• Journal of Applied Biological Chemistry
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• 제63권2호
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• pp.169-174
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• 2020

The objective of this study was to investigate the effects of a hypodermic injectable solution comprised of an LPM LB meso solution containing Melissa officinalis L. leaf extract (LPM) on the lipogenesis in the 3T3-L1 cells line. The lipid accumulation measured by oil red o staining in the 3T3-L1 adipocytes treated with LPM, which was reduced in a dose dependent manner and showed 91.7 to 62.9% compared to control group. Its effectiveness with a 50% solution was significantly higher than the hydroxycitric acid (positive control) treatment without showing cell cytotoxicity. In a quantitative real-time PCR, it was demonstrated that the LPM treatment appeared to upregulate the mRNA expression of the adipogenesis-related genes, which included the peroxisome proliferator-activated receptor gamma (50% concentration) while down-regulating the CCAAT-enhancer binding protein alpha (50% concentration) and the sterol regulatory element-binding protein 1c (10, 25, and 50% concentrations). The results from the current study suggest that the LPM could be useful biomaterials that can inhibit obesity in the 3T3-L1 cells, which could possibly be by regulating the specific adipogenic gene transcription factors.

• Molecules and Cells
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• 제43권6호
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• pp.551-571
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• 2020

Nuclear receptor-related 1 (Nurr1) protein has been identified as an obligatory transcription factor in midbrain dopaminergic neurogenesis, but the global set of human NURR1 target genes remains unexplored. Here, we identified direct gene targets of NURR1 by analyzing genome-wide differential expression of NURR1 together with NURR1 consensus sites in three human neural stem cell (hNSC) lines. Microarray data were validated by quantitative PCR in hNSCs and mouse embryonic brains and through comparison to published human data, including genome-wide association study hits and the BioGPS gene expression atlas. Our analysis identified ~40 NURR1 direct target genes, many of them involved in essential protein modules such as synapse formation, neuronal cell migration during brain development, and cell cycle progression and DNA replication. Specifically, expression of genes related to synapse formation and neuronal cell migration correlated tightly with NURR1 expression, whereas cell cycle progression correlated negatively with it, precisely recapitulating midbrain dopaminergic development. Overall, this systematic examination of NURR1-controlled regulatory networks provides important insights into this protein's biological functions in dopamine-based neurogenesis.

• Animal Bioscience
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• 제37권7호
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• pp.1289-1302
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• 2024

Objective: There is a strong relationship between the content of beneficial fatty acids in milk and milk fat metabolic activity in the mammary gland. To improve milk quality, it is therefore necessary to study fatty acid metabolism in bovine mammary gland tissue. In adipose tissue, peroxisome proliferator-activated receptor gamma (PPARG), the core transcription factor, regulates the fatty acid metabolism gene network and determines fatty acid deposition. However, its regulatory effects on mammary gland fatty acid metabolism during lactation have rarely been reported. Methods: Transcriptome sequencing was performed during the prelactation period and the peak lactation period to examine mRNA expression. The significant upregulation of PPARG drew our attention and led us to conduct further research. Results: According to bioinformatics prediction, dual-luciferase reporter system detection, real-time quantitative reverse transcription polymerase chain reaction and Western blotting, miR-130a and miR-130b could directly target PPARG and inhibit its expression. Furthermore, triglyceride and oil red O staining proved that miR-130a and miR-130b inhibited milk fat metabolism in bovine mammary epithelial cells (BMECs), while PPARG promoted this metabolism. In addition, we also found that the coexpression of miR-130a and miR-130b significantly enhanced their ability to regulate milk fat metabolism. Conclusion: In conclusion, our findings indicated that miR-130a and miR-130b could target and repress PPARG and that they also have a functional superposition effect. miR-130a and miR-130b seem to synergistically regulate lipid catabolism via the control of PPARG in BMECs. In the long-term, these findings might be helpful in developing practical means to improve high-quality milk.

• Molecules and Cells
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• 제37권10호
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• pp.705-712
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• 2014

The early steps of neural development in the vertebrate embryo are regulated by sets of transcription factors that control the induction of proliferative, pluripotent neural precursors, the expansion of neural plate stem cells, and their transition to differentiating neural progenitors. These early events are critical for producing a pool of multipotent cells capable of giving rise to the multitude of neurons and glia that form the central nervous system. In this review we summarize findings from gain- and loss-of-function studies in embryos that detail the gene regulatory network responsible for these early events. We discuss whether this information is likely to be similar in mammalian embryonic and induced pluripotent stem cells that are cultured according to protocols designed to produce neurons. The similarities and differences between the embryo and stem cells may provide important guidance to stem cell protocols designed to create immature neural cells for therapeutic uses.

• IMMUNE NETWORK
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• 제11권5호
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• pp.288-298
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• 2011

Background: Salvia miltiorrhiza (SM) has been used to treat inflammatory diseases including edema and arthritis; however, the anti-inflammatory mechanism of SM action remains unresolved. Methods: The effects of an ethanol extract of SM (ESM) on pro-inflammatory cytokines such as TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and NO, and on anti-inflammatory cytokines including IL-4, IL-10, TGF-${\beta}$, and IL-1Ra have been studied in an attempt to elucidate the anti-inflammatory mechanism in murine macrophages. Results: ESM inhibited the production of pro-inflammatory cytokines via down-regulation of gene and protein expression whereas it increased the anti-inflammatory cytokines. Furthermore, ESM inhibited the expression of the chemokines, RANTES and CX3CL1, as well as of inflammatory mediators such as TLR-4 and $11{\beta}$-HSD1. Conclusion: These results indicated that the regulatory effects of ESM may be mediated though the suppression of pro-inflammatory cytokines as well as the induction of anti-inflammatory cytokines. Consequently, we speculate that ESM has therapeutic potential for inflammation-associated disorders.

• Biotechnology and Bioprocess Engineering:BBE
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• 제10권5호
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• pp.385-399
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• 2005

The phenotypic response of a cell results from a well orchestrated web of complex interactions which propagate from the genetic architecture through the metabolic flux network. To rationally design cell factories which carry out specific functional objectives by controlling this hierarchical system is a challenge. Transcriptome analysis, the most mature high-throughput measurement technology, has been readily applied In strain improvement programs in an attempt to Identify genes involved in expressing a given phenotype. Unfortunately, while differentially expressed genes may provide targets for metabolic engineering, phenotypic responses are often not directly linked to transcriptional patterns, This limits the application of genome-wide transcriptional analysis for the design of cell factories. However, improved tools for integrating transcriptional data with other high-throughput measurements and known biological interactions are emerging. These tools hold significant promise for providing the framework to comprehensively dissect the regulatory mechanisms that identify the cellular control mechanisms and lead to more effective strategies to rewire the cellular control elements for metabolic engineering.

• BMB Reports
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• 제34권1호
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• pp.28-32
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• 2001

The Fos-Jun heterodimers are part of the regulatory network of gene expression and nuclear proteins encoded by proto-oncogenes. The activation of Fos-Jun is important in the transmission of the tumor-promoting signal from the extracellular environment to the nuclear transcription mechanism. To search for the inhibitors of the Fos-Jun DNA complex formation, several natural products were screened and water-soluble paeoniflorin reduced the binding activity of the Fos-Jun heterodimer. This active compound was purified by silica gel column chromatography and HPLC. The electrophoresis mobility shift assay and reverse-phase HPLC test showed that paeoniflorin reduced the AP-l function. The cytotoxic effect of paeoniflorin was observed in HL-60. These results indicate that paeoniflorin blocks the Fos-Jun heterodimer-binding site of the AP-l DNA and it also has cytotoxic effects on human leukemia cell lines.

• Journal of Computing Science and Engineering
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• 제11권4호
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• pp.111-120
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• 2017

Post-translational modifications (PTMs) of proteins play substantial roles in the gene regulation of cell physiological functions and in the generation of major diseases. However, the majority of existing studies only explored a certain PTM of proteins, while very few have investigated the PTMs of two or more domains and the effects of their interactions. In this study, after collecting data regarding a large number of breast cancer-related and validated PTMs, a sequence and domain analysis of breast cancer proteins was carried out using bioinformatics methods. Then, protein-protein interaction network-related tools were applied in order to determine the crosstalks between the PTMs of the proteins. Finally, statistical and functional analyses were conducted to identify more modification sites of domains and proteins that may interact with at least two or more PTMs. In addition to exploring the associations between the interactive effects of PTMs, the present study also provides important information that would allow biologists to further explore the regulatory pathways of biological functions and related diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제19권6호
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• pp.479-484
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• 2015

NOD2 (nucleotide-binding and oligomerization domain 2) was initially reported as a susceptibility gene for Crohn's disease, with several studies focused on elucidating its molecular mechanism in the progression of Crohn's disease. We now know that NOD2 is an intracellular bacterial sensing receptor, and that MDP-mediated NOD2 activation drives inflammatory signaling. Various mutations in NOD2 have been reported, with NOD2 loss of function being associated with the development of Crohn's disease and other autoimmune diseases. These results suggest that NOD2 not only has an immune stimulatory function, but also an immune regulatory function. Atherosclerosis is a chronic inflammatory disease of the arterial wall; its pathologic progression is highly dependent on the immune balance. This immune balance is regulated by infiltrating monocytes and macrophages, both of which express NOD2. These findings indicate a potential role of NOD2 in atherosclerosis. The purpose of this review is to outline the known roles of NOD2 signaling in the pathogenesis of atherosclerosis.

• BMB Reports
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• 제39권5호
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• pp.479-491
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• 2006

Heme oxygenase (HO), the rate limiting enzyme in the breakdown of heme into carbon monoxide (CO), iron and bilirubin, has recently received overwhelming research attention. To date three mammalian HO isozymes have been identified, and the only inducible form is HO-1 while HO-2 and HO-3 are constitutively expressed. Advances in unveiling signal transduction network indicate that a battery of redox-sensitive transcription factors, such as activator protein-1 (AP-1), nuclear factor-kappa B (NF-${\kappa}B$) and nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases including mitogen-activated protein kinases play an important regulatory role in HO-1 gene induction. The products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin have been shown to exert protective effects in several organs against oxidative and other noxious stimuli. In this context, it is interesting to note that induction of HO-1 expression contributes to protection against liver damage induced by several chemical compounds such as acetaminophen, carbon tetrachloride and heavy metals, suggesting HO-1 induction as an important cellular endeavor for hepatoprotection. The focus of this review is on the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect against chemically-induced liver injury as well as hepatocarcinogenesis.