• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3137-3140
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• 2015

Objective: To explore the immune reconstitution of $CD4^+T$ cells after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and its relationship with invasive fungal infection (IFI) in patients with hematological malignancies. Materials and Methods: Forty-seven patients with hematological malignancies undergoing Allo-HSCT in Binzhou Medical University Hospital from February, 2010 to October, 2014 were selected. At 1, 2 and 3 months after transplantation, the immune subpopulations and concentration of cytokines were assessed respectively using flow cytometry (FCM) and enzyme linked immunosorbent assay (ELISA). The incidence of IFI after transplantation and its correlation with immune reconstitution of $CD4^+T$ cells were investigated. Results: The number of $CD4^+T$ cells and immune subpopulations increased progressively after transplantation as time went on, but the subpopulation cell count 3 months after transplantation was still significantly lower than in the control group (p<0.01). In comparison to the control group, the levels of interleukin-6 (IL-6) and IL-10 after transplantation rose evidently (p<0.01), while that of transforming growth factor-${beta}$ (TGF-${beta}$) was decreased (p<0.01). There was no statistically significant difference level of interferon-${\gamma}$ (IFN-${\gamma}$) (p>0.05). The incidence of IFI was 19.2% (9/47), and multivariate logistic regression revealed that IFI might be related to Th17 cell count (p<0.05), instead of Th1, Th2 and Treg cell counts as well as IL-6, IL-10, TGF-${beta}$ and IFN-${\gamma}$ levels (p>0.05). Conclusions: After Allo-HSCT, the immune reconstitution of $CD4^+T$ cells is delayed and Th17 cell count decreases obviously, which may be related to occurrence of IFI.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.35 no.2
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• pp.73-81
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• 2013

Purpose: Smad4 is a central mediator for transforming growth factor-${\beta}$/bone morphogenetic protein ($TGF-{\beta}/BMP$) signals, which are involved in regulating cranial neural crest cell formation, migration, proliferation, and fate determination. Accumulated evidences indicate that $TGF-{\beta}/BMP$ signaling plays key roles in the early tooth morphogenesis. However, their roles in the late tooth formation, such as cellular differentiation and matrix formation are not clearly understood. The objective of this study is to understand the roles of Smad4 in vivo during enamel and dentin formation through tissue-specific inactivation of Smad4. Methods: We generated and analyzed mice with dental epithelium-specific inactivation of the Smad4 gene (K14-Cre:$Smad4^{fl/fl}$) and dental mesenchyme-specific inactivation of Smad4 gene (Osr2Ires-Cre:$Smad4^{fl/fl}$). Results: In the tooth germs of K14-Cre:$Smad4^{fl/fl}$, ameloblast differentiation was not detectable in inner enamel epithelial cells, however, dentin-like structure was formed in dental mesenchymal cells. In the tooth germs of Osr2Ires-Cre:$Smad4^{fl/fl}$ mice, ameloblasts were normally differentiated from inner enamel epithelial cells. Interestingly, we found that bone-like structures, with cellular inclusion, were formed in the dentin region of Osr2Ires-Cre:$Smad4^{fl/fl}$ mice. Conclusion: Taken together, our study demonstrates that Smad4 plays a crucial role in regulating ameloblast and odontoblast differentiation, as well as in regulating epithelial-mesenchymal interactions during tooth development.

• BMB Reports
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• v.43 no.1
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• pp.52-56
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• 2010

Silk fibroin, produced by the silkworm Bombyx mori, has been widely studied as a scaffold in tissue engineering. Although it has been shown to be slowly biodegradable, cellular responses to degraded silk fibroin fragments are largely unknown. In this study, silk fibroin was added to MG-63 cell cultures, and changes in gene expression in the MG-63 cells were screened by DNA microarray analysis. Genes showing a significant (2-fold) change were selected and their expression changes confirmed by quantitative RT-PCR and western blotting. DNA microarray results showed that alkaline phosphatase (ALP), collagen type-I alpha-1, fibronectin, and transforming growth factor-${\beta}1$ expressions significantly increased. The effect of degraded silk fibroin on osteoblastogenic gene expression was confirmed by observing up-regulation of ALP activity in MG-63 cells. The finding that small fragments of silk fibroin are able to increase the expression of osteoblastogenic genes suggests that controlled degradation of silk fibroin might accelerate new bone formation.

• Preventive Nutrition and Food Science
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• v.6 no.2
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• pp.126-132
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• 2001

Methanol extracts form four kinds of kimchi, which were differently prepared in kinds and levels of sub-ingredients, were given to Balb/c mice for 3 weeks (0.5 mg/kg/day). Peritoneal macrophages isolated from mice treated with kimchi extracts and saline were stimulated by lipopolysaccharide (LPS). K3 and K4 kimchis, containing more red pepper powder, garlic, Chinese pepper powder, mustard leaf and organically cultivated Korean cabbage, significantly increased NO production by the activated macrophages (p<0.05). K1, K2, K3 and K4 kimchi extracts (0.01, 0.1, 1.0 $\mu\textrm{g}$) significantly reduced the increased TGF-$\beta$1 production of H.pylori lysate (0.01 $\mu\textrm{g}$)-activated human epithelial RPMI 2650 cells (5$\times$10$^{4}$ cells/mL) at 24 and 48 hrs of treatment (p<0.01). However, the decreased TGF-$\beta$1 $\alpha$ production of RPMI 2650 cells by H. pylori lysate increased by treatment with kimchi extract for 72 hrs. Especially, K4 kimchi (containing organically cultivated Korean cabbage and more ingredients, modulated TGF-$\beta$1 production of H. pylori lysate-activated RPMI 2650 cells to the normal level (control) by treatment for 48 hrs. The treatment of K1 and K4 kimchi enhanced the LPS (0.01 $\mu\textrm{g}$/mL)-induced IL-6 production of splenocytes. The results suggest that kimchi might have an beneficial effect on cancer prevention due in part to the function enhancing NO production of activated macrophages. Our data suggest that kimchi could modulate TGF-$\beta$1 production by cancer cells and IL-6 production of splenocytes, thereby possibly contributing to control carcinogenesis and the immune system.

• Korean Journal of Poultry Science
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• v.44 no.3
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• pp.211-223
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• 2017

Transforming growth factor beta ($TGF-{\beta}$) signaling pathways are involved in the regulation of proliferation, differentiation, immunity, survival, and apoptosis of many cells. The aim of this study was to investigate the differential expression of $TGF-{\beta}$-related genes, and their interactions and regulators in the spleen of two genetically disparate chicken lines (Marek's disease resistant line 6.3 and Marek's disease-susceptible line 7.2) induced with necrotic enteritis (NE) by Eimeria maxima and Clostridium perfringens infection. By using high-throughput RNA-sequencing, we investigated 76 $TGF-{\beta}$-related genes that were significantly and differentially expressed in the spleens of the chickens. Approximately 20 $TGF-{\beta}$ pathway genes were further verified by qRT-PCR, and the results were consistent with our RNA sequencing data. All 76 identified genes were analyzed through Gene Ontology and mapped onto the KEGG chicken $TGF-{\beta}$ pathway. Our results demonstrated that several key genes, including $TGF-{\beta}$1-3, bone morphogenetic proteins (BMP)1-7, inhibitor of differentiation (ID) proteins ID1-3, SMAD1-9, and Jun, showed a markedly differential expression between the two chicken lines, relative to their respective controls. We then further predicted 24 known miRNAs that targeted BMP7 mRNA from 139 known miRNAs in the two chicken lines. Among these, six miRNAs were measured by qRT-PCR. In conclusion, this study is the first to analyze most of the genes, interactions, and regulators of the $TGF-{\beta}$ pathway in the innate immune responses of NE afflicted chickens.

• Parasites, Hosts and Diseases
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• v.50 no.4
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• pp.385-390
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• 2012

In order to know the effect of pre-existing Trichinella spiralis infection on experimentally induced intestinal inflammation and immune responses, we induced colitis in T. spiralis-infected mice and observed the severity of colitis and the levels of Th1, Th2, and regulatory cytokines and recruitment of $CD4^+CD25^+Foxp3^+$ T (regulatory T; $T_{reg}$) cells. Female C57BL/6 mice were infected with 250 muscle larvae; after 4 weeks, induction of experimental colitis was performed using 3% dextran sulfate sodium (DSS). During the induction period, we observed severity of colitis, including weight loss and status of stool, and evaluated the disease activity index (DAI). A significantly low DAI and degree of weight loss were observed in infected mice, compared with uninfected mice. In addition, colon length in infected mice was not contracted, compared with uninfected mice. We also observed a significant increase in production of pro-inflammatory cytokines, IL-6 and IFN-${\gamma}$, in spleen lymphocytes treated with DSS; however, such an increase was not observed in infected mice treated with DSS. Of particular interest, production of regulatory cytokines, IL-10 and transforming growth factor (TGF)-${\beta}$, in spleen lymphocytes showed a significant increase in mice infected with T. spiralis. A similar result was observed in mesenteric lymph nodes (MLN). Subsets of the population of $T_{reg}$ cells in MLN and spleen showed significant increases in mice infected with T. spiralis. In conclusion, T. spiralis infection can inhibit the DSS-induced colitis in mice by enhancing the regulatory cytokine and $T_{reg}$ cells recruitment.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.78-78
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• 1995

Increasing evidence indicates that the production of nitric oxide (NO) by inducible NO synthase (NOS) is tightely regulated. Transforming growth factor-${\beta}$ (TGF-${\beta}$) is a homodimeric protein secreted during macrophage activation, but several lines of evidence suggest that TGF-${\beta}$ is selectively suppressive for macrophage NO production. We therefore reasoned that a strategy employing oligodeoxynucleotides(ODNs) complemently to TGF-${\beta}$ mRNA (antisense ODNs) might increase NO production in IFN-${\gamma}$-treated murine peritoneal macrophages. To evaluate this concept, we tested the effects of antisense ODNs targeted to TGF-${\beta}$ mRNA (25-mer ODNs complemently to TGF-${\beta}$mRNA sequences) by introducing it into the medium of cultured macrophages. Phosphorothiolation of ODNs were employed to retard their degradation. Antisense ODNs had no effect on NO production by itself, whereas IFN-${\gamma}$ alone had modest effect. When antisense ODNs were used in combination with IFN-${\gamma}$, there was a marked cooperative induction of NO production, These effects of antisense ODNs were associated with decreased TGF-${\beta}$ expression in activated macrophages. ODNs with the same nucleotides but a scrambled sequence had no effect. Adding anti-TGF-${\beta}$ antibodies to the IFN-${\gamma}$-treated macrophages mimicked the positive effect of antisense ODNs on NO production. In addition, the effects of either antisense ODNs or anti-TGF-${\beta}$ antibodies were blocked by adding TGF-${\beta}$ in cultured macrophages. These results indicate that the generation of TGF-${\beta}$ by activated macrophages provides a self-regulating mechanism by which the temporal and perhaps spatial production of NO, a reactive and potentially toxic mediator, can be finely regulated.

• Journal of KIISE:Computer Systems and Theory
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• v.33 no.11
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• pp.830-835
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• 2006

Because of its exponential growth of data and voice transmissions through wireless communications, efficient resource management became more important factor when we design wireless networks. One of those limited resources in the wireless communications is frequency bandwidth. As a solution of increasing reusability of resources, the efficient frequency assignment problems on wireless networks have been widely studied. One suitable approach to solve these frequency assignment problems is transforming the problem into traditional graph coloring problems in graph theory. However, most of frequency assignments on arbitrary network topology are NP-Complete problems. In this paper, we consider the Chromatic Bandwidth Problem on the cellular topology wireless networks. It is known that the lower bound of the necessary number of frequencies for this problem is $O(k^2)$. We prove that the lower bound of the necessary number of frequencies for the Chromatic Bandwidth Problem is $O(k^3)$ which is tighter lower bound than the previous known result.

• Journal of Microbiology and Biotechnology
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• v.23 no.7
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• pp.1023-1030
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• 2013

Lipoteichoic acid (LTA), uniquely expressed on gram-positive bacteria, is recognized by Toll-like receptor 2 (TLR2) on not only antigen-presenting cells but also activated T cells. Therefore, it is reasonable to assume that LTA is acting on T cells. However, little is known about the effect of LTA on T-cell regulation. In the present study, we investigated the immunomodulatory effects of LTA on $CD4^+$ T cells. Effector $CD4^+$ T cells, induced after co-culture with S. aureus-pulsed dendritic cells, produced high levels of interferon-${\gamma}$, CD25, CD69, and TLRs 2 and 4. When effector $CD4^+$ T cells were treated with LTA, the expressions of the membrane-bound form of transforming growth factor (TGF)-${\beta}$ and forkhead box P3 increased. Coincidently, the proliferation of effector $CD4^+$ T cells was declined after LTA treatment. When TGF-${\beta}$ signaling was blocked by the TGF-${\beta}$ receptor 1 kinase inhibitor, LTA failed to suppress the proliferation of effector $CD4^+$ T cells. Therefore, the present results suggest that LTA suppresses the activity of effector $CD4^+$ T cells by enhancing TGF-${\beta}$ production.

• BMB Reports
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• v.53 no.6
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• pp.317-322
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• 2020

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. NAFLD can further progress to irreversible liver failure such as non-alcoholic steatohepatitis (NASH) fibrosis and cirrhosis. However, specific regulator of NASH-fibrosis has yet to be established. Here, we found that glutathione peroxidase 7 (GPx7) was markedly expressed in NASH fibrosis. Although GPx7 is an antioxidant enzyme protecting other organs, whether GPx7 plays a role in NASH fibrosis has yet to be studied. We found that knockdown of GPx7 in transforming growth factor-β (TGF-β) and free fatty acids (FFA)-treated LX-2 cells elevated the expression of pro-fibrotic and pro-inflammatory genes and collagen synthesis. Consistently, GPx7 overexpression in LX-2 cells led to the suppression of ROS production and reduced the expression of pro-fibrotic and pro-inflammatory genes. Further, NASH fibrosis induced by choline-deficient amino acid defined, high fat diet (CDAHFD) feeding was significantly accelerated by knockdown of GPx7, as evidenced by up-regulated liver fibrosis and inflammation compared with CDAHFD control mice. Collectively, these results suggest that GPx7 might be a novel therapeutic target to prevent the progression and development of NAFLD.