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  1. Mohd R, Mohammad Kazmin NE, Abdul Cader R, Abd Shukor N, Wong YP, Shah SA, et al.
    PLoS One, 2021;16(4):e0249592.
    PMID: 33831052 DOI: 10.1371/journal.pone.0249592
    INTRODUCTION: IgA nephropathy (IgAN) has a heterogeneous presentation and the progression to end stage renal disease (ESRD) is often influenced by demographics, ethnicity, as well as choice of treatment regimen. In this study, we investigated the long term survival of IgAN patients in our center and the factors affecting it.

    METHODS: This study included all biopsy-proven IgAN patients with ≥ 1year follow-up. Patients with diabetes mellitus at diagnosis and secondary IgAN were excluded. Medical records were reviewed for demographics, clinical presentation, blood pressure, 24-hour urine protein, serum creatinine, renal biopsy and treatment received. The primary outcome was defined as combined event of 50% estimated glomerular filtration rate (eGFR) reduction or ESRD.

    RESULTS: We included 130 (74 females; 56 males) patients of mean age 38.0 ± 14.0 years and median eGFR of 75.2 (interquartile range (IQR) 49.3-101.4) ml/min/1.73m2. Eighty-four (64.6%) were hypertensive at presentation, 35 (26.9%) had nephrotic syndrome and 57 (43.8%) had nephrotic range proteinuria (NRP). Median follow-up duration was 7.5 (IQR 4.0-13.0) years. It was noted that 18 (13.8%) developed ESRD and 34 (26.2%) reached the primary outcome. Annual eGFR decline was -2.1 (IQR -5.3 to -0.1) ml/min/1.73m2/year, with median survival of 20 years. Survival rates from the combined event (50% decrease in eGFR or ESRD) at 10, 20 and 30 years were 80%, 53% and 25%, while survival from ESRD were 87%, 73% and 65%, respectively. In the univariate analysis, time-average proteinuria (hazard ratio (HR) = 2.41, 95% CI 1.77-3.30), eGFR <45ml/min/1.73m2 at biopsy (HR = 2.35, 95% CI 1.03-5.32), hypertension (HR = 2.81, 95% CI 1.16-6.80), mean arterial pressure (HR = 1.02, 95% CI 1.01-1.04), tubular atrophy/interstitial fibrosis score (HR = 3.77, 95% CI 1.84-7.73), and cellular/fibrocellular crescent score (HR = 2.44, 95% CI 1.19-5.00) were found to be significant. Whereas only time-average proteinuria (TA-proteinuria) remained as a significant predictor in the multivariate analysis (HR = 2.23, 95% CI 1.57-3.16).

    CONCLUSION: In our cohort, TA-proteinuria was the most important predictor in the progression of IgAN, irrespective of degree of proteinuria at presentation.

    Matched MeSH terms: Survival Rate
  2. Abdulwanis Mohamed Z, Mohamed Eliaser E, Jaafaru MS, Nordin N, Ioannides C, Abdull Razis AF
    Molecules, 2020 Aug 15;25(16).
    PMID: 32824120 DOI: 10.3390/molecules25163724
    Neurodegenerative diseases (NDDs) are chronic conditions that have drawn robust interest from the scientific community. Phytotherapeutic agents are becoming an important source of chemicals for the treatment and management of NDDs. Various secondary metabolites have been isolated from Melicope lunu-ankenda plant leaves, including phenolic acid derivatives. However, their neuroprotective activity remains unclear. Thus, the aim of this study is to elucidate the in vitro neuroprotective activity of 7-geranyloxycinnamic acid isolated from Melicope lunu-ankenda leaves. The neuroprotective activity was evaluated in differentiated human neuroblastoma (SH-SY5Y) cells by monitoring cell viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Moreover, the potential to impair apoptosis in differentiated cells was investigated employing the Annexin V-FITC assay, acridine orange and propidium iodide (AO/PI) staining, and fluorescence microscopy. Morphological assessment and ultrastructural analysis were performed using scanning and transmission electron microscopy to evaluate the effect of 7-geranyloxycinnamic acid on surface morphology and internal features of the differentiated cells. Pre-treatment of neuronal cells with 7-geranyloxycinnamic acid significantly protected the differentiated SH-SY5Y cells against H2O2-induced apoptosis. Cytoskeleton and cytoplasmic inclusion were similarly protected by the 7-geranyloxycinnamic acid treatment. The present findings demonstrate the neuroprotective potential of 7-geranyloxycinnamic acid against H2O2-induced neurotoxicity in neuronal cells, which is an established hallmark of neuronal disorders.
    Matched MeSH terms: Cell Survival
  3. Moo EK, Osman NA, Pingguan-Murphy B
    Clinics (Sao Paulo), 2011;66(8):1431-6.
    PMID: 21915496
    INTRODUCTION: Although previous studies have been performed on cartilage explant cultures, the generalized dynamics of cartilage metabolism after extraction from the host are still poorly understood due to differences in the experimental setups across studies, which in turn prevent building a complete picture.

    METHODS: In this study, we investigated the response of cartilage to the trauma sustained during extraction and determined the time needed for the cartilage to stabilize. Explants were extracted aseptically from bovine metacarpal-phalangeal joints and cultured for up to 17 days.

    RESULTS: The cell viability, cell number, proteoglycan content, and collagen content of the harvested explants were analyzed at 0, 2, 10, and 17 days after explantation. A high percentage of the cartilage explants were found to be viable. The cell density initially increased significantly but stabilized after two days. The proteoglycan content decreased gradually over time, but it did not decrease to a significant level due to leakage through the distorted peripheral collagen network and into the bathing medium. The collagen content remained stable for most of the culture period until it dropped abruptly on day 17.

    CONCLUSION: Overall, the tested cartilage explants were sustainable over long-term culture. They were most stable from day 2 to day 10. The degradation of the collagen on day 17 did not reach diseased levels, but it indicated the potential of the cultures to develop into degenerated cartilage. These findings have implications for the application of cartilage explants in pathophysiological fields.

    Matched MeSH terms: Cell Survival
  4. Othman H, Rahman H, Mohan S, Aziz S, Marif H, Ford D, et al.
    PMID: 32922508 DOI: 10.1155/2020/8764096
    This study investigated the in vivo antileukemic activity of palladium nanoparticles ([email protected]) mediated by white tea extract in a murine model. The cell viability effect of [email protected], "blank" Pd nanoparticles, and white tea extract alone was determined in murine leukemia WEHI-3B cells and normal mouse fibroblasts (3T3 cells). Apoptotic and cell cycle arrest effects of [email protected] in WEHI-3B cells were evaluated. The effects of [email protected] administered orally to leukemic mice at 50 and 100 mg/kg daily over 28 days were evaluated. [email protected] reduced the viability of WHEI-3B cells with IC50 7.55 μg/ml at 72 h. Blank Pd nanoparticles and white tea extract alone had smaller effects on WHEI-3B viability and on normal fibroblasts. [email protected] increased the proportion of Annexin V-positive WHEI-3B cells and induced G2/M cell cycle arrest. Leukemic cells in the spleen were reduced by [email protected] with an increase in Bax/Bcl-2 and cytochrome-C protein and mRNA levels indicating the activation of the mitochondrial apoptotic pathway. These effects replicated the effects of ATRA and were not observed using blank Pd nanoparticles. [email protected] afford therapeutic efficacy against leukemia likely to pivot on activation of the mitochondrial pathway of apoptotic signaling and hence appear attractive potential candidates for development as a novel anticancer agent.
    Matched MeSH terms: Cell Survival
  5. Zheng X, Liao Y, Wang J, Hu S, Rudramurthy GR, Swamy MK, et al.
    PMID: 30524484 DOI: 10.1155/2018/9691085
    Microglial cells, upon hyperactivation, produce proinflammatory cytokines and other oxidative stress mediators causing neuroinflammation, which is associated with the progress of many neurodegenerative diseases. Suppressing the microglial activation has hence been used as an approach for treating such diseases. In this study, the antineuroinflammatory effect of simvastatin was examined in lipopolysaccharide (LPS)-activated rat C6 glioma cells. The cell proliferation and cytotoxic effect of LPS and simvastatin on C6 glioma cells was evaluated by (MTT) assay. Neuroinflammation was induced in differentiated cell lines by treatment with 3.125 μg/mL of LPS for 12 h. Upon induction, the cell lines were treated with different concentrations (3.125, 6.25, 12.5, 25, 50, 100 μM) of simvastatin and incubated in a humidified CO2 incubator for 24 to 48 h. The optimum concentrations of LPS and simvastatin were found to be 3.125 μg/mL and 25 μM, respectively, with a cell viability of more than 90% at 24 h postincubation. Furthermore, proinflammatory marker expression was analyzed by flow cytometry and showed a decrease in interferon-γ, interleukin 6, nuclear factor-κB p65, and tumor necrosis factor-α in simvastatin-treated and LPS-induced neuroinflammatory cells, and the mean fluorescent values were found to be 21.75 ± 0.76, 20.9 ± 1.90, 19.72 ± 1.29, and 16.82 ± 0.97, respectively, as compared to the untreated cells. Thus, we show that simvastatin has the potential to regulate the anti-inflammatory response in microglial cells upon LPS challenge. Hence, simvastatin can be employed as a potent anti-inflammatory drug against neuroinflammatory diseases and neurodegenerative disorders.
    Matched MeSH terms: Cell Survival
  6. Mohd-Radzman NH, Ismail WI, Jaapar SS, Adam Z, Adam A
    PMID: 24391675 DOI: 10.1155/2013/938081
    Stevioside from Stevia rebaudiana has been reported to exert antihyperglycemic effects in both rat and human subjects. There have been few studies on these effects in vitro. In this paper, radioactive glucose uptake assay was implemented in order to assess improvements in insulin sensitivity in 3T3-L1 cells by elevation of glucose uptake following treatment with stevioside. Oil Red-O staining and MTT assay were utilized to confirm adipocyte differentiation and cell viability, respectively. Findings from this research showed a significant increase in absorbance values in mature adipocytes following Oil Red-O staining, confirming the differentiation process. Stevioside was noncytotoxic to 3T3-L1 cells as cell viability was reduced by a maximum of 17%, making it impossible to determine its IC50. Stevioside increased glucose uptake activities by 2.1 times (p < 0.001) in normal conditions and up to 4.4 times (p < 0.001) in insulin-resistant states. At times, this increase was higher than that seen in positive control group treated with rosiglitazone maleate, an antidiabetic agent. Expressions of pY20 and p-IRS1 which were measured via Western blot were improved by stevioside treatment. In conclusion, stevioside has direct effects on 3T3-L1 insulin sensitivity via increase in glucose uptake and enhanced expression of proteins involved in insulin-signalling pathway.
    Matched MeSH terms: Cell Survival
  7. Tasyriq M, Najmuldeen IA, In LL, Mohamad K, Awang K, Hasima N
    PMID: 22997533
    In continuation of our interest towards the elucidation of apoptotic pathways of cytotoxic phytocompounds, we have embarked upon a study on the anticancer effects of 7α-hydroxy-β-sitosterol (CT1), a rare natural phytosterol oxide isolated from Chisocheton tomentosus. CT1 was found to be cytotoxic on three different human tumor cell lines with minimal effects on normal cell controls, where cell viability levels were maintained ≥80% upon treatment. Our results showed that cell death in MCF-7 breast tumor cells was achieved through the induction of apoptosis via downregulation of the ERK1/2 signaling pathway. CT1 was also found to increase proapoptotic Bax protein levels, while decreasing anti-apoptotic Bcl-2 protein levels, suggesting the involvement of the intrinsic pathway. Reduced levels of initiator procaspase-9 and executioner procaspase-3 were also observed following CT1 exposure, confirming the involvement of cytochrome c-mediated apoptosis via the mitochondrial pathway. These results demonstrated the cytotoxic and apoptotic ability of 7α-hydroxy-β-sitosterol and suggest its potential anti-cancer use particularly on breast adenocarcinoma cells.
    Matched MeSH terms: Cell Survival
  8. Reid F, Adams T, Adel RS, Andrade CE, Bajwa A, Bambury IG, et al.
    PLoS One, 2024;19(5):e0298154.
    PMID: 38809901 DOI: 10.1371/journal.pone.0298154
    BACKGROUND: Ovarian cancer is a challenging disease to diagnose and treat effectively with five-year survival rates below 50%. Previous patient experience research in high-income countries highlighted common challenges and opportunities to improve survival and quality of life for women affected by ovarian cancer. However, no comparable data exist for low-and middle-income countries, where 70% of women with the disease live. This study aims to address this evidence gap.

    METHODS: This is an observational multi-country study set in low- and middle-income countries. We aim to recruit over 2000 women diagnosed with ovarian cancer across multiple hospitals in 24 countries in Asia, Africa and South America. Country sample sizes have been calculated (n = 70-96 participants /country), taking account of varying national five-year disease prevalence rates. Women within five years of their diagnosis, who are in contact with participating hospitals, are invited to take part in the study. A questionnaire has been adapted from a tool previously used in high-income countries. It comprises 57 multiple choice and two open-ended questions designed to collect information on demographics, women's knowledge of ovarian cancer, route to diagnosis, access to treatments, surgery and genetic testing, support needs, the impact of the disease on women and their families, and their priorities for action. The questionnaire has been designed in English, translated into local languages and tested according to local ethics requirements. Questionnaires will be administered by a trained member of the clinical team.

    CONCLUSION: This study will inform further research, advocacy, and action in low- and middle-income countries based on tailored approaches to the national, regional and global challenges and opportunities. In addition, participating countries can choose to repeat the study to track progress and the protocol can be adapted for other countries and other diseases.

    Matched MeSH terms: Survival Rate
  9. Koh KH, Wong HS, Go KW, Morad Z
    Perit Dial Int, 2010 06 30;31(5):574-82.
    PMID: 20592100 DOI: 10.3747/pdi.2009.00140
    BACKGROUND: While phase angle of bioimpedance analysis (BIA) has great survival-predicting value in dialysis populations, it is known to be higher in male than in female subjects. In this study, we aimed to explore the factors influencing the predictive value of phase angle and to identify the appropriate physics terms for normalizing capacitance (C) and resistance (R).

    METHODS: We formulated body capacitive index (BCI), C(BMI) (capacitance × height(2)/weight), body resistive index (BRI), R(BMI) (resistance × weight/height(2)), and CH(2) (capacitance × height(2)). We also studied H(2)/R, R/H, and reactance of a capacitor/height (X(C) /H). There are 3 components in this study design: (1) establishment of normal values in a control Malaysian population, (2) comparison of these with a CAPD population, and (3) prediction of survival within a CAPD population. We initially performed a BIA study in 206 female and 116 male healthy volunteers, followed by a prospective study in a cohort of 128 CAPD patients [47 with diabetes mellitus (DM), 81 non-DM; 59 males, 69 females] for at least 2 years. All the parameters during enrolment, including BIA, serum albumin, peritoneal equilibrium test, age, and DM status, were analyzed. Outcome measurement was survival.

    RESULTS: In healthy volunteers, both genders had the same BCI (2.0 nF kg/m(2)). On the contrary, female normal subjects had higher BRI than male normal subjects (median 15 642 vs 13242 Ω kg/m(2), p < 0.001) due to higher fat percentage (35.4% ± 0.4% vs 28.0% ± 0.6%, p < 0.001), resulting in a lower phase angle (mean 5.82 ± 0.04 vs 6.86 ± 0.07 degrees, p < 0.001). Logistic regression showed that BCI was the best risk indicator in 128 CAPD patients versus 322 normal subjects. In age- and body mass index (BMI)-matched head-to-head comparison, BCI had the highest χ(2) value (χ(2) = 102.63), followed by CH(2) (or H(2)/X(C); χ(2) = 81.00), BRI (χ(2) = 20.54), and X(C)/H (χ(2) = 20.48), with p value < 0.001 for these parameters. In comparison, phase angle (χ(2) = 11.42), R/H (χ(2) = 7.19), and H(2)/R (χ(2) = 5.69) had lower χ(2) values. 35 (27.3%) patients died during the study period. Univariate analysis adjusted for DM status and serum albumin level demonstrated that non-surviving patients had significantly higher CH(2) (245 vs 169 nF m(2), p < 0.001) and BCI (4.0 vs 2.9 nF m(2)/kg, p = 0.005) than patients that survived. CH(2) was the best predictor for all-cause mortality in Cox regression analysis, followed by BCI, phase angle, and X(C)/H.

    CONCLUSION: Measures that normalize, such as BCI and CH(2), have higher risk discrimination and survival prediction ability than measures that do not normalize, such as phase angle. Unlike phase angle, measurement of BCI overcomes the gender effect. In this study, the best risk indicator for CAPD patients versus the general population is BCI, reflecting deficit in nutritional concentration, while CH(2) reflects total nutritional deficit and thus is the major risk indicator for survival of CAPD patients.

    Matched MeSH terms: Survival Analysis
  10. Cheng WT, Kantilal HK, Davamani F
    Malays J Med Sci, 2020 Jul;27(4):9-21.
    PMID: 32863742 MyJurnal DOI: 10.21315/mjms2020.27.4.2
    The Bacteroides fragilis (B. fragilis) produce biofilm for colonisation in the intestinal tract can cause a series of inflammatory reactions due to B. fragilis toxin (BFT) which can lead to chronic intestinal inflammation and tissue injury and play a crucial role leading to colorectal cancer (CRC). The enterotoxigenic B. fragilis (ETBF) forms biofilm and produce toxin and play a role in CRC, whereas the non-toxigenic B. fragilis (NTBF) does not produce toxin. The ETBF triggers the expression of cyclooxygenase (COX)-2 that releases PGE2 for inducing inflammation and control cell proliferation. From chronic intestinal inflammation to cancer development, it involves signal transducers and activators of transcription (STAT)3 activation. STAT3 activates by the interaction between epithelial cells and BFT. Thus, regulatory T-cell (Tregs) will activates and reduce interleukin (IL)-2 amount. As the level of IL-2 drops, T-helper (Th17) cells are generated leading to increase in IL-17 levels. IL-17 is implicated in early intestinal inflammation and promotes cancer cell survival and proliferation and consequently triggers IL-6 production that activate STAT3 pathway. Additionally, BFT degrades E-cadherin, hence alteration of signalling pathways can upregulate spermine oxidase leading to cell morphology and promote carcinogenesis and irreversible DNA damage. Patient with familial adenomatous polyposis (FAP) disease displays a high level of tumour load in the colon. This disease is caused by germline mutation of the adenomatous polyposis coli (APC) gene that increases bacterial adherence to the mucosa layer. Mutated-APC gene genotype with ETBF increases the chances of CRC development. Therefore, the colonisation of the ETBF in the intestinal tract depicts tumour aetiology can result in risk of hostility and effect on human health.
    Matched MeSH terms: Cell Survival
  11. Kho GS, Abdullah JM
    Malays J Med Sci, 2018 Sep;25(5):151-157.
    PMID: 30914871 MyJurnal DOI: 10.21315/mjms2018.25.5.14
    Traumatic brain injury is the major contributing factor in non-obstetric mortality in developing countries. Approximately 20% of maternal mortality is directly correlated to injuries. Road traffic accidents and domestic violence are the most common nonlethal injuries that can threaten either the maternal or foetal life, and such events occur in one out of every 12 pregnancies. The treatment of severe traumatic brain injury in pregnancy requires a multidisciplinary team approach. The management of a pregnant trauma patient warrants consideration of several issues specific to pregnancy, such as the alterations in the maternal physiology and anatomy. In the case of maternal cardiac arrest with amniotic fluid embolism, intact neonatal survival is linked with the timing of caesarean section after maternal cardiac arrest. Moreover, the decision for perimortem caesarean section is clear after maternal cardiac arrest. The foetal survival rate is 67% if the operation is done before 15 min of cardiopulmonary compromise has occurred, and it drops to 40% at the duration range of 16-25 min. Whether minor or severe, traumatic brain injury during pregnancy is associated with unfavourable maternal outcomes. Injuries considered minor for the general population are not minor for pregnant women. Therefore, these patients should be intensively monitored, and multidisciplinary approaches should always be involved.
    Matched MeSH terms: Survival Rate
  12. Azizi S, Mohamad R, Bahadoran A, Bayat S, Rahim RA, Ariff A, et al.
    PMID: 27318600 DOI: 10.1016/j.jphotobiol.2016.06.007
    The use of nontoxic biological compounds in the synthesis of nanomaterials is an economic and eco-friendly approach. The present work was undertaken to develop zinc oxide nanoparticles (ZnO-NPs) by a green method using simple precursor from the solution consisting of zinc acetate and the flower extract of Anchusa italica (A. italica). Effect of annealing temperature on structural and antimicrobial properties was investigated. The crystalline structure of ZnO-NPs was shown using X-ray diffraction (XRD) analysis. Transmission electron microscopy (TEM) results showed that ZnO-NPs are hexagonal in shapes with mean particle size of ~8 and ~14nm at 100°C and 200°C annealing temperatures respectively. The optical band gap was increased from 3.27eV to 3.30eV with the decreasing of the particle size. The antimicrobial activity of ZnO-NPs towards Gram positive (Bacillus megaterium and Stapphylococcus aureus) and Gram negative (Escherichia coli and Salmonella typhimurium) pathogens decreased with the increasing of the heat treating temperature. In vitro cytotoxicity studies on Vero cells, a dose dependent toxicity with non-toxic effect of concentration below 142μg/mL was shown. The results indicated that A. italica is an appropriate reaction media to prepare ZnO-NPs for cosmetic and bio-medical productions.
    Matched MeSH terms: Cell Survival/drug effects
  13. Batumalaie K, Amin MA, Murugan DD, Sattar MZ, Abdullah NA
    Sci Rep, 2016 06 02;6:27236.
    PMID: 27250532 DOI: 10.1038/srep27236
    Activation of inflammatory pathways via reactive oxygen species (ROS) by free fatty acids (FFA) in obesity gives rise to insulin resistance and endothelial dysfunction. Withaferin A (WA), possesses both antioxidant and anti-inflammatory properties and therefore would be a good strategy to suppress palmitic acid (PA)-induced oxidative stress and inflammation and hence, insulin resistance and dysfunction in the endothelium. Effect of WA on PA-induced insulin resistance in human umbilical vein endothelial cells (HUVECs) was determined by evaluating insulin signaling mechanisms whilst effect of this drug on PA-induced endothelial dysfunction was determined in acetylcholine-mediated relaxation in isolated rat aortic preparations. WA significantly inhibited ROS production and inflammation induced by PA. Furthermore, WA significantly decreased TNF-α and IL-6 production in endothelial cells by specifically suppressing IKKβ/NF-κβ phosphorylation. WA inhibited inflammation-stimulated IRS-1 serine phosphorylation and improved the impaired insulin PI3-K signaling, and restored the decreased nitric oxide (NO) production triggered by PA. WA also decreased endothelin-1 and plasminogen activator inhibitor type-1 levels, and restored the impaired endothelium-mediated vasodilation in isolated aortic preparations. These findings suggest that WA inhibited both ROS production and inflammation to restore impaired insulin resistance in cultured endothelial cells and improve endothelial dysfunction in rat aortic rings.
    Matched MeSH terms: Cell Survival/drug effects
  14. Fani S, Kamalidehghan B, Lo KM, Hashim NM, Chow KM, Ahmadipour F
    Drug Des Devel Ther, 2015;9:6191-201.
    PMID: 26648695 DOI: 10.2147/DDDT.S87064
    A new monoorganotin Schiff base compound, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, (compound C1), was synthesized, and its structural features were investigated by spectroscopic techniques and single-crystal X-ray diffractometry. Compound C1 was exposed to several human cancer cell lines, including breast adenocarcinoma cell lines MCF-7 and MDA-MB-231, ovarian adenocarcinoma cell lines Skov3 and Caov3, and prostate cancer cell line PC3, in order to examine its cytotoxic effect for different forms of cancer. Human hepatic cell line WRL-68 was used as a normal cell line. We concentrated on the MCF-7 cell line to detect possible underlying mechanism involvement of compound C1. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed the strongest cytotoxicity of compound C1 against MCF-7 cells, with a half maximal inhibitory concentration (IC50) value of 2.5±0.50 μg/mL after 48 hours treatment. The IC50 value was >30 μg/mL in WRL-68 cells. Induced antiproliferative activity of compound C1 for MCF-7 cells was further confirmed by lactate dehydrogenase, reactive oxygen species, acridine orange/propidium iodide staining, and DNA fragmentation assays. A significant increase of lactate dehydrogenase release in treated cells was observed via fluorescence analysis. Luminescent analysis showed significant growth in intracellular reactive oxygen species production after treatment. Morphological changes of necrosis and early and late apoptosis stages were observed in treated cells after staining with acridine orange/propidium iodide. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Results of the present study obviously reveal potential cytotoxic effects of compound C1 against human breast cancer MCF-7 cells.
    Matched MeSH terms: Cell Survival/drug effects
  15. Murni NS, Dambatta MS, Yeap SK, Froemming GRA, Hermawan H
    Mater Sci Eng C Mater Biol Appl, 2015 Apr;49:560-566.
    PMID: 25686984 DOI: 10.1016/j.msec.2015.01.056
    The recent proposal of using Zn-based alloys for biodegradable implants was not supported with sufficient toxicity data. This work, for the first time, presents a thorough cytotoxicity evaluation of Zn-3Mg alloy for biodegradable bone implants. Normal human osteoblast cells were exposed to the alloy's extract and three main cell-material interaction parameters: cell health, functionality and inflammatory response, were evaluated. Results showed that at the concentration of 0.75mg/ml alloy extract, cell viability was reduced by ~50% through an induction of apoptosis at day 1; however, cells were able to recover at days 3 and 7. Cytoskeletal changes were observed but without any significant DNA damage. The downregulation of alkaline phosphatase protein levels did not significantly affect the mineralization process of the cells. Significant differences of cyclooxygenase-2 and prostaglandin E2 inflammatory biomarkers were noticed, but not interleukin 1-beta, indicating that the cells underwent a healing process after exposure to the alloy. Detailed analysis on the cell-material interaction is further discussed in this paper.
    Matched MeSH terms: Cell Survival/drug effects
  16. Balan T, Sani MH, Mumtaz Ahmad SH, Suppaiah V, Mohtarrudin N, Zakaria ZA
    J Ethnopharmacol, 2015 Apr 22;164:1-15.
    PMID: 25540923 DOI: 10.1016/j.jep.2014.12.017
    In traditional medicine, the leaves, flowers, barks and roots of Muntingia calabura L. (Muntingiaceae) have been employed as a treatment for various ailments including dyspepsia and to relieve pain caused by gastritis and peptic ulcer disease. The methanolic extract of Muntingia calabura leaves (MEMC) has been proven in the previous study to possess significant antiulcer activity. In this study, we attempted to determine the prophylactic effect of the fractions obtained from MEMC against ethanol-induced gastric lesion in rats and the involvement of antioxidants and anti-inflammatory mediators.
    Matched MeSH terms: Cell Survival/drug effects
  17. Kasi RA, Moi CS, Kien YW, Yian KR, Chin NW, Yen NK, et al.
    Mol Med Rep, 2015 Mar;11(3):2262-8.
    PMID: 25411820 DOI: 10.3892/mmr.2014.2979
    para‑Phenylenediamine (p‑PD) is a potential carcinogen, and widely used in marketed hair dye formulations. In the present study, the role of the protein tyrosine kinase (PTK)/Ras/Raf/c‑Jun N‑terminal kinase (JNK) and phosphoinositide 3‑kinase (PI3k)/protein kinase B (Akt) pathways on the growth of NRK‑52E cells was investigated. The results demonstrated that p‑PD reduced cell viability in a dose‑dependent manner. The cell death due to apoptosis was confirmed by cell cycle analysis and an Annexin‑V‑fluorescein isothiocyanate binding assay. Subsequent to staining with 2',7'‑dichlorofluorescin diacetate, the treated cells demonstrated a significant increase in reactive oxygen species (ROS) generation compared with the controls. The effects of p‑PD on the signalling pathways were analysed by western blotting. p‑PD‑treated cells exhibited an upregulated phospho‑stress‑activated protein kinase/JNK protein expression level and downregulated Ras and Raf protein expression levels; however, Akt, Bcl‑2, Bcl‑XL and Bad protein expression levels were not significantly altered compared with the control. In conclusion, p‑PD induced apoptosis by a PTK/Ras/Raf/JNK‑dependent pathway and was independent of the PI3K/Akt pathway in NRK‑52E cells.
    Matched MeSH terms: Cell Survival/drug effects
  18. Koh RY, Lim CL, Uhal BD, Abdullah M, Vidyadaran S, Ho CC, et al.
    Mol Med Rep, 2015 May;11(5):3808-13.
    PMID: 25585520 DOI: 10.3892/mmr.2015.3193
    Idiopathic pulmonary fibrosis is a chronic pulmonary disease that is characterized by formation of scar tissue in lungs. Transforming growth factor-β (TGF-β) is considered an important cytokine in the pathogenesis of this disease. Hence, the antifibrotic effect of an inhibitor of the TGF-β type I receptor, namely, SB 431542, was investigated in our study. SB 431542 was used to treat TGF-β-treated IMR-90 cells; the expression of α-smooth muscle actin (α-SMA) was detected at the protein level by using an anti-α-SMA antibody, and at the gene level by reverse transcription-quantitative PCR. The effect of the inhibitor on cell proliferation was determined by a cell growth assay. The inhibitor was also administered into bleomycin-treated mice. Histopathological assessment and determination of total collagen levels were carried out to evaluate the severity of lung fibrosis in these mice. Our results demonstrated that treatment with SB 431542 inhibits TGF-β‑induced α-SMA expression in lung fibroblasts, at both the protein and the mRNA levels (P<0.05). However, the inhibitor did not significantly reduce lung fibroblast proliferation. In the bleomycin-induced pulmonary fibrosis mouse model, bleomycin treatment caused important morphological changes, accompanied by an increase in the collagen level of the lungs. Early treatment with SB 431542 prevented the manifestation of histopathological alterations, whereas delayed treatment significantly decreased the collagen level (P<0.05). These results suggest that inhibition of TGF-β signaling, via inhibition of the activin receptor-like kinase-5 (ALK-5) by SB 431542, may attenuate pulmonary fibrosis.
    Matched MeSH terms: Cell Survival/drug effects
  19. Tham CL, Hazeera Harith H, Wai Lam K, Joong Chong Y, Singh Cheema M, Roslan Sulaiman M, et al.
    Eur J Pharmacol, 2015 Feb 15;749:1-11.
    PMID: 25560198 DOI: 10.1016/j.ejphar.2014.12.015
    2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone (BHMC) has been proven to selectively inhibit the synthesis of proinflammatory mediators in lipopolysaccharide-induced U937 monocytes through specific interruption of p38 Mitogen-Activated Protein Kinase enzymatic activity and improves the survival rate in a murine lethal sepsis model. The present study addressed the effects of BHMC upon lipopolysaccharide-induced endothelial dysfunction in human umbilical vein endothelial cells to determine the underlying mechanisms. The cytotoxicity effect of BHMC on HUVEC were determined by MTT assay. The effects of BHMC on endothelial dysfunction induced by lipopolysaccharide such as endothelial hyperpermeability, monocyte-endothelial adhesion, transendothelial migration, up-regulation of adhesion molecules and chemokines were evaluated. The effects of BHMC at transcriptional and post-translational levels were determined by Reverse Transcriptase-Polymerase Chain Reaction and Western Blots. The mode of action of BHMC was dissected by looking into the activation of Nuclear Factor-kappa B and Mitogen-Activated Protein Kinases. BHMC concentration-dependently reduced endothelial hyperpermeability, leukocyte-endothelial cell adhesion and monocyte transendothelial migration through inhibition of the protein expression of adhesion molecules (Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1) and secretion of chemokines (Monocyte Chemotactic Protein-1) at the transcriptional level. BHMC restored endothelial dysfunction via selective inhibition of p38 Mitogen-Activated Protein Kinase enzymatic activity which indirectly prevents the activation of Nuclear Factor-kappaB and Activator Protein-1 transcription factors. These findings further support earlier observations on the inhibition of BHMC on inflammatory events through specific disruption of p38 Mitogen-Activated Protein Kinase enzymatic activity and provide new insights into the inhibitory effects of BHMC on lipopolysaccharide-induced endothelial dysfunction.
    Matched MeSH terms: Cell Survival/drug effects
  20. Achoui M, Heyninck K, Looi CY, Mustafa AM, Haegeman G, Mustafa MR
    Drug Des Devel Ther, 2014;8:1993-2007.
    PMID: 25349474 DOI: 10.2147/DDDT.S68659
    The terpenoid 17-O-acetylacuminolide (AA) was shown to inhibit the production of several inflammatory mediators. However, the mechanisms by which this compound elicited its anti-inflammatory activity remain to be elucidated. In this study, we analyzed the effects of AA on inflammatory gene expression in two different cell types with primordial importance in the inflammatory processes - endothelial cells and macrophages. In human umbilical vein endothelial cells, AA inhibited the expression of inflammatory proteins including the adhesion molecules intercellular adhesion molecule 1; vascular cell adhesion molecule 1; and E-selectin, as well as the release of the chemokine interleukin-8. Additionally, AA hindered the formation of capillary-like tubes in an in vitro model of angiogenesis. AA's effects in endothelial cells can be attributed at least in part to AA's inhibition of tumor necrosis factor alpha-induced nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)'s translocation. Also, in lipopolysaccharide-stimulated macrophage-like RAW264.7 cells, AA was able to downregulate the expression of the genes cyclooxygenase 2, inducible nitric oxide synthase, interleukin-6, and chemokine (C-C motif) ligand 2. Moreover, AA inhibited the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (IκBα), IκB kinase (IKK), and the mitogen-activated protein kinases JNK, ERK, and p38. In conclusion, the present results further support the anti-inflammatory potential of AA in different models of inflammation.
    Matched MeSH terms: Cell Survival/drug effects
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