Si-Yeon Kim’s research while affiliated with Jeju National University and other places

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Publications (3)


Lactobacillus johnsonii JERA01 upregulates the production of Th1 cytokines and modulates dendritic cells-mediated immune response
  • Article

November 2024

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7 Reads

Korean Journal of Physiology and Pharmacology

Si-Yeon Kim

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Figure 2. FBZ and CHOP induced the apoptosis and necrosis of EL-4 cells. For cell death analysis, EL-4 cells (2 × 10 5 cells/mL) were treated with FBZ or CHOP. (A) After 72 h incubation, the cells were double-stained with Hoechst 33342 and PI, and the images were captured using a fluorescence microscope. Early apoptotic cells (arrows) are the cells with blue chromatin, which is highly condensed, marginated, or fragmented. Late apoptotic cells (arrow heads) indicate the cells with bright red condensed and fragmented chromatin. Necrotic cells (open arrows) are the cells with bright red or red enlarged nuclei with normal structures. Scale bar: 50 µm. (B) After 48 h incubation, annexin V/PI staining was performed. The quadrants of the dot plot indicate live cells (annexin V − /PI − ) and cells in early apoptosis (annexin V + /PI − ), late apoptosis (annexin V + /PI + ), and necrosis (annexin V − /PI + ). The graphs were generated using data from three independent experiments. Statistical significance was performed via two-way ANOVA, followed by Dunnett's multiple comparisons test. *, **, and *** indicate p < 0.05, 0.01, and 0.001 of the live cells compared to the control (0 µg/mL).
Figure 4. Body weight and tumor growth of EL-4 induced mouse lymphoma model. (A) After in vivo passage of EL-4 cells, tmEL-4 cells were harvested and injected subcutaneously into the right flank. Day 0 for treatment was defined as the day when the tumor reached a volume of approximately 100 mm 3 . Each group of mice was treated intraperitoneally with the following regimen: vehicle control (PBS 120 µL + DMSO 20 µL), CHOP (CHOP 40 mg/kg), or FBZ (FBZ 25 mg/kg). Body weight (B) and tumor volume (C) were checked daily. (D) On day 10, the mice were sacrificed, and the weights of tumors were determined. (E) Three representative photos of tumors in each group are shown. Scale bar: 1 cm. Statistical significance was performed via one-way ANOVA, followed by Dunnett's multiple comparisons test. *, **, and *** indicate p < 0.05, 0.01, and 0.001 compared to day 0 (B) or CHOP-treated group (D). #, ##, and ### indicate p < 0.05, 0.01, and 0.001 between vehicle control and CHOP 40 mg/kg. NS: not significant.
Figure 5. Effects of FBZ and CHOP on EL-4 lymphoma were assessed historically. (A) Mitotic index (arrows), tingible body macrophages (arrow heads), apoptotic bodies (open arrow heads), and necrosis region (N) were observed via H&E staining. Scale bar: 200 µm (a-c) and 20 µm (d-f). (B) PCNA staining was performed to confirm proliferative cells. Scale bar: 20 µm. (C) Average of the PCNA-positive area of 3-5 visual fields observed at 100× per mouse is graphically shown. Statistical significance was performed via one-way ANOVA, followed by Dunnett's multiple comparisons test. * indicates p < 0.05 compared to the vehicle control.
Figure 7. FBZ recruited M2 macrophages in tumor, while M1 macrophages were predominant in CHOP-treated tumor. (A) To investigate the polarized form of TAMs in tumor, IHC was performed. Tumor tissues are stained with Iba1 (Aa-Ac), Arg1 (Ad-Af), and iNOS (Ag-Ai). Apoptotic bodies (arrow) and tingible body macrophages (arrow heads) are shown in FBZ-treated tumor. IHC revealed Arg1-positive status of tingible body macrophages, forming the starry sky pattern (Af). Scale bar: 20 µm. (B) Average of the Iba-1-, Arg1-, and iNOS-positive areas of 3−5 visual fields observed at 100× per mouse is graphically shown. Statistical significance was performed via one-way ANOVA, followed by Dunnett's multiple comparisons test. * and ** indicate p < 0.05 and 0.01 compared to vehicle control.
Primary antibodies for IHC staining.
Fenbendazole Exhibits Differential Anticancer Effects In Vitro and In Vivo in Models of Mouse Lymphoma
  • Article
  • Full-text available

November 2023

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1,090 Reads

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1 Citation

Fenbendazole (FBZ) has been safely used as an antiparasitic agent in animals for decades, and the anticancer effects of FBZ have been studied through various mechanisms. However, there is a lack of in vivo studies that include lymphoma. Therefore, this study examined the effects of FBZ on EL-4 cells and a mouse T lymphoma model. FBZ induced G2/M phase arrest in EL-4 cells, resulting in cell death and decreased metabolic activity. However, FBZ had no anticancer effects on an EL-4 mouse lymphoma model in vivo, as evident by rapid weight loss and tumor growth comparable to the control. The FBZ-treated EL-4 cells expressed higher levels of PD-L1 and CD86, which are associated with T cell immunity in the tumor microenvironment (TME), than the controls. Furthermore, the hematoxylin and eosin staining of the FBZ-treated tumor tissues showed a starry sky pattern, which is seen in actively proliferating cancer tissues, and an immunohistochemical analysis revealed a high percentage of immunosuppressive M2 macrophages. These changes in the immune activity in the TME contradict the results of the in vitro experiments, and further studies are needed to determine the detailed mechanisms by which FBZ induces these responses.

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Anticancer effect of metformin alone and in combination with 2-deoxy-D-glucose on mouse T cell lymphoma EL4 cells

September 2023

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16 Reads

Korean Journal of Veterinary Research

Metformin is a treatment used widely for non-insulin-dependent diabetes mellitus with few side effects and acts by inhibiting hepatic gluconeogenesis and glucose absorption from the gastrointestinal tract. Lymphoma is one of the most common hematological malignancies in dogs. Chemotherapy is used mainly on lymphoma, but further research on developing anticancer drugs for lymphoma is needed because of its severe side effects. This study examined the anticancer effects of metformin alone and in combination with 2-deoxy-D-glucose (2-DG), a glucose analog, on EL4 cells (mouse T-cell lymphoma). Metformin reduced the metabolic activity of EL4 cells and showed an additive effect when combined with 2-DG. In addition, cell death was confirmed using a trypan blue exclusion test, Hochest 33342/propidium iodide (PI) staining, and Annexin V/PI staining. An analysis of the cell cycle and mitochondria membrane potential (MMP) to investigate the mechanism of action showed that metformin stopped the G2/M phase of EL4 cells, and metformin + 2-DG decreased MMP. Metformin exhibited anticancer effects as a G2/M phase arrest mechanism in EL4 cells and showed additive effects when combined with 2-DG via MMP reduction. Unlike cytotoxic chemotherapeutic anticancer drugs, metformin and 2-DG are related to cellular glucose metabolism and have little toxicity. Therefore, metformin and 2-DG can be an alternative to reduce the toxicity caused by chemotherapeutic anticancer drugs. Nevertheless, research is needed to verify the in vivo efficacy of metformin and 2-DG before they can be used in lymphoma treatments.

Citations (1)


... We have also confirmed the excellent activity of both the Ulmus genus extract and catechin 7-O-β-D-apiofuranoside in terms of cell viability, antioxidant activity, expression of the apoptosis inhibitor Bcl-2, reduction of apoptosis-inducing factors caspase-3 and PARP, decrease in muscle decomposition factors Atrogin1 and MuRF1, and expression of muscle synthesis factors Myogenin and MyoD [37]. However, while these results are promising in the controlled in vitro stage, it is important to note that the more complex in vivo stage may yield different outcomes due to various biological interactions [38]. That is why in vivo experiments are deemed necessary for pre-clinical studies on drug development, research, and the creation of health functional foods. ...

Reference:

The Impact of Ulmus macrocarpa Extracts on a Model of Sarcopenia-Induced C57BL/6 Mice
Fenbendazole Exhibits Differential Anticancer Effects In Vitro and In Vivo in Models of Mouse Lymphoma