• Mycobiology
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• v.39 no.4
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• pp.249-256
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• 2011

Microorganisms are significantly affected when the ambient pH of their environment changes. They must therefore be able to sense and respond to these changes in order to survive. Previous investigators have studied various fungal species to define conserved pH-responsive signaling pathways. One of these pathways, known as the Pal/Rim pathway, is activated in response to alkaline pH signals, ultimately targeting the PacC/Rim101 transcription factor. Although the central signaling components are conserved among divergent filamentous and yeast-like fungi, there is some degree of signaling specificity between fungal species. This specificity exists primarily in the downstream transcriptional targets of this pathway, likely allowing differential adaptation to species-specific environmental niches. In this review, the role of the Pal/Rim pathway in fungal pH response is discussed. Also highlighted are functional differences present in this pathway among human fungal pathogens, differences that allow these specialized microorganisms to survive in the various micro-environments of the infected human host.

• Biomedical Science Letters
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• v.24 no.3
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• pp.253-262
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• 2018

Platelets are activated at sites of vascular injury via several molecules, such as adenosine diphosphate, collagen and thrombin. Full platelet aggregation is absolutely essential for normal hemostasis. Moreover, this physiological event can trigger circulatory disorders, such as thrombosis, atherosclerosis, and cardiovascular disease. Therefore, platelet function inhibition is a promising approach in preventing platelet-mediated circulatory disease. Many studies reported the involvement of mitogen-activated protein kinases (MAPKs) signaling pathways in platelet functions. However, these studies were limited. Thus, we examined MAPK signaling pathways in human platelets using specific MAPK inhibitors, such as PD98059, SB203580, and SP600125. We observed that these inhibitors were involved in calcium mobilization and influx in human platelets. They also suppressed thrombin-induced ${\alpha}$- and ${\delta}$-granule release. These results suggest that PD98059, SB203580, and SP600125 exhibit $Ca^{2+}$ antagonistic effects.

• Molecules and Cells
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• v.27 no.2
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• pp.211-215
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• 2009

Toll-like receptors (TLRs) play a critical role in sensing microbial components and inducing innate immune and inflammatory responses by recognizing invading microbial pathogens. Lipopolysaccharide-induced dimerization of TLR4 is required for the activation of downstream signaling pathways including nuclear factor-kappa B ($NF-{\kappa}B$). Therefore, TLR4 dimerization may be an early regulatory event in activating ligand-induced signaling pathways and induction of subsequent immune responses. Here, we report biochemical evidence that 6-shogaol, the most bioactive component of ginger, inhibits lipopolysaccharide-induced dimerization of TLR4 resulting in the inhibition of $NF-{\kappa}B$ activation and the expression of cyclooxygenase-2. Furthermore, we demonstrate that 6-shogaol can directly inhibit TLR-mediated signaling pathways at the receptor level. These results suggest that 6-shogaol can modulate TLR-mediated inflammatory responses, which may influence the risk of chronic inflammatory diseases.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.217.1-217.1
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• 2003

In previous study, we investigated the mechanism of suppression of inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) by ergolide, sesquiterpene lactone from Inula Britannica. In this study, the suppression of iNOS and COX-2 by ergolide might be attributed to selective inhibition of NF-$\_$K/B signaling pathways. Here, we investigated the suppressionmechanism of NF-$\_$K/B signaling pathways by ergolide in TPA-stimulated HeLa cells. (omitted)

• Biomolecules & Therapeutics
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• v.30 no.3
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• pp.213-220
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• 2022

Although there have been advances in cancer therapy and surgical improvement, lung cancer has the lowest survival rate (19%) at all stages. This is because most patients are diagnosed with concurrent metastasis, which occurs due to numerous related reasons. Especially, lung cancer is one of the most common and malignant cancers in the world. Although there are advanced therapeutic strategies, lung cancer remains one of the main causes of cancer death. Recent work has proposed that epithelial-mesenchymal transition (EMT) is the main cause of metastasis in most cases of human cancers including lung cancer. EMT involves the conversion of epithelial cells, wherein the cells lose their epithelial abilities and become mesenchymal cells involved in embryonic development, such as gastrulation and neural crest formation. In addition, recent research has indicated that EMT contributes to altering the cancer cells into cancer stem cells (CSCs). Although EMT is important in the developmental stages, this process also activates lung cancer progression, including complicated and diverse signaling pathways. Despite the numerous investigations on signaling pathways involved in the progression of lung cancer, this malignancy is considered critical for treatment. EMT in lung cancer involves many transcription factors and inducers, for example, Snail, TWIST, and ZEB are the master regulators of EMT. EMT-related factors and signaling pathways are involved in the progression of lung cancer, proposing new approaches to lung cancer therapy. In the current review, we highlight the signaling pathways implicated in lung cancer and elucidate the correlation of these pathways, indicating new insights to treat lung cancer and other malignancies.

• Animal cells and systems
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• v.13 no.4
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• pp.363-370
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• 2009

Since vitamin $D_3$ is an important regulator of osteoblastic differentiation, a presently-established vitamin $D_3$-entrapped calcium phosphate film (VCPF) was evaluated for hard tissue engineering. The entrapped vitamin $D_3$ more rapidly induced bone nodule formation. To characterize the cellular events leading to regulations including faster differentiation, signal transduction pathways were investigated in osteoblastic MG63 cells at a molecular level. Major signaling pathways for MG63 cell proliferation including phosphatidylinositol-3-kinase, extracellular signal-regulated kinase, c-Jun N-terminal kinase and focal adhesion kinase pathways were markedly down-regulated when cells were cultured on calcium phosphate film (CPF) and VCPF. This agreed with our earlier observations of the immediate delay in proliferation of MG63 cells upon culture on CPF and VCPF. On the other hand, the p38 mitogen-activated protein kinase (p38 MAPK) and protein kinase A (PKA) pathways were significantly up-regulated on both CPF and VCPF. CPF alone could simulate differential behaviors of MG63 cells even in the absence of osteogenic stimulation and entrapment of vitamin $D_3$ within CPF further amplified the signal pathways, resulting in continued promotion of MG63 cell differentiation. Interplay of p38 MAPK and PKA signaling pathways likely is a significant event for the promotion of differentiation and mineralization of MG63 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1731-1735
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• 2013

Objective: We aimed to identify key genes, pathways and function modules in the development of diffuse large B-cell lymphoma (DLBCL) with microarray data and interaction network analysis. Methods: Microarray data sets for 7 DLBCL samples and 7 normal controls was downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified with Student's t-test. KEGG functional enrichment analysis was performed to uncover their biological functions. Three global networks were established for immune system, signaling molecules and interactions and cancer genes. The DEGs were compared with the networks to observe their distributions and determine important key genes, pathways and modules. Results: A total of 945 DEGs were obtained, 272 up-regulated and 673 down-regulated. KEGG analysis revealed that two groups of pathways were significantly enriched: immune function and signaling molecules and interactions. Following interaction network analysis further confirmed the association of DEGs in immune system, signaling molecules and interactions and cancer genes. Conclusions: Our study could systemically characterize gene expression changes in DLBCL with microarray technology. A range of key genes, pathways and function modules were revealed. Utility in diagnosis and treatment may be expected with further focused research.

• Molecules and Cells
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• v.44 no.5
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• pp.335-341
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• 2021

Zinc is an essential micronutrient with crucial roles in multiple facets of biological processes. Dysregulated zinc homeostasis impairs overall immune function and resultantly increases susceptibility to infection. Clinically, zinc supplementation is practiced for treatment of several infectious diseases, such as diarrhea and malaria. Recent focus on zinc as a beneficial element for immune system support has resulted in investigation of the immunomodulatory roles of zinc in a variety of immune cells. Besides its classical role as a cofactor that regulates the structural function of thousands of proteins, accumulating evidence suggests that zinc also acts, in a manner similar to calcium, as an ionic regulator of immune responses via participation as an intracellular messenger in signaling pathways. In this review, we focus on the role of zinc as a signaling molecule in major pathways such as those downstream of Toll-like receptors-, T cell receptor-, and cytokine-mediated signal transduction that regulate the activity and function of monocytes/macrophages and T cells, principal players in the innate and adaptive immune systems.

• Molecules and Cells
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• v.45 no.7
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• pp.435-443
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• 2022

In response to environmental changes, signaling pathways rewire gene expression programs through transcription factors. Epigenetic modification of the transcribed RNA can be another layer of gene expression regulation. N⁶-adenosine methylation (m⁶A) is one of the most common modifications on mRNA. It is a reversible chemical mark catalyzed by the enzymes that deposit and remove methyl groups. m⁶A recruits effector proteins that determine the fate of mRNAs through changes in splicing, cellular localization, stability, and translation efficiency. Emerging evidence shows that key signal transduction pathways including TGFβ (transforming growth factor-β), ERK (extracellular signal-regulated kinase), and mTORC1 (mechanistic target of rapamycin complex 1) regulate downstream gene expression through m⁶A processing. Conversely, m⁶A can modulate the activity of signal transduction networks via m⁶A modification of signaling pathway genes or by acting as a ligand for receptors. In this review, we discuss the current understanding of the crosstalk between m⁶A and signaling pathways and its implication for biological systems.

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.141-148
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• 2011

Osteoclasts are bone-resorbing cells of monocyte/macrophage origin and are culprits of bone destruction associated with osteoporosis, rheumatoid arthritis, and cancer bone metastasis. Recent advances in osteoclast biology revealed central roles of various cytokines in regulating osteoclastogenesis both in vitro and in vivo. However, exact underlying mechanisms including signaling pathways downstream of receptor ligation are still under pursuit. In the present review, the role of Jak/STAT proteins and their regulators will be discussed in connection with osteoclastogenesis, since growing evidence indicates that a number of cytokines and growth factors utilizing Jak/STAT signaling pathways affect osteoclastogenesis. A better understanding on the role of Jak/STAT pathways in osteoclast differentiation will not only strengthen our knowledge on osteoclast biology but also provide invaluable insights into the development of anti-resorptive strategies for treating bone-lytic diseases.