• Journal of Veterinary Clinics
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• v.26 no.2
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• pp.138-143
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• 2009

Ischemia/reperfusion injury(I/RI) is the major cause of acute renal failure and delayed graft function(DGF) unavoidable in renal transplantation. Enormous studies on ischemia damage playing a role in activating graft rejection factors, such as T cells or macrophages, are being reported. Present study was performed to determine whether ischemia time would play an important role in activating rejection-related factors or not in rat models of I/RI. Male Sprague-Dawley rats were submitted to 30, 45, and 60 minutes of warm renal ischemia with nephrectomy or control animals underwent sham operation(unilateral nephrectomy). Renal function and survival rates were evaluated on day 0, 1, 2, 3, 5 and 7. Immunofluorescence staining of dendritic cells(DCs), natural killer(NK) cells, macrophages, B cells, CD4+ and CD8+ T cells were measured on day 1 and 7 after renal I/RI. Survival rates dropped below 50% after day 3 in 45 minutes ischemia. Histologic analysis of ischemic kidneys revealed a significant loss of tubular architecture and infiltration of inflammatory cells. DCs, NK cells, macrophages, CD4+ and CD8+ T cells were infiltrated from a day after I/RI depending on ischemia time. Antigen presenting cells(DCs, NK cells or macrophages) and even T cells were infiltrated 24 hours post-I/RI, which is at the time of acute tubular necrosis. During the regeneration phase, not only these cells increased but B cells also appeared in more than 45 minutes ischemia. The numbers of the innate and the adaptive immune cells increased depending on ischemia as well as reperfusion time. These changes of infiltrating cells resulting from each I/RI model show that ischemic time plays a role in activating rejection related immune factors and have consequences on progression of renal disease in transplanted and native kidneys.

• Journal of Microbiology and Biotechnology
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• v.25 no.7
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• pp.1036-1046
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• 2015

Extracts from Asian medicinal herbs are known to be successful therapeutic agents against cancer. In this study, the effects of three types of herbal extracts on anti-tumor growth were examined. Among the three types of herbal extracts, H9 showed stronger anti-tumor growth effects than H5 and H11 in vivo. To find the molecular mechanism by which H9 inhibited the proliferation of breast cancer cell lines, the levels of apoptotic markers were examined. Proapoptotic markers, including cleaved PARP and cleaved caspases 3 and 9, were increased, whereas the anti-apoptotic marker Bcl-2 was decreased by H9 treatment. Next, the combined effect of H9 with the chemotherapeutic drugs doxorubicin/cyclophosphamide (AC) on tumor growth was examined using 4T1-tumor-bearing mice. The combined treatment of H9 with AC did not show additive or synergetic anti-tumor growth effects. However, when tumor-bearing mice were co-treated with H9 and the targeted anti-tumor drug trastuzumab, a delay in tumor growth was observed. The combined treatment of H9 and trastuzumab caused an increase of natural killer (NK) cells and a decrease of myeloid-derived suppressor cells (MDSC). Taken together, H9 induces the apoptotic death of tumor cells while increasing anti-tumor immune activity through the enhancement of NK activity and diminishment of MDSC.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.1 no.1
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• pp.167-190
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• 1995

Bikiwhan is one of the oriental medicines that have been used for the treatment of tumors since ancient times. However, the mechanism of the drug action is not closely surved. This study was made to investigate the effects of Bikiwhan on the innate immunity were analysed by measuring the functions of phagocytes, and those of specific immunity were analysed by measuring T and B cells activities. The followings are the results obtained from this study : 1. Bikiwhan has direct cytotoxic effects against human lymphoma cell lines (K562) in a dose dependent manner. 2. An administration of Bikiwhan increased allogenic immune response in the mouse. 3. An administration of Bikiwhan increased the antibodies formation against SRBC. 4. An administration of Bikiwhan enhanced the apperance of rosette forming cells in the spleen. 5. An administration of Bikiwhan decreased the delayed-type hypersensitivity against dinitrofluorobenzene. 6. An administration of Bikiwhan has no effect on natural killer cells. 7. Bikiwhan increased the phagocyte activity of peritoneal macrophages in vitro and in in vivo as well. 8. Bikiwhan depressed the formation of reactive oxygen intermediated in vitro and in vivo as well. 9. Bikiwhan has the capacity to make peritoneal macrophages secrete nitric oxide. The above results demonstrate that Bikiwhan has enhancing effects of immune responses against tumors by decreasing tissue demages caused by immune responses.

• Journal of Ginseng Research
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• v.33 no.4
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• pp.278-282
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• 2009

The in-vitro immunomodulatory function of the activity of murine natural-killer (NK) cells induced by redginseng acidic polysaccharide (RGAP) was examined. RGAP induced the significant enhancement of NK cell activity against the Yac-1 tumor cells. The treatment of splenocytes cultured with RGAP for 16 h resulted in a significant increase in NK activity at the E:T ratio of 100:1, and in a 239 and 250% increase at 10 and $100{\mu}g$/ml, respectively. We also demonstrate that RGAP treatment increased the production of interferon (IFN)-$\gamma$ (17-125%) and tumor necrosis factor (TNF)-${\alpha}$ (15-100%), suggesting that the increase in NK cell cytotoxicity could be due to the enhancement of the NK cell production of both cytokines. In addition, RGAP had a stimulating effect on lymphocyte proliferation in the presence of mitogens. Overall, these results suggest that RGAP has an immunopotentiating effect on NK cells, which can support the development of clinical studies on RGAP.

• Fisheries and Aquatic Sciences
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• v.26 no.2
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• pp.97-104
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• 2023

CD96 is a membrane-bound receptor discovered in humans in 1992 that is mainly present in natural killer cells and T cells derived from haematopoietic cells and performs immune functions. Based on the sequence of CD96 obtained from red seabream (Pagrus major), phylogenetic analysis with other species, infections of normal fish, Streptococcus iniae and red sea bream iridovirus (RSIV), and expression analysis was conducted using real-time polymerase chain reaction. Phylogenetic analysis showed the highest homology with Sparus aurata, and multiple sequence analysis confirmed the conservation of major domains between different fish species. Normal fish high expression results were confirmed in the head kidney, and spleen, which are the haematopoietic organs of the fish. High expression levels were confirmed in the gills, liver, spleen, and kidney on day three after RSIV infection. After S. iniae infection, high expression was confirmed in the gills and liver on day one, and high expression was confirmed in the spleen from 12 hours. These results show that PmCD96 functions as an immune gene in P. major and is considered a basic research case for CD96 in fish's hematopoietic organ immune system.

• Herbal Formula Science
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• v.30 no.4
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• pp.241-248
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• 2022

Objective : The purpose of this trial is to observe the preliminary effects of Salvia plebeia (SP) extract on quality of life in patients with solid cancer. Methods : This is a prospective, open-label, single-arm, and single-dose clinical trial. Twenty participants who have been diagnosed with solid cancer between the ages of 20 and 65 will be included. All participants will be administered SP granules for 12 weeks. Data will be collected at 4, 8, and 12 weeks after enrollment. The primary outcome is quality of life, using the Korean version of the Functional Assessment Cancer Therapy-General questionnaire. Secondary outcomes include tumor markers in blood tests for each cancer type, soluble programmed death-ligand 1, the percentage of natural killer cells among lymphocytes, ratio of T-helper and T-suppressor cells, ratio of total T, T-helper, T-suppressor, and B cells in lymphocytes, level of C-reactive protein, and tumor size via radiology examination. Safety will be assessed by clinical laboratory tests and monitoring of adverse events. Discussion : This study aims to observe the effects of an oral administration of SP preparations in patients with solid cancer on changes in quality of life and an improvement in immune function. It is expected to provide objective evidence of the effect and safety of SP for patients with solid cancer. Trial registration: KCT0007315 (Clinical Research Information Service)

• Radiation Oncology Journal
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• v.14 no.3
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• pp.229-236
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• 1996

Purpose : To evaluate the changes of differential counts and lymphocyte subsets in cancer patients' leukocyte before and after radiotherapy. Materials and Methods : From Dec. 1994 to Mar 1995, the changes of leukocyte and its subsets in 16 patients who received radiotherapy in the Dept. of Radiation Oncology of Dong-A University Hospital were investigated. Radiation was delivered from 2700 cGy to 6660 cGy with median dose of 5400 cGy. The results of pre- and Post-radiotherapy were analyzed by paired T-test. The results of patients Who received < 50 Gy and $\geq$ 50 Gy were analyzed by Wilcoxon test. Results : Before and after radiotherapy, there was not any significant differences in the counts of leukocyte, granulocyte and monocyte. A remarkable decrease was noted in lymphocyte counts after radiotherapy(p=0.015). T cells, B cells and natural killer cells were also decreased in number after radiotherapy but it was not significant statistically. 1 helper cells and T suppressor cells were also decreased in number(p>0.05). The ratio of T helper/suppressor cell was decreased from 1.52 to 1, 11 and it was significant statistically(p=0.016). The portion of T suppressor cell among all T cells was increased after radiotherapy (p=0.0195). No significant difference was observed in the analysis of leukocyte and its subsets between patients who received < 50 Gy and $\geq$ 50 Gy, Conclusion : Radiotherapy caused remarkable decrease in lymphocyte count and its subsets. Among all lymphocyte subsets, T helper cell might be the most vulnerable to radiation, considering decreased ratio of T helper/suppressor cell count after radiotherapy.

• Genomics & Informatics
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• v.14 no.3
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• pp.78-84
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• 2016

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them, KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggested KMT2D as a novel driver gene in NKTCL. Mutations were also found in ARID1A, a chromatin remodeling gene, and TP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future.

• Journal of Life Science
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• v.26 no.11
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• pp.1345-1354
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• 2016

Alopecia areata (AA) is a common and tissue-specific autoimmune disease of hair follicle resulting in the loss of hair on the scalp and elsewhere on the body. Hair follicles is a unique organ because it has its own immune system and hormonal milieu and has a different immune state at each hair cycle stage. The collapses of anagen-dependent hair follicle immune privilege arise autoimmune attack, inducing ectopic MHC class I expression in the hair follicle epithelium and autoantigen presentation to autoreactive CD8+T cells, which results in AA. Clinical and experimental studies have pointed that psychological stress may also influence the hair follicle immune/hormone systems and contribute to the induction of AA. The key pathogenesis of AA is associated with immune privilege guardians (including ACTH, ${\alpha}-MSH$, and $TGF-{\beta}$), natural killer group 2D-positive (NKG2D+) cells (including NK and CD8+T cells), and stress hormones (including CRH and substance P). Effective treatments for AA are still demanded. One of the future targets of treatment will be the modification of hair follicle immune privilege including stress. Recent studies have reported that JAK inhibitors and immunomodulators used in other autoimmune disease, such as psoriasis, atopic dermatitis, and rheumatoid arthritis, Tregs, platelet-rich plasma therapy, statins, and prostaglandin anaolgues are effective for AA. Here the article reviews the recent understanding in the pathogenesis associated with perifollicular endocrine/immunology and new treatments of AA.

• Journal of Microbiology and Biotechnology
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• v.16 no.10
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• pp.1605-1612
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• 2006

Interleukin (IL)-18, a member of the family of IL-l cytokine, is one of the principal inducers of $interferon-{\gamma}(IFN-{\gamma})$ in T lymphocytes and natural killer cells. The objective of the present study was to evaluate the effect of IL-18 on the expression of chemokine IP-10 (CXCL-10) mRNA in mouse peritoneal macrophages. IL-18 had very weak direct effect or synergistic effect with IL-12 on the expression of IP-10 mRNA in C57BL/6 mouse peritoneal macrophages. However, IL-18 pretreatment was found to playa cooperative role in the expression of lipopolysaccharide (LPS)-induced IP-10 mRNA. For the expression of LPS-induced IP-10 mRNA, the synergistic effect was detected after 16 h of IL-18 pretreatment prior to LPS stimulation. The expression level of CD14 in cells stimulated with LPS was not changed by IL-18 pretreatment, and the level of $IFN-{\gamma}$ production during IL-18 pretreatment plus LPS stimulation was barely discernible ($0.36{\pm}0.31pg/ml$). Namely, the synergistic effect of IL-18 pretreatment was not related to a change of LPS receptor, CD14 expression, and the production of $IFN-{\gamma}$ by the interaction between IL-18 and LPS. The synergistic effect of IL-18 pretreatment on the expression of LPS-induced IP-10 was related to not NF-kB but AP-1 activation, and associated with the extracellular signal-regulated kinase (ERK) pathway, one of the mitogen-activated protein kinase signaling pathways. These results provide useful information that may elucidate the mechanisms underlying the effect of IL-18 on the expression of IP-10 mRNA.