 3-dimensional, blood-brain barrier model exemplifies tight-junction integrity.
    Matched MeSH terms: Endothelial Cells/cytology; Endothelial Cells/metabolism
  14. Novel drug delivery approaches in treating pulmonary fibrosis
    Dua K, Awasthi R, Madan JR, Chellappan DK, Nalluri BN, Gupta G, et al.
    Panminerva Med, 2018 Dec;60(4):238-240.
    PMID: 29480673 DOI: 10.23736/S0031-0808.18.03428-6
    Matched MeSH terms: Th1 Cells; Th2 Cells; HEK293 Cells
  15. Fulltext Effects of annexin A1 on apoptosis and cell cycle arrest in human leukemic cell lines
    Sabran A, Kumolosasi E, Jantan I
    Acta Pharm, 2019 Mar 01;69(1):75-86.
    PMID: 31259717 DOI: 10.2478/acph-2019-0005
    Recent studies suggest that annexin A1 (ANXA1) promotes apoptosis in cancerous cells. This study aims to investigate the effects of ANXA1 on apoptosis and cell cycle arrest in K562, Jurkat and U937 cells and peripheral blood mononu-clear cells (PBMC). Cells were treated with ANXA1 and cyclophosphamide prior to flow cytometry analysis for apoptosis and cell cycle arrest induction. At 2.5µM, ANXA1 induced significant apoptosis in K562 (p ≤ 0.001) and U937 (p ≤ 0.05) cells, with EC50 values of 3.6 and 3.8 µM, respectively. In Jurkat cells, induction was not significant (EC50, 17.0 µM). No significant apoptosis induction was observed in PBMC. ANXA1 caused cycle arrest in the G0/G1 phase in K562 and U937 cells with p ≤ 0.001 for both, and (p ≤ 0.01) for Jurkat cells. ANXA1 induced apoptosis and cycle arrest in the G0/G1 phase in K562 and U937 cells, causing only cell cycle arrest in Jurkat cells.
    Matched MeSH terms: Jurkat Cells; K562 Cells; U937 Cells
  16. Fulltext Current Progress in Tendon and Ligament Tissue Engineering
    Lim WL, Liau LL, Ng MH, Chowdhury SR, Law JX
    Tissue Eng Regen Med, 2019 Dec;16(6):549-571.
    PMID: 31824819 DOI: 10.1007/s13770-019-00196-w
    BACKGROUND: Tendon and ligament injuries accounted for 30% of all musculoskeletal consultations with 4 million new incidences worldwide each year and thus imposed a significant burden to the society and the economy. Damaged tendon and ligament can severely affect the normal body movement and might lead to many complications if not treated promptly and adequately. Current conventional treatment through surgical repair and tissue graft are ineffective with a high rate of recurrence.

    METHODS: In this review, we first discussed the anatomy, physiology and pathophysiology of tendon and ligament injuries and its current treatment. Secondly, we explored the current role of tendon and ligament tissue engineering, describing its recent advances. After that, we also described stem cell and cell secreted product approaches in tendon and ligament injuries. Lastly, we examined the role of the bioreactor and mechanical loading in in vitro maturation of engineered tendon and ligament.

    RESULTS: Tissue engineering offers various alternative ways of treatment from biological tissue constructs to stem cell therapy and cell secreted products. Bioreactor with mechanical stimulation is instrumental in preparing mature engineered tendon and ligament substitutes in vitro.

    CONCLUSIONS: Tissue engineering showed great promise in replacing the damaged tendon and ligament. However, more study is needed to develop ideal engineered tendon and ligament.

    Matched MeSH terms: Stem Cells/cytology; Stem Cells/metabolism
  17. Fulltext Enhanced in vitro angiogenic behaviour of human umbilical vein endothelial cells on thermally oxidized TiO2 nanofibrous surfaces
    Tan AW, Liau LL, Chua KH, Ahmad R, Akbar SA, Pingguan-Murphy B
    Sci Rep, 2016 Feb 17;6:21828.
    PMID: 26883761 DOI: 10.1038/srep21828
    One of the major challenges in bone grafting is the lack of sufficient bone vascularization. A rapid and stable bone vascularization at an early stage of implantation is essential for optimal functioning of the bone graft. To address this, the ability of in situ TiO2 nanofibrous surfaces fabricated via thermal oxidation method to enhance the angiogenic potential of human umbilical vein endothelial cells (HUVECs) was investigated. The cellular responses of HUVECs on TiO2 nanofibrous surfaces were studied through cell adhesion, cell proliferation, capillary-like tube formation, growth factors secretion (VEGF and BFGF), and angiogenic-endogenic-associated gene (VEGF, VEGFR2, BFGF, PGF, HGF, Ang-1, VWF, PECAM-1 and ENOS) expression analysis after 2 weeks of cell seeding. Our results show that TiO2 nanofibrous surfaces significantly enhanced adhesion, proliferation, formation of capillary-like tube networks and growth factors secretion of HUVECs, as well as leading to higher expression level of all angiogenic-endogenic-associated genes, in comparison to unmodified control surfaces. These beneficial effects suggest the potential use of such surface nanostructures to be utilized as an advantageous interface for bone grafts as they can promote angiogenesis, which improves bone vascularization.
    Matched MeSH terms: Cells, Cultured; Human Umbilical Vein Endothelial Cells/physiology*
  18. Hot water extract of Chlorella vulgaris induced DNA damage and apoptosis
    Yusof YA, Saad SM, Makpol S, Shamaan NA, Ngah WZ
    Clinics (Sao Paulo), 2010;65(12):1371-7.
    PMID: 21340229
    OBJECTIVES: The aim of this study was to determine the antiproliferative and apoptotic effects of hot water extracts of Chlorella vulgaris on hepatoma cell line HepG2.

    INTRODUCTION: The search for food and spices that can induce apoptosis in cancer cells has been a major study interest in the last decade. Chlorella vulgaris, a unicellular green algae, has been reported to have antioxidant and anti-cancer properties. However, its chemopreventive effects in inhibiting the growth of cancer cells have not been studied in great detail.

    METHODS: HepG2 liver cancer cells and WRL68 normal liver cells were treated with various concentrations (0-4 mg/ml) of hot water extract of C. vulgaris after 24 hours incubation. Apoptosis rate was evaluated by TUNEL assay while DNA damage was assessed by Comet assay. Apoptosis proteins were evaluated by Western blot analysis.

    RESULTS: Chlorella vulgaris decreased the number of viable HepG2 cells in a dose dependent manner (p < 0.05), with an IC50 of 1.6 mg/ml. DNA damage as measured by Comet assay was increased in HepG2 cells at all concentrations of Chlorella vulgaris tested. Evaluation of apoptosis by TUNEL assay showed that Chlorella vulgaris induced a higher apoptotic rate (70%) in HepG2 cells compared to normal liver cells, WRL68 (15%). Western blot analysis showed increased expression of pro-apoptotic proteins P53, Bax and caspase-3 in the HepG2 cells compared to normal liver cells WRL68, and decreased expression of the anti-apoptotic protein Bcl-2.

    CONCLUSIONS: Chlorella vulgaris may have anti-cancer effects by inducing apoptosis signaling cascades via an increased expression of P53, Bax and caspase-3 proteins and through a reduction of Bcl-2 protein, which subsequently lead to increased DNA damage and apoptosis.

    Matched MeSH terms: Hep G2 Cells/cytology; Hep G2 Cells/drug effects*
  19. Fulltext Natural Compound 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al from Momordica charantia Acts as PPARγ Ligand
    Noruddin NAA, Hamzah MF, Rosman Z, Salin NH, Shu-Chien AC, Muhammad TST
    Molecules, 2021 May 03;26(9).
    PMID: 34063700 DOI: 10.3390/molecules26092682
    Momordica charantia is a popular vegetable associated with effective complementary and alternative diabetes management in some parts of the world. However, the molecular mechanism is less commonly investigated. In this study, we investigated the association between a major cucurbitane triterpenoid isolated from M. charantia, 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (THCB) and peroxisome proliferator activated receptor gamma (PPARγ) activation and its related activities using cell culture and molecular biology techniques. In this study, we report on both M. charantia fruit crude extract and THCB in driving the luciferase activity of Peroxisome Proliferator Response Element, associated with PPARγ activation. Other than that, THCB also induced adipocyte differentiation at far less intensity as compared to the full agonist rosiglitazone. In conjunction, THCB treatment on adipocytes also resulted in upregulation of PPAR gamma target genes expression; AP2, adiponectin, LPL and CD34 at a lower magnitude compared to rosiglitazone's induction. THCB also induced glucose uptake into muscle cells and the mechanism is via Glut4 translocation to the cell membrane. In conclusion, THCB acts as one of the many components in M. charantia to induce hypoglycaemic effect by acting as PPARγ ligand and inducing glucose uptake activity in the muscles by means of Glut4 translocation.
    Matched MeSH terms: Muscle Cells/cytology; 3T3-L1 Cells
  20. Allogeneic and autologous mode of stem cell transplantation in regenerative medicine: which way to go?
    Mamidi MK, Dutta S, Bhonde R, Das AK, Pal R
    Med Hypotheses, 2014 Dec;83(6):787-91.
    PMID: 25456787 DOI: 10.1016/j.mehy.2014.10.010
    Stem cell transplantation is a generic term covering different techniques. However there is argument over the pros and cons of autologous and allogeneic transplants of mesenchymal stem cells (MSCs) for regenerative therapy. Given that the MSCs have already been proven to be safe in patients, we hypothesize that allogeneic transplantation could be more effective and cost-effective as compared to autologous transplantation specifically in older subjects who are the likely victims of degenerative diseases. This analysis is based on the scientific logic that allogeneic stem cells extracted in large numbers from young and healthy donors could be physiologically, metabolically and genetically more stable. Therefore stem cells from young donors may be expected to exhibit higher vigor in secreting trophic factors leading to activation of host tissue-specific stem cells and also be more efficient in remodeling the micro-environmental niche of damaged tissue.
    Matched MeSH terms: Bone Marrow Cells/cytology; Mesenchymal Stromal Cells/cytology
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