Displaying publications 4761 - 4780 of 8213 in total

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  1. Genomic analysis revealing the resistance mechanisms of extended-spectrum β-lactamase-producing Klebsiella pneumoniae isolated from pig and humans in Malaysia
    Mobasseri G, Thong KL, Teh CSJ
    Int Microbiol, 2021 May;24(2):243-250.
    PMID: 33469786 DOI: 10.1007/s10123-021-00161-5
    Extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae has been associated with a wide range of infections in humans and animals. The objective of this study was to determine the genomic characteristics of two multiple drug resistant, ESBLs-producing K. pneumoniae strains isolated from a swine in 2013 (KP2013Z28) and a hospitalized patient in 2014 (KP2014C46) in Malaysia. Genomic analyses of the two K. pneumoniae strains indicated the presence of various antimicrobial resistance genes associated with resistance to β-lactams, aminoglycosides, colistin, fluoroquinolones, phenicols, tetracycline, sulfonamides, and trimethoprim, corresponding to the antimicrobial susceptibility profiles of the strains. KP2013Z28 (ST25) and KP2014C46 (ST929) harbored 5 and 2 genomic plasmids, respectively. The phylogenomics of these two Malaysian K. pneumoniae, with other 19 strains around the world was determined based on SNPs analysis. Overall, the strains were resolved into five clusters that comprised of strains with different resistance determinants. This study provided a better understanding of the resistance mechanisms and phylogenetic relatedness of the Malaysian strains with 19 strains isolated worldwide. This study also highlighted the needs to monitor the usage of antibiotics in hospital settings, animal husbandry, and agricultural practices due to the increase of β-lactam, aminoglycosides, tetracycline, and colistin resistance among pathogenic bacteria for better infection control.
    Matched MeSH terms: Bacterial Proteins/genetics; beta-Lactamases/genetics; Klebsiella pneumoniae/genetics*; Plasmids/genetics
  2. Fulltext T4-like coliphage ΦKAZ14 virulent to pathogenic and extended spectrum β-lactamase-producing Escherichia coli of poultry origin
    Ahmad KA, Mohanmmed AS, Abas F, Chin SC
    Virol Sin, 2015 Feb;30(1):73-5.
    PMID: 25662886 DOI: 10.1007/s12250-014-3541-8
    Matched MeSH terms: beta-Lactamases/genetics; Coliphages/genetics; Escherichia coli/genetics; Escherichia coli Proteins/genetics
  3. Silencing of ZFP36L2 increases sensitivity to temozolomide through G2/M cell cycle arrest and BAX mediated apoptosis in GBM cells
    Che Mat MF, Mohamad Hanif EA, Abdul Murad NA, Ibrahim K, Harun R, Jamal R
    Mol Biol Rep, 2021 Feb;48(2):1493-1503.
    PMID: 33590411 DOI: 10.1007/s11033-021-06144-z
    Despite the advancements in primary brain tumour diagnoses and treatments, the mortality rate remains high, particularly in glioblastoma (GBM). Chemoresistance, predominantly in recurrent cases, results in decreased mean survival of patients with GBM. We aimed to determine the chemosensitisation and oncogenic characteristics of zinc finger protein 36-like 2 (ZFP36L2) in LN18 GBM cells via RNA interference (RNAi) delivery. We conducted a meta-analysis of microarray datasets and RNAi screening using pooled small interference RNA (siRNA) to identify the druggable genes responsive to GBM chemosensitivity. Temozolomide-resistant LN18 cells were used to evaluate the effects of gene silencing on chemosensitisation to the sub-lethal dose (1/10 of the median inhibitory concentration [IC50]) of temozolomide. ZFP36L2 protein expression was detected by western blotting. Cell viability, proliferation, cell cycle and apoptosis assays were carried out using commercial kits. A human apoptosis array kit was used to determine the apoptosis pathway underlying chemosensitisation by siRNA against ZFP36L2 (siZFP36L2). Statistical analyses were performed using one-way analysis of variance; p > 0.05 was considered significant. The meta-analysis and RNAi screening identified ZFP36L2 as a potential marker of GBM. ZFP36L2 knockdown significantly induced apoptosis (p 
    Matched MeSH terms: Glioblastoma/genetics; Transcription Factors/genetics*; Drug Resistance, Neoplasm/genetics; bcl-2-Associated X Protein/genetics*
  4. Fulltext Discovery of New Genes Involved in Curli Production by a Uropathogenic Escherichia coli Strain from the Highly Virulent O45:K1:H7 Lineage
    Nhu NTK, Phan MD, Peters KM, Lo AW, Forde BM, Min Chong T, et al.
    mBio, 2018 08 21;9(4).
    PMID: 30131362 DOI: 10.1128/mBio.01462-18
    Curli are bacterial surface-associated amyloid fibers that bind to the dye Congo red (CR) and facilitate uropathogenic Escherichia coli (UPEC) biofilm formation and protection against host innate defenses. Here we sequenced the genome of the curli-producing UPEC pyelonephritis strain MS7163 and showed it belongs to the highly virulent O45:K1:H7 neonatal meningitis-associated clone. MS7163 produced curli at human physiological temperature, and this correlated with biofilm growth, resistance of sessile cells to the human cationic peptide cathelicidin, and enhanced colonization of the mouse bladder. We devised a forward genetic screen using CR staining as a proxy for curli production and identified 41 genes that were required for optimal CR binding, of which 19 genes were essential for curli synthesis. Ten of these genes were novel or poorly characterized with respect to curli synthesis and included genes involved in purine de novo biosynthesis, a regulator that controls the Rcs phosphorelay system, and a novel repressor of curli production (referred to as rcpA). The involvement of these genes in curli production was confirmed by the construction of defined mutants and their complementation. The mutants did not express the curli major subunit CsgA and failed to produce curli based on CR binding. Mutation of purF (the first gene in the purine biosynthesis pathway) and rcpA also led to attenuated colonization of the mouse bladder. Overall, this work has provided new insight into the regulation of curli and the role of these amyloid fibers in UPEC biofilm formation and pathogenesis.IMPORTANCE Uropathogenic Escherichia coli (UPEC) strains are the most common cause of urinary tract infection, a disease increasingly associated with escalating antibiotic resistance. UPEC strains possess multiple surface-associated factors that enable their colonization of the urinary tract, including fimbriae, curli, and autotransporters. Curli are extracellular amyloid fibers that enhance UPEC virulence and promote biofilm formation. Here we examined the function and regulation of curli in a UPEC pyelonephritis strain belonging to the highly virulent O45:K1:H7 neonatal meningitis-associated clone. Curli expression at human physiological temperature led to increased biofilm formation, resistance of sessile cells to the human cationic peptide LL-37, and enhanced bladder colonization. Using a comprehensive genetic screen, we identified multiple genes involved in curli production, including several that were novel or poorly characterized with respect to curli synthesis. In total, this study demonstrates an important role for curli as a UPEC virulence factor that promotes biofilm formation, resistance, and pathogenesis.
    Matched MeSH terms: Amyloid/genetics*; Escherichia coli Proteins/genetics*; Virulence Factors/genetics*; Uropathogenic Escherichia coli/genetics*
  5. Fulltext Quantitative MS-Based Proteomics: Comparing the MCF-7 Cellular Response to Hypoxia and a 2-Oxoglutarate Analogue
    Bush JT, Chan MC, Mohammed S, Schofield CJ
    Chembiochem, 2020 06 02;21(11):1647-1655.
    PMID: 31919953 DOI: 10.1002/cbic.201900719
    The hypoxia-inducible factors (HIFs) are key transcription factors in determining cellular responses involving alterations in protein levels in response to limited oxygen availability in animal cells. 2-Oxoglutarate-dependent oxygenases play key roles in regulating levels of HIF and its transcriptional activity. We describe MS-based proteomics studies in which we compared the results of subjecting human breast cancer MCF-7 cells to hypoxia or treating them with a cell-penetrating derivative (dimethyl N-oxalylglycine; DMOG) of the stable 2OG analogue N-oxalylglycine. The proteomic results are consistent with reported transcriptomic analyses and support the proposed key roles of 2OG-dependent HIF prolyl- and asparaginyl-hydroxylases in the hypoxic response. Differences between the data sets for hypoxia and DMOG might reflect context-dependent effects or HIF-independent effects of DMOG.
    Matched MeSH terms: Cell Hypoxia/genetics*; Proteome/genetics*; Hypoxia-Inducible Factor 1, alpha Subunit/genetics*; Metabolic Networks and Pathways/genetics
  6. Succinic Semialdehyde Dehydrogenase Deficiency in a Chinese Boy: A Novel ALDH5A1 Mutation With Severe Phenotype
    Tay CG, Ariffin H, Yap S, Rahmat K, Sthaneshwar P, Ong LC
    J Child Neurol, 2015 Jun;30(7):927-31.
    PMID: 25122112 DOI: 10.1177/0883073814540523
    Succinic semialdehyde dehydrogenase deficiency is a rare autosomal recessive disorder affecting catabolism of the neurotransmitter gamma-aminobutyric acid (GABA), with a wide range of clinical phenotype. We report a Malaysian Chinese boy with a severe early onset phenotype due to a previously unreported mutation. Urine organic acid chromatogram revealed elevated 4-hydroxybutyric acid. Magnetic resonance imaging (MRI) of the brain demonstrated cerebral atrophy with atypical putaminal involvement. Molecular genetic analysis showed a novel homozygous 3-bp deletion at the ALDH5A1 gene c.1501_1503del (p.Glu501del). Both parents were confirmed to be heterozygotes for the p.Glu501del mutation. The clinical course was complicated by the development of subdural hemorrhage probably as a result of rocking the child to sleep for erratic sleep-wake cycles. This case illustrates the need to recognize that trivial or unintentional shaking of such children, especially in the presence of cerebral atrophy, can lead to subdural hemorrhage.
    Matched MeSH terms: Amino Acid Metabolism, Inborn Errors/genetics*; Developmental Disabilities/genetics*; Asian Continental Ancestry Group/genetics; Succinate-Semialdehyde Dehydrogenase/genetics
  7. Genetics of spinosad resistance in a multi-resistant field-selected population of Plutella xylostella
    Sayyed AH, Omar D, Wright DJ
    Pest Manag Sci, 2004 Aug;60(8):827-32.
    PMID: 15307676
    Resistance to the bacteria-derived insecticides spinosad (Conserve), abamectin (Vertimec), Bacillus thuringiensis var kurstaki (Btk) (Dipel), B thuringiensis var aizawai (Bta) (Xentari), B thuringiensis crystal endotoxins Cry1Ac and Cry1Ca, and to the synthetic insecticide fipronil was estimated in a freshly-collected field population (CH1 strain) of Plutella xylostella (L) from the Cameron Highlands, Malaysia. Laboratory bioassays at G1 indicated significant levels of resistance to spinosad, abamectin, Cry1Ac, Btk, Cry1Ca, fipronil and Bta when compared with a laboratory insecticide-susceptible population. Logit regression analysis of F1 reciprocal crosses indicated that resistance to spinosad in the CH1 population was inherited as a co-dominant trait. At the highest dose of spinosad tested, resistance was close to completely recessive, while at the lowest dose it was incompletely dominant. A direct test of monogenic inheritance based on a back-cross of F1 progeny with CH1 suggested that resistance to spinosad was controlled by a single locus.
    Matched MeSH terms: Genes, Dominant/genetics; Genes, Recessive/genetics; Insecticide Resistance/genetics; Moths/genetics*
  8. Development of a dry reagent-based triplex PCR for the detection of toxigenic and non-toxigenic Vibrio cholerae
    Chua AL, Elina HT, Lim BH, Yean CY, Ravichandran M, Lalitha P
    J Med Microbiol, 2011 Apr;60(Pt 4):481-485.
    PMID: 21183596 DOI: 10.1099/jmm.0.027433-0
    Vibrio cholerae has caused severe outbreaks of cholera worldwide with thousands of recorded deaths annually. Molecular diagnosis for cholera has become increasingly important for rapid detection of cholera as the conventional methods are time-consuming and labour intensive. However, traditional PCR tests still require cold-chain transportation and storage as well as trained personnel to perform, which makes them user-unfriendly. The aim of this study was to develop a thermostabilized triplex PCR test for cholera which is in a ready-to-use form and requires no cold chain. The PCR test specifically detects both toxigenic and non-toxigenic strains of V. cholerae based on the cholera toxin A (ctxA) and outer-membrane lipoprotein (lolB) genes. The thermostabilized triplex PCR also incorporates an internal amplification control that helps to check for PCR inhibitors in samples. PCR reagents and the specific primers were lyophilized into a pellet form in the presence of trehalose, which acts as an enzyme stabilizer. The triplex PCR was validated with 174 bacteria-spiked stool specimens and was found to be 100 % sensitive and specific. The stability of the thermostabilized PCR was evaluated using the Q10 method and it was found to be stable for approximately 7 months at 24 °C. The limit of detection of the thermostabilized triplex PCR assay was 2×10(4) c.f.u. at the bacterial cell level and 100 pg DNA at the genomic DNA level, comparable to conventional PCR methods. In conclusion, a rapid thermostabilized triplex PCR assay was developed for detecting toxigenic and non-toxigenic V. cholerae which requires minimal pipetting steps and is cold chain-free.
    Matched MeSH terms: Bacterial Outer Membrane Proteins/genetics*; Cholera Toxin/genetics*; Vibrio cholerae/genetics; Virulence Factors/genetics*
  9. Phenotypic and genotypic characterization of two closely related subgroups of Candida rugosa in clinical specimens
    Tay ST, Tan HW, Na SL, Lim SL
    J Med Microbiol, 2011 Nov;60(Pt 11):1591-1597.
    PMID: 21700741 DOI: 10.1099/jmm.0.032854-0
    In this study, six clinical isolates (two from blood, two from urine and one each from a bronchoalveolar lavage and a vaginal swab) were identified as Candida rugosa based on carbohydrate assimilation profiles using API 20C AUX and ID32 C kits (bioMérieux). Sequence analysis of the D1/D2 domain of the yeasts differentiated the isolates into two subgroups, A and B (three isolates per subgroup), which were closely related (99.1-99.6 % nucleotide similarity) to C. rugosa strain ATCC 10571. Compared with the C. rugosa type strain, the intergenic transcribed spacer (ITS) nucleotide similarity for subgroup A was only 89.2 % (29 mismatches and one deletion) and for subgroup B was 93.7 % (20 mismatches). All isolates grew green colonies on Oxoid Chromogenic Candida Agar, with darker pigmentation observed for subgroup A. All isolates were able to grow at 25-42 °C but not at 45 °C. The isolates had identical enzymic profiles, as determined by API ZYM (bioMérieux) analysis, and produced proteinase. High amphotericin MICs (≥1 µg ml(-1)) were noted for two isolates from each subgroup. Dose-dependent susceptibility to fluconazole (MIC 32 µg ml(-1)) was noted in a blood isolate. The biofilms of the isolates demonstrated increased resistance to amphotericin and fluconazole. The greater ITS sequence variability of subgroup A isolates is in support of this yeast being recognized as a distinct species; however, further verification using more sophisticated molecular approaches is required. A sequence comparison study suggested the association of subgroup A with environmental sources and subgroup B with clinical sources. Accurate identification and antifungal susceptibility testing of C. rugosa are important in view of its decreased susceptibility to amphotericin and fluconazole. The ITS region has been shown to be a valuable region for differentiation of closely related subgroups of C. rugosa.
    Matched MeSH terms: Candida/genetics*; DNA, Fungal/genetics; Peptide Hydrolases/genetics*; RNA, Ribosomal/genetics
  10. High resolution melting analysis for the differentiation of Mycobacterium species
    Issa R, Abdul H, Hashim SH, Seradja VH, Shaili N', Hassan NAM
    J Med Microbiol, 2014 Oct;63(Pt 10):1284-1287.
    PMID: 25038139 DOI: 10.1099/jmm.0.072611-0
    A quantitative real-time PCR (qPCR) followed by high resolution melting (HRM) analysis was developed for the differentiation of Mycobacterium species. Rapid differentiation of Mycobacterium species is necessary for the effective diagnosis and management of tuberculosis. In this study, the 16S rRNA gene was tested as the target since this has been identified as a suitable target for the identification of mycobacteria species. During the temperature gradient and primer optimization process, the melting peak (Tm) analysis was determined at a concentration of 50 ng DNA template and 0.3, 0.4 and 0.5 µM primer. The qPCR assay for the detection of other mycobacterial species was done at the Tm and primer concentration of 62 °C and 0.4 µM, respectively. The HRM analysis generated cluster patterns that were specific and sensitive to distinguished small sequence differences of the Mycobacterium species. This study suggests that the 16S rRNA-based real-time PCR followed by HRM analysis produced unique cluster patterns for species of Mycobacterium and could differentiate the closely related mycobacteria species.
    Matched MeSH terms: DNA, Bacterial/genetics*; DNA, Ribosomal/genetics; Mycobacterium/genetics*; RNA, Ribosomal, 16S/genetics
  11. Fulltext Molecular epidemiology of Cryptosporidium in HIV/AIDS patients in Malaysia
    Asma I, Sim BL, Brent RD, Johari S, Yvonne Lim AL
    Trop Biomed, 2015 Jun;32(2):310-22.
    PMID: 26691260 MyJurnal
    Cryptosporidiosis is a particular concern in immunocompromised individuals where symptoms may be severe. The aim of this study was to examine the epidemiological and molecular characteristics of Cryptosporidium infections in HIV/AIDS patients in Malaysia in order to identify risk factors and facilitate control measures. A modified Ziehl-Neelsen acid fast staining method was used to test for the presence of Cryptosporidium oocysts in the stools of 346 HIV/AIDS patients in Malaysia. Standard coproscopical methods were used to identify infections with other protozoan or helminths parasites. To identify the species of Cryptosporidium, DNA was extracted and nested-PCR was used to amplify a portion of the SSU rRNA gene. A total of 43 (12.4%) HIV-infected patients were found to be infected with Cryptosporidium spp. Of the 43 Cryptosporidium-positive HIV patients, 10 (23.3%) also harboured other protozoa, and 15 (34.9%) had both protozoa and helminths. The highest rates of cryptosporidiosis were found in adult males of Malay background, intravenous drug users, and those with low CD4 T cell counts (i.e., < 200 cells/mm3). Most were asymptomatic and had concurrent opportunistic infections mainly with Mycobacterium tuberculosis. DNA sequence analysis of 32 Cryptosporidium isolates identified C. parvum (84.3%), C. hominis (6.3%), C. meleagridis (6.3%), and C. felis (3.1%). The results of the present study revealed a high prevalence of Cryptosporidium infection in hospitalized HIV/AIDS patients. The results also confirmed the potential significance of zoonotic transmission of C. parvum in HIV infected patients, as it was the predominant species found in this study. However, these patients were found to be susceptible to a wide range of Cryptosporidium species. Epidemiological and molecular characterization of Cryptosporidium isolates provides clinicians and researchers with further information regarding the origin of the infection, and may enhance treatment and control strategies.
    Matched MeSH terms: Cryptosporidium/genetics*; DNA, Ribosomal/genetics; RNA, Ribosomal, 18S/genetics; DNA, Protozoan/genetics
  12. Fulltext Methicillin sensitive Staphylococcus aureus (MSSA) isolates as a potential source for the emergence of USA 300 methicillin resistant Staphylococcus aureus (MRSA) in Malaysia
    Ghasemzadeh-Moghaddam H, Neela V, Goering R, Mariana NS
    Trop Biomed, 2012 Sep;29(3):429-33.
    PMID: 23018506
    We investigated the potential of USA300 MRSA emergence in Malaysia by examining 268 MSSA isolates from both community (110) and healthcare (158) settings. Nine isolates from both the environments were similar to the USA300 MRSA background based on MLST, spa and PFGE type. These results underscore the importance of continued surveillance to monitor the emergence of USA300 MRSA in Malaysia.
    Matched MeSH terms: DNA, Bacterial/genetics; Staphylococcus aureus/genetics; Methicillin Resistance/genetics*; Methicillin-Resistant Staphylococcus aureus/genetics
  13. Fulltext Cloning and expression of Toxoplasma gondii dense granular protein 4 (GRA4) in Pichia pastoris
    Lau YL, Hasan MT, Thiruvengadam G, Idris MM, Init I
    Trop Biomed, 2010 Dec;27(3):525-33.
    PMID: 21399595
    GRA4 of Toxoplasma gondii has been shown to prompt IgG, IgM and IgA responses in previous studies and is thus considered one of the major immunogenic proteins from T. gondii that can be used for both diagnostics purposes and vaccine development. This study seeks to clone and express the GRA4 in Pichia pastoris, which has numerous advantages over other systems for expression of eukaryotic proteins. In order to achieve this, the gene was cloned into the pPICZα A expression vector, which was then incorporated into the P. pastoris genome via insertional integration for expression of the recombinant protein, under the AOX1 promoter. The antigen was expressed along with the prepro sequence of the α-factor of yeast so that it could be excreted out of the P. pastoris cells and obtained from the medium. Upon SDS-PAGE analysis it was found that the recombinant protein was expressed optimally as a 40 kDa protein after 96 hours of induction with 0.75% of methanol. The expressed GRA4 protein showed discrepancy in size with the calculated molecular mass. This may be attributed to the various posttranslational modifications including glycosylation and phosphorylation. Despite the difference in molecular weight, the recombinant protein was able to detect toxoplasmosis in Western blot format. The recombinant GRA4 was expressed with an intact polyhistidine-tag, which could be used for future purification of the antigen.
    Matched MeSH terms: Pichia/genetics*; Recombinant Proteins/genetics; Toxoplasma/genetics*; Protozoan Proteins/genetics*
  14. Genetic variability of Ehrlichia canis TRP36 in ticks, dogs, and red foxes from Eurasia
    Bezerra-Santos MA, Nguyen VL, Iatta R, Manoj RRS, Latrofa MS, Hodžić A, et al.
    Vet Microbiol, 2021 Apr;255:109037.
    PMID: 33740731 DOI: 10.1016/j.vetmic.2021.109037
    Ehrlichia canis is among the most prevalent tick-borne pathogens infecting dogs worldwide, being primarily vectored by brown dog ticks, Rhipicephalus sanguineus sensu lato (s.l.). The genetic variability of E. canis has been assessed by analysis of different genes (e.g., disulfide bond formation protein gene, glycoprotein 19, tandem repeat protein 36 - TRP36) in the Americas, Africa, Asia, and in a single dog sample from Europe (i.e., Spain). This study was aimed to assess the variations in the TRP36 gene of E. canis detected in naturally infected canids and R. sanguineus s.l. ticks from different countries in Asia and Europe. DNA samples from dogs (n = 644), foxes (n = 146), and R. sanguineus s.l. ticks (n = 658) from Austria, Italy, Iran, Pakistan, India, Indonesia, Malaysia, the Philippines, Singapore, Thailand, Vietnam, and Taiwan were included in this study. Ehrlichia canis 16S rRNA positive samples (n = 115 from the previous studies; n = 14 from Austria in this study) were selected for molecular examination by analyses of TRP36 gene. Out of 129 E. canis 16S rRNA positive samples from dogs (n = 88), foxes (n = 7), and R. sanguineus s.l. ticks (n = 34), the TRP36 gene was successfully amplified from 52. The phylogenetic analysis of the TRP36 pre-repeat, tandem repeat, and post repeat regions showed that most samples were genetically close to the United States genogroup, whereas two samples from Austria and one from Pakistan clustered within the Taiwan genogroup. TRP36 sequences from all samples presented a high conserved nucleotide sequence in the tandem repeat region (from 6 to 20 copies), encoding for nine amino acids (i.e., TEDSVSAPA). Our results confirm the US genogroup as the most frequent group in dogs and ticks tested herein, whereas the Taiwan genogroup was present in a lower frequency. Besides, this study described for the first time the US genogroup in red foxes, thus revealing that these canids share identical strains with domestic dogs and R. sanguineus s.l. ticks.
    Matched MeSH terms: Bacterial Proteins/genetics; RNA, Bacterial/genetics; RNA, Ribosomal, 16S/genetics; Ehrlichia canis/genetics*
  15. Fulltext Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer
    Lawrenson K, Li Q, Kar S, Seo JH, Tyrer J, Spindler TJ, et al.
    Nat Commun, 2015 Sep 22;6:8234.
    PMID: 26391404 DOI: 10.1038/ncomms9234
    Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations (P<1.4 × 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.
    Matched MeSH terms: Neoplasm Proteins/genetics*; Neoplasms, Glandular and Epithelial/genetics*; Ovarian Neoplasms/genetics*; Homeodomain Proteins/genetics
  16. Fulltext Prevalence of Asymptomatic and/or Low-Density Malaria Infection among High-Risk Groups in Peninsular Malaysia
    Noordin NR, Lee PY, Mohd Bukhari FD, Fong MY, Abdul Hamid MH, Jelip J, et al.
    Am J Trop Med Hyg, 2020 09;103(3):1107-1110.
    PMID: 32618263 DOI: 10.4269/ajtmh.20-0268
    Asymptomatic and/or low-density malaria infection has been acknowledged as an obstacle to achieving a malaria-free country. This study aimed to determine the prevalence of asymptomatic and/or low-density malaria infection in previously reported malarious localities using nested PCR in four states, namely, Johor, Pahang, Kelantan, and Selangor, between June 2019 and January 2020. Blood samples (n = 585) were collected and were extracted using a QIAamp blood kit. The DNA was concentrated and subjected to nested PCR. Thin and thick blood smears were examined as well. Of the 585 samples collected, 19 were positive: 10 for Plasmodium knowlesi, eight for Plasmodium vivax, and one for Plasmodium ovale. Asymptomatic and/or low-density malaria infection is a threat to malaria elimination initiatives. Eliminating countries should develop guidance policy on the importance of low-density malaria infection which includes detection and treatment policy.
    Matched MeSH terms: Plasmodium/genetics; Plasmodium vivax/genetics; Plasmodium knowlesi/genetics; Plasmodium ovale/genetics
  17. Genetic variations in transcription factor 7-like 2 (TCF7L2) gene: association of TCF7L2 rs12255372(G/T) or rs7903146(C/T) with breast cancer risk and clinico-pathological parameters
    Naidu R, Yip CH, Taib NA
    Med Oncol, 2012 Jun;29(2):411-7.
    PMID: 21301999 DOI: 10.1007/s12032-011-9837-8
    The purpose of the present study was to evaluate the association between TCF7L2 rs12255372(G/T) or rs7903146(C/T) polymorphism and breast cancer risk, and clinico-pathologic characteristics of the patients. Genotyping of these polymorphisms was performed on 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Malaysian population. The allele (P = 0.033) frequency of rs7903146 (T) polymorphism was significantly higher in the cancer patients than normal individuals. No significant association was demonstrated between CT (OR(adj) = 1.386; 95% CI, 0.985-1.949) or TT (OR(adj) = 1.579; 95% CI, 0.869-2.870) genotype and breast cancer risk. However, women who were carriers of T allele (OR(adj) = 1.316; 95% CI, 1.022-1.695) or T allele genotype (OR(adj) = 1.419; 95% CI, 1.027-1.960) showed significant increased risk of breast cancer. Women who were GT heterozygotes (OR(adj) = 1.329; 95% CI, 0.948-1.862) or TT homozygotes (OR(adj) = 1.574; 95% CI, 0.829-2.987), and carriers of T allele genotype (OR(adj) = 1.365; 95% CI, 0.989-1.883) or T allele (OR(adj) = 1.284; 95% CI, 0.995-1.657) were not associated with breast cancer risk. The rs7903146(T) allele genotype was significantly associated with nodal involvement (P = 0.003) but rs12255372 (T) allele genotype was not associated with the clinico-pathologic characteristics. In conclusion, our findings suggest that rs7903146 (T) variant may elevate the risk of breast cancer, thus could be a potential candidate for breast cancer susceptibility. The variant may also increase the metastatic potential of the tumor.
    Matched MeSH terms: Breast Neoplasms/genetics*; Polymorphism, Genetic/genetics*; Carcinoma, Ductal, Breast/genetics*; Transcription Factor 7-Like 2 Protein/genetics*
  18. Emerging strategies for sensitization of therapy resistant tumors toward cancer therapeutics by targeting the Bcl-2 family, TGF-β, Wnt/β-Catenin, RASSF and miRNA regulated signaling pathways
    Veerasamy T, Eugin Simon S, Tan KO
    Int J Biochem Cell Biol, 2021 08;137:106016.
    PMID: 34082133 DOI: 10.1016/j.biocel.2021.106016
    Conventional chemotherapy relies on the cytotoxicity of chemo-drugs to inflict destructive effects on tumor cells. However, as most tumor cells develop resistance to chemo-drugs, small doses of chemo-drugs are unlikely to provide significant clinical benefits in cancer treatment while high doses of chemo-drugs have been shown to impact normal human cells negatively due to the non-specific nature and cytotoxicity associated with chemo-drugs. To overcome this challenge, sensitizations of tumor cells with bioactive molecules that specifically target the pro-survival and pro-apoptosis signaling pathways of the tumor cells are likely to increase the therapeutic impacts and improve the clinical outcomes by reducing the dependency and adverse effects associated with using high doses of chemo-drugs in cancer treatment. This review focuses on emerging strategies to enhance the sensitization of tumor cells toward cancer therapies based on our understanding of tumor cell biology and underlying signaling pathways.
    Matched MeSH terms: Transforming Growth Factor beta/genetics; Proto-Oncogene Proteins c-bcl-2/genetics; MicroRNAs/genetics; beta Catenin/genetics
  19. Insights into rubber biosynthesis from transcriptome analysis of Hevea brasiliensis latex
    Chow KS, Wan KL, Isa MN, Bahari A, Tan SH, Harikrishna K, et al.
    J Exp Bot, 2007;58(10):2429-40.
    PMID: 17545224
    Hevea brasiliensis is the most widely cultivated species for commercial production of natural rubber (cis-polyisoprene). In this study, 10,040 expressed sequence tags (ESTs) were generated from the latex of the rubber tree, which represents the cytoplasmic content of a single cell type, in order to analyse the latex transcription profile with emphasis on rubber biosynthesis-related genes. A total of 3,441 unique transcripts (UTs) were obtained after quality editing and assembly of EST sequences. Functional classification of UTs according to the Gene Ontology convention showed that 73.8% were related to genes of unknown function. Among highly expressed ESTs, a significant proportion encoded proteins related to rubber biosynthesis and stress or defence responses. Sequences encoding rubber particle membrane proteins (RPMPs) belonging to three protein families accounted for 12% of the ESTs. Characterization of these ESTs revealed nine RPMP variants (7.9-27 kDa) including the 14 kDa REF (rubber elongation factor) and 22 kDa SRPP (small rubber particle protein). The expression of multiple RPMP isoforms in latex was shown using antibodies against REF and SRPP. Both EST and quantitative reverse transcription-PCR (QRT-PCR) analyses demonstrated REF and SRPP to be the most abundant transcripts in latex. Besides rubber biosynthesis, comparative sequence analysis showed that the RPMPs are highly similar to sequences in the plant kingdom having stress-related functions. Implications of the RPMP function in cis-polyisoprene biosynthesis in the context of transcript abundance and differential gene expression are discussed.
    Matched MeSH terms: Membrane Proteins/genetics; Plant Proteins/genetics*; Protein Isoforms/genetics; Hevea/genetics*
  20. Potential biomarkers in NASH-induced liver cirrhosis with hepatocellular carcinoma: A preliminary work on roles of exosomal miR-182, miR-301a, and miR-373
    Muhammad Yusuf AN, Raja Ali RA, Muhammad Nawawi KN, Mokhtar NM
    Malays J Pathol, 2020 Dec;42(3):377-384.
    PMID: 33361718
    INTRODUCTION: Recent studies have published the roles of exosomal miRNAs in the pathogenesis of various type of malignancies and can be developed as potential biomarkers for diagnostic, prognostic and therapeutic purposes. The aim of this study was to identify the expression level of selected miRNAs (miR-182, miR-301a, and miR-373) in exosomes of the serum and ascitic fluid in patients with non-alcoholic steatohepatitis (NASH)-related liver cirrhosis with or without hepatocellular carcinoma (HCC).

    MATERIALS AND METHODS: A literature search was performed to identify potential miRNAs involved in the pathogenesis of HCC. Unpaired serum and ascitic fluid were obtained from 52 patients with NASH related liver cirrhosis (n=26 for each group of with and without HCC). Exosomal miRNA was isolated from all samples. Expression levels of miR-182, miR-301a and miR- 373 were determined using quantitative real-time PCR.

    RESULTS: Serum-derived exosomal mir-182, miR-301a and miR-373 were significantly up-regulated with fold change of 1.77, 2.52, and 1.67 (p< 0.05) respectively in NASH-induced liver cirrhosis with HCC as compared to NASH-induced liver cirrhosis without HCC. We identified the expression levels of ascitic fluid-derived exosomal mir-182, miR-301a, and miR-373 were significantly up-regulated with fold change of 1.6, 1.94 and 2.13 respectively in NASH-induced liver cirrhosis with HCC as compared to NASH-induced liver cirrhosis without HCC (p <0.05). There was poor correlation expression of all the selected exosomal miRNA between serum- and ascitic fluid-derived in HCC group.

    CONCLUSIONS: This preliminary data showed significant increase in the expression levels of exosomal miR-182, miR-301a and miR- 373 in both serum and ascetic fluid suggesting the possible roles of these miRNAs as circulating biomarkers for NASH-induced liver cirrhosis with hepatocellular carcinoma.

    Matched MeSH terms: Carcinoma, Hepatocellular/genetics; Liver Neoplasms/genetics; Biomarkers, Tumor/genetics; Exosomes/genetics
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