Displaying publications 801 - 820 of 894 in total

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  1. High cut-off hemofiltration versus standard hemofiltration: a pilot assessment of effects on indices of apoptosis
    Atan R, Virzi GM, Peck L, Ramadas A, Brocca A, Eastwood G, et al.
    Blood Purif., 2014;37(4):296-303.
    PMID: 25096908 DOI: 10.1159/000363220
    To measure plasma pro-apoptotic and pro-necrotic activity in severe acute kidney injury (AKI) patients within a randomized controlled trial of continuous veno-venous hemofiltration with high cut-off filters (CVVH-HCO) versus standard filters (CVVH-Std).
    Matched MeSH terms: Cell Survival
  2. Synthesis of a novel acrylated abietic acid-g-bacterial cellulose hydrogel by gamma irradiation
    Abeer MM, Amin MC, Lazim AM, Pandey M, Martin C
    Carbohydr Polym, 2014 Sep 22;110:505-12.
    PMID: 24906785 DOI: 10.1016/j.carbpol.2014.04.052
    Acrylated abietic acid (acrylated AbA) and acrylated abietic acid-grafted bacterial cellulose pH sensitive hydrogel (acrylated AbA-g-BC) were prepared by a one-pot synthesis. The successful dimerization of acrylic acid (AA) and abietic acid (AbA) and grafting of the dimer onto bacterial cellulose (BC) was confirmed by 13C solid state NMR as well as FT-IR. X-ray diffraction analysis showed characteristic peaks for AbA and BC; further, there was no effect of increasing amorphous AA content on the overall crystallinity of the hydrogel. Differential scanning calorimetry revealed a glass transition temperature of 80°C. Gel fraction and swelling studies gave insight into the features of the hydrogel, suggesting that it was suitable for future applications such as drug delivery. Scanning electron microscopy observations showed an interesting interpenetrating network within the walls of hydrogel samples with the lowest levels of AA and gamma radiation doses. Cell viability test revealed that the synthesized hydrogel is safe for future use in biomedical applications.
    Matched MeSH terms: Cell Survival
  3. Aerosol-based delivery of fibroblast cells for treatment of lung diseases
    Kardia E, Yusoff NM, Zakaria Z, Yahaya B
    J Aerosol Med Pulm Drug Deliv, 2014 Feb;27(1):30-4.
    PMID: 23409833 DOI: 10.1089/jamp.2012.1020
    Cell-based therapy has great potential to treat patients with lung diseases. The administration of cells into an injured lung is one method of repairing and replacing lost lung tissue. However, different types of delivery have been studied and compared, and none of the techniques resulted in engraftment of a high number of cells into the targeted organ. In this in vitro study, a novel method of cell delivery was introduced to investigate the possibility of delivering aerosolized skin-derived fibroblasts.
    Matched MeSH terms: Cell Survival
  4. Fulltext Real space flight travel is associated with ultrastructural changes, cytoskeletal disruption and premature senescence of HUVEC
    Kapitonova MY, Muid S, Froemming GR, Yusoff WN, Othman S, Ali AM, et al.
    Malays J Pathol, 2012 Dec;34(2):103-13.
    PMID: 23424772 MyJurnal
    Microgravity, hypergravity, vibration, ionizing radiation and temperature fluctuations are major factors of outer space flight affecting human organs and tissues. There are several reports on the effect of space flight on different human cell types of mesenchymal origin while information regarding changes to vascular endothelial cells is scarce. Ultrastructural and cytophysiological features of macrovascular endothelial cells in outer space flight and their persistence during subsequent culturing were demonstrated in the present investigation. At the end of the space flight, endothelial cells displayed profound changes indicating cytoskeletal lesions and increased cell membrane permeability. Readapted cells of subsequent passages exhibited persisting cytoskeletal changes, decreased metabolism and cell growth indicating cellular senescence.
    Matched MeSH terms: Cell Survival
  5. Production and scale-up of a monoclonal antibody against 17-hydroxyprogesterone
    Chua GK, Abdul-Rahman B, Chisti Y
    Biotechnol Prog, 2013 Jan-Feb;29(1):154-64.
    PMID: 23125182 DOI: 10.1002/btpr.1656
    The hybridoma 192 was used to produce a monoclonal antibody (MAb) against 17-hydroxyprogesterone (17-OHP), for possible use in screening for congenital adrenal hyperplasia (CAH). The factors influencing the MAb production were screened and optimized in a 2 L stirred bioreactor. The production was then scaled up to a 20 L bioreactor. All of the screened factors (aeration rate, stirring speed, dissolved oxygen concentration, pH, and temperature) were found to significantly affect production. Optimization using the response surface methodology identified the following optimal production conditions: 36.8°C, pH 7.4, stirring speed of 100 rpm, 30% dissolved oxygen concentration, and an aeration rate of 0.09 vvm. Under these conditions, the maximum viable cell density achieved was 1.34 ± 0.21 × 10(6) cells mL(-1) and the specific growth rate was 0.036 ± 0.004 h(-1) . The maximum MAb titer was 11.94 ± 4.81 μg mL(-1) with an average specific MAb production rate of 0.273 ± 0.135 pg cell(-1) h(-1) . A constant impeller tip speed criterion was used for the scale-up. The specific growth rate (0.040 h(-1) ) and the maximum viable cell density (1.89 × 10(6) cells mL(-1) ) at the larger scale were better than the values achieved at the small scale, but the MAb titer in the 20 L bioreactor was 18% lower than in the smaller bioreactor. A change in the culture environment from the static conditions of a T-flask to the stirred bioreactor culture did not affect the specificity of the MAb toward its antigen (17-OHP) and did not compromise the structural integrity of the MAb.
    Matched MeSH terms: Cell Survival
  6. Light-activated cytotoxic compounds from Malaysian microorganisms for photodynamic therapy of cancer
    Kamal N, Sabaratnam V, Abdullah N, Ho AS, Teo SH, Lee HB
    Antonie Van Leeuwenhoek, 2009 Feb;95(2):179-88.
    PMID: 19125347 DOI: 10.1007/s10482-008-9301-8
    Photodynamic therapy (PDT) is a promising cancer treatment which involves activation of a photosensitizing drug with light to produce reactive oxygen species that kill tumors without causing damage to unirradiated normal tissues. To date, only Photofrin, Foscan and Levulan have been approved for clinical treatment of cancer. Tropical habitats such as those found in Malaysia are attractive sources of new therapeutic compounds as tremendous chemical diversity is found in a large number of plants, animals, marine- and micro-organisms. In our screening program for novel photosensitizers from nature, colorful strains of fungi (from Aspergillus and Penicillium genus) and bacteria (including actinomycetes and photosynthetic bacteria) were collected from various habitats in Peninsular Malaysia, such as coastal soil, peat soil, marine sponges and wastewater ponds. Methanolic extracts from a total of 85 different species were evaluated with a short-term cell viability assay for photo-cytotoxicity, where a promyelocytic leukemia cell-line, HL60 incubated with 20 microg/ml of extracts was irradiated with 9.6 J/cm(2) of a broad spectrum light. Two of these extracts, one from Rhodobacter sphaeroides (PBUM003) and one from Rhodopseudomonas palustris (PBUM001) showed moderate to strong photo-cytotoxicity. Subsequent bioassay guided isolation of the PBUM001 extract yielded known photosensitisers that are based on bacteriochlorophyll-a by comparing their molecular weight data, HPLC profiles and UV-vis absorption spectra with literature values, thereby demonstrating the validity of our screening approach.
    Matched MeSH terms: Cell Survival
  7. Effect of keratin-gelatin and bFGF-gelatin composite film as a sandwich layer for full-thickness skin mesh graft in experimental dogs
    Thilagar S, Jothi NA, Omar AR, Kamaruddin MY, Ganabadi S
    J Biomed Mater Res B Appl Biomater, 2009 Jan;88(1):12-6.
    PMID: 18161832
    Skin grafts are indicated when there is a major loss of skin. Full-thickness skin graft is an ideal choice to reconstruct defect of irregular surface that is difficult to immobilize. Full-thickness mesh grafts can be applied to patch large skin defect when there is less donor site in extensively traumatized and burned surgical patients. The concept of using natural biomaterials such as keratin, basic fibroblast growth factor is slowly gaining popularity in the field of medical research to achieve early healing. The main objective of this study is to evaluate the efficacy of gelatin conjoined with keratin processed from the poultry feather and commercially available basic fibroblast growth factor (bFGF) as a sandwich layer in promoting the viability of full-thickness skin mesh grafts. The efficacy was assessed from the observation of clinical, bacteriological, and histopathological findings in three groups of experimental dogs. The clinical observations such as color, appearance and discharge, and hair growth were selected as criteria which indicated good and early acceptance of graft in keratin-gelatin (group II). On bacteriological examination, Staphylococcus aureus and Proteus was identified in few animals. Histopathological study of the patched graft revealed early presences of hair follicles; sebaceous gland, and normal thickness of the epidermis in keratin-gelatin in group II treated animals compared with other group (group I-control, group III-bFGF-gelatin).
    Matched MeSH terms: Cell Survival
  8. Transcriptome profiling of endothelial cells during infections with high and low densities of C. albicans cells
    Lim CS, Rosli R, Seow HF, Chong PP
    Int J Med Microbiol, 2011 Aug;301(6):536-46.
    PMID: 21371935 DOI: 10.1016/j.ijmm.2010.12.002
    Systemic infections of Candida albicans, the most prevalent fungal pathogen in humans, are on the rise in recent years. However, the exact mode of pathogenesis of this fungus is still not well elucidated. Previous studies using C. albicans mutants locked into the yeast form via gene deletion found that this form was avirulent and did not induce significant differential expression of host genes in vitro. In this study, a high density of C. albicans was used to infect human umbilical vein endothelial cells (HUVEC), resulting in yeast-form infections, whilst a low density of C. albicans resulted in hyphae infections. Transcriptional profiling of HUVEC response to these infections showed that high densities of C. albicans induced a stronger, broader transcriptional response from HUVEC than low densities of C. albicans infection. Many of the genes that were significantly differentially expressed were involved in apoptosis and cell death. In addition, conditioned media from the high-density infections caused a significant reduction in HUVEC viability, suggesting that certain molecules released during C. albicans and HUVEC interactions were capable of causing cell death. This study has shown that C. albicans yeast-forms, at high densities, cannot be dismissed as avirulent, but instead could possibly contribute to C. albicans pathogenesis.
    Matched MeSH terms: Cell Survival
  9. Fulltext Phenotypic and functional characterization of long-term cryopreserved human adipose-derived stem cells
    Yong KW, Pingguan-Murphy B, Xu F, Abas WA, Choi JR, Omar SZ, et al.
    Sci Rep, 2015;5:9596.
    PMID: 25872464 DOI: 10.1038/srep09596
    Cryopreservation represents an effective technique to maintain the functional properties of human adipose-derived stem cells (ASCs) and allows pooling of cells via long-term storage for clinical applications, e.g., cell-based therapies. It is crucial to reduce freezing injury during the cryopreservation process by loading the ASCs with the optimum concentration of suitable cryoprotective agents (CPAs). In this study, human ASCs were preserved for 3 months in different combinations of CPAs, including 1) 0.25 M trehalose; 2) 5% dimethylsulfoxide (DMSO); 3) 10% DMSO; 4) 5% DMSO + 20% fetal bovine serum (FBS); 5) 10% DMSO + 20% FBS; 6) 10% DMSO + 90% FBS. Interestingly, even with a reduction of DMSO to 5% and without FBS, cryopreserved ASCs maintained high cell viability comparable with standard cryomedium (10% DMSO + 90% FBS), with normal cell phenotype and proliferation rate. Cryopreserved ASCs also maintained their differentiation capability (e.g., to adipocytes, osteocytes and chondrocytes) and showed an enhanced expression level of stemness markers (e.g., NANOG, OCT-4, SOX-2 and REX-1). Our findings suggest that 5% DMSO without FBS may be an ideal CPA for an efficient long-term cryopreservation of human ASCs. These results aid in establishing standardized xeno-free long-term cryopreservation of human ASCs for clinical applications.
    Matched MeSH terms: Cell Survival
  10. Fulltext Modulation of Hydrogen Peroxide-Induced Oxidative Stress in Human Neuronal Cells by Thymoquinone-Rich Fraction and Thymoquinone via Transcriptomic Regulation of Antioxidant and Apoptotic Signaling Genes
    Ismail N, Ismail M, Azmi NH, Abu Bakar MF, Basri H, Abdullah MA
    Oxid Med Cell Longev, 2016;2016:2528935.
    PMID: 26823946 DOI: 10.1155/2016/2528935
    Nigella sativa Linn. (N. sativa) and its bioactive constituent Thymoquinone (TQ) have demonstrated numerous pharmacological attributes. In the present study, the neuroprotective properties of Thymoquinone-rich fraction (TQRF) and TQ against hydrogen peroxide- (H2O2-) induced neurotoxicity in differentiated human SH-SY5Y cells were investigated. TQRF was extracted using supercritical fluid extraction while TQ was acquired commercially, and their effects on H2O2 were evaluated using cell viability assay, reactive oxygen species (ROS) assay, morphological observation, and multiplex gene expression. Both TQRF and TQ protected the cells against H2O2 by preserving the mitochondrial metabolic enzymes, reducing intracellular ROS levels, preserving morphological architecture, and modulating the expression of genes related to antioxidants (SOD1, SOD2, and catalase) and signaling genes (p53, AKT1, ERK1/2, p38 MAPK, JNK, and NF-κβ). In conclusion, the enhanced efficacy of TQRF over TQ was likely due to the synergism of multiple constituents in TQRF. The efficacy of TQRF was better than that of TQ alone when equal concentrations of TQ in TQRF were compared. In addition, TQRF also showed comparable effects to TQ when the same concentrations were tested. These findings provide further support for the use of TQRF as an alternative to combat oxidative stress insults in neurodegenerative diseases.
    Matched MeSH terms: Cell Survival
  11. Investigating the addition of SiO₂-CaO-ZnO-Na₂O-TiO₂ bioactive glass to hydroxyapatite: Characterization, mechanical properties and bioactivity
    Yatongchai C, Placek LM, Curran DJ, Towler MR, Wren AW
    J Biomater Appl, 2015 Nov;30(5):495-511.
    PMID: 26116020 DOI: 10.1177/0885328215592866
    Hydroxyapatite (Ca10(PO4)6(OH)2) is widely investigated as an implantable material for hard tissue restoration due to its osteoconductive properties. However, hydroxyapatite in bulk form is limited as its mechanical properties are insufficient for load-bearing orthopedic applications. Attempts have been made to improve the mechanical properties of hydroxyapatite, by incorporating ceramic fillers, but the resultant composite materials require high sintering temperatures to facilitate densification, leading to the decomposition of hydroxyapatite into tricalcium phosphate, tetra-calcium phosphate and CaO phases. One method of improving the properties of hydroxyapatite is to incorporate bioactive glass particles as a second phase. These typically have lower softening points which could possibly facilitate sintering at lower temperatures. In this work, a bioactive glass (SiO2-CaO-ZnO-Na2O-TiO2) is incorporated (10, 20 and 30 wt%) into hydroxyapatite as a reinforcing phase. X-ray diffraction confirmed that no additional phases (other than hydroxyapatite) were formed at a sintering temperature of 560 ℃ with up to 30 wt% glass addition. The addition of the glass phase increased the % crystallinity and the relative density of the composites. The biaxial flexural strength increased to 36 MPa with glass addition, and there was no significant change in hardness as a function of maturation. The pH of the incubation media increased to pH 10 or 11 through glass addition, and ion release profiles determined that Si, Na and P were released from the composites. Calcium phosphate precipitation was encouraged in simulated body fluid with the incorporation of the bioactive glass phase, and cell culture testing in MC-3T3 osteoblasts determined that the composite materials did not significantly reduce cell viability.
    Matched MeSH terms: Cell Survival
  12. Comparative effects of alpha-tocopherol and gamma-tocotrienol against hydrogen peroxide induced apoptosis on primary-cultured astrocytes
    Mazlan M, Sue Mian T, Mat Top G, Zurinah Wan Ngah W
    J Neurol Sci, 2006 Apr 15;243(1-2):5-12.
    PMID: 16442562
    Oxidative stress is thought to be one of the factors that cause neurodegeneration and that this can be inhibited by antioxidants. Since astrocytes support the survival of central nervous system (CNS) neurons, we compared the effect of alpha-tocopherol and gamma-tocotrienol in minimizing the cytotoxic damage induced by H(2)O(2), a pro-oxidant. Primary astrocyte cultures were pretreated with either alpha-tocopherol or gamma-tocotrienol for 1 h before incubation with 100 microM H(2)O(2) for 24 h. Cell viability was then assessed using the MTS assay while apoptosis was determined using a commercial ELISA kit as well as by fluorescent staining of live and apoptotic cells. The uptake of alpha-tocopherol and gamma-tocotrienol by astrocytes were also determined using HPLC. Results showed that gamma-tocotrienol is toxic at concentrations >200 microM but protects against H(2)O(2) induced cell loss and apoptosis in a dose dependent manner up to 100 microM. alpha-Tocopherol was not cytotoxic in the concentration range tested (up to 750 microM), reduced apoptosis to the same degree as that of gamma-tocotrienol but was less effective in maintaining the viable cell number. Since the uptake of alpha-tocopherol and gamma-tocotrienol by astrocytes is similar, this may reflect the roles of these 2 vitamin E subfamilies in inhibiting apoptosis and stimulating proliferation in astrocytes.
    Matched MeSH terms: Cell Survival/drug effects; Cell Survival/physiology
  13. Fulltext Artonin E Induces Apoptosis via Mitochondrial Dysregulation in SKOV-3 Ovarian Cancer Cells
    Rahman MA, Ramli F, Karimian H, Dehghan F, Nordin N, Ali HM, et al.
    PLoS One, 2016;11(3):e0151466.
    PMID: 27019365 DOI: 10.1371/journal.pone.0151466
    Artonin E is a prenylated flavonoid isolated from the stem bark of Artocarpus elasticus Reinw.(Moraceae). This study aimed to investigate the apoptotic mechanisms induced by artonin E in a metastatic human ovarian cancer cell line SKOV-3 in vitro. MTT assay, clonogenic assay, acridine orange and propidium iodide double staining, cell cycle and annexin V analyses were performed to explore the mode of artonin E-induced cell death at different time points. DNA laddering, activation of caspases-3, -8, and -9, multi-parametric cytotoxicity-3 analysis by high-content screening, measurement of reactive oxygen species generation, and Western blot were employed to study the pathways involved in the apoptosis. MTT results showed that artonin E inhibited the growth of SKOV-3 cells, with IC50 values of 6.5±0.5 μg/mL after 72 h treatment, and showed less toxicity toward a normal human ovarian cell line T1074, with IC50 value of 32.5±0.5 μg/mL. Results showed that artonin E induced apoptosis and cell cycle arrest at the S phase. This compound also promoted the activation of caspases-3, -8, and -9. Further investigation into the depletion of mitochondrial membrane potential and release of cytochrome c revealed that artonin E treatment induced apoptosis via regulation of the expression of pro-survival and pro-apoptotic Bcl-2 family members. The expression levels of survivin and HSP70 proteins were also down regulated in SKOV-3 cells treated with artonin E. We propose that artonin E induced an antiproliferative effect that led to S phase cell cycle arrest and apoptosis through dysregulation of mitochondrial pathways, particularly the pro- and anti-apoptosis signaling pathways.
    Matched MeSH terms: Cell Survival/drug effects; Cell Survival/genetics
  14. Fulltext Modulation of Human Macrophage Responses to Mycobacterium tuberculosis by Silver Nanoparticles of Different Size and Surface Modification
    Sarkar S, Leo BF, Carranza C, Chen S, Rivas-Santiago C, Porter AE, et al.
    PLoS One, 2015;10(11):e0143077.
    PMID: 26580078 DOI: 10.1371/journal.pone.0143077
    Exposure to silver nanoparticles (AgNP) used in consumer products carries potential health risks including increased susceptibility to infectious pathogens. Systematic assessments of antimicrobial macrophage immune responses in the context of AgNP exposure are important because uptake of AgNP by macrophages may lead to alterations of innate immune cell functions. In this study we examined the effects of exposure to AgNP with different particle sizes (20 and 110 nm diameters) and surface chemistry (citrate or polyvinlypyrrolidone capping) on cellular toxicity and innate immune responses against Mycobacterium tuberculosis (M.tb) by human monocyte-derived macrophages (MDM). Exposures of MDM to AgNP significantly reduced cellular viability, increased IL8 and decreased IL10 mRNA expression. Exposure of M.tb-infected MDM to AgNP suppressed M.tb-induced expression of IL1B, IL10, and TNFA mRNA. Furthermore, M.tb-induced IL-1β, a cytokine critical for host resistance to M.tb, was inhibited by AgNP but not by carbon black particles indicating that the observed immunosuppressive effects of AgNP are particle specific. Suppressive effects of AgNP on the M.tb-induced host immune responses were in part due to AgNP-mediated interferences with the TLR signaling pathways that culminate in the activation of the transcription factor NF-κB. AgNP exposure suppressed M.tb-induced expression of a subset of NF-κB mediated genes (CSF2, CSF3, IFNG, IL1A, IL1B, IL6, IL10, TNFA, NFKB1A). In addition, AgNP exposure increased the expression of HSPA1A mRNA and the corresponding stress-induced Hsp72 protein. Up-regulation of Hsp72 by AgNP can suppress M.tb-induced NF-κB activation and host immune responses. The observed ability of AgNP to modulate infectious pathogen-induced immune responses has important public health implications.
    Matched MeSH terms: Cell Survival/drug effects; Cell Survival/immunology
  15. Bio-corrosion behavior and mechanical characteristics of magnesium-titania-hydroxyapatite nanocomposites coated by magnesium-oxide flakes and silicon for use as resorbable bone fixation material
    Khalajabadi SZ, Abu ABH, Ahmad N, Yajid MAM, Hj Redzuan NB, Nasiri R, et al.
    J Mech Behav Biomed Mater, 2018 Jan;77:360-374.
    PMID: 28985616 DOI: 10.1016/j.jmbbm.2017.09.032
    This study was aimed to improve of the corrosion resistance and mechanical properties of Mg/15TiO2/5HA nanocomposite by silicon and magnesium oxide coatings prepared using a powder metallurgy method. The phase evolution, chemical composition, microstructure and mechanical properties of uncoated and coated samples were characterized. Electrochemical and immersion tests used to investigate the in vitro corrosion behavior of the fabricated samples. The adhesion strength of ~36MPa for MgO and ~32MPa for Si/MgO coatings to substrate was measured by adhesion test. Fabrication a homogenous double layer coating with uniform thicknesses consisting micro-sized particles of Si as outer layer and flake-like particles of MgO as the inner layer on the surface of Mg/15TiO2/5HA nanocomposite caused the corrosion resistance and ductility increased whereas the ultimate compressive stress decreased. However, after immersion in SBF solution, Si/MgO-coated sample indicates the best mechanical properties compared to those of the uncoated and MgO-coated samples. The increase of cell viability percentage of the normal human osteoblast (NHOst) cells indicates the improvement in biocompatibility of Mg/15TiO2/5HA nanocomposite by Si/MgO coating.
    Matched MeSH terms: Cell Survival
  16. Microfluidic production of bioactive fibrin micro-beads embedded in crosslinked collagen used as an injectable bulking agent for urinary incontinence treatment
    Vardar E, Larsson HM, Allazetta S, Engelhardt EM, Pinnagoda K, Vythilingam G, et al.
    Acta Biomater, 2018 02;67:156-166.
    PMID: 29197579 DOI: 10.1016/j.actbio.2017.11.034
    Endoscopic injection of bulking agents has been widely used to treat urinary incontinence, often due to urethral sphincter complex insufficiency. The aim of the study was to develop a novel injectable bioactive collagen-fibrin bulking agent restoring long-term continence by functional muscle tissue regeneration. Fibrin micro-beads were engineered using a droplet microfluidic system. They had an average diameter of 140 μm and recombinant fibrin-binding insulin-like growth factor-1 (α2PI1-8-MMP-IGF-1) was covalently conjugated to the beads. A plasmin fibrin degradation assay showed that 72.5% of the initial amount of α2PI1-8-MMP-IGF-1 loaded into the micro-beads was retained within the fibrin micro-beads. In vitro, the growth factor modified fibrin micro-beads enhanced cell attachment and the migration of human urinary tract smooth muscle cells, however, no change of the cellular metabolic activity was seen. These bioactive micro-beads were mixed with genipin-crosslinked homogenized collagen, acting as a carrier. The collagen concentration, the degree of crosslinking, and the mechanical behavior of this bioactive collagen-fibrin injectable were comparable to reference samples. This novel injectable showed no burst release of the growth factor, had a positive effect on cell behavior and may therefore induce smooth muscle regeneration in vivo, necessary for the functional treatment of stress and other urinary incontinences.

    STATEMENT OF SIGNIFICANCE: Urinary incontinence is involuntary urine leakage, resulting from a deficient function of the sphincter muscle complex. Yet there is no functional cure for this devastating condition using current treatment options. Applied physical and surgical therapies have limited success. In this study, a novel bioactive injectable bulking agent, triggering new muscle regeneration at the injection site, has been evaluated. This injectable consists of cross-linked collagen and fibrin micro-beads, functionalized with bound insulin-like growth factor-1 (α2PI1-8-MMP-IGF-1). These bioactive fibrin micro-beads induced human smooth muscle cell migration in vitro. Thus, this injectable bulking agent is apt to be a good candidate for regeneration of urethral sphincter muscle, ensuring a long-lasting treatment for urinary incontinence.

    Matched MeSH terms: Cell Survival
  17. Development of an In Vitro Cardiac Ischemic Model Using Primary Human Cardiomyocytes
    Hafez P, Chowdhury SR, Jose S, Law JX, Ruszymah BHI, Mohd Ramzisham AR, et al.
    Cardiovasc Eng Technol, 2018 09;9(3):529-538.
    PMID: 29948837 DOI: 10.1007/s13239-018-0368-8
    Developing experimental models to study ischemic heart disease is necessary for understanding of biological mechanisms to improve the therapeutic approaches for restoring cardiomyocytes function following injury. The aim of this study was to develop an in vitro hypoxic/re-oxygenation model of ischemia using primary human cardiomyocytes (HCM) and define subsequent cytotoxic effects. HCM were cultured in serum and glucose free medium in hypoxic condition with 1% O2 ranging from 30 min to 12 h. The optimal hypoxic exposure time was determined using Hypoxia Inducible Factor 1α (HIF-1α) as the hypoxic marker. Subsequently, the cells were moved to normoxic condition for 3, 6 and 9 h to replicate the re-oxygenation phase. Optimal period of hypoxic/re-oxygenation was determined based on 50% mitochondrial injury via 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay and cytotoxicity via lactate dehydrogenase (LDH) assay. It was found that the number of cells expressing HIF-1α increased with hypoxic time and 3 h was sufficient to stimulate the expression of this marker in all the cells. Upon re-oxygenation, mitochondrial activity reduced significantly whereas the cytotoxicity increased significantly with time. Six hours of re-oxygenation was optimal to induce reversible cell injury. The injury became irreversible after 9 h as indicated by > 60% LDH leakage compared to the control group cultured in normal condition. Under optimized hypoxic reoxygenation experimental conditions, mesenchymal stem cells formed nanotube with ischemic HCM and facilitated transfer of mitochondria suggesting the feasibility of using this as a model system to study molecular mechanisms of myocardial injury and rescue.
    Matched MeSH terms: Cell Survival
  18. Fulltext In vitro cellular localization and efficient accumulation of fluorescently tagged biomaterials from monodispersed chitosan nanoparticles for elucidation of controlled release pathways for drug delivery systems
    Hassan UA, Hussein MZ, Alitheen NB, Yahya Ariff SA, Masarudin MJ
    Int J Nanomedicine, 2018;13:5075-5095.
    PMID: 30233174 DOI: 10.2147/IJN.S164843
    Background: Inefficient cellular delivery and poor intracellular accumulation are major drawbacks towards achieving favorable therapeutic responses from many therapeutic drugs and biomolecules. To tackle this issue, nanoparticle-mediated delivery vectors have been aptly explored as a promising delivery strategy capable of enhancing the cellular localization of biomolecules and improve their therapeutic efficacies. However, the dynamics of intracellular biomolecule release and accumulation from such nanoparticle systems has currently remained scarcely studied.

    Objectives: The objective of this study was to utilize a chitosan-based nanoparticle system as the delivery carrier for glutamic acid, a model for encapsulated biomolecules to visualize the in vitro release and accumulation of the encapsulated glutamic acid from chitosan nanoparticle (CNP) systems.

    Methods: CNP was synthesized via ionic gelation routes utilizing tripolyphosphate (TPP) as a cross-linker. In order to track glutamic acid release, the glutamic acid was fluorescently-labeled with fluorescein isothiocyanate prior encapsulation into CNP.

    Results: Light Scattering data concluded the successful formation of small-sized and mono-dispersed CNP at a specific volume ratio of chitosan to TPP. Encapsulation of glutamic acid as a model cargo into CNP led to an increase in particle size to >100 nm. The synthesized CNP exhibited spherical shape under Electron Microscopy. The formation of CNP was reflected by the reduction in free amine groups of chitosan following ionic crosslinking reactions. The encapsulation of glutamic acid was further confirmed by Fourier Transform Infrared (FTIR) analysis. Cell viability assay showed 70% cell viability at the maximum concentration of 0.5 mg/mL CS and 0.7 mg/mL TPP used, indicating the low inherent toxicity property of this system. In vitro release study using fluorescently-tagged glutamic acids demonstrated the release and accumulation of the encapsulated glutamic acids at 6 hours post treatment. A significant accumulation was observed at 24 hours and 48 hours later. Flow cytometry data demonstrated a gradual increase in intracellular fluorescence signal from 30 minutes to 48 hours post treatment with fluorescently-labeled glutamic acids encapsulated CNP.

    Conclusion: These results therefore suggested the potential of CNP system towards enhancing the intracellular delivery and release of the encapsulated glutamic acids. This CNP system thus may serves as a potential candidate vector capable to improve the therapeutic efficacy for drugs and biomolecules in medical as well as pharmaceutical applications through the enhanced intracellular release and accumulation of the encapsulated cargo.

    Matched MeSH terms: Cell Survival
  19. Fulltext Differential Burden of Rare and Common Variants on Tumor Characteristics, Survival, and Mode of Detection in Breast Cancer
    Li J, Ugalde-Morales E, Wen WX, Decker B, Eriksson M, Torstensson A, et al.
    Cancer Res, 2018 11 01;78(21):6329-6338.
    PMID: 30385609 DOI: 10.1158/0008-5472.CAN-18-1018
    Genetic variants that increase breast cancer risk can be rare or common. This study tests whether the genetic risk stratification of breast cancer by rare and common variants in established loci can discriminate tumors with different biology, patient survival, and mode of detection. Multinomial logistic regression tested associations between genetic risk load [protein-truncating variant (PTV) carriership in 31 breast cancer predisposition genes-or polygenic risk score (PRS) using 162 single-nucleotide polymorphisms], tumor characteristics, and mode of detection (OR). Ten-year breast cancer-specific survival (HR) was estimated using Cox regression models. In this unselected cohort of 5,099 patients with breast cancer diagnosed in Sweden between 2001 and 2008, PTV carriers (n = 597) were younger and associated with more aggressive tumor phenotypes (ER-negative, large size, high grade, high proliferation, luminal B, and basal-like subtype) and worse outcome (HR, 1.65; 1.16-2.36) than noncarriers. After excluding 92 BRCA1/2 carriers, PTV carriership remained associated with high grade and worse survival (HR, 1.76; 1.21-2.56). In 5,007 BRCA1/2 noncarriers, higher PRS was associated with less aggressive tumor characteristics (ER-positive, PR-positive, small size, low grade, low proliferation, and luminal A subtype). Among patients with low mammographic density (<25%), non-BRCA1/2 PTV carriers were more often interval than screen-detected breast cancer (OR, 1.89; 1.12-3.21) than noncarriers. In contrast, higher PRS was associated with lower risk of interval compared with screen-detected cancer (OR, 0.77; 0.64-0.93) in women with low mammographic density. These findings suggest that rare and common breast cancer susceptibility loci are differentially associated with tumor characteristics, survival, and mode of detection.Significance: These findings offer the potential to improve screening practices for breast cancer by providing a deeper understanding of how risk variants affect disease progression and mode of detection. Cancer Res; 78(21); 6329-38. ©2018 AACR.
    Matched MeSH terms: Cell Survival
  20. Improvement of physicochemical properties of nanocolloidal carrier loaded with low water solubility drug for parenteral cancer treatment by Response Surface Methodology
    Izadiyan Z, Basri M, Fard Masoumi HR, Abedi Karjiban R, Salim N, Kalantari K
    Mater Sci Eng C Mater Biol Appl, 2019 Jan 01;94:841-849.
    PMID: 30423770 DOI: 10.1016/j.msec.2018.10.015
    Nanoemulsions have been used as a drug carrier system, particularly for poorly water-soluble drugs. Sorafenib is a poorly soluble drug and also there is no parenteral treatment. The aim of this study is the development of nanoemulsions for intravenous administration of Sorafenib. The formulations were prepared by high energy emulsification method and optimized by using Response Surface Methodology (RSM). Here, the effect of independent composition variables of lecithin (1.16-2.84%, w/w), Medium-Chain Triglycerides (2.32-5.68%, w/w) and polysorbate 80 (0.58-1.42%, w/w) amounts on the properties of Sorafenib-loaded nanoemulsion was investigated. The three responses variables were particle size, zeta potential, and polydispersity index. Optimization of the conditions according to the three dependent variables was performed for the preparation of the Sorafenib-loaded nanoemulsions with the minimum value of particle size, suitable rage of zeta potential, and polydispersity index. A formulation containing 0.05% of Sorafenib kept its properties in a satisfactory range over the evaluated period. The composition with 3% Medium-Chain Triglycerides, 2.5% lecithin and 1.22% polysorbate 80 exhibited the smallest particle size and polydispersity index (43.17 nm and 0.22, respectively) with the zeta potential of -38.8 mV was the optimized composition. The fabricated nanoemulsion was characterized by the transmission electron microscope (TEM), viscosity, and stability assessment study. Also, the cytotoxicity result showed that the optimum formulations had no significant effect on a normal cell in a low concentration of the drug but could eliminate the cancer cells. The dose-dependent toxicity made it a suitable candidate for parenteral applications in the treatment of breast cancer. Furthermore, the optimized formulation indicated good storage stability for 3 months at different temperatures (4 ± 2 °C, 25 ± 2 °C and 45 ± 2 °C).
    Matched MeSH terms: Cell Survival
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