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  1. Fulltext King cobra (Ophiophagus hannah) venom L-amino acid oxidase induces apoptosis in PC-3 cells and suppresses PC-3 solid tumor growth in a tumor xenograft mouse model
    Lee ML, Fung SY, Chung I, Pailoor J, Cheah SH, Tan NH
    Int J Med Sci, 2014;11(6):593-601.
    PMID: 24782648 DOI: 10.7150/ijms.8096
    King cobra (Ophiophagus hannah) venom L-amino acid oxidase (OH-LAAO), a heat stable enzyme, has been shown to exhibit very potent anti-proliferative activity against human breast and lung tumorigenic cells but not in their non-tumorigenic counterparts. We further examine its in vitro and in vivo anti-tumor activity in a human prostate adenocarcinoma (PC-3) model. OH-LAAO demonstrated potent cytotoxicity against PC-3 cells with IC50 of 0.05 µg/mL after 72 h incubation in vitro. It induced apoptosis as evidenced with an increase in caspase-3/7 cleavages and an increase in annexin V-stained cells. To examine its in vivo anti-tumor activity, we treated PC-3 tumor xenograft implanted subcutaneously in immunodeficient NU/NU (nude) mice with 1 µg/g OH-LAAO given intraperitoneally (i.p.). After 8 weeks of treatment, OH-LAAO treated PC-3 tumors were markedly inhibited, when compared to the control group (P <0.05). TUNEL staining analysis on the tumor sections showed a significantly increase of apoptotic cells in the LAAO-treated animals. Histological examinations of the vital organs in these two groups showed no significant differences with normal tissues, indicating no obvious tissue damage. The treatment also did not cause any significant changes on the body weight of the mice during the duration of the study. These observations suggest that OH-LAAO cytotoxic effects may be specific to tumor xenografts and less to normal organs. Given its potent anti-tumor activities shown in vitro as well as in vivo, the king cobra venom LAAO can potentially be developed to treat prostate cancer and other solid tumors.
  2. Fulltext 9-Benzyl-6-benzyl-sulfanyl-9H-purin-2-amine
    Hariono M, Wahab HA, Tan ML, Rosli MM, Razak IA
    Acta Crystallogr Sect E Struct Rep Online, 2014 Mar 1;70(Pt 3):o288.
    PMID: 24764997 DOI: 10.1107/S1600536814001986
    In the title compound, C19H17N5S, the dihedral angles between the purine ring system (r.m.s. deviation = 0.009 Å) and the S-bound and methyl-ene-bound phenyl rings are 74.67 (8) and 71.28 (7)°, respectively. In the crystal, inversion dimers linked by pairs of N-H⋯N hydrogen bonds generate R 2 (2)(8) loops. C-H⋯N inter-actions link the dimers into (100) sheets.
  3. Fulltext 4-Nitro-phthalo-nitrile
    Jan CY, Shamsudin NB, Tan AL, Young DJ, Ng SW, Tiekink ER
    Acta Crystallogr Sect E Struct Rep Online, 2014 Mar 1;70(Pt 3):o323.
    PMID: 24765021 DOI: 10.1107/S1600536814003468
    In the title compound, C8H3N3O2 (systematic name: 4-nitro-benzene-1,2-dicarbo-nitrile), the nitro group is twisted out of the plane of the benzene ring to which it is attached [O-N-Cring-Cring torsion angle = 9.80 (13)°]. In the crystal packing, supra-molecular layers with a zigzag topology in the ac plane are sustained by C-H⋯N inter-actions.
  4. Fulltext 4-Nitro-phthalamide
    Jan CY, Shamsudin NB, Tan AL, Young DJ, Ng SW, Tiekink ER
    Acta Crystallogr Sect E Struct Rep Online, 2014 Mar 1;70(Pt 3):o293.
    PMID: 24765000 DOI: 10.1107/S1600536814002955
    In the title compound, C8H7N3O4 (systematic name: 4-nitro-benzene-1,2-dicarboxamide), each of the substituents is twisted out of the plane of the benzene ring to which it is attached [dihedral angles of 11.36 (2)° for the nitro group, and 60.89 (6) and 34.39 (6)° for the amide groups]. The amide groups are orientated to either side of the least-squares plane through the benzene ring with the amine groups being directed furthest apart. In the crystal, a three-dimensional architecture is established by a network of N-H⋯O hydrogen bonds.
  5. Fulltext A classical genetic solution to enhance the biosynthesis of anticancer phytochemicals in Andrographis paniculata Nees
    Valdiani A, Talei D, Tan SG, Abdul Kadir M, Maziah M, Rafii MY, et al.
    PLoS One, 2014;9(2):e87034.
    PMID: 24586262 DOI: 10.1371/journal.pone.0087034
    Andrographolides, the diterpene lactones, are major bioactive phytochemicals which could be found in different parts of the medicinal herb Andrographis paniculata. A number of such compounds namely andrographolide (AG), neoandrographolide (NAG), and 14-deoxy-11,12-didehydroandrographolide (DDAG) have already attracted a great deal of attention due to their potential therapeutic effects in hard-to-treat diseases such as cancers and HIV. Recently, they have also been considered as substrates for the discovery of novel pharmaceutical compounds. Nevertheless, there is still a huge gap in knowledge on the genetic pattern of the biosynthesis of these bioactive compounds. Hence, the present study aimed to investigate the genetic mechanisms controlling the biosynthesis of these phytochemicals using a diallel analysis. The high performance liquid chromatography analysis of the three andrographolides in 210 F1 progenies confirmed that the biosynthesis of these andrographolides was considerably increased via intraspecific hybridization. The results revealed high, moderate and low heterosis for DDAG, AG and NAG, respectively. Furthermore, the preponderance of non-additive gene actions was affirmed in the enhancement of the three andrographolides contents. The consequence of this type of gene action was the occurrence of high broad-sense and low narrow-sense heritabilities for the above mentioned andrographolides. The prevalence of non-additive gene action suggests the suitability of heterosis breeding and hybrid seed production as a preferred option to produce new plant varieties with higher andrographolide contents using the wild accessions of A. paniculata. Moreover, from an evolutionary point of view, the occurrence of population bottlenecks in the Malaysian accessions of A. paniculata was unveiled by observing a low level of additive genetic variance (VA ) for all the andrographolides.
  6. Distribution and haplotype associations of XPD Lys751Gln, XRCC1 Arg280His and XRCC1 Arg399Gln polymorphisms with nasopharyngeal carcinoma in the Malaysian population
    Visuvanathan S, Chong PP, Yap YY, Lim CC, Tan MK, Lye MS
    Asian Pac J Cancer Prev, 2014;15(6):2747-51.
    PMID: 24761895
    BACKGROUND: DNA repair pathways play a crucial role in maintaining the human genome. Previous studies associated DNA repair gene polymorphisms (XPD Lys751Gln, XRCC1 Arg280His and XRCC1 Arg399Gln) with nasopharyngeal carcinoma. These non-synonymous polymorphisms may alter DNA repair capacity and thus increase or decrease susceptibility. The present study aimed to determine the genotype distribution of XPD codon 751, XRCC1 codon 280 and codon 399 polymorphisms and haplotype associations among NPC cases and controls in the Malaysian population.

    MATERIALS AND METHODS: We selected 157 NPC cases and 136 controls from two hospitals in Kuala Lumpur, Malaysia for this study. The polymorphisms studied were genotyped by PCR-RFLP assay and allele and genotype frequencies, haplotype and linkage disequilibrium were determined using SNPstat software.

    RESULTS: For the XPD Lys751Gln polymorphism, the frequency of the Lys allele was higher in cases than in controls (94.5% versus 85.0%). For the XRCC1 Arg280His polymorphism, the frequency of Arg allele was 90.0% and 89.0% in cases and controls, respectively and for XRCC1 Arg399Gln the frequency of the Arg allele was 72.0% and 72.8% in cases and controls respectively. All three polymorphisms were in linkage disequilibrium. The odds ratio from haplotype analysis for these three polymorphisms and their association with NPC was 1.93 (95%CI: 0.90-4.16) for haplotype CGC vs AGC allele combinations. The global haplotype association with NPC gave a p-value of 0.054.

    CONCLUSIONS: Our study provides an estimate of allele and genotype frequencies of XRCC1Arg280His, XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms in the Malaysian population and showed no association with nasopharyngeal cancer.

  7. The complete mitogenome of the Australian land crayfish Engaeus lyelli (Clark 1936) (Crustacea: Decapoda: Parastacidae)
    Gan HM, Tan MH, Lee YP, Schultz MB, Austin CM
    Mitochondrial DNA, 2016;27(1):595-6.
    PMID: 24730605 DOI: 10.3109/19401736.2014.908361
    The complete mitochondrial genome of the enigmatic freshwater crayfish Engaeus lyelli was sequenced using the MiSeq Personal Sequencer (Illumina, San Diego, CA). The mitogenome has 16,027 bp consisting of 13 protein-coding genes, 2 ribosomal subunit genes, 23 transfer RNAs, and a non-coding AT-rich region. The base composition of E. lyelli is 29.01% for T, 27.13% for C, 31.43% for A, and 12.44% for G, with an AT bias of 60.44%. The species has the distinctive gene order characteristic of parastacid crayfish with the exception of some minor rearrangements involving the tRNA genes.
  8. Fulltext Using project performance to measure effectiveness of quality management system maintenance and practices in construction industry
    Leong TK, Zakuan N, Mat Saman MZ, Ariff MS, Tan CS
    ScientificWorldJournal, 2014;2014:591361.
    PMID: 24701182 DOI: 10.1155/2014/591361
    This paper proposed seven existing and new performance indicators to measure the effectiveness of quality management system (QMS) maintenance and practices in construction industry. This research is carried out with a questionnaire based on QMS variables which are extracted from literature review and project performance indicators which are established from project management's theory. Data collected was analyzed using correlation and regression analysis. The findings indicate that client satisfaction and time variance have positive and significant relationship with QMS while other project performance indicators do not show significant results. Further studies can use the same project performance indicators to study the effectiveness of QMS in different sampling area to improve the generalizability of the findings.
  9. Morpho-molecular analysis as a prognostic model for repulsive feedback of the medicinal plant "Andrographis paniculata" to allogamy
    Valdiani A, Talei D, Javanmard A, Tan SG, Kadir MA, Maziah M
    Gene, 2014 Jun 1;542(2):156-67.
    PMID: 24680780 DOI: 10.1016/j.gene.2014.03.039
    Andrographis paniculata Nees. (AP) is a self-pollinated medicinal herb with a wide range of pharmaceutical properties, facing a low diversity in Malaysia. Cross-pollination of AP accessions leads to considerable rates of heterosis in the agro-morphological characteristics and anticancer phytochemicals of this eminent medicinal herb. However, the poor crossability of the plant at the interpopulation or intraspecific levels is an obstacle from the evolutionary and breeding points of view as an average of 4.56% crossability was recorded for AP in this study. Hence, this research aimed to elicit the impact of parental genetic distances (GDs) on the rate of crossability of AP using seven accessions in 21 possible cross combinations. To this end, a set of 55 randomly amplified polymorphic DNA (RAPD) primers and a total of 13 agro-morphological markers were employed to test the hypothesis. Twenty-two out of the 55 RAPD primers amplified a total of 257 bands of which 107 bands were found to be polymorphic. The principal component analysis (PCA) based on the RAPD markers revealed that the studied AP accessions were distributed to three distinct groups. Furthermore, it was noticed that even a minor increase in GD between two parents can cause a decline in their crossability. Unlike, the morphological-based GDs acted neutrally to crossability. This finding suggests that, despite the low genetic diversity among the Malaysian APs, a population prescreening using RAPD markers would be useful to enhance the rate of fruit set through selecting the genetically adjacent parents.
  10. Fulltext Depression, anxiety, stress and hyperemesis gravidarum: temporal and case controlled correlates
    Tan PC, Zaidi SN, Azmi N, Omar SZ, Khong SY
    PLoS One, 2014;9(3):e92036.
    PMID: 24637791 DOI: 10.1371/journal.pone.0092036
    To evaluate the temporal and case-controlled correlations of anxiety, depression and stress with hyperemesis gravidarum.
  11. The complete mitogenome of the Australian crayfish Geocharax gracilis Clark 1936 (Crustacea: Decapoda: Parastacidae)
    Gan HM, Tan MH, Gan HY, Lee YP, Schultz MB, Austin CM
    Mitochondrial DNA A DNA Mapp Seq Anal, 2016;27(2):826-7.
    PMID: 24845437 DOI: 10.3109/19401736.2014.919460
    The mitogenome of the black yabby, Geocharax gracilis, was sequenced using the MiSeq Personal Sequencer. It has 15,924 base pairs consisting of 13 protein-coding genes, 2 ribosomal subunit genes, 23 transfer RNAs, and a non-coding AT-rich region. The base composition of G. gracilis mitogenome is 32.18% for T, 22.32% for C, 34.83% for A, and 10.68% for G, with an AT bias of 67.01%. The mitogenome gene order is typical for that of parastacid crayfish with the exception of some minor rearrangements involving tRNA genes.
  12. Medium-term (5-year) comparison of the functional outcomes of combined anterior cruciate ligament and posterolateral corner reconstruction compared with isolated anterior cruciate ligament reconstruction
    Cartwright-Terry M, Yates J, Tan CK, Pengas IP, Banks JV, McNicholas MJ
    Arthroscopy, 2014 Jul;30(7):811-7.
    PMID: 24794571 DOI: 10.1016/j.arthro.2014.02.039
    To present a 5-year comparison of the functional outcomes of combined anterior cruciate ligament (ACL) and posterolateral corner (PLC) reconstruction with those of isolated ACL reconstruction.
  13. Fulltext Influence of physical activity on bone strength in children and adolescents: a systematic review and narrative synthesis
    Tan VP, Macdonald HM, Kim S, Nettlefold L, Gabel L, Ashe MC, et al.
    J. Bone Miner. Res., 2014 Oct;29(10):2161-81.
    PMID: 24737388 DOI: 10.1002/jbmr.2254
    A preponderance of evidence from systematic reviews supports the effectiveness of weight-bearing exercises on bone mass accrual, especially during the growing years. However, only one systematic review (limited to randomized controlled trials) examined the role of physical activity (PA) on bone strength. Thus, our systematic review extended the scope of the previous review by including all PA intervention and observational studies, including organized sports participation studies, with child or adolescent bone strength as the main outcome. We also sought to discern the skeletal elements (eg, mass, structure, density) that accompanied significant bone strength changes. Our electronic-database, forward, and reference searches yielded 14 intervention and 23 observational studies that met our inclusion criteria. We used the Effective Public Health Practice Project (EPHPP) tool to assess the quality of studies. Due to heterogeneity across studies, we adopted a narrative synthesis for our analysis and found that bone strength adaptations to PA were related to maturity level, sex, and study quality. Three (of five) weight-bearing PA intervention studies with a strong rating reported significantly greater gains in bone strength for the intervention group (3% to 4%) compared with only three significant (of nine) moderate intervention studies. Changes in bone structure (eg, bone cross-sectional area, cortical thickness, alone or in combination) rather than bone mass most often accompanied significant bone strength outcomes. Prepuberty and peripuberty may be the most opportune time for boys and girls to enhance bone strength through PA, although this finding is tempered by the few available studies in more mature groups. Despite the central role that muscle plays in bones' response to loading, few studies discerned the specific contribution of muscle function (or surrogates) to bone strength. Although not the focus of the current review, this seems an important consideration for future studies.
  14. Ultrasonography-diagnosed non-alcoholic fatty liver disease is not associated with prevalent ischemic heart disease among diabetics in a multiracial Asian hospital clinic population
    Chan WK, Tan AT, Vethakkan SR, Tah PC, Vijayananthan A, Goh KL
    Clin Res Hepatol Gastroenterol, 2014 Jun;38(3):284-91.
    PMID: 24736032 DOI: 10.1016/j.clinre.2014.02.009
    BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases are both common among patients with diabetes mellitus.
    OBJECTIVE: The aim of this study is to determine if ultrasonography-diagnosed NAFLD is associated with prevalent ischemic heart disease (IHD) among patients with diabetes mellitus.
    METHODS: This is a cross-sectional study on consecutive patients seen at the Diabetic Clinic, University of Malaya Medical Centre. The medical record for each patient was reviewed for documented IHD. Patients without documented IHD but had symptoms and/or electrocardiographic changes suggestive of IHD were referred for cardiac evaluation.
    RESULTS: Data for 399 patients were analyzed. Mean age was 62.8±10.5 years with 43.1% male. NAFLD and IHD were present in 49.6 and 26.6%, respectively. The prevalence of IHD among patients with and without NAFLD was 24.7 and 28.4%, respectively (P=0.414). The prevalence of IHD was highest among the Indians (34.1%) followed by the Malays (29.2%) and the Chinese (20.1%). No association was found between NAFLD and IHD when analyzed according to ethnicity. On multivariate analysis, independent factors associated with IHD were older age, lower levels of physical activity, greater waist circumference and higher serum glycated hemoglobin level.
    CONCLUSIONS: Ultrasonography-diagnosed NAFLD was not associated with prevalent IHD among patients with diabetes mellitus in a multiracial Asian hospital clinic population.

    Study site: Diabetic clinc, University Malaya Medical Centre (UMMC)
  15. Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II
    Bera H, Ojha Pk, Tan BJ, Sun L, Dolzhenko AV, Chui WK, et al.
    Eur J Med Chem, 2014 May 6;78:294-303.
    PMID: 24686016 DOI: 10.1016/j.ejmech.2014.03.063
    In our drug discovery program, a series of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones were designed, synthesized and evaluated for their TP inhibitory potential. All the synthesized analogues conferred a varying degree of TP inhibitory activity, comparable or better than positive control, 7-deazaxanthine (7-DX, 2) (IC50 value = 42.63 μM). A systematic approach to the lead optimization identified compounds 3c and 4a as the most promising TP inhibitors, exhibiting mixed mode of enzyme inhibition. Moreover, selected compounds demonstrated the ability to attenuate the expression of the angiogenic markers (viz. MMP-9 and VEGF) in MDA-MB-231 cells at sublethal concentrations. In addition, molecular docking studies revealed the plausible binding orientation of these inhibitors towards TP, which was in accordance with the experimental results. Taken as a whole, these compounds would constitute a new direction for the design of novel TP inhibitors with promising antiangiogenic properties.
  16. Fulltext Review on cold-formed steel connections
    Lee YH, Tan CS, Mohammad S, Tahir MM, Shek PN
    ScientificWorldJournal, 2014;2014:951216.
    PMID: 24688448 DOI: 10.1155/2014/951216
    The concept of cold-formed light steel framing construction has been widespread after understanding its structural characteristics with massive research works over the years. Connection serves as one of the important elements for light steel framing in order to achieve its structural stability. Compared to hot-rolled steel sections, cold-formed steel connections perform dissimilarity due to the thin-walled behaviour. This paper aims to review current researches on cold-formed steel connections, particularly for screw connections, storage rack connections, welded connections, and bolted connections. The performance of these connections in the design of cold-formed steel structures is discussed.
  17. Fulltext Role of laparoscopy and ultrasound in the management of "impalpable testis" in children
    Budianto IR, Tan HL, Kinoshita Y, Tamba RP, Leiri S, Taguchi T
    Asian J Surg, 2014 Oct;37(4):200-4.
    PMID: 24661449 DOI: 10.1016/j.asjsur.2014.01.013
    Undescended testes is one of the most common congenital abnormalities in boys. In cases of impalpable testes, ultrasound is often used to find the testis, which frequently provides false-negative results. Recently, laparoscopy has become popular in the management of impalpable testes.
  18. Copper complexes with phosphonium containing hydrazone ligand: topoisomerase inhibition and cytotoxicity study
    Chew ST, Lo KM, Lee SK, Heng MP, Teoh WY, Sim KS, et al.
    Eur J Med Chem, 2014 Apr 9;76:397-407.
    PMID: 24602785 DOI: 10.1016/j.ejmech.2014.02.049
    Four new copper(II) complexes containing phosphonium substituted hydrazone (L) with the formulations [CuL]Cl(3), [Cu(phen)L]Cl(4), [Cu(bpy)L]Cl(5), [Cu(dbpy)L]Cl(6), (where L = doubly deprotonated hydrazone; phen = 1,10'-phenanthroline; bpy = 2,2'-bipyridine; dbpy = 5,5'-dimethyl-2,2'-bipyridine) have been synthesized. The compounds were characterized by elemental analysis, spectroscopic methods and in the case of crystalline products by X-ray crystallography. The cytotoxicity and topoisomerase I (topo I) inhibition activities of these compounds were studied. It is noteworthy that the addition of N,N-ligands to the copper(II) complex lead to the enhancement in the cytotoxicity of the compounds, especially against human prostate adenocarcinoma cell line (PC-3). Complex 4 exhibits the highest activity against PC-3 with the IC₅₀ value of 3.2 μΜ. The complexes can also inhibit topo I through the binding to DNA and the enzyme.
  19. Biological activity and molecular docking studies of curcumin-related α,β-unsaturated carbonyl-based synthetic compounds as anticancer agents and mushroom tyrosinase inhibitors
    Bukhari SN, Jantan I, Unsal Tan O, Sher M, Naeem-Ul-Hassan M, Qin HL
    J Agric Food Chem, 2014 Jun 18;62(24):5538-47.
    PMID: 24901506 DOI: 10.1021/jf501145b
    Hyperpigmentation in human skin and enzymatic browning in fruits, which are caused by tyrosinase enzyme, are not desirable. Investigations in the discovery of tyrosinase enzyme inhibitors and search for improved cytotoxic agents continue to be an important line in drug discovery and development. In present work, a new series of 30 compounds bearing α,β-unsaturated carbonyl moiety was designed and synthesized following curcumin as model. All compounds were evaluated for their effects on human cancer cell lines and mushroom tyrosinase enzyme. Moreover, the structure-activity relationships of these compounds are also explained. Molecular modeling studies of these new compounds were carried out to explore interactions with tyrosinase enzyme. Synthetic curcumin-like compounds (2a-b) were identified as potent anticancer agents with 81-82% cytotoxicity. Five of these newly synthesized compounds (1a, 8a-b, 10a-b) emerged to be the potent inhibitors of mushroom tyrosinase, providing further insight into designing compounds useful in fields of food, health, and agriculture.
  20. Fulltext Tualang honey improves human corneal epithelial progenitor cell migration and cellular resistance to oxidative stress in vitro
    Tan JJ, Azmi SM, Yong YK, Cheah HL, Lim V, Sandai D, et al.
    PLoS One, 2014;9(5):e96800.
    PMID: 24802273 DOI: 10.1371/journal.pone.0096800
    Stem cells with enhanced resistance to oxidative stress after in vitro expansion have been shown to have improved engraftment and regenerative capacities. Such cells can be generated by preconditioning them with exposure to an antioxidant. In this study we evaluated the effects of Tualang honey (TH), an antioxidant-containing honey, on human corneal epithelial progenitor (HCEP) cells in culture. Cytotoxicity, gene expression, migration, and cellular resistance to oxidative stress were evaluated. Immunofluorescence staining revealed that HCEP cells were holoclonal and expressed epithelial stem cell marker p63 without corneal cytokeratin 3. Cell viability remained unchanged after cells were cultured with 0.004, 0.04, and 0.4% TH in the medium, but it was significantly reduced when the concentration was increased to 3.33%. Cell migration, tested using scratch migration assay, was significantly enhanced when cells were cultured with TH at 0.04% and 0.4%. We also found that TH has hydrogen peroxide (H2O2) scavenging ability, although a trace level of H2O2 was detected in the honey in its native form. Preconditioning HCEP cells with 0.4% TH for 48 h showed better survival following H2O2-induced oxidative stress at 50 µM than untreated group, with a significantly lower number of dead cells (15.3 ± 0.4%) were observed compared to the untreated population (20.5 ± 0.9%, p<0.01). Both TH and ascorbic acid improved HCEP viability following induction of 100 µM H2O2, but the benefit was greater with TH treatment than with ascorbic acid. However, no significant advantage was demonstrated using 5-hydroxymethyl-2-furancarboxaldehyde, a compound that was found abundant in TH using GC/MS analysis. This suggests that the cellular anti-oxidative capacity in HCEP cells was augmented by native TH and was attributed to its antioxidant properties. In conclusion, TH possesses antioxidant properties and can improve cell migration and cellular resistance to oxidative stress in HCEP cells in vitro.
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