• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.457-463
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• 2015

The pathogenesis of mantle cell lymphoma, a special subtype of lymphoma that is invasive and indolent and has a median survival of 3 to 4 years, is still partially unexplained. Much research about genes and miRNAs has been conducted in recent years, but interactions and regulatory relations of genetic elements which may play a vital role in genesis of MCL have attracted only limited attention. The present study concentrated on regulatory relations about genes and miRNAs contributing to MCL pathogenesis. Numerous experimentally validated raw data were organized into three topology networks, comprising differentially expressed, associated and global examples. Comparison of similarities and dissimilarities of the three regulating networks, paired with the analysis of the interactions between pairs of elements in every network, revealed that the differentially expressed network illuminated the carcinogenicity mechanism of MCL and the related network further described the regulatory relations involved, including prevention, diagnosis, development and therapy. Three kinds of regulatory relations for host genes including miRNAs, miRNAs targeting genes and genes regulating miRNAs were concluded macroscopically. Regulation of the differentially expressed miRNAs was also analyzed, in terms of abnormal gene expression affecting the MCL pathogenesis. Special regulatory relations were uncovered. For example, auto-regulatory loops were found in the three topology networks, key pathways of the nodes being highlighted. The present study focused on a novel point of view revealing important influencing factors for MCL pathogenesis.

• Journal of Microbiology and Biotechnology
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• v.22 no.7
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• pp.990-999
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• 2012

The microbial biosynthesis of fatty acid of lipid metabolism, which can be used as precursors for the production of fuels of chemicals from renewable carbon sources, has attracted significant attention in recent years. The regulation of fatty acid biosynthesis pathways has been mainly studied in a model prokaryote, Escherichia coli. During the recent period, global regulation of fatty acid metabolic pathways has been demonstrated in another model prokaryote, Bacillus subtilis, as well as in Streptococcus pneumonia. The goal of this study was to increase the production of long-chain fatty acids by developing recombinant E. coli strains that were improved by an elongation cycle of fatty acid synthesis (FAS). The fabB, fabG, fabZ, and fabI genes, all homologous of E. coli, were induced to improve the enzymatic activities for the purpose of overexpressing components of the elongation cycle in the FAS pathway through metabolic engineering. The ${\beta}$-oxoacyl-ACP synthase enzyme catalyzed the addition of acyl-ACP to malonyl-ACP to generate ${\beta}$-oxoacyl-ACP. The enzyme encoded by the fabG gene converted ${\beta}$-oxoacyl-ACP to ${\beta}$-hydroxyacyl-ACP, the fabZ catalyzed the dehydration of ${\beta}$-3-hydroxyacyl-ACP to trans-2-acyl-ACP, and the fabI gene converted trans-2-acyl-ACP to acyl-ACP for long-chain fatty acids. In vivo productivity of total lipids and fatty acids was analyzed to confirm the changes and effects of the inserted genes in E. coli. As a result, lipid was increased 2.16-fold higher and hexadecanoic acid was produced 2.77-fold higher in E. coli JES1030, one of the developed recombinants through this study, than those from the wild-type E. coli.

• BMB Reports
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• v.50 no.11
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• pp.539-545
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• 2017

The Integrated Stress Response (ISR) refers to a signaling pathway initiated by stress-activated $eIF2{\alpha}$ kinases. Once activated, the pathway causes attenuation of global mRNA translation while also paradoxically inducing stress response gene expression. A detailed analysis of this pathway has helped us better understand how stressed cells coordinate gene expression at translational and transcriptional levels. The translational attenuation associated with this pathway has been largely attributed to the phosphorylation of the translational initiation factor $eIF2{\alpha}$. However, independent studies are now pointing to a second translational regulation step involving a downstream ISR target, 4E-BP, in the inhibition of eIF4E and specifically cap-dependent translation. The activation of 4E-BP is consistent with previous reports implicating the roles of 4E-BP resistant, Internal Ribosome Entry Site (IRES) dependent translation in ISR active cells. In this review, we provide an overview of the translation inhibition mechanisms engaged by the ISR and how they impact the translation of stress response genes.

• Journal of Microbiology and Biotechnology
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• v.16 no.9
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• pp.1477-1480
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• 2006

The 63-amino-acid-encoding afsR2 is a global antibiotics-stimulating regulatory gene identified from the chromosome of Streptomyces lividans. To dissect a putative functional domain in afsR2, several afsR2-derivative deletion constructs were generated and screened for the loss of actinorhodin-stimulating capability. The afsR2-derivative construct missing a 50-bp C-terminal region significantly lost its actinorhodin-stimulating capability in S. lividans. In addition, site-directed mutagenesis on amino acid positions of #57-#61 in a 50-bp C-terminal region, some of which are conserved among known Sigma 70 family proteins, significantly changed the AfsR2's activity. These results imply that the C-terminal region of AfsR2 is functionally important for antibiotics-stimulating capability and the regulatory mechanism might be somehow related to the sigma-like domain present in the C-terminal of AfsR2.

• Journal of Microbiology and Biotechnology
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• v.17 no.2
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• pp.244-252
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• 2007

Escherichia coli has a PhoR-PhoB two-component regulatory system to detect and respond to the changes of environmental phosphate concentration. For the E. coli W3110 strain growing under phosphate-limiting condition, the changes of global gene expression levels were investigated by using DNA microarray analysis. The expression levels of some genes that are involved in phosphate metabolism were increased as phosphate became limited, whereas those of the genes involved in ribosomal protein or amino acid metabolism were decreased, owing to the stationary phase response. The upregulated genes could be divided into temporarily and permanently inducible genes by phosphate starvation. At the peak point showing the highest expression levels of the phoB and phoR genes under phosphate-limiting condition, the phoB- and/or phoR-dependent regulatory mechanisms were investigated in detail by comparing the gene expression levels among the wild-type and phoB and/or phoR mutant strains. Overall, the phoB mutation was epistatic over the phoR mutation. It was found that PhoBR and PhoB were responsible for the upregulation of the phosphonate or glycerol phosphate metabolism and high-affinity phosphate transport system, respectively. These results show the complex regulation by the PhoR-PhoB two-component regulatory system in E. coli.

• Journal of Microbiology and Biotechnology
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• v.32 no.12
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• pp.1515-1526
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• 2022

Eukaryotic chromatin is highly organized in the 3D nuclear space and dynamically regulated in response to environmental stimuli. This genomic organization is arranged in a hierarchical fashion to support various cellular functions, including transcriptional regulation of gene expression. Like other host cellular mechanisms, viral pathogens utilize and modulate host chromatin architecture and its regulatory machinery to control features of their life cycle, such as lytic versus latent status. Combined with previous research focusing on individual loci, recent global genomic studies employing conformational assays coupled with high-throughput sequencing technology have informed models for host and, in some cases, viral 3D chromosomal structure re-organization during infection and the contribution of these alterations to virus-mediated diseases. Here, we review recent discoveries and progress in host and viral chromatin structural dynamics during infection, focusing on a subset of DNA (human herpesviruses and HPV) as well as RNA (HIV, influenza virus and SARS-CoV-2) viruses. An understanding of how host and viral genomic structure affect gene expression in both contexts and ultimately viral pathogenesis can facilitate the development of novel therapeutic strategies.

• International Journal of Oral Biology
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• v.36 no.2
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• pp.91-101
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• 2011

MspTL is the major surface protein of Treponema lecithinolyticum associated with periodontitis and endodontic infections. Our recent investigation revealed that MspTL induces proinflammatory cytokines and intercellular adhesion molecule 1 in THP-1 cells and periodontal ligament cells. In this study we conducted oligonucleotide microarray analysis to investigate the global transcriptional regulation in THP-1 cells stimulated with purified recombinant MspTL. MspTL upregulated the expression of 90 genes in THP-1 cells at least four fold, and the functions of these genes were categorized into adhesion, apoptosis/antiapoptosis, cell cycle/growth/differentiation, chemotaxis, cytoskeleton organization, immune response, molecular metabolism, proteolysis, signaling, and transcription. The majority of the modified genes are known to be NF-${\kappa}B$-responsive and interferon-stimulated genes (ISGs). The expression of 12 selected genes was confirmed by real-time RT-PCR. Because prostaglandin $E_2(PGE_2)$ is an important inflammatory mediator and Cox-2 was found to be induced by MspTL in the microarray analysis, we determined the level of $PGE_2$ in the culture supernatants of MspTL-treated cells and found that MspTL significantly increased $PGE_2$. Our results provide insight into the gene regulation of host cells in response to MspTL, and may contribute to the understanding of the molecular mechanism in periodontitis.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.116-126
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• 2023

Mainly due to the slanted focus on the mechanism and regulation of neuronal aging, research on astrocyte aging and its modulation during brain aging is scarce. In this study, we established aged astrocyte culture model by long-term culturing. Cellular senescence was confirmed through SA-β-gal staining as well as through the examination of morphological, molecular, and functional markers. RNA sequencing and functional analysis of astrocytes were performed to further investigate the detailed characteristics of the aged astrocyte model. Along with aged phenotypes, decreased astrocytic proliferation, migration, mitochondrial energetic function and support for neuronal survival and differentiation has been observed in aged astrocytes. In addition, increased expression of cytokines and chemokine-related factors including plasminogen activator inhibitor -1 (PAI-1) was observed in aged astrocytes. Using the RNA sequencing results, we searched potential drugs that can normalize the dysregulated gene expression pattern observed in long-term cultured aged astrocytes. Among several candidates, minoxidil, a pyrimidine-derived anti-hypertensive and anti-pattern hair loss drug, normalized the increased number of SA-β-gal positive cells and nuclear size in aged astrocytes. In addition, minoxidil restored up-regulated activity of PAI-1 and increased mitochondrial superoxide production in aged astrocytes. We concluded that long term culture of astrocytes can be used as a reliable model for the study of astrocyte senescence and minoxidil can be a plausible candidate for the regulation of brain aging.

• BMB Reports
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• v.46 no.5
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• pp.237-243
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• 2013

Heart failure is one of the leading causes of sudden death in developed countries. While current therapies are mostly aimed at mitigating associated symptoms, novel therapies targeting the subcellular mechanisms underlying heart failure are emerging. Failing hearts are characterized by reduced contractile properties caused by impaired $Ca^{2+}$ cycling between the sarcoplasm and sarcoplasmic reticulum (SR). Sarcoplasmic/endoplasmic reticulum $Ca^{2+}$ ATPase 2a (SERCA2a) mediates $Ca^{2+}$ reuptake into the SR in cardiomyocytes. Of note, the expression level and/or activity of SERCA2a, translating to the quantity of SR $Ca^{2+}$ uptake, are significantly reduced in failing hearts. Normalization of the SERCA2a expression level by gene delivery has been shown to restore hampered cardiac functions and ameliorate associated symptoms in pre-clinical as well as clinical studies. SERCA2a activity can be regulated at multiple levels of a signaling cascade comprised of phospholamban, protein phosphatase 1, inhibitor-1, and $PKC{\alpha}$. SERCA2 activity is also regulated by post-translational modifications including SUMOylation and acetylation. In this review, we will highlight the molecular mechanisms underlying the regulation of SERCA2a activity and the potential therapeutic modalities for the treatment of heart failure.

• Molecules and Cells
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• v.27 no.4
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• pp.481-490
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• 2009

Diverse posttranslational modifications of histones, such as acetylation and methylation, play important roles in controlling gene expression. Histone methylation in particular is involved in a broad range of biological processes, including heterochromatin formation, X-chromosome inactivation, genomic imprinting, and transcriptional regulation. Recently, it has been demonstrated that proteins containing the Jumonji (Jmj) C domain can demethylate histones. In Arabidopsis, twenty-one genes encode JmjC domain-containing proteins, which can be clustered into five clades. To address the biological roles of the Arabidopsis genes encoding JmjC-domain proteins, we analyzed the temporal and spatial expression patterns of nine genes. RT-PCR analyses indicate all nine Arabidopsis thaliana Jmj (AtJmj) genes studied are actively expressed in various tissues. Furthermore, studies of transgenic plants harboring AtJmj::${\beta}$-glucuronidase fusion constructs reveal that these nine AtJmj genes are expressed in a developmentally and spatially regulated manner.