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        Adenosine triphosphate-based chemotherapy response assay-guided chemotherapy in unresectable colorectal liver metastasis

        Hur, H,Kim, N K,Kim, H G,Min, B S,Lee, K Y,Shin, S J,Cheon, J H,Choi, S H Nature Publishing Group 2012 The British journal of cancer Vol.106 No.1

        <P><B>Background:</B></P><P>This study aims to evaluate the effectiveness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided neoadjuvant chemotherapy for increasing resectability in patients with unresectable colorectal liver metastasis.</P><P><B>Patients and methods:</B></P><P>Patients were randomised into two groups: Group A was treated by conventional chemotherapy regimen and Group B was treated by chemotherapy regimen according to the ATP-CRA. Three chemotherapeutic agents (5-fluorouracil, oxaliplatin and irinotecan) were tested by ATP-CRA and more sensitive agents were selected. Either FOLFOX or FOLFIRI was administered. Between Group A and B, treatment response and resectability were compared.</P><P><B>Results:</B></P><P>Between November 2008 and October 2010, a total 63 patients were randomised to Group A (<I>N</I>=32) or Group B (<I>N</I>=31). FOLFOX was more preferred in Group A than in Group B (26 out of 32 (81.3%) <I>vs</I> 20 out of 31 (64.5%)). Group B showed better treatment response than Group A (48.4% <I>vs</I> 21.9%, <I>P</I>=0.027). The resectability of hepatic lesion was higher in Group B (35.5% <I>vs</I> 12.5%, <I>P</I>=0.032). Mean duration from chemotherapy onset to the time of liver resection was 11 cycles (range 4–12) in Group A and 8 cycles (range 8–16) in Group B.</P><P><B>Conclusion:</B></P><P>This study showed that tailored-chemotherapy based on ATP-CRA could improve the treatment response and resectability in initially unresectable colorectal liver metastasis.</P>

      • The long-term relationship between dietary pantothenic acid (vitamin B<sub>5</sub>) intake and C-reactive protein concentration in adults aged 40 years and older

        Jung, S.,Kim, M.K.,Choi, B.Y. Elsevier 2017 Nutrition, metabolism, and cardiovascular diseases Vol.27 No.9

        <P><B>Abstract</B></P> <P><B>Background and aims</B></P> <P>Low-grade inflammation, represented by minor C-reactive protein (CRP) elevation, has a critical role in the early stages of atherosclerosis, and pantothenic acid (PA) may have an antioxidant effect in inflammatory process. However, the long-term relationship between PA intake and CRP has not yet been studied. The objective of the present study was to evaluate the long-term relationship of PA intake to CRP concentration in healthy adults aged 40 years or older living in a rural area of South Korea.</P> <P><B>Methods and Results</B></P> <P>A total of 908 subjects (349 men, 559 women) with repeated data on dietary PA intake and CRP concentration were included in the final analysis. To represent the long-term effect of PA intake, both PA intake at the baseline and average PA intake were used as the exposure, and CRP concentration at the third visit and its change from the baseline to the third visit were used as the outcome. After adjustment for potential confounders, a significant inverse relationship between PA intake and CRP concentration at the third visit was observed (<I>P</I> for trend = 0.001, <I>β</I> = −0.07 (<I>P</I>-value = 0.001) for PA <SUB>baseline</SUB>; <I>P</I> for trend = <0.0001, <I>β</I> = −0.11 (<I>P</I>-value = 0.0004) for PA <SUB>average (baseline, 2nd, 3rd)</SUB>). Higher PA intake was significantly related to lower or attenuated increase in CRP concentration (<I>P</I> for trend = 0.002, <I>β</I> = −0.24 (<I>P</I>-value = 0.002) for PA <SUB>baseline</SUB>; <I>P</I> for trend = 0.001, <I>β</I> = −0.35 (<I>P</I>-value = 0.001) for PA <SUB>average (baseline, 2nd, 3rd)</SUB>).</P> <P><B>Conclusions</B></P> <P>In conclusion, dietary PA intake was inversely related to subsequent CRP concentration in both men and women aged 40 years or older in South Korea.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Higher baseline and average PA intakes were significantly related to lower CRP concentration at the end of follow-up. </LI> <LI> Higher average PA intakes were significantly related to lower CRP concentration or attenuated increase in CRP concentration. </LI> <LI> PA should not be overlooked in regard to its effects on inflammation, because it might have an antioxidant effect. </LI> </UL> </P>

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        Induction of interleukin-8 production via nuclear factor-&kgr;B activation in human intestinal epithelial cells infected with <i>Vibrio vulnificus</i>

        Lee, B. C.,Kim, S. H.,Choi, S. H.,Kim, T. S. Blackwell Science Ltd 2005 Immunology Vol.115 No.4

        <P>Summary</P><P><I>Vibrio vulnificus</I>, a Gram-negative estuarine bacterium, is a causative agent of food-borne diseases, such as life-threatening septicaemia and wound infection disease. <I>V. vulnificus</I> penetrating into the epithelial barrier stimulates an inflammatory response in the adjacent mucosa. Therefore, interaction between <I>V. vulnificus</I> and epithelial cells is important for understanding of both the immunology of mucosal surfaces and <I>V. vulnificus</I>. In this study, we investigated the effect and action mechanism of <I>V. vulnificus</I> infection on production of interleukin (IL)-8, a proinflammatory cytokine, in human intestinal epithelial INT-407 cells. <I>V. vulnificus</I> infection significantly induced IL-8 production in a time- and multiplicity of infection (MOI)-dependent manner, as determined by human IL-8 enzyme-linked immunosorbent assay (ELISA). In addition, <I>V. vulnificus</I> infection significantly increased IL-8 mRNA levels in INT-407 cells, indicating that the increased IL-8 production by <I>V. vulnificus</I> occurred at the transcriptional level. <I>V. vulnificus</I> infection also enhanced IL-8 gene promoter activity in INT-407 cells transiently transfected with IL-8 promoter constructs, but this effect was impaired in INT-407 cells transfected with IL-8 promoter constructs deleted or mutated of a &kgr;B site. <I>V. vulnificus</I> infection increased the nuclear factor-kappaB (NF-&kgr;B) binding activity to a &kgr;B site and the degradation of I&kgr;B-&agr; protein in a time- and a MOI-dependent manner. Furthermore, BAY11-7082, an inhibitor of NF-&kgr;B activation, significantly reduced the IL-8 production, NF-&kgr;B binding activity and I&kgr;B-&agr; degradation induced by <I>V. vulnificus</I> infection. Taken together, these results indicate clearly that <I>V. vulnificus</I> infection significantly induces IL-8 production in human intestinal epithelial cells via NF-&kgr;B activation.</P>

      • 비육돈에 미생물제제 급여시 분뇨 특성에 미치는 효과

        곽정훈,최동윤,박치호,김재환,정광화,양창범,유용희,천현식,라창식,Kwag, J.H.,Choi, D.Y.,Park, Ch.H.,Kim, J.H.,Jeong, K.H.,Yang, Ch.B.,Yoo, Y.H.,Chen, H.S.,La, C.S. 한국축산환경학회 2007 축산시설환경학회지 Vol.13 No.3

        본시험은 비육돈사료에 미생물제제를 사료에 미생물제제 A 및 B 0.1 미생물제제 C를 0.2% 혼합 급여할 경우 사료섭취량 및 돈분의 오염물질 배설농도에 미치는 영향을 분석하기 위하여 4처리$\times$반복당 5두로서 총 20두를 공시하여 실시하였는데 그 결과를 요약하면 다음과 같다. 1. 비육돈의 일일 평균사료섭취량은 대조구 3.15 kg/일.두였고 미생물A, B, C구는 각각 3.14kg/일/두, 3.31, 3.42로 미생물제제 C구에서 일일 사료섭취량이 가장 높게 조사되었으며(p<0.05), 2. 일일평균 음수량은 사료섭취량이 높았던 미생물 C구에서 3.95kg/일/두로 가장 높게 조사되었다(p<0.05). 3. 미생물제제 처리구별로 분뇨배설량은 사료섭취량이 높았던 미생물제제 C구에서 가장 많이 배설되는 것으로 조사되었으며(p<0.05), 돈뇨의 배설량도 미생물제제 C구에서 2.23kg/일/두에서 높았다(p<0.05). 4. 돈분뇨의 수분 함량은 및 비료성분인 T-N, $P_{2}O_{5}$, $K_{2}O$ 성분도 처리 간에 큰 차이를 보이지 않았다(p<0.05). 5. 돈분뇨의 평균 BOD 농도는 돈분의 경우 미생물제제 B, C제제 급여구가 유의적으로 높게 조사되었다(p<0.05). 그리고 돈뇨의 BOD의 경우에는 대조구에서 $8,657.5mg/{\ell}$로 가장 높은 것으로 조사되었다(p<0.05). 6. COD 농도는 대조구에서 가장 높게 조사되었으며(p<0.05). 돈뇨의 경우에는 미생물제제 A급여구에서 평균 $9,545mg/{\ell}$로 가장 높았다(p<0.05). 7. SS 농도는 미생물제제 B급여구에서 가장 높게 조사되었으며(p<0.05), 돈분뇨중의 T-N 농도는 처리구간에 유의적인 차이가 나타나지 않았다(p<0.05). 그리고 T-P 농도의 경우에는 미생물제제 C급여구에서 유의적인 차이가 나는 것으로 조사되었다(p<0.05). 이상의 결과를 요약해보면 비육돈에 미생물제제 혼합급여시 사료섭취량과 음수량을 증가시키는데 효과가 있는 것으로 조사되었으나, 비료성분 배설량에는 큰 차이를 보이지 않는 것으로 조사되었으나, BOD 등 오염물질농도의 경우에는 미생물제제 A급여구에서 가장 낮게 조사되어 비육돈사료에 미생물제제 급여시 오염물질 저감효과가 있는 것으로 조사되었다. Study for the effect of three different microbial feed additives(henceforth MA-A, MA-B, and MA-C) on feed coversion rate, and physical and chemical characteristics of swine finisher was conducted. MA-B had higher number of Lactobacillus spp. and yeast, compared to any other. The amylase activity of MA-B was also higher than any other. The daily feed intake rates of pigs fed control, MA-A, MA-B and MA-C were 3.15, 3.14, 3.31 and 3.42 kg, respectively. MA-C had the highest weight gain. However, there was no significant difference between treatments. The weights of feces daily excreted by pigs fed control, MA-A, MA-B, and MA-C were 2.14, 2.02, 2.18, and 2.23 kg/day, respectively. The volume of urine daily excreted by pigs fed control, MA-A, MA-B, and MA-C were 3.14, 3.26, 3.27, and $3.41\;{\ell}/day$, respectively. Water content, T-N, $P_{2}O_{5}$, and $K_{2}O$ in swine manure were not significantly different between treatments. The BOD were between 42,576 and $67,450\;mg/{\ell}$ for feces and were between 5,882.5 and $8,657.5\;mg/{\ell}$ for urine, respectively. The SS were between 138,000 and $180,000\;mg/{\ell}$ for feces and were between 875.0 and $1450.0mg/{\ell}$ for urine, respectively.

      • Molecular characterization and expression analysis of IκB from Haliotis discus discus

        Kasthuri, S.R.,Whang, I.,Navaneethaiyer, U.,Lim, B.S.,Choi, C.Y.,Lee, J. Academic Press 2013 Fish & shellfish immunology Vol.34 No.6

        Innate immune system relies on the recognition of pathogen associated molecular patterns present in the microbes by the pattern recognition receptors leading to the activation of signaling cascade and subsequent synthesis of cytokines. NF-κB is a major stimulus activated transcription factor, which regulates the expression of a diverse array of genes. IκB is an inhibitor of NF-κB, retaining NF-κB in an inactive state in the cytoplasm. In this study, we have reported the characterization of first abalone IκB (HdIκB). The cDNA possessed an ORF of 1200 bp coding for a protein of 400 amino acids with molecular mass of 45 kDa and isoelectric point of 4.7. HdIκB protein possessed a conserved phosphorylation site <SUP>58</SUP>DSGIFS<SUP>63</SUP> in the N-terminal region, six ankyrin repeats, and a PEST sequence in the C-terminal region. A casein kinase II phosphorylation site could also be observed in the PEST sequence. Constitutive expression of HdIκB revealed its physiological significance since NF-κB is known to be activated by various stimuli. Elevated expression of HdIκB transcripts could be observed in abalones challenged with various mitogens and live microbes. This novel characterization of abalone IκB would further be a positive approach in the affirmation of evolutionary conservation and significance of this protein as a repressor/inhibitor of a pleiotropic transcription factor like NF-κB.

      • 육성돈에 미생물제제 급여시 분뇨 특성에 미치는 효과 연구

        곽정훈,최동윤,박치호,김재환,정광화,양창범,유용희,라창식,Kwag, J.H.,Choi, D.Y.,Park, Ch.H.,Kim, J.H.,Jeong, K.H.,Yang, Ch.B.,Yoo, Y.H.,La, C.S. 한국축산환경학회 2007 축산시설환경학회지 Vol.13 No.1

        본 시험은 육성돈 사료에 미생물제제를 사료에 미생물제제 A 및 B 0.1 미생물제제 C를 0.2% 혼합 급여할 경우 사료섭취량 및 돈분의 오염물질 배설농도에 미치는 영향을 분석하기 위하여 4처리$\times$반복당 5두로서 총 20두를 공시하여 실시하였는데 그 결과를 요약하면 다음과 같다. 1. 육성비육돈의 일일 평균사료섭취량은 대조구 2.06kg/일.두였고 미생물 A, B, C 구는 각각 2.13kg/일.두, 2.17, 2.34로 미생물제제 C구에서 일일 사료섭취량이 가장 높게 조사되었으며(p<0.05), 2. 일일평균 음수량은 사료섭취량이 높았던 미생물 C구에서 2.89kg/일/두로 가장 높게 조사되었다(p<0.05). 3. 미생물제제 처리구별로 분뇨 배설량은 사료섭취량이 높았던 미생물제제 C 구에서 가장 많이 배설되는 것으로 조사되었으며 (0<0.05), 돈뇨의 배설량도 미생물제제 C구에서 2.31kg/일/두에서 높았다(p<0.05). 4. 육성돈의 성장단계별 돈분뇨의 수분 함량은 및 비료성분인 T-N, $P_2O_5,\;K_2O$ 성분도 처리간에 큰 차이를 보이지 않았다(p<0.05). 5. 육성돈 분뇨의 평균 BOD 농도는 돈분의 경우 미생물제제 A, B제제 급여구가 유의적으로 높게 조사되었다(p<0.05). 그리고 돈뇨의 BOD의 경우에도 미생물제제 A급 여구에서 $6,537mg/\ell$로 가장 높은 것으로 조사되었다(p<0.05). 6. COD의 경우에도 미생물 C급여구에서 가장 높게 조사되었으며(p<0.05). 돈뇨의 경우에는 미생물제제 A급여구에서 평균 $8,566mg\ell$로 가장 높았다(p<0.05). 7. SS 농도는 대조구에서 가장 높게 조사 되었으며(p<0.05), 그 다음이 미생물 B> 미생물 C> 대조구 순으로 조사되었다. 8. 돈분뇨중의 T-N 농도는 처리구간에 유의적인 차이가 나타나지 않았다(p<0.05). 9. 돈분중의 T-P 농도는 미생물제제 처리 구간별로 미생물제제 A, C 급여구에서 유의적인 차이가 나는 것으로 조사되었다(p<0.05). 이상의 결과를 요약해보면 육성돈에 미생물제제 혼합급여는 사료섭취량을 증가시키는데 효과가 있으나 비료성분 배설량에는 큰 차이를 보이지 않는 것으로 조사되었으며, 오염물질 배설량의 경우에는 사료섭취량이 높은 미생물제제 C 급여구에서 높은 것으로 조사되었다. The effects of microbial feedstuff additives on feed conversion rate and physical and chemical characteristics of excreta in growing pigs were investigated. Three different products (A, B and C) were compared. Microbial population tests showed B contained higher numbers of total bacteria, Lactobacillus spp. and yeasts. The amylase activity of B was also higher than that of A and C. The daily feed intake rates fer control, A, B and C were 2.06, 2.13, 2.17 and 2.34 kg, respectively. Pigs feed product C had the highest liveweight gain(2.89 kg). However, the results of feed conversion rate were not significantly different between treatments. Amount of faces excreted for control, A, B and C was 1.18, 1,19, 1.23 and 1.32 kg, respectively. Urine volume for control, A, B, and C was 1.91, 1.80, 2.19 and 2.31 kg respectively. Moisture content, T-N, $P_2O_5$ and $K_2O$ in pig manure were not significantly different between treatments. The range of BOD values was 63,453 to $73,758mg/\ell$ for faeces, and 5,678 to $7,428mg/\ell$, for urine. SS values of solid and liquid excreta ranged from 142,200 to 176,000 and from 710 to $1,025mg/\ell$, respectively.

      • Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive–compulsive disorder

        Jung, W. H.,Kang, D.‐,H.,Han, J. Y.,Jang, J. H.,Gu, B.,M.,Choi, J.‐,S.,Jung, M. H.,Choi, C.‐,H.,Kwon, J. S. Blackwell Publishing Ltd 2011 Acta psychiatrica Scandinavica Vol.123 No.5

        <P>Jung WH, Kang D‐H, Han JY, Jang JH, Gu B‐M, Choi J‐S, Jung MH, Choi C‐H, Kwon JS. Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive–compulsive disorder.</P><P><B>Objective: </B> Obsessive–compulsive disorder (OCD) is characterized by the dysfunction of control and reward mechanisms. However, only few neuroimaging studies of OCD have examined the reward processing. We examined the neural responses during incentive processing in OCD.</P><P><B>Method: </B> Twenty unmedicated patients with OCD and 20 age‐, sex‐, and IQ‐matched healthy controls underwent functional magnetic resonance imaging while performing a modified monetary incentive delay task.</P><P><B>Results: </B> Compared with controls, patients with OCD showed increased ventral striatal activation in the no‐loss minus loss outcome contrast and a significant positive correlation between the ventral striatal activation and compulsion symptom severity. In addition, patients with OCD showed increased activations in the frontostriatal regions in the gain minus no‐gain outcomes contrast. During loss anticipation, patients with OCD showed less activations in the lateral prefrontal and inferior parietal cortices. However, during gain anticipation, patients with OCD and healthy controls did not differ in the ventral striatal activation.</P><P><B>Conclusion: </B> These findings provide neural evidence for altered incentive processing in unmedicated patients with OCD, suggesting an elevated sensitivity to negatively affect stimuli as well as dysfunction of the ventral striatum.</P>

      • Granulocyte Macrophage Colony-Stimulating Factor Shows Anti-apoptotic Activity via the PI3K–NF-κB–HIF-1α–Survivin Pathway in Mouse Neural Progenitor Cells

        Choi, J. K.,Kim, K. H.,Park, S. R.,Choi, B. H. HUMANA PRESS INC 2014 Molecular neurobiology Vol.49 No.2

        Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic cytokine that plays a crucial role in regulating the proliferation, differentiation, and survival of hematopoietic cells. Recent studies have shown that GM-CSF also has anti-apoptotic effects and regulates the expression of anti-apoptotic genes including Bcl-2 family proteins in neuronal cells in vitro and in vivo. However, the mechanism underlying the anti-apoptotic function of GM-CSF is not well understood. In the present work, we examined the role of phosphoinositide 3-kinase (PI3K)-AKT signal pathway in the anti-apoptotic activity of GM-CSF in mouse neural progenitor cells (NPCs). In terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, the anti-apoptotic effect of GM-CSF (apoptotic population of approximately 8.17 %) on staurosporine-induced apoptosis of NPCs (31.09 %) was significantly blocked by LY294002, an inhibitor of PI3K signal (24.04 %). We found that the PI3K-AKT signal pathway induced by GM-CSF treatment activated nuclear factor kappa B (NF-kappa B) and increased the expression of hypoxia-inducible factor 1 alpha (HIF-1 alpha) in normoxic conditions. Analyses using specific small interfering RNAs (siRNAs) showed that NF-kappa B was an upstream molecule of HIF-1 alpha and activated its expression at the mRNA level. Further analyses using the siRNAs and chromatin immunoprecipitation (ChIP) showed that HIF-1 alpha was responsible for the induced expression of survivin, a member of the inhibitor of apoptosis proteins (IAPs). Each of the specific siRNAs for NF-kappa B, HIF-1 alpha, and survivin inhibited significantly the anti-apoptotic activity of GM-CSF on the staurosporine-induced apoptosis in NPCs in TUNEL assays. The results of this study showed the downstream signals and mechanism of PI3K/AKT-mediated anti-apoptotic activity of GM-CSF in NPCs, particularly revealing the role of the NF-kappa B-HIF-1 alpha-survivin cascade.

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