Displaying publications 41 - 54 of 54 in total

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  1. Hii KS, Lim PT, Kon NF, Usup G, Gu H, Leaw CP
    Gene, 2019 Aug 30;711:143950.
    PMID: 31255736 DOI: 10.1016/j.gene.2019.143950
    The marine dinoflagellate Alexandrium minutum is known to produce saxitoxins that cause paralytic shellfish poisoning in human worldwide through consumption of the contaminated shellfish mollusks. Despite numerous studies on the growth physiology and saxitoxin production of this species, the knowledge on the molecular basis of nutrient uptakes in relation to toxin production in this species is limited. In this study, relative expressions of the high-affinity transporter genes of nitrate, ammonium, and phosphate (AmNrt2, AmAmt1 and AmPiPT1) and the assimilation genes, nitrate reductase (AmNas), glutamine synthase (AmGSIII) and carbamoyl phosphate synthase (AmCPSII) from A. minutum were studied in batch clonal culture condition with two nitrogen sources (nitrate: NO3- or ammonium: NH4+) under different N:P ratios (high-P: N:P of 14 and 16, and low-P: N:P of 155). The expression of AmAmt1 was suppressed in excess NH4+-grown condition but was not observed in AmNrt2 and AmNas. Expressions of AmAmt1, AmNrt2, AmNas, AmGSIII, AmCPSII, and AmPiPT1 were high in P-deficient condition, showing that A. minutum is likely to take up nutrients for growth under P-stress condition. Conversely, relative expression of AmCPSII was incongruent with cell growth, but was well correlated with toxin quota, suggesting that the gene might involve in arginine metabolism and related toxin production pathway. The expression of AmGSIII is found coincided with higher toxin production and is believed to involve in mechanism to detoxify the cells from excess ammonium stress. The gene regulation observed in this study has provided better insights into the ecophysiology of A. minutum in relation to its adaptive strategies in unfavorable environments.
    Matched MeSH terms: Gene Expression Regulation
  2. Ahmad A, Riaz Z, Sattar MA, Khan SA, John EJ, Rashid S, et al.
    Gene, 2020 May 05;737:144479.
    PMID: 32068124 DOI: 10.1016/j.gene.2020.144479
    BACKGROUND: Cardiac and renal dysfunction are often co-morbid pathologies leading to worsening prognosis resulting in difficulty in therapy of left ventricular hypertrophy (LVH). The aim of the current study was to determine the changes in expression of human ortholog genes of hypertension, vascular and cardiac remodeling and hypertensive nephropathy phenotypes under normal, disease and upon treatment with gasotransmitter including H2S (hydrogen sulphide), NO (nitric oxide) and combined (H2S + NO).

    METHODS: A total of 72 Wistar Kyoto rats (with equivalent male and female animals) were recruited in the present study where LVH rat models were treated with H2S and NO individually as well as with both combined. Cardiac and renal physical indices were recorded and relative gene expression were quantified.

    RESULTS: Both cardiac and renal physical indices were significantly modified with individual as well as combined H2S + NO treatment in control and LVH rats. Expression analysis revealed, hypertension, vascular remodeling genes ACE, TNFα and IGF1, mRNAs to be significantly higher (P ≤ 0.05) in the myocardia and renal tissues of LVH rats, while individual and combined H2S + NO treatment resulted in lowering the gene expression to normal/near to normal levels. The cardiac remodeling genes MYH7, TGFβ, SMAD4 and BRG1 expression were significantly up-regulated (P ≤ 0.05) in the myocardia of LVH where the combined H2S + NO treatment resulted in normal/near to normal expression more effectively as compared to individual treatments. In addition individual as well as combined H2S and NO treatment significantly decreased PKD1 expression in renal tissue, which was up-regulated in LVH rats (P ≤ 0.05).

    CONCLUSIONS: The reduction in hemodynamic parameters and cardiac indices as well as alteration in gene expression on treatment of LVH rat model indicates important therapeutic potential of combined treatment with H2S + NO gasotransmitters in hypertension and cardiac hypertrophy when present as co-morbidity with renal complications.

  3. Mohamad Isa II, Jamaluddin J, Achim NH, Abubakar S
    Gene, 2020 Jun 01;754:144821.
    PMID: 32497559 DOI: 10.1016/j.gene.2020.144821
    CC chemokine ligand 3 like-1 (CCL3L1) encodes for CCL3L1 protein, which is a human immunodeficiency virus (HIV) suppressive chemokine and a potent ligand of HIV CCR5 co-receptor. CCL3L1 exhibits variation in the gene copy number (CN) and could influence HIV susceptibility through gene dosage effect. The study aims to determine the distribution of CCL3L1 CN among HIV subjects of Malay, Chinese, and Indian ethnics in Malaysia and to evaluate the impact of CCL3L1 CN on susceptibility to HIV. This study involved 182 HIV patients who attended outpatient clinics of three hospitals in Malaysia and 150 non-HIV (control) subjects. Typing of CCL3L1 CN was conducted via multiplex paralogue ratio tests (PRTs), followed by validation of the CCL3L1 CN by microsatellite analyses. Both Malay and Indian HIV subjects had the CN mode of two, while the CN mode for the Chinese was four. The CCL3L1 gene CN was found to be strongly associated with ethnicity (p 
  4. Haghvirdizadeh P, Sadat Haerian M, Haghvirdizadeh P, Sadat Haerian B
    Gene, 2020 07 20;748:144687.
    PMID: 32386973 DOI: 10.1016/j.gene.2020.144687
  5. Haghvirdizadeh P, Haerian MS, Haghvirdizadeh P, Haerian BS
    Gene, 2020 06 20;744:144686.
    PMID: 32345518 DOI: 10.1016/j.gene.2020.144686
  6. Hashem Boroojerdi M, Hosseinpour Sarmadi V, Maqbool M, Ling KH, Safarzadeh Kozani P, Safarzadeh Kozani P, et al.
    Gene, 2022 Feb 05;820:146218.
    PMID: 35134469 DOI: 10.1016/j.gene.2022.146218
    OBJECTIVES: Hematopoietic stem cells (HSCs) reside in a specialised microenvironment in the bone marrow, which is majorly composed of mesenchymal stem cells (MSCs) and its' derivatives. This study aimed to investigate the regulatory role of MSCs to decipher the cellular and humoral communications on HSCs' proliferation, self-renewal, and differentiation at the transcriptomic level.

    MATERIALS AND METHODS: Microarray assay was employed to analyse the gene expression profile of HSCs that imparted by MSCs during co-culture.

    RESULTS: The proliferation of human umbilical cord blood-derived HSCs (hUC-HSCs) markedly propagated when MSCs were used as the feeder layer, without disturbing the undifferentiated state of HSCs, and reduced the cell death of HSCs. Upon co-culture with MSCs, the global microarray analysis of HSCs disclosed 712 differentially expressed genes (DEGs) (561 up-regulated and 151 down-regulated). The dysregulations of various transcripts were enriched for cellular functions such as cell cycle (including CCND1), apoptosis (including TNF), and genes related to signalling pathways governing self-renewal, as well as WNT5A from the Wnt signalling pathway, MAPK, Hedgehog, FGF2 from FGF, Jak-STAT, and PITX2 from the TGF-β signalling pathway. To concur this, real-time quantitative PCR (RT-qPCR) was utilised for corroborating the microarray results from five of the most dysregulated genes.

    CONCLUSION: This study elucidates the underlying mechanisms of the mitogenic influences of MSCs on the propagation of HSCs. The exploitation of such mechanisms provides a potential means for achieving larger quantities of HSCs in vitro, thus obviating the need for manipulating their differentiation potential for clinical application.

  7. Rajendram A, Mostaffa NH, Dumin W, Oke MA, Simarani K, Somasundram C, et al.
    Gene, 2022 Jan 30;809:146041.
    PMID: 34710526 DOI: 10.1016/j.gene.2021.146041
    Plant immunity to pathogen infections is a dynamic response that involves multiple organelles and defence signalling systems such as hypersensitive response (HR) and systemic acquired resistance (SAR). The latter requires the function of Pathogenesis-related (PR) proteins, a common plant protein family with diverse roles in plant innate immunity. Our previous proteomics study showed that a PR gene (ITC1587_Bchr9_P26466_MUSBA) was differentially regulated during a compatible banana-M. incognita interaction, substantiating the isolation of this gene in the current study. Here, we successfully isolated and characterised Pathogenesis-related-10 (PR10) gene with β-1,3-glucanase and ribonuclease (RNase) activities from two Musa acuminata cultivars (denoted as MaPR10) namely Berangan and Grand Naine (ITC1256). We found that MaPR10 cloned sequences possess glycine-rich loop domain and shared conserved motifs specific to PR10 gene group, confirming its identity as a member of this group. Interestingly, we also found a catalytic domain sequence for glycoside hydrolase family 16 (EXDXXE), unique only to MaPR10 cloned sequences. Two peptide variants closely related to the reference sequence ITC1587_Bchr9_P26466_MUSBA namely MaPR10-BeB5 and MaPR10-GNA5 were overexpressed and purified to test for their functionality. Here, we confirmed that both protein variants possess β-1,3-glucanase and ribonuclease (RNase) activities, and inhibit the growth of Aspergillus fumigatus, a human opportunistic pathogen. To our knowledge, this is the first PR10 plant proteins with such properties to be reported thus far.
  8. Shahid M, Azfaralariff A, Zubair M, Abdulkareem Najm A, Khalili N, Law D, et al.
    Gene, 2022 Feb 20;812:146104.
    PMID: 34864095 DOI: 10.1016/j.gene.2021.146104
    Among the 22 Fanconi anemia (FA) reported genes, 90% of mutational spectra were found in three genes, namely FANCA (64%), FANCC (12%) and FANCG (8%). Therefore, this study aimed to identify the high-risk deleterious variants in three selected genes (FANCA, FANCC, and FANCG) through various computational approaches. The missense variant datasets retrieved from the UCSC genome browser were analyzed for their pathogenicity, stability, and phylogenetic conservancy. A total of 23 alterations, of which 16 in FANCA, 6 in FANCC and one variant in FANCG, were found to be highly deleterious. The native and mutant structures were generated, which demonstrated a profound impact on the respective proteins. Besides, their pathway analysis predicted many other pathways in addition to the Fanconi anemia pathway, homologous recombination, and mismatch repair pathways. Hence, this is the first comprehensive study that can be useful for understanding the genetic signatures in the development of FA.
  9. Jamalpour S, Zain SM, Mosavat M, Mohamed Z, Omar SZ
    Gene, 2018 Apr 15;650:34-40.
    PMID: 29410004 DOI: 10.1016/j.gene.2018.01.091
    BACKGROUND: Although the influence of a common variant in the glucokinase regulatory gene (GCKR rs780094) in type 2 diabetes mellitus has been well documented, less data however, is available of its role in gestational diabetes mellitus (GDM). We carried out a case control study to assess the association between GCKR rs780094 and GDM in the Asian, and also a meta-analysis to further assess the strength of the association.

    METHODS: Demographic, clinical and genotype data were determined for 1122 women (267 cases and 855 controls) recruited from the University of Malaya Medical Centre in the Klang Valley, Kuala Lumpur. Relevant articles were identified from Pubmed, Embase, MEDLINE, and Web of Science. Extraction of data was carried out and summary estimates of the association between rs780094 and GDM were examined.

    RESULTS: The frequency of risk allele C was significantly higher in the cases than controls (OR 1.34, 95% CI 1.09-1.66, P = 0.006). The C allele was also associated with increased level of random 2-hour fasting plasma glucose and pregravid body mass index. Meta-analysis further confirmed the association of the GCKR rs780094 with GDM (OR 1.32, 95% CI 1.14-1.52, P = 0.0001).

    CONCLUSION: This study strongly suggests that GCKR rs780094-C is associated with increased risk of GDM.

    Matched MeSH terms: Gene Frequency
  10. Guan Q, Yu J, Zhu W, Yang B, Li Y, Zhang L, et al.
    Gene, 2018 Mar 01;645:60-68.
    PMID: 29274907 DOI: 10.1016/j.gene.2017.12.045
    Ultraviolet-B (UVB) irradiation induces oxidative stress in plant cells due to the generation of excessive reactive oxygen species. Morus alba L. (M. abla) is an important medicinal plant used for the treatment of human diseases. Also, its leaves are widely used as food for silkworms. In our previous research, we found that a high level of UVB irradiation with dark incubation led to the accumulation of secondary metabolites in M. abla leaf. The aim of the present study was to describe and compare M. alba leaf transcriptomics with different treatments (control, UVB, UVB+dark). Leaf transcripts from M. alba were sequenced using an Illumina Hiseq 2000 system, which produced 14.27Gb of data including 153,204,462 paired-end reads among the three libraries. We de novo assembled 133,002 transcripts with an average length of 1270bp and filtered 69,728 non-redundant unigenes. A similarity search was performed against the non-redundant National Center of Biotechnology Information (NCBI) protein database, which returned 41.08% hits. Among the 20,040 unigenes annotated in UniProtKB/SwissProt database, 16,683 unigenes were assigned 102,232 gene ontology terms and 6667 unigenes were identified in 287 known metabolic pathways. Results of differential gene expression analysis together with real-time quantitative PCR tests indicated that UVB irradiation with dark incubation enhanced the flavonoid biosynthesis in M. alba leaf. Our findings provided a valuable proof for a better understanding of the metabolic mechanism under abiotic stresses in M. alba leaf.
    Matched MeSH terms: Gene Expression Regulation, Plant/radiation effects; Gene Expression Profiling/methods*; Gene Ontology
  11. Ong SN, Tan BC, Hanada K, Teo CH
    Gene, 2023 Aug 20;878:147579.
    PMID: 37336274 DOI: 10.1016/j.gene.2023.147579
    Drought is a major abiotic stress that influences rice production. Although the transcriptomic data of rice against drought is widely available, the regulation of small open reading frames (sORFs) in response to drought stress in rice is yet to be investigated. Different levels of drought stress have different regulatory mechanisms in plants. In this study, drought stress was imposed on four-leaf stage rice, divided into two treatments, 40% and 30% soil moisture content (SMC). The RNAs of the samples were extracted, followed by the RNA sequencing analysis on their sORF expression changes under 40%_SMC and 30%_SMC, and lastly, the expression was validated through NanoString. A total of 122 and 143 sORFs were differentially expressed (DE) in 40%_SMC and 30%_SMC, respectively. In 40%_SMC, 69 sORFs out of 696 (9%) DEGs were found to be upregulated. On the other hand, 69 sORFs out of 449 DEGs (11%) were significantly downregulated. The trend seemed to be higher in 30%_SMC, where 112 (12%) sORFs were found to be upregulated from 928 significantly upregulated DEGs. However, only 8% (31 sORFs out of 385 DEGs) sORFs were downregulated in 30%_SMC. Among the identified sORFs, 110 sORFs with high similarity to rice proteome in the PsORF database were detected in 40%_SMC, while 126 were detected in 30%_SMC. The Gene Ontology (GO) enrichment analysis of DE sORFs revealed their involvement in defense-related biological processes, such as defense response, response to biotic stimulus, and cellular homeostasis, whereas enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways indicated that DE sORFs were associated with tryptophan and phenylalanine metabolisms. Several DE sORFs were identified, including the top five sORFs (OsisORF_3394, OsisORF_0050, OsisORF_3007, OsisORF_6407, and OsisORF_7805), which have yet to be characterised. Since these sORFs were responsive to drought stress, they might hold significant potential as targets for future climate-resilient rice development.
    Matched MeSH terms: Gene Expression Regulation, Plant; Gene Expression Profiling
  12. Koh CP, Bahirvani AG, Wang CQ, Yokomizo T, Ng CEL, Du L, et al.
    Gene, 2023 Jan 30;851:147049.
    PMID: 36384171 DOI: 10.1016/j.gene.2022.147049
    A cis-regulatory genetic element which targets gene expression to stem cells, termed stem cell enhancer, serves as a molecular handle for stem cell-specific genetic engineering. Here we show the generation and characterization of a tamoxifen-inducible CreERT2 transgenic (Tg) mouse employing previously identified hematopoietic stem cell (HSC) enhancer for Runx1, eR1 (+24 m). Kinetic analysis of labeled cells after tamoxifen injection and transplantation assays revealed that eR1-driven CreERT2 activity marks dormant adult HSCs which slowly but steadily contribute to unperturbed hematopoiesis. Fetal and child HSCs that are uniformly or intermediately active were also efficiently targeted. Notably, a gene ablation at distinct developmental stages, enabled by this system, resulted in different phenotypes. Similarly, an oncogenic Kras induction at distinct ages caused different spectrums of malignant diseases. These results demonstrate that the eR1-CreERT2 Tg mouse serves as a powerful resource for the analyses of both normal and malignant HSCs at all developmental stages.
  13. Azizan S, Cheng KJ, Mejia Mohamed EH, Ibrahim K, Faruqu FN, Vellasamy KM, et al.
    Gene, 2024 Feb 20;896:148057.
    PMID: 38043836 DOI: 10.1016/j.gene.2023.148057
    Colorectal cancer (CRC) is ranked as the second leading cause of mortality worldwide, mainly due to metastasis. Epithelial to mesenchymal transition (EMT) is a complex cellular process that drives CRC metastasis, regulated by changes in EMT-associated gene expression. However, while numerous genes have been identified as EMT regulators through various in vivo and in vitro studies, little is known about the genes that are differentially expressed in CRC tumour tissue and their signalling pathway in regulating EMT. Using an integration of systematic search and bioinformatic analysis, gene expression profiles of CRC tumour tissues were compared to non-tumour adjacent tissues to identify differentially expressed genes (DEGs), followed by performing systematic review on common identified DEGs. Fifty-eight common DEGs were identified from the analysis of 82 tumour tissue samples obtained from four gene expression datasets (NCBI GEO). These DEGS were then systematically searched for their roles in modulating EMT in CRC based on previously published studies. Following this, 10 common DEGs (CXCL1, CXCL8, MMP1, MMP3, MMP7, TACSTD2, VIP, HPGD, ABCG2, CLCA4) were included in this study and subsequently subjected to further bioinformatic analysis. Their roles and functions in modulating EMT in CRC were discussed in this review. This study enhances our understanding of the molecular mechanisms underlying EMT and uncovers potential candidate genes and pathways that could be targeted in CRC.
    Matched MeSH terms: Gene Expression; Gene Expression Regulation, Neoplastic
  14. Hui San S, Ching Ngai S
    Gene, 2024 May 30;909:148293.
    PMID: 38373660 DOI: 10.1016/j.gene.2024.148293
    The major limitation of conventional chemotherapy drugs is their lack of specificity for cancer cells. As a selective apoptosis-inducing agent, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has emerged as an attractive alternative. However, most of the cancer cells are found to be either intrinsically resistant to the TRAIL protein or may develop resistance after multiple treatments, and TRAIL resistance can induce epithelial-to-mesenchymal transition (EMT) at a later stage, promoting cancer invasion and migration. Interestingly, E-cadherin loss has been linked to TRAIL resistance and initiation of EMT, making E-cadherin re-expression a potential target to overcome these obstacles. Recent research suggests that re-expressing E-cadherin may reduce TRAIL resistance by enhancing TRAIL-induced apoptosis and preventing EMT by modulating EMT signalling factors. This reversal of EMT, can also aid in improving TRAIL-induced apoptosis. Therefore, this review provides remarkable insights into the mechanisms underlying E-cadherin re-expression, clinical implications, and potentiation, as well as the research gaps of E-cadherin re-expression in the current cancer treatment.
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