• Journal of Gastric Cancer
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• 제17권1호
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• pp.1-10
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• 2017

Gastric cancer (GC) has high mortality owing to its aggressive nature. Tumor angiogenesis plays an essential role in the growth, invasion, and metastatic spread of GC. The aim of this work was to review the angiogenic biomarkers related to the behavior of GC, documented in the literature. A search of the PubMed database was conducted with the MeSH terms: "Stomach neoplasms/blood [MeSH] or stomach neoplasms/blood supply [MeSH] and angiogenic proteins/blood [Major]". A total of 30 articles were initially collected, and 4 were subsequently excluded. Among the 26 articles collected, 16 examined the role of vascular endothelial growth factor (VEGF), 4 studied endostatin, 3 investigated angiopoietin (Ang)-2, 2 studied the Ang-like protein 2 (ANGTPL2), and 1 each examined interleukin (IL)-12, IL-8, and hypoxia inducible factor. Regarding VEGF, 6 articles concluded that the protein was related to lymph node metastasis or distant metastases. Five articles concluded that VEGF levels were elevated in the presence of GC and decreased following tumor regression, suggesting that VEGF levels could be a predictor of recurrence. Four articles concluded that high VEGF levels were correlated with poor prognosis and lower survival rates. Ang-2 and ANGTPL2 were elevated in GC and associated with more aggressive disease. Endostatin was associated with intestinal GC. VEGF is the most extensively studied angiogenic factor. It is associated with the presence of neoplastic disease and lymph node metastasis. It appears to be a good biomarker for disease progression and remission, but not for diagnosis. The data regarding other biomarkers are inconclusive.

• Parasites, Hosts and Diseases
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• 제52권5호
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• pp.459-469
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• 2014

Entamoeba histolytica is a tissue-invasive protozoan parasite causing dysentery in humans. During infection of colonic tissues, amoebic trophozoites are able to kill host cells via apoptosis or necrosis, both of which trigger IL-8-mediated acute inflammatory responses. However, the signaling pathways involved in host cell death induced by E. histolytica have not yet been fully defined. In this study, we examined whether calpain plays a role in the cleavage of pro-survival transcription factors during cell death of colonic epithelial cells, induced by live E. histolytica trophozoites. Incubation with amoebic trophozoites induced activation of m-calpain in a time- and dose-dependent manner. Moreover, incubation with amoebae resulted in marked degradation of STAT proteins (STAT3 and STAT5) and NF-${\kappa}B$ (p65) in Caco-2 cells. However, $I{\kappa}B$, an inhibitor of NF-${\kappa}B$, was not cleaved in Caco-2 cells following adherence of E. histolytica. Entamoeba-induced cleavage of STAT proteins and NF-${\kappa}B$ was partially inhibited by pretreatment of cells with a cell-permeable calpain inhibitor, calpeptin. In contrast, E. histolytica did not induce cleavage of caspase-3 in Caco-2 cells. Furthermore, pretreatment of Caco-2 cells with a calpain inhibitor, calpeptin (but not the pan-caspase inhibitor, z-VAD-fmk) or m-calpain siRNA partially reduced Entamoeba-induced DNA fragmentation in Caco-2 cells. These results suggest that calpain plays an important role in E. histolytica-induced degradation of NF-${\kappa}B$ and STATs in colonic epithelial cells, which ultimately accelerates cell death.

• Korean Journal of Microbiology
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• 제49권3호
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• pp.215-220
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• 2013

Against environmental stresses, many bacteria utilize the alternate sigma factor RpoS that induces transcription of the specific set of genes helpful in promoting bacterial survival. Intracellular levels of RpoS are determined mainly by its turnover through proteolysis of ClpXP protease. Delivery of RpoS to ClpXP strictly requires the adaptor protein RssB. The two-component-type response regulator RssB constantly interacts with RpoS, but diverse environmental changes inhibit this interaction through modification of RssB activity, which increases RpoS levels in bacteria. This review discusses and summarizes recent findings on regulatory factors in RssB-RpoS interactions, including IraD, IraM, IraP anti-adaptor proteins of RssB and phosphorylation of N-terminal receiver domain of RssB. New information shows that the coordinated regulation of RssB activity in controlling RpoS turnover confers efficient bacterial defense against stresses.

• Journal of Microbiology and Biotechnology
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• 제27권3호
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• pp.616-623
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• 2017

Ginsenoside Rg3, a saponin extracted from ginseng, has various pharmacological and biological activities; however, its effects against Brucella infection are still unclear. Herein, the inhibitory effects of ginsenoside Rg3 against intracellular parasitic Brucella infection were evaluated through bacterial infection, adherence assays, and LAMP-1 colocalization, as well as immunoblotting and FACS for detecting MAPK signaling proteins and F-actin polymerization, respectively. The internalization, intracellular growth, and adherence of Brucella abortus in Rg3-treated RAW 264.7 cells were significantly decreased compared with the Rg3-untreated control. Furthermore, an apparent reduction of F-actin content and intensity of F-actin fluorescence in Rg3-treated cells was observed compared with B. abortus-infected cells without treatment by flow cytometry analysis and confocal microscopy, respectively. In addition, treating cells with Rg3 decreased the phosphorylation of MAPK signaling proteins such as ERK 1/2 and p38 compared with untreated cells. Moreover, the colocalization of B. abortus-containing phagosomes with LAMP-1 was markedly increased in Rg3-treated cells. These findings suggest that ginsenoside Rg3 inhibits B. abortus infection in mammalian cells and can be used as an alternative approach in the treatment of brucellosis.

• Clinical and Experimental Reproductive Medicine
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• 제29권3호
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• pp.195-200
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• 2002

Objective : To investigate the expression of apoptosis related proteins and apoptotic cells on the human ovarian follicles. Materials and Methods: Thirty five Formalin-fixed paraffin-embedded human ovarian tissue blocks were selected from the surgical pathology files of the department of pathology, College of Medicine, Yonsei University, for the period from 1996 to 1998. All specimen were from premenopausal women aged from $32{\sim}45$. Ovarian tissues were collected from the patients performing hysterectomy for benign uterine diseases. Immunohistochemical staining was performed for the detection of DNA fragmented cell, Bcl-2, Bax, Fas and Fas-ligand. Results: Bcl-2 and bax were not expressed on the surrounding cells and oocyte of the primary, primordial and preantral follicles. Fas and Fas-ligand (Fas-L) were not expressed on the surrounding cells on the primordial and primary follicles. But expressed on the surrounding granulosa cells and oocyte in the primordial and primary follicles. In the healthy follicles, Bcl-2 was expressed on the granulosa cells, however, Bax was not expressed. DNA fragmented cells were expressed on the inner granulosa cell layer of atretic follicles. Conclusion: Fas, Fas-ligand, and Bax may be responsible for the follicular atresia and Bcl-2 may be involved in the follicular survival in the human ovary.

• Journal of Pharmacopuncture
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• 제12권3호
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• pp.49-59
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• 2009

Background : Anticancer effects of herbal medicine have been reported in various types of cancer, but the systematic approaches to explain molecular mechanism(s) are not established yet. Objective : The purpose of this study is to investigate the apoptotic cell death by Egg White combined Chalcanthite in NCI-H460 human lung cancer cells. Methods : Inhibitory effects were estimated by the MTT-assay. Cancer cells were stained with DAPI and showed condensed and fragmented nuclei. The expression of cleaved caspase-3, bcl-2, and bax was detected by western blotting. To establish a basis of understanding for anti-cancer mechanism, whole proteins have been obtained from NCI-H460 harvested at 24 hrs after the treatment of Egg White combined Chalcanthite, protein expression has been profiled by 2DE-based proteomic approach. Results : NCI-H460 human lung cancer cells were treated by three samples of IS3, IS4 and IS5. IS4 inhibited most effectively the growth of NCI-H460 human lung cancer cells. The expression of cleaved caspase-3 increased in IS4 in a concentration-dependent manner. Various changes of the protein expression have been monitored, and most frequent dysregulation was found in Vimentin, Lamin-A/C. Conclusion : Egg White combined-Chacanthite inhibited the growth of NCI-H460 human lung cancer cells by inducing the apoptotic cell death via caspase-3 activation. Based upon the present findings, the further study will focus on monitoring various cancer survival factors after artificial regulation of the proteins identified, and it would be the basis for the understanding of the Chacabthite anticancer effect(s) at the molecular level.

• International Journal of Oral Biology
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• 제33권2호
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• pp.71-76
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• 2008

The neurotrophin plays an important role in the development, differentiation and survival of the nervous system in vertebrates. It exerts its cellular effects through two different receptors, the Trk receptor tyrosine kinase neurotrophin receptor and the p75 neurotrophin receptor, a member of the tumor necrosis factor receptor superfamily. Trk and p75 neurotrophin receptors utilize specific target proteins to transmit signals into the cell. An ankyrin-rich membrane spanning protein (ARMS) was identified as a new p75 interacting protein and serves as a novel downstream target of p75 neurotrophin receptor. We sought to delineate the interaction between p75 and ARMS by deletion constructs of p75 and green fluorescent protein (GFP)-tagged ARMS. We examined the interaction between these two proteins after overexpressing them in HEK-293 cells. Using both Western blot analysis and immunocytochemistry followed by confocal laser scanning microscopy, we found out that the intracellular domain of the p75 neurotrophin receptor was important for the interaction with ARMS. The results from this study suggest that ARMS may play an important role for mediating the signals from p75 neurotrophin receptor into the cell.

• KSBB Journal
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• 제28권5호
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• pp.303-309
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• 2013

The extract from Lysimachia foenum-graecum (LFE) has been known to possess various instructive characters including anti-oxidant, anti-obesity, fungicidal activities. However, the accurate mechanism of those effects of LFE is not well known. In that respect, we evaluated the apoptotic effect and anti-cancer efficacy of extracts of LFE in MCF-7 breast cancer cells. In this study, we hypothesized that LFE may exert cancer cell apoptosis through regulating p53 and mitochondria-mediated apoptotic proteins. And this substance can generate ROS to cause free radical-induced apoptosis. Accordingly, the generation of ROS by LFE triggers the activation of p53 which are accompanied by pro-apoptotic protein activation and suppression of pro-survival proteins. We determined with MTT assay, flow cytometry for detection of intracellular ROS and Annexin V-PI staining, Western blotting. Consequently, our researches demonstrated that the treatment of LFE to breast cancer cells resulted in an activation of p53, Puma, Bax, cleaved-PARP and an inhibition of Bcl-2 expressions.

• Korean journal of applied entomology
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• 제36권3호
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• pp.256-263
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• 1997

Supercooling points (SCP) and cold tolerance of the tobacco cutworm, Spodol~rera litura Fabricius. were measured in response to subzero temperatures. SCPs were varied among developmental stages. Eggs showed the lowest SCP (-27$^{\circ}$C). Pupae and adults had the intermediate SCP(- 18$^{\circ}$C). The SCPs (- I0 to - 16$^{\circ}$C) of larvae increased with their ages. Lethal low temperature of each stage was higher than its SCP. Preexposure of eggs and larvae to a sublethal low temperature increased their survival capacities under lethal low temperatures. The sublethal temperature also induced the fifth instar larvae to increase hemolymph osmolality and to produce cold-induced proteins of apparent molecular weights of 20 and 27 kD. These results indicate that this species is classified into a freeze-susceptible insect.

• BMB Reports
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• 제51권10호
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• pp.508-513
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• 2018

Fibronectin fragments found in the synovial fluid of patients with osteoarthritis (OA) induce the catabolic responses in cartilage. Nuclear high-mobility group protein Box 1 (HMGB1), a damage-associated molecular pattern, is responsible for the regulation of signaling pathways related to cell death and survival in response to various stimuli. In this study, we investigated whether changes induced by 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) in HMGB1 expression influences the pathogenesis of OA via an HMGB1-modulated autophagy signaling pathway. Human articular chondrocytes were enzymatically isolated from articular cartilage. The level of mRNA was measured by quantitative real-time PCR. The expression of proteins was examined by western blot analysis, immnunofluorescence assay, and enzyme-linked immunosorbent assay. Interaction of proteins was evaluated by immunoprecipitation. The HMGB1 level was significantly lower in human OA cartilage than in normal cartilage. Although 29-kDa FN-f significantly reduced the HMGB1 expression at the mRNA and protein levels 6 h after treatment, the cytoplasmic level of HMGB1 was increased in chondrocytes treated with 29-kDa FN-f, which significantly inhibited the interaction of HMGB1 with Beclin-1, increased the interaction of Bcl-2 with Beclin-1, and decreased the levels of Beclin-1 and phosphorylated Bcl-2. In addition, the level of microtubule-associated protein 1 light chain 3-II, an autophagy marker, was down-regulated in chondrocytes treated with 29-kDa FN-f, whereas the effect was antagonized by mTOR knockdown. Furthermore, prolonged treatment with 29-kDa FN-f significantly increased the release of HMGB1 into the culture medium. These results demonstrated that 29-kDa FN-f inhibits chondrocyte autophagy by modulating the HMGB1 signaling pathway.