Background: Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West. Methods: A genetically engineered $Apc^{Min/+}$ mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis. Results: After oral ginseng administration (10-20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-$1{\alpha}$ (IL-$1{\alpha}$), IL-$1{\beta}$, IL-6, tumor necrosis factor-${\alpha}$, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01). Conclusion: Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention.
Park, Young-Su;Lee, Kang-Joon;Kim, Hyun;Chung, Young-Cho
Sleep Medicine and Psychophysiology
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v.11
no.2
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pp.100-105
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2004
Objectives: Major depression is associated with an increased risk of cardiovascular mortality. One possible explanation for this association is that major depression influences autonomic neurocardiac regulation. However, previous studies on the relationship between heart rate variability (HRV) and major depression have revealed conflicting results. The purpose of this study is to clarify that major depressive patients compared to healthy controls show a reduction in HRV as an expression of reduced modulation of vagal activity to the heart. Methods: According to DSM-IV, the time and frequency domain HRV indices (5-min resting study) of 30 patients with major depressive disorder were compared with those of 30 healthy controls. Standardized HRV tests enable quantitative estimation of autonomic nervous system function. Results: After controlling for age and gender, subjects with major depression showed a higher heart rate and significantly lower modulation of cardiovagal activity compared to controls. The total power (TP) band, very low frequency (VLF: 0.003-0.04 Hz) band, low frequency (LF: 0.04-0.15 Hz) band, and high frequency (HF: 0.15-0.4 Hz) band were significantly reduced in subjects with major depression compared to control subjects. Conclusion: Patients with major depression may suffer from functional disturbances in the interaction between the sympathetic and parasympathetic autonomic systems.
Secondary prevention via earlier detection would afford the greatest chance for a cure in premalignant lesions. We investigated the exomic profiles of non-malignant and malignant changes in head and neck squamous cell carcinoma (HNSCC) and the genomic blueprint of human papillomavirus (HPV)-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC). Whole-exome (WES) and whole-genome (WGS) sequencing were performed on peripheral blood and adjacent non-tumor and tumor specimens obtained from eight Korean HNSCC patients from 2013 to 2015. Next-generation sequencing yielded an average coverage of $94.3{\times}$ for WES and $35.3{\times}$ for WGS. In comparative genomic analysis of non-tumor and tumor tissue pairs, we were unable to identify common cancer-associated early mutations and copy number alterations (CNA) except in one pair. Interestingly, in this case, we observed that non-tumor tonsillar crypts adjacent to HPV-positive OPSCC appeared normal under a microscope; however, this tissue also showed weak p16 expression. WGS revealed the infection and integration of high-risk type HPV16 in this tissue as well as in the matched tumor. Furthermore, WES identified shared and tumor-specific genomic alterations for this pair. Clonal analysis enabled us to infer the process by which this transitional crypt epithelium (TrCE) evolved into a tumor; this evolution was accompanied by the subsequent accumulation of genomic alterations, including an ERBB3 mutation and large-scale CNAs, such as 3q27-qter amplification and 9p deletion. We suggest that HPV16-driven OPSCC carcinogenesis is a stepwise evolutionary process that is consistent with a multistep carcinogenesis model. Our results highlight the carcinogenic changes driven by HPV16 infection and provide a basis for the secondary prevention of OPSCC.
Neoliberalism became a catch word of a post-cold war era. It began to develop in the middle of welfare state crisis in developed countries. It promoted both a unified world market through mutual penetration of national boundaries in International scene and maximization of efficiency through market competition in domestic scene. Privatization of public corporations is a major policy to pursue market efficiency through deregulation. Two reasons are often adduced to support the cause The socio-economic changes diminished the necessity to establish public corporation on the one hand. On the other hand gross inefficiency has been observed in the management of public corporation. 'Government failure' is an apt expression of the inefficiency. In analysing the experiences of privatization of utility industries of some other countries we found a couple of lessons for a Korean case. First, it is doubtful if privatization, that is a change in the form of ownership, is a necessary condition for achieving market efficiency. Because it is possible to operate a mechanism of market competition while maintaining competition among public corporations and with private actors. Second, the patron-agent dilemma is often cited as a major culprit of an inefficient management of public corporations. But it is without saying that the dilemma is also found in the management of private firms. So, the issue is not the privatization per se but to realize responsible management through discipline and incentives.
Hu, Bo;Liang, Minjian;Hong, Guoqiang;Li, Zhaoxia;Zhu, Zhenyu;Li, Lin
BMB Reports
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v.38
no.6
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pp.683-689
/
2005
Antibody to hepatitis B surface antigen (HBsAb) is the important serological marker of the hepatitis B virus (HBV) infection. Conventionally, the hepatitis B surface antigen (HBsAg) obtained from the plasma of HBV carriers is used as the diagnostic antigen for detection of HBsAb. This blood-origin antigen has some disadvantages involved in high cost, over-elaborate preparation, risk of infection, et al. In an attempt to explore the suitable recombinant HBsAg for the diagnostic purpose, the HBV S gene was expressed in Pichia pastoris and the product was applied for detection of HBsAb. Hepatitis B virus S gene was inserted into the yeast vector and the expressed product was analyzed by sodium dodecyl sulphate polyacrolamide gel electrophoresis (SDS-PAGE), immunoblot, electronic microscope and enzyme linked immunosorbent assay (ELISA). The preparations of synthesized S protein were applied to detect HBsAb by sandwich ELISA. The S gene encoding the 226 amino acid of HBsAg carrying ahexa-histidine tag at C terminus was successfully expressed in Pichia pastoris. The His-Tagged S protein in this strain was expressed at a level of about 14.5% of total cell protein. Immunoblot showed the recombinant HBsAg recognized by monoclonal HBsAb and there was no cross reaction between all proteins from the host and normal sera. HBsAb detection indicated that the sensitivity reached 10 mIu (micro international unit)/ml and the specificity was 100% with HBsAb standard of National Center for Clinical Laboratories. A total of 293 random sera were assayed using recombinant S protein and a commercial HBsAb ELISA kit (produced by blood-origin HBsAg), 35 HBsAb positive sera and 258 HBsAb negative sera were examined. The same results were obtained with two different reagents and there was no significant difference in the value of S/CO between the two reagents. The recombinant HBV S protein with good immunoreactivity and specificity was successfully expressed in Pichia pastoris. The reagent for HBsAb detection prepared by Pichia pastoris-derived S protein showed high sensitivity and specificity for detection of HBsAb standard. And a good correlation was obtained between the reagent produced by recombinant S protein and commercial kit produced by blood-origin HBsAg in random samples.
Insect-resistant transgenic rice was developed by inserting the mCry1Ac1 a modified gene from the soil bacterium Bacillus thuringiensis (Bt). For biosafety assessment, we studied the effects on survival of cantor Daphnia magna, a commonly used as a model organism in ecotoxicological studies. D. magna fed on Bt rice and its near non-genetically modified (GM) counterparts (Nakdong) grown in the same environment (100% ground rice suspension). The Bt rice was comfirmed to have the insertion of T-DNA and protein expression by the polymerase chain reaction and ELISA analysis. Feeding study showed similar cumulative immobility and abnormal response of D. magna between Bt rice and non-GM counterparts. 48 h-$EC_{50}$ values of Bt rice and non-GM rice showed 4,429 and 2,889 mg/L respectively. The rice no observed effect concentration (NOEC) values for D. magna was suggested 1,000 mg/L. We conclude that the tested Bt-rice and Nakdong similar cumulative immobility for D. magna the widely used model organism. We found out that there is strong possibility that the growth of Bt rice didn't affect to non-target insects.
This study analyzes the legal reasoning of Seoul Central District Court, which imposed legal liability on portals for posting defamatory user replies to news articles, written and provided by the news media, onto their 'News Windows'. Saddling portals with the burden of verifying the facts associated in news articles and imposing the legal obligation as a publisher entail a grave risk of impairment of free flow of information and freedom of expression. Of course, it would ultimately result in tightening up private censorship of information which the Constitution does not allow, and funker keep portals from posting even news articles in which expressed views and opinions are lawful. When judging whether portals should assume liability fur libelous user replies to news articles, it is necessary to distinguish the territory under the direct authority of portals from cafes and bulletin boards managed by third parties. In addition, imposing legal liability above the level of common carrier should be limited to the cases; when portals arbitrarily change the contents of news articles or when the articles portals changed contain libelous contents. Even if those conditions are met, the altered contents should obviously constitute libel. Only in the presence of proof that portals knew the illegality of news articles and did not take proper steps including deleting those replies, should portals not be considered as an accomplice. Nor should portals take responsibility for users' defamatory replies for those reasons.
Park, Jin-Hong;Kwon, Jung-Taek;Minai-Teherani, Arassh;Hwang, Soon-Kyung;Chang, Seung-Hee;Lim, Hwang-Tae;Cho, Hyun-Seon;Cho, Myung-Haing
Toxicological Research
/
v.26
no.4
/
pp.261-266
/
2010
In the workplace, the arsenic is used in the semiconductor production and the manufacturing of pigments, glass, pesticides and fungicides. Therefore, workers may be exposed to airborne arsenic during its use in manufacturing. The purpose of this study was to evaluate the potential toxicity of particulate matters (PMs) doped with arsenic (PMs-Arsenic) using a rodent model and to compare the genotoxicity in various concentrations and to examine the role of PMs-Arsenic in the induction of signaling pathway in the lung. Mice were exposed to PMs $124.4{\pm}24.5\;{\mu}g/m^3$ (low concentration), $220.2{\pm}34.5\;{\mu}g/m^3$ (middle concentration), $426.4{\pm}40.3\;{\mu}g/m^3$ (high concentration) doped with arsenic $1.4\;{\mu}g/m^3$ (Low concentration), $2.5\;{\mu}g/m^3$ (middle concentration), $5.7\;{\mu}g/m^3$ (high concentration) for 4 wks (6 h/d, 5 d/wk), respectively in the whole-body inhalation exposure chambers. To determine the level of genotoxicity, Chromosomal aberration (CA) assay in splenic lymphocytes and Supravital micronucleus (SMN) assay were performed. Then, signal pathway in the lung was analyzed. In the genotoxicity experiments, the increases of aberrant cells were concentration-dependent. Also, PMs-arsenic caused peripheral blood micronucleus frequency at high concentration. The inhalation of PMs-Arsenic increased an expression of phosphorylated Akt (p-Akt: protein kinase B) and phpsphorylated mammalian target of rapamycin (p-mTOR) at high concentration group. Taken together, inhaled PMs-Arsenic caused genotoxicity and altered Akt signaling pathway in the lung. Therefore, the inhalation of PMs-Arsenic needs for a careful risk assessment in the workplace.
Roh, Seung-Young;Kim, Ji Yeon;Cha, Hyo Kyeong;Lim, Hye Young;Park, Youngran;Lee, Kwang-No;Shim, Jaemin;Choi, Jong-Il;Kim, Young-Hoon;Son, Gi Hoon
Molecules and Cells
/
v.43
no.4
/
pp.408-418
/
2020
The sinus node (SN) is located at the apex of the cardiac conduction system, and SN dysfunction (SND)-characterized by electrical remodeling-is generally attributed to idiopathic fibrosis or ischemic injuries in the SN. SND is associated with increased risk of cardiovascular disorders, including syncope, heart failure, and atrial arrhythmias, particularly atrial fibrillation. One of the histological SND hallmarks is degenerative atrial remodeling that is associated with conduction abnormalities and increased right atrial refractoriness. Although SND is frequently accompanied by increased fibrosis in the right atrium (RA), its molecular basis still remains elusive. Therefore, we investigated whether SND can induce significant molecular changes that account for the structural remodeling of RA. Towards this, we employed a rabbit model of experimental SND, and then compared the genome-wide RNA expression profiles in RA between SND-induced rabbits and sham-operated controls to identify the differentially expressed transcripts. The accompanying gene enrichment analysis revealed extensive pro-fibrotic changes within 7 days after the SN ablation, including activation of transforming growth factor-β (TGF-β) signaling and alterations in the levels of extracellular matrix components and their regulators. Importantly, our findings suggest that periostin, a matricellular factor that regulates the development of cardiac tissue, might play a key role in mediating TGF-β-signaling-induced aberrant atrial remodeling. In conclusion, the present study provides valuable information regarding the molecular signatures underlying SND-induced atrial remodeling, and indicates that periostin can be potentially used in the diagnosis of fibroproliferative cardiac dysfunctions.
In this study, nitric oxide (NO) production in a macrophage-lymphocyte co-culture system was used to assess the cytokine producing capability of cells during endotoxin tolerance in mice. Incubation of peritoneal macrophages with interferon-$\tau$ (IFN-$\tau$) in the presence of lipopolysaccharide (LPS) augmented NO synthesis. Exogenous tumor necrosis factor-$\alpha$(TNF-$\alpha$) could also replace LPS for the stimulation of NO production. Macrophages co-cultured with splenic lymphocytes showed augmented NO synthesis by LPS alone. However, pretreatment of mice with 2.5 mg/kg LPS completely prevented the lethality and the increase of blood TNF-$\alpha$ and IFN-$\tau$ after the second challenge with a lethal dose of LPS. In addition, when macrophages prepared from LPS-tolerant mice were co-cultured with normal splenocytes, LPS also could not induce the production of NO, even in the presence of exogenous TNF-$\alpha$. Moreover, when normal macrophages were co-cultured with splenocytes obtained from LPS-tolerant mice, stimulation with LPS could not evoke the NO production enhancement. However, this down-regulation was able to reverse by exogenous IFN-$\tau$ or concanavalin A (ConA), a stimulator of IFN-$\tau$ production. Our results indicate that not only macrophages but also lymphocytes contribute to LPS tolerance. As INF-$\tau$ can enhance the expression of TNF-$\alpha$, the decrease of INF-$\tau$synthesis from lymphocytes may orchestrate with the decrease of TNF-$\alpha$ synthesis from LPS-tolerant macrophages for the production of tolerant state and the prevention of excessive inflammation. Therefore, LPS tolerance may be exploited for prophylaxis of severe sepsis in patients at risk.
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