• Journal of Ginseng Research
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• 제44권4호
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• pp.580-592
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• 2020

Background: Radix et Rhizoma Ginseng (thereafter called ginseng) has been used as a medicinal herb for thousands of years to maintain people's physical vitality and is also a non-organ-specific cancer preventive and therapeutic traditional medicine in several epidemiologic and preclinical studies. Owing to few toxic side effects and strong enhancement on body immunity, ginseng has admirable application potential and value in cancer chemoprevention. The study aims at investigating the chemopreventive effects of ginseng on cutaneous carcinoma and the underlying mechanisms. Methods: The mouse skin cancer model was induced by 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate. Ultraperformance liquid chromatography/mass spectrometry was used for identifying various ginsenosides, the main active ingredients of ginseng. Comprehensive approaches (including network pharmacology, bioinformatics, and experimental verification) were used to explore the potential targets of ginseng. Results: Ginseng treatment inhibited cutaneous carcinoma in terms of initiation and promotion. The content of Rb1, Rb2, Rc, and Rd ginsenosides was the highest in both mouse blood and skin tissues. Ginseng and its active components well maintained the redox homeostasis and modulated the immune response in the model. Specifically, ginseng treatment inhibited the initiation of skin cancer by enhancing T-cell-mediated immune response through upregulating HSP27 expression and inhibited the promotion of skin cancer by maintaining cellular redox homeostasis through promoting nuclear translocation of Nrf2. Conclusion: According to the study results, ginseng can be potentially used for cutaneous carcinoma as a chemopreventive agent by enhancing cell-mediated immunity and maintaining redox homeostasis with multiple components, targets, and links.

• IMMUNE NETWORK
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• 제11권3호
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• pp.135-154
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• 2011

The great discovery of microRNAs (miRNAs) has revolutionized current cell biology and medical science. miRNAs are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region of specific messenger RNAs for degradation or translational repression. New members of the miRNA family are being discovered on a daily basis and emerging evidence has demonstrated that miRNAs play a major role in a wide range of developmental process including cell proliferation, cell cycle, cell differentiation, metabolism, apoptosis, developmental timing, neuronal cell fate, neuronal gene expression, brain morphogenesis, muscle differentiation and stem cell division. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as cancer, psychiatric and neurological diseases, cardiovascular disease, and autoimmune disease. Interestingly, in addition, miRNA deficiencies or excesses have been correlated with a number of clinically important diseases ranging from cancer to myocardial infarction. miRNAs can repress the gene translation of hundreds of their targets and are therefore well-positioned to target a multitude of cellular mechanisms. As a consequence of extensive participation in normal functions, it is quite logical to ask the question if abnormalities in miRNAs should have importance in human diseases. Great discoveries and rapid progress in the past few years on miRNAs provide the hope that miRNAs will in the near future have a great potential in the diagnosis and treatment of many diseases. Currently, an explosive literature has focussed on the role of miRNA in human cancer and cardiovascular disease. In this review, I briefly summarize the explosive current studies about involvement of miRNA in various human cancers and cardiovascular disease.

• Journal of Microbiology and Biotechnology
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• 제27권10호
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• pp.1855-1866
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• 2017

The synergistic activation mediator (SAM) system can robustly activate endogenous gene expression by a single-guide RNA. This transcriptional modulation has been shown to enhance gene promoter activity and leads to epigenetic changes. Human $interferon-{\gamma}$ is a common natural glycoprotein involved in antiviral effects and inhibition of cancer cell growth. Large quantities of high-purity $interferon-{\gamma}$ are important for medical research and clinical therapy. To investigate the possibility of employing the SAM system to enhance endogenous human $interferon-{\gamma}$ with normal function in innate immunity, we designed 10 single-guide RNAs that target 200 bp upstream of the transcription start sites of the $interferon-{\gamma}$ genome, which could significantly activate the $interferon-{\gamma}$ promoter reporter. We confirmed that the system can effectively and highly activate $interferon-{\gamma}$ expression in several humanized cell lines. Moreover, we found that the $interferon-{\gamma}$ induced by the SAM system could inhibit tumorigenesis. Taken together, our results reveal that the SAM system can modulate epigenetic traits of non-immune cells through activating $interferon-{\gamma}$ expression and triggering JAK-STAT signaling pathways. Thus, this strategy could offer a novel approach to inhibit tumorigenesis without using exogenous $interferon-{\gamma}$.

• Asian-Australasian Journal of Animal Sciences
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• 제24권7호
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• pp.889-897
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• 2011

Mycoplasma Pneumonia of swine (MPS) decreases the daily growth of pigs, and, co-infection with a virus sometimes causes severe pneumonia. Genetic selection of pigs resistant to the pulmonary MPS lesion might solve the economic loss due to MPS in animal production. Here, we examined the immunophenotype of Landrace line (Miyagino L2), genetically selected to reduce the incidence of pulmonary MPS lesion for 5 generations in Miyagi Prefecture Animal Industry Experiment Station. Although this line is expected to be resistant to the pulmonary MPS lesion, the biological characteristics of its immune function are not clear. We investigated details of the immunorelated phenotype of Miyagino L2 at the hematological and molecular biological level, including cytokine expression, and compared the results with that of non-genetically selected Landrace. Miyagino L2 showed decreased antigen-specific IgG and IgM production and increased CD8-positive T-cell population, and high levels of cortisol concentration, suggesting that the MPS-resistant phenotype is associated these immunological differences. Additionally, T-cell CD4 expression was highly correlated with the MPS expected breeding value. Although the detailed mechanisms underlying this high correlation remain unknown, our result suggested that the genetic selection of the expression level of CD4 might be useful to improve MPS resistance in pig production.

• Pediatric Infection and Vaccine
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• 제8권2호
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• pp.222-228
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• 2001

아직도 우리나라에서는 미국과 같은 선진국과 비교해 폐결핵의 유병률이 높은 상태이다. 그리고 높은 폐결핵 발생과 함께 장결핵의 발생도 높을 것으로 예상되나 정확한 통계 및 연구는 미비한 실정이다. 또한, 발생 가능성이 높을 것으로 예상되는 장결핵에 의한 영양실조에 대한 관심도 부족한 실정이다. 저자 등은 결핵 발생이 현격하게 감소되지 않는 한 앞으로도 계속 발생할 수 있는 장결핵에 의한 영양실조의 가능성을 상기하고자 장결핵에 의한 영양실조 1례를 경험하였기에 문헌 고찰과 함께 보고하는 바이다.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제33권1호
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• pp.26-31
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• 2011

Purpose: Chronic inflammatory gingival lesions occur as pyogenic granulomas or non-specific chronic suppurative lesions. Methods: Of the 59 chronic inflammatory gingival lesions examined, plasma cell granuloma (n=14), which showed an intense antibody-mediated immune reaction with the increased infiltration of plasma cells, was observed as a pseudotumor-like gingival overgrowth and myofibroblastic or fibrohistiocytitc proliferation of stromal cells with a heavy collection of plasma cells. The levels of CD3, CD20, CD31, CD68, RANKL, cathepsin G, cathepsin K, lysozyme, TNF${\alpha}$, MMP-2, and MMP-9 in the 14 cases of gingival plasma cell granuloma with immunohistochemical detection were measured to determine the pathogenetic progresses of the plasma cell granuloma compared to the common pyogenic granuloma (n=45) in the gingiva. Results: The gingival lesions of the plasma cell granuloma could be divided into three histological types, plasma cell predominant type (PPT, n=8), mixed inflammatory cell type (MICT, n=2), and sclerosed fibrosis type (SFT, n=4). The PPT showed a condensed infiltration of plasma cells into the perivascular spaces of the granulomatous lesion with frequent formation of Russel's body in their cytoplasm. The MICT showed the concomitant infiltration of many macrophages together with plasma cells, resulting in the diffuse destruction of stromal fibrous tissue. The SFT showed granulomatous lesions replaced gradually by thick collagenous fibrous tissue, resembling an inflammatory pseudotumor. The SFT expressed strongly the lymphocytic markers, CD3 and CD20, and the macrophage/monocyte markers, CD31 and CD68, but showed reduced expression of common inflammatory markers, TNF${\alpha}$, cathepsin G, lysozyme, MMP-2, and MMP-9, as well as the reduced expression of osteoclastogenic markers, RANKL and cathepsin K. Conclusion: These results suggest that a gingival plasma cell granuloma shows variable gene expression for cell-mediated immunity and stromal tissue degeneration, undergoing sclerotic fibrosis with a persistent inflammatory reaction.

• BMB Reports
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• 제38권6호
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• pp.661-667
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• 2005

Since conflicting results have been reported on non-specific immune response in type 1 diabetes, this study evaluates polymorphonuclear neutrophil (PMN) functions in the infection free Long Evan diabetic rats (type 1) by using tests that include: polarization assay, phagocytosis of baker's yeasts (Saccharomyces cerevisiae) and nitroblue tetrazolium (NBT) dye reduction. Polarization assay showed that neutrophils from diabetic rats were significantly activated at the basal level compared to those from the controls (p < 0.001). After PMN activation with N-formyl-methionyl-leucyl-phenylalanine (FMLP), control neutrophils were found to be more polarized than those of the diabetic neutrophils and the highest proportions of polarization were found to be 67% and 57% at $10^{-7}\;M$ FMLP, respectively. In the resting state, neutrophils from the diabetic rats reduced significantly more NBT dye than that of the controls (p < 0.001). The percentages of phagocytosis of opsonized yeast cells by the neutrophils from control and diabetic rats were 87% and 61%, respectively and the difference was statistically significant (p < 0.001). Evaluation of the phagocytic efficiency of PMNs revealed that control neutrophils could phagocytose $381{\pm}17$ whereas those from the diabetic rats phagocytosed $282{\pm}16$ yeast cells, and the efficiency of phagocytosis varied significantly (p < 0.001). Further, both the percentages of phagocytosis and the efficiency of phagocytosis by the diabetic neutrophils were inversely related with the levels of their corresponding plasma glucose (p = 0.02; r = -0.498 and p < 0.05; r = -0.43, respectively), which indicated that increased plasma glucose reduced the phagocytic ability of neutrophils. Such relationship was not observed with the control neutrophils. These data clearly indicate that PMN functions are altered in the streptozotocin (STZ) - induced diabetic rats, and hyperglycemia may be the cause for the impairment of their functions leading to many infectious episodes.

• Reproductive and Developmental Biology
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• 제39권4호
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• pp.105-115
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• 2015

Toll-like receptor 7 (TLR7) is critical for the triggering of innate immune response by recognizing the conserved molecular patterns of single-stranded RNA (ssRNA) viruses and mediated antigenic adaptive immunity. To understand how TLR7 distinguish pathogen-derived molecular patterns from the host self, it is essential to be able to identify TLR7 receptor interaction interfaces, such as active sites or R848-agonist binding sites. The functional interfaces of TLR7 can serve as targets for structure-based drug design in studying the TLR7 receptor's structure-function relationship. In contrast to mammalian TLR7, chicken TLR7 (chTLR7) is unknown for its important biological function. Therefore, it has been targeted to mediate contrasting evolutionary patterns of positive selection into non-synonymous SNPs across eleven species using TLR7 conservation patterns (evolutionary conserved and class-specific trace residues), where protein sequence differences to the TLR7 receptors of interest record mutation that have passed positive section across the species. In this study, we characterized the Lys609 residue on chTLR7-ECD homodimer interfaces to reflect the current tendency of evolving positive selection to be transfer into a stabilization direction of the R848-agonist/chTLR7-ECDs complex under the phylogenetically variable position across species and we suggest a potential indicator for contrasting evolutionary patterns of both the species TLR-ECDs.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6905-6910
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• 2014

Background: The relation ofsurvivin gene expression to survival and surgical prognostic factors in the patients with endometrial carcinoma is unclear. Materials and Methods: In this study, 62 cases who were operated due to endometrial carcinoma were investigated between 2003 and 2011 in the the gynecological oncology clinic of Female Disease Training and Investigation Hospital of Etlik Zubeyde, Hanim, Turkey. Clinical and surgical prognostic factors were investigated by screening the records of these cases. With the standard streptavidin-biotin immune peroxidase method, cytoplasmic and nuclear expression of survivin was investigated in sections with specific antibodies (1:100, diagnostic Bio Systems, USA) primer. The aim was to elucidate any relation between survivin expression and defined prognostic factors and survival. Results: There was no statistically significant relationship between cytoplasmic and nuclear indexes identified for survivin and age, body mass index, the levels of preoperative hemoglobin, platelet and Ca 125, stage, grade, lymph node meastasis, the number of meta statical lymph nodes (total, paraaortic and pelvic), myometrial invasion, serosal invasion, adnexal involvement, the presence of acid in the first diagnosis, the involvement of omentum, the adjuvant treatment application of the cases, the presence of recurrence and rate of mortality (p>0.05). Statistical significance was noted for the presence of advanced stage lymph node metastasis (pelvic, paraaortic, pelvic and paraaortic), serosal involvement, positive cytology, lymph vascular space invasion, intra abdominal metastasis, and omentum involvement. When investigated the relation between cytoplasmic and nuclear survivin indexes and total survival, the result was not statistically significant (p>0.05). Conclusions: In our study, there was no statistically significant relationship between the rates of cytoplasmic and nuclear survivin expression with identified prognostic factors and total or non-disease survival.

• 한국수산과학회지
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• 제46권4호
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• pp.399-406
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• 2013

Our aim was to determine the effects of a citrus by-product (CBP) and CBP fermented by Lactobacillus plantarum (LP-CBP), provided as dietary supplements, on the growth performance, feed utilization, innate immunity and temperature tolerance of red seabream. A diet without inclusion of CBP or LP-CBP was used as a control and four other experimental diets were formulated to replace wheat flour by 4% and 8% of either CBP or LP-CBP (designated as Con, LP-CBP4%, LP-CBP8%, CBP4% and CBP8%, respectively). Experimental diets were fed to triplicate groups of 25 fish (initial body weight, 55.0 g) for 9 weeks. Growth performance and feed utilization were not significantly different among all the groups. Bone collagen content was significantly increased by supplementation with CBP and LP-CBP. Vitamin C concentration tended to be higher in livers of fish fed the supplements than in the control group. Myeloperoxidase, lysozyme and superoxide dismutase activities were higher in fish fed CBP or LP-CBP than in fish fed the control diet. When fish were exposed to low water temperature, cumulative mortalities of those fed CBP or LP-CBP supplemented diets were lower (29%, 33%, 34% and 33% mortalities for LP-CBP4%, LP-CBP8%, CBP4% and CBP8%, respectively) than in the control group (58%). Therefore, inclusion of either CBP or LP-CBP at up to 8% in red seabream diet brings benefits through enhanced innate immunity and better tolerance of low water temperature.