3′‐Sialyllactose as an inhibitor of p65 phosphorylation ameliorates the progression of experimental rheumatoid arthritis

Kang, Li&#x2010,Jung,Kwon, Eun&#x2010,Soo,Lee, Kwang Min,Cho, Chanmi,Lee, Jae&#x2010,In,Ryu, Young Bae,Youm, Tae Hyun,Jeon, Jimin,Cho, Mi Ra,Jeong, Seon&#x2010,Yong,Lee, Sang‐,Rae,Kim, Wook,Yang John Wiley and Sons Inc. 2018 British journal of pharmacology Vol.175 No.23

<P><B>Background and Purpose</B></P><P>3′‐Sialyllactose (3′‐SL) is a safe compound that is present in high levels in human milk. Although it has anti‐inflammatory properties and supports immune homeostasis, its effect on collagen‐induced arthritis (CIA) is unknown. In this study, we investigated the prophylactic and therapeutic effect of 3′‐SL on the progression of rheumatoid arthritis (RA) in <I>in vitro</I> and <I>in vivo</I> models.</P><P><B>Experimental Approach</B></P><P>The anti‐arthritic effect of 3′‐SL was analysed with fibroblast‐like synoviocytes <I>in vitro</I> and an <I>in vivo</I> mouse model of CIA. RT‐PCR, Western blotting and ELISA were performed to evaluate its effects <I>in vitro</I>. Histological analysis of ankle and knee joints of mice with CIA was performed using immunohistochemistry, as well as safranin‐O and haematoxylin staining.</P><P><B>Key Results</B></P><P>3′‐SL markedly alleviated the severity of CIA in the mice by reducing paw swelling, clinical scores, incidence rate, serum levels of inflammatory cytokines and autoantibody production. Moreover, 3′‐SL reduced synovitis and pannus formation and suppressed cartilage destruction by blocking secretion of chemokines, pro‐inflammatory cytokines, https://en.wikipedia.org/wiki/Matrix_metalloproteinases and osteoclastogenesis <I>via</I> NF‐κB signalling. Notably, phosphorylation of p65, which is a key protein in the NF‐κB signalling pathway, was totally blocked by 3′‐SL in the RA models.</P><P><B>Conclusions and Implications</B></P><P>3′‐SL ameliorated pathogenesis of CIA by suppressing catabolic factor expression, proliferation of inflammatory immune cells and osteoclastogenesis. These effects were mediated <I>via</I> blockade of the NF‐κB signalling pathway. Therefore, 3′‐SL exerted prophylactic and therapeutic effects and could be a novel therapeutic agent for the treatment of RA.</P>

Safety and efficacy of single‐agent docetaxel ( T axotere) administered weekly in non‐small cell lung carcinoma patients in K orea: An observational study

Lim, Sun Min,Park, Byeong Bae,Park, Keun&#x2010,Chil,Kim, Hoon&#x2010,Kyo,Lee, Jong Seok,Bae, Sung Hwa,Lee, Seung&#x2010,Sei,Kang, Jin&#x2010,Hyoung,Park, Se&#x2010,Hoon,Lee, Gyeong&#x2010,Won,Lee, Hy John Wiley and Sons Inc. 2016 Thoracic cancer Vol.7 No.2

<P><B>Abstract</B></P><P><B>Background</B></P><P>To investigate the efficacy, safety, and tolerability of weekly docetaxel treatment in advanced non‐small cell lung cancer (NSCLC) patients in Korea.</P><P><B>Methods</B></P><P>This prospective observational study included Korean advanced NSCLC patients with Eastern Cooperative Oncology Group performance status <2 who received weekly monotherapy of docetaxel at a dose determined by the physician. Efficacy measurements included tumor response rate, overall survival (OS), progression‐free survival, and one‐year survival rate. Safety was analyzed through recorded incidences of adverse events (AEs), serious adverse events (SAEs), deaths, and other related safety parameters, along with their toxicity grades.</P><P><B>Results: </B></P><P>Of 274 patients analyzed, one patient achieved a complete response and 42 partial responses; thus, the overall response rate was 15.7%. The OS rate at baseline and at one‐year follow‐up was 38.3% and 33.8%, respectively. AEs were reported in 229 (83.6%) patients. The most frequently reported hematologic AE of grade ≥3 was a decrease in neutrophils, with 6.6% of the patients developing neutropenia. In non‐hematologic AEs of grade ≥3, the most common were infection with unknown absolute neutrophil count and death not associated with Common Terminology Criteria for Adverse Events (CTCAE) (4.7% each). The most common SAE reported was death, not associated with CTCAE (7.3%).</P><P><B>Conclusions</B></P><P>In Korean patients, the weekly regimen of docetaxel monotherapy was safe and efficacious against advanced NSCLC.</P>

Three‐bed PVSA process for high‐purity O₂ generation from ambient air

Jee, Jeong&#x2010,Geun,Lee, Sang‐,Jin,Kim, Min&#x2010,Bae,Lee, Chang&#x2010,Ha Wiley Subscription Services, Inc., A Wiley Company 2005 AIChE journal Vol.51 No.11

<P><B>Abstract</B></P><P>A three‐bed PVSA (pressure vacuum swing adsorption) process, combining equilibrium separation with kinetic separation, was developed to overcome the 94% O<SUB>2</SUB> purity restriction inherent to air separation in the adsorption process. To produce 97+% and/or 99+% purity O<SUB>2</SUB> directly from air, the PVSA process with two zeolite 10X beds and one CMS bed was executed at 33.44–45.60 to 253.31 kPa. In addition, the effluent gas from the CMS bed to be used for O<SUB>2</SUB> purification was backfilled to the zeolite 10X bed to improve its purity, recovery, and productivity in bulk separation of the air. PVSA I, which made use of a single blowdown/backfill step, produced an O<SUB>2</SUB> product with a purity of 95.4–97.4% and a recovery of 43.4–84.8%, whereas PVSA II, which used two consecutive blowdown/backfill steps, produced O<SUB>2</SUB> with a purity of 98.2–99.2% and a recovery of 47.2–63.6%. Because the primary impurity in the O<SUB>2</SUB> product was Ar, the amounts of N<SUB>2</SUB> contained in the product were in the range of 4000–5000 ppm at PVSA I and several tens of ppm at PVSA II. A nonisothermal dynamic model incorporating mass, energy, and momentum balances was applied to predict the process dynamics. Using the linear driving force (LDF) model with constant diffusivity for the equilibrium separation bed and a modified LDF model with concentration dependency of the diffusion rate for the kinetic separation bed, the dynamic model was able to accurately predict the results of the experiment. © 2005 American Institute of Chemical Engineers AIChE J, 2005</P>

Sixty‐five gene‐based risk score classifier predicts overall survival in hepatocellular carcinoma

Kim, Soo Mi,Leem, Sun&#x2010,Hee,Chu, In&#x2010,Sun,Park, Yun&#x2010,Yong,Kim, Sang Cheol,Kim, Sang‐,Bae,Park, Eun Sung,Lim, Jae Yun,Heo, Jeonghoon,Kim, Yoon Jun,Kim, Dae&#x2010,Ghon,Kaseb, Ahme Wiley Subscription Services, Inc., A Wiley Company 2012 Hepatology Vol.55 No.5

<P><B>Abstract</B></P><P>Clinical application of the prognostic gene expression signature has been delayed due to the large number of genes and complexity of prediction algorithms. In the current study we aimed to develop an easy‐to‐use risk score with a limited number of genes that can robustly predict prognosis of patients with hepatocellular carcinoma (HCC). The risk score was developed using Cox coefficient values of 65 genes in the training set (n = 139) and its robustness was validated in test sets (n = 292). The risk score was a highly significant predictor of overall survival (OS) in the first test cohort (<I>P</I> = 5.6 × 10<SUP>−5</SUP>, n = 100) and the second test cohort (<I>P</I> = 5.0 × 10<SUP>−5</SUP>, n = 192). In multivariate analysis, the risk score was a significant risk factor among clinical variables examined together (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.13‐1.64; <I>P</I> = 0.001 for OS). <I>Conclusion:</I> The risk score classifier we have developed can identify two clinically distinct HCC subtypes at early and late stages of the disease in a simple and highly reproducible manner across multiple datasets. (H<SMALL>EPATOLOGY</SMALL> 2011)</P>

Overexpression of the <i>IbMYB1</i> gene in an orange‐fleshed sweet potato cultivar produces a dual‐pigmented transgenic sweet potato with improved antioxidant activity

Park, Sung&#x2010,Chul,Kim, Yun&#x2010,Hee,Kim, Sun Ha,Jeong, Yu Jeong,Kim, Cha Young,Lee, Joon Seol,Bae, Ji&#x2010,Yeong,Ahn, Mi&#x2010,Jeong,Jeong, Jae Cheol,Lee, Haeng&#x2010,Soon,Kwak, Sang‐ Blackwell Publishing Ltd 2015 Physiologia plantarum Vol.153 No.4

<P>The R2R3-type protein IbMYB1 is a key regulator of anthocyanin biosynthesis in the storage roots of sweet potato [Ipomoea batatas (L.) Lam]. Previously, we demonstrated that IbMYB1 expression stimulated anthocyanin pigmentation in tobacco leaves and Arabidopsis. Here, we generated dual-pigmented transgenic sweet potato plants that accumulated high levels of both anthocyanins and carotenoids in a single sweet potato storage root. An orange-fleshed cultivar with high carotenoid levels was transformed with the IbMYB1 gene under the control of either the storage root-specific sporamin 1 (SPO1) promoter or the oxidative stress-inducible peroxidase anionic 2 (SWPA2) promoter. The SPO1-MYB transgenic lines exhibited higher anthocyanin levels in storage roots than empty vector control (EV) or SWPA2-MYB plants, but carotenoid content was unchanged. SWPA2-MYB transgenic lines exhibited higher levels of both anthocyanin and carotenoids than EV plants. Analysis of hydrolyzed anthocyanin extracts indicated that cyanidin and peonidin predominated in both overexpression lines. Quantitative reverse transcription-polymerase chain reaction analysis demonstrated that IbMYB1 expression in both IbMYB1 transgenic lines strongly induced the upregulation of several genes in the anthocyanin biosynthetic pathway, whereas the expression of carotenoid biosynthetic pathway genes varied between transgenic lines. Increased anthocyanin levels in transgenic plants also promoted the elevation of proanthocyanidin and total phenolic levels in fresh storage roots. Consequently, all IbMYB1 transgenic plants displayed much higher antioxidant activities than EV plants. In field cultivations, storage root yields varied between the transgenic lines. Taken together, our results indicate that overexpression of IbMYB1 is a highly promising strategy for the generation of transgenic plants with enhanced antioxidant capacity.</P>

Melatonin promotes puromycin‐induced apoptosis with activation of caspase‐3 and 5′‐adenosine monophosphate‐activated kinase‐alpha in human leukemia HL‐60 cells

Koh, Wonil,Jeong, Soo&#x2010,Jin,Lee, Hyo&#x2010,Jung,Ryu, Ho&#x2010,Geon,Lee, Eun&#x2010,Ok,Ahn, Kyoo Seok,Bae, Hyunsu,Kim, Sung&#x2010,Hoon Blackwell Publishing Ltd 2011 Journal of pineal research Vol.50 No.4

<P><B>Abstract: </B> Melatonin, a naturally occurring molecule, is produced by the pineal gland in a circadian manner to regulate biologic rhythms in humans. Recent studies report that melatonin may be an attractive candidate as an anticancer agent or for combined therapy because of its antioxidant, oncostatic and immunoregulatory activities. In this study, the potentiating effect of melatonin was evaluated on the apoptosis induced by puromycin as an anticancer drug in acute promyelocytic leukemia HL‐60 cells. Melatonin did not show significant cytotoxicity against HL‐60 cells compared to puromycin. However, melatonin significantly augmented the cytotoxicity of puromycin. Consistently, combined treatment of melatonin and puromycin reduced the expression of anti‐apoptotic proteins, such as bcl‐2 and bcl‐x<SUB>L</SUB>, and also induced caspase‐3 activation and poly (ADP‐ribose) polymerase (PARP) cleavage compared to puromycin treatment alone. Furthermore, cell cycle analysis revealed that melatonin promoted puromycin‐induced apoptosis by increasing the sub‐G1 population, but suppressing G2/M arrest in HL‐60 cells. Interestingly, melatonin activated the phosphorylation of 5′‐adenosine monophosphate‐activated kinase (AMPK) in combination with puromycin. Taken together, our results suggest that melatonin potentiates puromycin‐induced apoptosis with caspase‐3 and AMPK activation in HL‐60 cells, and thus, melatonin treatment can be effectively applied to leukemia treatment as a potential sensitizer for chemotherapeutic agents.</P>

Administration of 6‐gingerol greatly enhances the number of tumor‐infiltrating lymphocytes in murine tumors

Ju, Seong&#x2010,A,Park, Sang‐,Min,Lee, Yea&#x2010,Sol,Bae, Jun&#x2010,Hyeong,Yu, Rina,An, Won G.,Suh, Jae&#x2010,Hee,Kim, Byung&#x2010,Sam Wiley Subscription Services, Inc., A Wiley Company 2012 International journal of cancer: Journal internati Vol.130 No.11

<P><B>Abstract</B></P><P>Tumor‐infiltrating lymphocytes (TILs) play critical roles in host antitumor immune responses. It is known that cancer patients with tumor‐reactive lymphocyte infiltration in their tumors have better prognoses, while patients with tumors infiltrated by immunosuppressive cells have worse prognoses. We found that administration of 6‐gingerol, which is a component of ginger, inhibited tumor growth in several types of murine tumors, such as B16F1 melanomas, Renca renal cell carcinomas and CT26 colon carcinomas, which were established by inoculating tumor cells on the flanks of mice. However, administration of 6‐gingerol did not lead to complete eradication of the tumors. 6‐Gingerol treatment of tumor‐bearing mice caused massive infiltration of CD4 and CD8 T‐cells and B220<SUP>+</SUP> B‐cells, but reduced the number of CD4<SUP>+</SUP>Foxp3<SUP>+</SUP> regulatory T‐cells. The CD8 tumor‐infiltrating T lymphocytes in 6‐gingerol‐treated mice strongly expressed IFN‐γ, a marker of activation of cytotoxic T lymphocytes (CTL) CD107a and chemokine receptors that are expressed on T<SUB>H</SUB>1 cells, such as CXCR3 and CCR5. To test whether 6‐gingerol could promote infiltration of tumor antigen‐specific CD8 T‐cells into tumors, we adoptively transferred CFSE‐labeled OT‐1 CD8 T‐cells into EG7 tumor‐bearing mice. We found that CD8 T cells isolated from 6‐gingerol pretreated OT‐1 mice, but not from control OT‐1 mice, massively infiltrated tumors and tumor draining lymph nodes and divided several times. Our results strongly suggest that 6‐gingerol can be used in tumor immunotherapy to increase the number of TILs.</P>

Polymer Nanomicelles for Efficient Mucus Delivery and Antigen‐Specific High Mucosal Immunity

Noh, Young&#x2010,Woock,Hong, Ji Hyun,Shim, Sang‐,Mu,Park, Hye Sun,Bae, Hee Ho,Ryu, Eun Kyoung,Hwang, Jung Hwan,Lee, Chul&#x2010,Ho,Cho, Seong Hun,Sung, Moon&#x2010,Hee,Poo, Haryoung,Lim, Yong T WILEY‐VCH Verlag 2013 Angewandte Chemie Vol.125 No.30

<P><B>Micellen für die Schleimhautimmunität</B>: Ein mukosales Impfsystem wurde hergestellt, das auf γ‐PGA‐Nanomicellen und viralen Antigenen basiert. Die intranasale Verabreichung des Impfsystems löst eine starke Immunreaktion der humoralen sowie der zellulären Immunität aus (siehe Bild).</P>

Calcium transport genes are differently regulated in maternal and fetal placenta in the knockout mice of calbindin‐D_9k and ‐D_28k

Koo, Tae&#x2010,Hyoung,Yang, Hyun,An, Beum&#x2010,Soo,Choi, Kyung&#x2010,Chul,Hyun, Sang‐,Hwan,Jeung, Eui&#x2010,Bae Wiley Subscription Services, Inc., A Wiley Company 2012 Molecular reproduction and development Vol.79 No.5

<P><B>Abstract</B></P><P>Calbindin‐D<SUB>9k</SUB> (CaBP‐9k) and ‐D<SUB>28k</SUB> (CaBP‐28k) are cytosolic proteins with EF‐hand motifs that have a high affinity for calcium ions. Many types of calcium channels and intracellular calcium binding proteins, such as sodium/calcium exchangers (NCXs) and transient receptor potential cation channels (TRPVs), have been detected in the placenta. In this study, the expression of calcium channels involved in maternal–fetal calcium transport were investigated in wild‐type mice versus CaBP‐9k, CaBP‐28k, and CaBP‐9k/28k double knockout (KO) mouse models. The expression of calcium transport genes in three dissected sections of the placenta (maternal, central, and fetal) was examined on gestational day 19 (GD 19). The expression of CaBP‐9k, TRPV6, TRPV5, and NCX1 mRNA was high in fetal compared to maternal placenta, while CaBP‐28k was abundant in the maternal placenta. CaBP‐9k was enhanced in all sections of placenta in CaBP‐28k KO mice, whereas CaBP‐28k was reduced in CaBP‐9k KO mice. The expression of TRPV6, TRPV5, and NCX1 were induced in both maternal and fetal placentas in CaBP‐9k KO mice, but were upregulated in maternal and central placentas of CaBP‐28k KO mice. The levels of these proteins showed similar patterns with those of their mRNA. Placental CaBP‐9k, TRPV6, TRPV5, and NCX1 proteins were abundantly expressed in the intraplacental yolk sac located in the fetal placenta. CaBP‐28k did not colocalize with other calcium transport genes, although it was enriched in the placental trophoblasts of the decidual zone in the maternal placenta. These results indicate that placental TRPV6, TRPV5, and NCX1 compensate for CaBPs in CaBP‐9k and/or CaBP‐28k KO mice, and may take over the roles of CaBP‐9k and CaBP‐28k to transfer calcium ions in the placenta. Taken together, these results indicate that TRPV6, NCX1, and CaBP‐9k in the fetal placenta and CaBP‐28k in the maternal placenta may play key roles in controlling calcium transport across the placenta during pregnancy. Mol. Reprod. Dev. 79: 346–355, 2012. © 2012 Wiley Periodicals, Inc.</P>

Bioactivity of Ti‐6Al‐4V alloy implants treated with ibandronate after the formation of the nanotube TiO₂ layer

Moon, So&#x2010,Hee,Lee, Seung&#x2010,Jae,Park, Il&#x2010,Song,Lee, Min&#x2010,Ho,Soh, Yun&#x2010,Jo,Bae, Tae&#x2010,Sung,Kim, Hyung&#x2010,Seop Wiley Subscription Services, Inc., A Wiley Company 2012 Journal of Biomedical Materials Research Part B Vol. No.

<P><B>Abstract</B></P><P>Nanostructure surface of titanium implants treated with anodic oxidation, heat, and bisphosphonates, has been introduced to improve osseointegration of the implants. However, no information could be found about the efficiency of these approaches on Ti‐6Al‐4V alloy surfaces. This study examined the drug loading capacity of anodized nanotubular Ti‐6Al‐4V alloy surfaces <I>in vitro</I> as well as the bone response to surface immobilized bisphosphonates (BPs) on anodized nanotubular Ti‐6Al‐4V alloy surface in tibiae of rats. Ti‐6Al‐4V alloy titanium was divided into two groups: (1) control group (nontreated); (2) test group (anodized, heat‐, and bisphosphonate‐treated group). <I>In vitro</I>, amount of the drug released from the both groups' specimens was examined; all samples were 1 × 2 cm in size. <I>In vivo</I>, the 10 implants were placed inside of tibias of five rats. After 4 weeks, the bone response of the implants was evaluated using a removal torque test, and measuring bone contact and bone area. In addition, the surfaces of the extracted implants were observed by FE‐SEM and EDS. <I>In vitro</I>, the drug loading capacity of the Ti‐6Al‐4V alloy surfaces was enhanced by anodizing surface modification. The values of the removal torque, bone contact, and bone area were significantly higher in the test group (<I>p</I> < 0.05). Furthermore, according to the EDS analysis, the amounts of Ca and P on the surface of the extracted implants were higher in the test group. Within the limits of this experiment, results of this research demonstrated that bisphosphonate‐treated Ti‐6Al‐4V alloy implants with nanotubular surfaces have positive effects in bone‐to‐implant contact. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.</P>