• Animal cells and systems
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• 제4권4호
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• pp.389-394
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• 2000

The Tcf-1 (1-cell factor-1) protein binds to the T-cell specific enhancer sequences and plays an architectural role in the assembly of transcriptional machinery. One of the Tcf family proteins, Tcf-4, was found to be an important regulator for colon cancer development where it activates specific genes upon binding to $\beta$-catenin following Wnt signaling. We were interested in the transcriptional regulatory activities of Tcf-1 and Tcf-4 proteins in T-cells and colon cancer cells. Transactivation assay was developed using a reporter plasmid containing luciferase gene under the control of Tcf responsive elements. Luciferase activity was determined following co-transfection of the reporter along with Tcf-1 and/or $\beta$-catenin expressing plasmids. Transcription was significantly induced by $\beta$-catenin expression in all cells. Tcf-1 by itself did not induce transcription in the mature T-cell lines, but overexpressed Tcf-1 greatly activated transcription in the immature T-cell line. In addition, transfected $\beta$-catenin induced apoptosis, but co-transfected Tcf-1 suppressed apoptosis in HEK293 cells. These results suggest that Tcf-1 and $\beta$-catenin differently regulate transcription and apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2027-2030
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• 2016

Objective: To investigate the effect of peripheral blood CD4 + CD25 + regulatory T cell on postoperative immunotherapy in patients with renal carcinoma. Methods: 38 patients with renal cell carcinoma were recruited, and 20 patients from the operation group purely underwent the radical nephrectomy therapy, 18 patients from the combined group successively underwent the radical nephrectomy therapy and IFN-${\alpha}$ adjuvant immunotherapy. Additionally, 12 healthy subjects were recruited in the same period of time and regarded as the control group. Flow cytometry was used to detect CD4 +, CD8 +, CD4 + CD25+ T lymphocyte subset content and the ratio of all parts in the pre-operative period, in the first post-operative week and in the third post-operative month, compare and analyze its variation trend. Results: The CD4+CD25+ T lymphocyte subset content of individual renal carcinoma patients was significantly higher than that of the control group, also increases with the progression in the tumor stage (P<0.05). The post-operative CD4 + CD25+T lymphocytes of individual operation group and combined group patients showed different degrees of increment, but the increment of the combined group was significantly lower than that of the operation group (P<0.05). For the combined group patients with less pre-operative CD4 + CD25+T lymphocytes, their levels would increase after the immunotherapy, while the pre-operative patients with more CD4 + CD25+ T lymphocytes were the opposite situation. Conclusion: The detection of peripheral blood CD4+CD25+ regulatory T lymphocyte subset can reflect the anti-tumor immune status of renal cell carcinoma patient body. It can contribute to predict the prognosis of immunotherapy and provide reference for the choice of renal carcinoma post-operative adjuvant immunotherapy.

• Biomolecules & Therapeutics
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• 제30권4호
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• pp.299-308
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• 2022

T cells are attractive targets for the development of immunotherapy to treat cancer due to their biological features, capacity of cytotoxicity, and antigen-specific binding of receptors. Novel strategies that can modulate T cell functions or receptor reactivity provide effective therapies, including checkpoint inhibitor, bispecific antibody, and adoptive transfer of T cells transduced with tumor antigen-specific receptors. T cell-based therapies have presented successful pre-clinical/clinical outcomes despite their common immune-related adverse effects. Ongoing studies will allow us to advance current T cell therapies and develop innovative personalized T cell therapies. This review summarizes immunotherapeutic approaches with a focus on T cells. Anti-cancer T cell therapies are also discussed regarding their biological perspectives, efficacy, toxicity, challenges, and opportunities.

• 대한한방내과학회지
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• 제31권2호
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• pp.189-200
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• 2010

Objectives : Regulatory T cells can reduce inflammation and allergic reactions through their inhibitory functions. Gardeniae Fructus(GF) is a Heat-clearing herb used in traditional Korean medicine, and a wide range of studies on its antiinflammatory effects are being carried out. The authors investigated the effect that Gardeniae Fructus has on regulatory T cells. Methods : The authors screened 14 herbs for their effects on regulatory T cells. 100mg of each herb were separately dissolved in 1ml of sterile saline and the supernatant was harvested after 10 minutes of centrifuge at 15,000 rpm. The supernatant was filtered through a 0.2 ${\mu}m$ syringe filter, and the resulting stock was refrigerated at $4^{\circ}C$. The stock was diluted before testing and used at a final concentration of $0.01{\mu}g/ml$. CD4+CD25+ T cells from healthy BALB/c spleens were used as natural regulatory T cells (nTreg), and CD4+CD25- T cells were used as reactive T cells. CD4+CD25+ and CD4+CD25- T cells were activated with anti-CD3e ($10{\mu}g/m{\ell}$)/anti-CD28 ($1{\mu}g/m{\ell}$) and cultured. IL-10 from supernatant of the culture medium was measured by IL-10 cytokine ELISA. The percentages, cell numbers, phenotype and function of CD4+CD25+ Treg cells were determined by flow cytometry. Results : Gardeniae Fructus was shown to be the most potent herb among the 14 herbs tested for suppressing CD4+CD25- reactive T cell proliferation by stimulating CD4+CD25+ natural regulatory T cells. Gardeniae Fructus induces IL-10 secretion increase by stimulating CD4+CD25+ natural regulatory T cells, and indirectly suppresses CD4+CD25- reactive T cell proliferation through increasing CD25 (IL-2 receptor $\alpha$) expression and thus promoting bonding with IL-2. Gardeniae Fructus did not directly affect CD4+CD25- reactive T cell proliferation. Conclusions : Gardeniae Fructus suppressed reactive T cell proliferation through inducing increases in IL-10 secretion and CD25 (IL-2 receptor $\alpha$) expression.

• 생명과학회지
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• 제23권9호
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• pp.1177-1182
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• 2013

선모충(Trichinella spiralis)은 감염 후 nurse cell 형성과정에서 영양분 공급 및 배설을 위해 혈관신생인자인 vascular endothelial cell growth factor (VEGF)를 유도하여 혈관신생을 촉진한다. 하지만 이러한 과정 중 선모충이 어떻게 VEGF의 발현을 유도하는지에 대해서는 아직 밝혀지지 않았다. Nurse cell 형성 과정에서 저산소현상이 발생되고 이러한 저산소 현상이 VEGF의 발현을 유도할 것이라는 제안이 있지만 실제 nurse cell 형성 과정에 저산호 현상이 일어나는지도 조사되지 않았으며 저산소 현상이 실제 VEGF를 통한 혈관신생을 유도하는지도 규명되지 않았다. 최근 연구결과에 의하면 VEGF의 발현을 유도하는 티모신베타4 단백질이 초기의 선모충 감염 nurse cell에서 강력하게 유도되는 것이 관찰되었다. 게다가 저산소 현상이 nurse cell 형성 과정에서 관찰되지 않았고 면역세포들이 응집되어 있는 파괴되는 nurse cell에서만 관찰되는 것이 밝혀졌다. 이러한 결과는 티모신베타4가 저산소 현상과 무관하게 선모충 감염 nurse cell에서의 VEGF 유도 및 혈관신생을 유도할 가능성을 제시해 준다.

• BMB Reports
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• 제53권5호
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• pp.254-259
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• 2020

Increasing evidence suggests the role of miR-449a in the regulation of tumorigenesis and autophagy. Autophagy plays an important role in the malignancy of T-cell lymphoma. However, it is still unknown whether miR-449a is associated with autophagy to regulate the malignancy of T-cell lymp homa. In this study, we for the first time demonstrated that miR-449a enhanced apoptosis of T-cell lymphoma cells by decreasing the degree of autophagy. Further, miR-449a downregulated autophagy-associated 4B (ATG4B) expression, which subsequently reduced the autophagy of T-cell lymphoma cells. Mechanistically, miR-449a decreased ATG4B protein level by binding to its mRNA 3'UTR, thus reducing the mRNA stability. In addition, studies with nude mice showed that miR-449a significantly inhibited lymphoma characteristics in vivo. In conclusion, our results demonstrated that the "miR-449a/ATG4B/autophagy" pathway played a vital role in the malignancy of T-cell lymphoma, suggesting a novel therapeutic target.

• 생약학회지
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• 제35권4호통권139호
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• pp.330-337
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• 2004

Based on the traditional application of Carthamus tinctorious L. (CF) as a component of Korean medicinal decoctions, in the present study, we investigated in vitro an immunomodulatory activity of water extract of CF(WECF). Water extract of CF significantly increased the in vitro proliferative responses of spleen cells (SPC). However, addition of WECF during anti-CD3 activation resulted in a significant decrease in SPC proliferation. Flow cytometric analysis showed that WECF addition chanced T and B cell frequencies in anti-CD3-activated spleen cell populations. Using purified cells, it was revealed that WECF is mitogenic to B cells but rather inhibitory to T cell Proliferation. Upon anti-CD3 stimulation, high concentration (1 mg/ml) of WECF significantly inhibited T cell proliferation until day 2 of stimulation. At day 3, anti-CD3-activated cells exposed to WECF recovered their proliferation to the level comparable to control. Although B cell proliferation was also inhibited in proliferation at day 1, it recovered sooner and then was rather augmented by WECF at day 3. These data indicate that WECF down-regulates lymphocyte proliferation at early phase of activation but T cells are more vulnerable than B cells to WECF, However, CD4+ and CD8+ T cells did not differ in WECF-mediated immunotoxicity. Data of propidium iodide (PI) staining showed that WECF accelerates activated T cell, but not B cell, apoptosis and WECF concurrently inhibited cytokine production of activated T cells. Taken together, WECF exhibits B cell mitogenic activity and differential toxicity more pronounced to T cells, suggesting a possible in vivo application of WECF for specific control of T cells without alteration of B cell activity.

• 대한의생명과학회지
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• 제9권4호
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• pp.189-193
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• 2003

This study was undertaken to investigate the effect of baicalein, a major flavone component of Scutellaria balicalensis Georgi, on oxidant-induced cell injury in renal epithelial cells. Opossum kidney cells, an established proximal tubular epithelial cells, were used as a cell model of renal epithelial cells and t-butylhydroperoxide (tBHP) as an oxidant drug model. Cell viability was measured by MTT assay and lipid peroxidation was estimated by measuring the content of malondialdehyde, a product of lipid peroxidation. Exposure of cells to tBHP caused cell death and its effect was dose-dependent over concentration range of 0.1~1.0 mM. When cells were exposed to tBHP in the presence of various concentrations (0.1~10 $\mu$M) of baicalein, tBHP-induced cell death was prevented with a manner dependent of baicalein concentration. tBHP induced A TP depletion, which was significantly prevented by baicalein. Similarly, tBHP-induced DNA damage was prevented by baicalein. tBHP produced a marked increase in lipid peroxidation and its effect was completely inhibited by baicalein. These results indue ate that tBHP induces cell injury through a lipid peroxidation-dependent mechanism in renal epithelial cells, and baicalein prevented oxidant-induced cell injury via antioxidant action inhibiting lipid peroxidation. In addition, these results suggest that baicalein may be a candidate for development of drugs which are effective in preventing and treating renal diseases.

• Journal of Microbiology and Biotechnology
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• 제32권12호
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• pp.1553-1560
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• 2022

A Gram-stain-negative, rod-shaped bacterial strain, JC4^T, was isolated from a freshwater sample and determined the taxonomic position. Initial identification based on 16S rRNA gene sequences revealed that strain JC4^T is affiliated to the genus Mucilaginibacter with a sequence similarity of 97.97% to Mucilaginibacter rigui WPCB133^T. The average nucleotide identity and digital DNA-DNA hybridization values between strain JC4^T and Mucilaginibacter species were estimated below 80.92% and 23.9%, respectively. Strain JC4^T contained summed feature 3 (C_16:1 ω7c and/or C_16:1 ω6c) and iso-C_15:0 as predominant cellular fatty acids. The dominant polar lipids were identified as phosphatidylethanolamine, one unidentified aminophospholipid, one unidentified phospholipid, and two unidentified lipids. The respiratory quinone was MK-7. The genomic DNA G+C content of strain JC4^T was determined to be 42.44%. The above polyphasic evidences support that strain JC4^T represents a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter aquariorum sp. nov. is proposed. The type strain is JC4^T (= KCTC 92230^T = LMG 32715^T).

• Journal of Ginseng Research
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• 제48권1호
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• pp.68-76
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• 2024

Background: Although the survival outcomes of childhood cancer patients have improved, childhood cancer survivors suffer from various degrees of immune dysfunction or delayed immune reconstitution. This study aimed to investigate the effect of Korean Red Ginseng (KRG) on T cell recovery in childhood cancer patients who underwent autologous hematopoietic stem cell transplantation (ASCT) from the perspective of inflammatory and senescent phenotypes. Methods: This was a single-arm exploratory trial. The KRG group (n = 15) received KRG powder from month 1 to month 12 post-ASCT. We compared the results of the KRG group with those of the control group (n = 23). The proportions of T cell populations, senescent phenotypes, and cytokine production profiles were analyzed at 1, 3, 6, and 12 months post-ASCT using peripheral blood samples. Results: All patients in the KRG group completed the treatment without any safety issues and showed a comparable T cell repopulation pattern to that in the control group. In particular, KRG administration influenced the repopulation of CD4⁺ T cells via T cell expansion and differentiation into effector memory cell re-expressing CD45RA (EMRA) cells. Although the KRG group showed an increase in the number of CD4⁺ EMRA cells, the expression of senescent and exhausted markers in these cells decreased, and the capacity for senescence-related cytokine production in the senescent CD28^- subset was ameliorated. Conclusions: These findings suggest that KRG promotes the repopulation of CD4⁺ EMRA T cells and regulates phenotypical and functional senescent changes after ASCT in pediatric patients with cancer.