Nutrikinetics of Isoflavone Metabolites After Fermented Soybean Product (Cheonggukjang) Ingestion in Ovariectomized Mice

Lee, Da&#x2010,Hye,Kim, Min Jung,Ahn, Jiyun,Lee, Sang Hee,Lee, Hyunjung,Kim, Jin Hee,Park, So&#x2010,Hyun,Jang, Young&#x2010,Jin,Ha, Tae&#x2010,Youl,Jung, Chang Hwa John Wiley and Sons Inc. 2017 Molecular Nutrition & Food Research (Print) Vol.61 No.12

<P><B>Scope</B></P><P>Cheonggukjang (CGJ) is a soybean‐based quick‐fermented food popular in Korea that contains a variety of biologically active compounds including isoflavones and saponins. Isoflavone bioavailability may be important for the bone health of postmenopausal women; therefore, the aim of this study is to evaluate the influence of fermentation on the isoflavone metabolite nutrikinetic profile after single dose CGJ or unfermented soybean administration in ovariectomized (OVX) and sham mice.</P><P><B>Methods and results</B></P><P>We identify 34 isoflavone metabolites using UPLC–QTOF‐MS and analyze their nutrikinetics at different time points (0.25, 0.5, 1, 2, 4, 8, 16, and 24 h) to understand their fermentation‐ and OVX‐mediated time‐dependent concentration changes. Nutrikinetics analysis shows that genistein, daidzein, genistein 4′‐sulfate, dihydrodaidzein sulfate, equol 4′‐sulfate, and equol‐7‐glucuronide are present at high concentrations in all groups based on area‐under‐the‐curve analysis. OVX mice appear to show lower isoflavone bioavailability than mice in the sham group. CGJ enhances various isoflavone metabolite bioavailability including genistein, 3‐hydroxygenistein, and equol 7‐glucuronide, compared to the unfermented soybean‐treated group. Among these metabolites, intact isoflavones, 3‐hydroxygenistein, genistein 4′‐sulfate, and equol 7‐glucuronide promote osteoblastogenesis and inhibit osteoclast formation.</P><P><B>Conclusions</B></P><P>CGJ has good isoflavone bioavailability and may be beneficial for the bone health of postmenopausal women.</P>

Caveolin‐1 deficiency induces premature senescence with mitochondrial dysfunction

Yu, Dong&#x2010,Min,Jung, Seung Hee,An, Hyoung&#x2010,Tae,Lee, Sungsoo,Hong, Jin,Park, Jun Sub,Lee, Hyun,Lee, Hwayeon,Bahn, Myeong&#x2010,Suk,Lee, Hyung Chul,Han, Na&#x2010,Kyung,Ko, Jesang,Lee, Jae&# BLACKWELL PUBLISHING 2017 AGING CELL Vol.16 No.4

<P><B>Summary</B></P><P>Paradoxical observations have been made regarding the role of caveolin‐1 (Cav‐1) during cellular senescence. For example, caveolin‐1 deficiency prevents reactive oxygen species‐induced cellular senescence despite mitochondrial dysfunction, which leads to senescence. To resolve this paradox, we re‐addressed the role of caveolin‐1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and Cav‐1<SUP><I>−/−</I></SUP> mouse embryonic fibroblasts. Cav‐1 deficiency (knockout or knockdown) induced cellular senescence via a p53‐p21‐dependent pathway, downregulating the expression level of the cardiolipin biosynthesis enzymes and then reducing the content of cardiolipin, a critical lipid for mitochondrial respiration. Our results showed that Cav‐1 deficiency decreased mitochondrial respiration, reduced the activity of oxidative phosphorylation complex I (CI), inactivated SIRT1, and decreased the NAD<SUP>+</SUP>/NADH ratio. From these results, we concluded that Cav‐1 deficiency induces premature senescence via mitochondrial dysfunction and silent information regulator 2 homologue 1 (SIRT1) inactivation.</P>

Identification and metabolite profiling of alkaloids in aerial parts of <i>Papaver rhoeas</i> by liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry

Oh, Jae&#x2010,Hyeon,Ha, In Jin,Lee, Min Young,Kim, Eun&#x2010,Ok,Park, Dain,Lee, Jun&#x2010,Hee,Lee, Seok&#x2010,Geun,Kim, Do&#x2010,Wan,Lee, Tae&#x2010,Ho,Lee, Eui&#x2010,Ju,Kim, Chang&#x2010,Kug John Wiley and Sons Inc. 2018 Journal of Separation Science Vol.41 No.12

<P><B>Abstract</B></P><P><I>Papaver</I> plants can produce diverse bioactive alkaloids. <I>Papaver rhoeas</I> Linnaeus (common poppy or corn poppy) is an annual flowering medicinal plant used for treating cough, sleep disorder, and as a sedative, pain reliever, and food. It contains various powerful alkaloids like rhoeadine, benzylisoquinoline, and proaporphine. To investigate and identify alkaloids in the aerial parts of <I>P. rhoeas</I>, samples were collected at different growth stages and analyzed using liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry. A liquid chromatography with mass spectrometry method was developed for the identification and metabolite profiling of alkaloids for <I>P. rhoeas</I> by comparing with <I>Papaver somniferum</I>. Eighteen alkaloids involved in benzylisoquinoline alkaloid biosynthesis were used to optimize the liquid chromatography gradient and mass spectrometry conditions. Fifty‐five alkaloids, including protoberberine, benzylisoquinoline, aporphine, benzophenanthridine, and rhoeadine‐type alkaloids, were identified authentically or tentatively by liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry in samples taken during various growth stages. Rhoeadine alkaloids were observed only in <I>P. rhoeas</I> samples, and codeine and morphine were tentatively identified in <I>P. somniferum</I>. The liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry method can be a powerful tool for the identification of diverse metabolites in the genus <I>Papaver</I>. These results may help understand the biosynthesis of alkaloids in <I>P. rhoeas</I> and evaluate the quality of this plant for possible medicinal applications.</P>

Development of a prognosis‐prediction model incorporating genetic polymorphism with pathologic stage in stage I non‐small cell lung cancer: A multicenter study

Lee, Won Kee,Lee, Shin Yup,Choi, Jin Eun,Seok, Yangki,Lee, Eung Bae,Lee, Hyun Cheol,Kang, Hyo&#x2010,Gyoung,Yoo, Seung Soo,Lee, Myung Hoon,Cho, Sukki,Jheon, Sanghoon,Kim, Young Chul,Oh, In Jae,Na, Koo John WileySons Australia, Ltd 2017 Thoracic cancer Vol.8 No.3

<P><B>Background</B></P><P>This multicenter study was performed to develop a prognosis‐prediction model incorporating genetic polymorphism with pathologic stage for surgically treated non‐small cell lung cancer (NSCLC) patients.</P><P><B>Methods</B></P><P>A replication study including 720 patients and a panel of eight single nucleotide polymorphisms (SNPs), which predicted the prognosis of surgically treated NSCLC in our previous study, was conducted. Using the combined cohort of current and previous studies including 1534 patients, a nomogram for predicting overall survival was made using Cox proportional hazards regression.</P><P><B>Results</B></P><P>Among the eight SNPs, C3 rs2287845, GNB2L1 (alias RACK1), and rs3756585 were significantly associated with overall survival. A nomogram was constructed based on pathologic stage and the genotypes of the two SNPs, and the risk score was calculated for each patient in the combined cohort. Using the prognosis‐prediction model, we categorized patients into low, intermediate, and high‐risk groups, which had greater accuracy in predictive ability (log‐rank statistics = 54.66) than the conventional tumor node metastasis staging (log‐rank statistics = 39.56). Next, we generated a prognosis‐prediction model for stage I to identify a subgroup of potential candidates for adjuvant chemotherapy. Notably, 97 out of 499 stage IB patients were classified as high‐risk patients with a similar prognosis to stage II patients, suggesting the benefit of adjuvant chemotherapy.</P><P><B>Conclusions</B></P><P>This prognosis‐prediction model incorporating genetic polymorphism with pathologic stage may lead to more precise prognostication in surgically resected NSCLC patients. In particular, this model may be useful in selecting a subgroup of stage IB patients who may benefit from adjuvant chemotherapy.</P>

The deubiquitinating enzyme, ubiquitin‐specific peptidase 50, regulates inflammasome activation by targeting the ASC adaptor protein

Lee, Jae Young,Seo, Dongyeob,You, Jiyeon,Chung, Sehee,Park, Jin Seok,Lee, Ji&#x2010,Hyung,Jung, Su Myung,Lee, Youn Sook,Park, Seok Hee John Wiley and Sons Inc. 2017 FEBS letters Vol.591 No.3

<P>NOD‐like receptor family protein 3 (NLRP3)‐mediated inflammasome activation promotes caspase‐1‐dependent production of interleukin‐1β (IL‐1β) and requires the adaptor protein ASC. Compared with the priming and activation mechanisms of the inflammasome signaling pathway, post‐translational ubiquitination/deubiquitination mechanisms controlling inflammasome activation have not been clearly addressed. We here demonstrate that the deubiquitinating enzyme USP50 binds to the ASC protein and subsequently regulates the inflammasome signaling pathway by deubiquitinating the lysine 63‐linked polyubiquitination of ASC. USP50 knockdown in human THP‐1 cells and mouse bone marrow‐derived macrophages shows a significant decrease in procaspase‐1 cleavage, resulting in a reduced secretion of IL‐1β and interleukin‐18 (IL‐18) upon treatment with NLRP3 stimuli and a reduction in ASC speck formation and oligomerization. Thus, we elucidate a novel regulatory mechanism of the inflammasome signaling pathway mediated by the USP50 deubiquitinating enzyme.</P>

Permanent Chemotherapy‐Induced Alopecia in Patients with Breast Cancer: A 3‐Year Prospective Cohort Study

Kang, Danbee,Kim, Im&#x2010,Ryung,Choi, Eun&#x2010,Kyung,Im, Young Hyuck,Park, Yeon Hee,Ahn, Jin Seok,Lee, Jeong Eon,Nam, Seok Jin,Lee, Hae Kwang,Park, Ji&#x2010,Hye,Lee, Dong&#x2010,Youn,Lacouture, M AlphaMed Press 2019 The oncologist Vol.24 No.3

<P>Chemotherapy‐induced alopecia is (CIA) considered temporary; however, some patients report persistent alopecia several years after chemotherapy. Long‐term prospective data on the incidence and impact of permanent CIA is scarce. This article reports the results of a study conducted to estimate the long‐term incidence of persistent CIA in a cohort of breast cancer patients with measurements of hair volume and density before and after chemotherapy.</P><P><B>Background.</B></P><P>Although chemotherapy‐induced alopecia (CIA) is considered temporary, some patients report persistent alopecia several years after chemotherapy. There is, however, a paucity of long‐term prospective data on the incidence and impact of permanent CIA (PCIA). The objective of our study was to estimate the long‐term incidence of PCIA in a cohort of patients with breast cancer whose hair volume and density were measured prior to chemotherapy and who were followed for 3 years after chemotherapy.</P><P><B>Materials and Methods.</B></P><P>Prospective cohort study of consecutive patients ≥18 years of age with postoperative diagnosis of stage I–III breast cancer expected to receive adjuvant chemotherapy at the outpatient breast cancer clinic at the Samsung Medical Center in Seoul, Korea, from February 2012 to July 2013 (<I>n</I> = 61). Objective hair density and thickness were measured using a noninvasive bioengineering device.</P><P><B>Results.</B></P><P>The proportion of participants who had PCIA at 6 months and 3 years was 39.5% and 42.3%, respectively. PCIA was characterized in most patients by incomplete hair regrowth. Patients who received a taxane‐based regimen were more likely to experience PCIA compared with patients with other types of chemotherapy. At a 3‐year follow‐up, hair thinning was the most common problem reported by study participants (75.0%), followed by reduced hair volume (53.9%), hair loss (34.6%), and gray hair (34.6%).</P><P><B>Conclusion.</B></P><P>PCIA is a common adverse event of breast cancer adjuvant cytotoxic chemotherapy. Clinicians should be aware of this distressing adverse event and develop supportive care strategies to counsel patients and minimize its impact on quality of life.</P><P><B>Implications for Practice.</B></P><P>Knowledge of permanent chemotherapy‐induced alopecia, an under‐reported adverse event, should lead to optimized pretherapy counseling, anticipatory coping techniques, and potential therapeutic strategies for this sequela of treatment.</P>

The rice Os NAC 6 transcription factor orchestrates multiple molecular mechanisms involving root structural adaptions and nicotianamine biosynthesis for drought tolerance

Lee, Dong&#x2010,Keun,Chung, Pil Joong,Jeong, Jin Seo,Jang, Geupil,Bang, Seung Woon,Jung, Harin,Kim, Youn Shic,Ha, Sun&#x2010,Hwa,Choi, Yang Do,Kim, Ju&#x2010,Kon BLACKWELL 2017 PLANT BIOTECHNOLOGY JOURNAL Vol.15 No.6

<P><B>Summary</B></P><P>Drought has a serious impact on agriculture worldwide. A plant's ability to adapt to rhizosphere drought stress requires reprogramming of root growth and development. Although physiological studies have documented the root adaption for tolerance to the drought stress, underlying molecular mechanisms is still incomplete, which is essential for crop engineering. Here, we identified <I>OsNAC6</I>‐mediated root structural adaptations, including increased root number and root diameter, which enhanced drought tolerance. Multiyear drought field tests demonstrated that the grain yield of <I>OsNAC6</I> root‐specific overexpressing transgenic rice lines was less affected by drought stress than were nontransgenic controls. Genome‐wide analyses of loss‐ and gain‐of‐function mutants revealed that OsNAC6 up‐regulates the expression of direct target genes involved in membrane modification, nicotianamine (NA) biosynthesis, glutathione relocation, 3′‐phophoadenosine 5′‐phosphosulphate accumulation and glycosylation, which represent multiple drought tolerance pathways. Moreover, overexpression of <I>NICOTIANAMINE SYNTHASE</I> genes, direct targets of OsNAC6, promoted the accumulation of the metal chelator NA and, consequently, drought tolerance. Collectively, OsNAC6 orchestrates novel molecular drought tolerance mechanisms and has potential for the biotechnological development of high‐yielding crops under water‐limiting conditions.</P>

XIAP inhibitor embelin induces autophagic and apoptotic cell death in human oral squamous cell carcinoma cells

Lee, You&#x2010,Jin,Park, Bong&#x2010,Soo,Park, Hae&#x2010,Ryoun,Yu, Su&#x2010,Bin,Kang, Hae&#x2010,Mi,Kim, In&#x2010,Ryoung John Wiley and Sons Inc. 2017 Environmental toxicology Vol.32 No.11

<P><B>Abstract</B></P><P>Embelin is an active ingredient of traditional herbal remedies for cancer and other diseases. Recently, it has been suggested that autophagy may play an important role in cancer therapy. However, little data are available regarding the role of autophagy in oral cancers. Therefore, we conducted this study to examine whether Embelin modulates autophagy in Ca9‐22. Our results showed that Embelin had anticancer activity against the Ca9‐22 human tongue squamous cell, and we observed that autophagic vacuoles were formed by MDC and AO. We also analyzed Embelin‐treated Ca9‐22 cells for the presence of biochemical markers and found that it directly affected the conversion of LC3‐II, the degradation of p62/SQSTM1, full‐length cleavage formation of ATG5‐ATG12 complex and Beline‐1, and caspase activation. Rescue experiments using an autophagy inhibitor showed Embelin‐induced cell death in Ca9‐22, confirming that autophagy acts as a pro‐death signal. Furthermore, Embelin exhibited anticancer activity against Ca9‐22 via both autophagy and apoptosis. These findings suggest that Embelin may potentially contribute to oral cancer treatment and provide useful information for the development of a new therapeutic agent.</P>

Highly Efficient p‐i‐n and Tandem Organic Light‐Emitting Devices Using an Air‐Stable and Low‐Temperature‐Evaporable Metal Azide as an n‐Dopant

Yook, Kyoung Soo,Jeon, Soon Ok,Min, Sung&#x2010,Yong,Lee, Jun Yeob,Yang, Ha&#x2010,Jin,Noh, Taeyong,Kang, Sung&#x2010,Kee,Lee, Tae&#x2010,Woo WILEY‐VCH Verlag 2010 Advanced Functional Materials Vol.20 No.11

<P><B>Abstract</B></P><P>Cesium azide (CsN<SUB>3</SUB>) is employed as a novel n‐dopant because of its air stability and low deposition temperature. CsN<SUB>3</SUB> is easily co‐deposited with the electron transporting materials in an organic molecular beam deposition chamber so that it works well as an n‐dopant in the electron transport layer because its evaporation temperature is similar to that of common organic materials. The driving voltage of the p‐i‐n device with the CsN<SUB>3</SUB>‐doped n‐type layer and a MoO<SUB>3</SUB>‐doped p‐type layer is greatly reduced, and this device exhibits a very high power efficiency (57 lm W<SUP>−1</SUP>). Additionally, an n‐doping mechanism study reveals that CsN<SUB>3</SUB> was decomposed into Cs and N<SUB>2</SUB> during the evaporation. The charge injection mechanism was investigated using transient electroluminescence and capacitance–voltage measurements. A very highly efficient tandem organic light‐emitting diodes (OLED; 84 cd A<SUP>−1</SUP>) is also created using an n–p junction that is composed of the CsN<SUB>3</SUB>‐doped n‐type organic layer/MoO<SUB>3</SUB> p‐type inorganic layer as the interconnecting unit. This work demonstrates that an air‐stable and low‐temperature‐evaporable inorganic n‐dopant can very effectively enhance the device performance in p‐i‐n and tandem OLEDs, as well as simplify the material handling for the vacuum deposition process.</P>

Anti‐inflammatory mechanism of ginsenoside Rh1 in lipopolysaccharide‐stimulated microglia: critical role of the protein kinase A pathway and hemeoxygenase‐1 expression

Jung, Ji&#x2010,Sun,Shin, Jin A.,Park, Eun&#x2010,Mi,Lee, Jung&#x2010,Eun,Kang, Young&#x2010,Sook,Min, Sung&#x2010,Won,Kim, Dong&#x2010,Hyun,Hyun, Jin‐,Won,Shin, Chan&#x2010,Young,Kim, Hee&#x201 Blackwell Publishing Ltd 2010 Journal of Neurochemistry Vol.115 No.6

<P> <I>J. Neurochem.</I> (2010) <B>115,</B> 1668–1680.</P><P><B>Abstract</B></P><P>Microglia activation plays a pivotal role in neurodegenerative diseases, and thus controlling microglial activation has been suggested as a promising therapeutic strategy for neurodegenerative diseases. In the present study, we showed that ginsenoside Rh1 inhibited inducible nitric oxide synthase, cyclooxygenase‐2, and pro‐inflammatory cytokine expression in lipopolysaccharide (LPS)‐stimulated microglia, while Rh1 increased anti‐inflammatory IL‐10 and hemeoxygenase‐1 (HO‐1) expression. Suppression of microglial activation by Rh1 was also observed in the mouse brain following treatment with LPS. Subsequent mechanistic studies revealed that Rh1 inhibited LPS‐induced MAPK phosphorylation and nuclear factor‐κB (NF‐κB)‐mediated transcription without affecting NF‐κB DNA binding. As the increase of pCREB (cAMP responsive element‐binding protein) is known to result in suppression of NF‐κB‐mediated transcription, we examined whether Rh1 increased pCREB levels. As expected, Rh1 increased pCREB, which was shown to be related to the anti‐inflammatory effect of Rh1 because pre‐treatment with protein kinase A inhibitors attenuated the Rh1‐mediated inhibition of nitric oxide production and the up‐regulation of IL‐10 and HO‐1. Furthermore, treatment of HO‐1 shRNA attenuated Rh1‐mediated inhibition of nitric oxide and reactive oxygen species production. Through this study, we have demonstrated that protein kinase A and its downstream effector, HO‐1, play a critical role in the anti‐inflammatory mechanism of Rh1 by modulating pro‐ and anti‐inflammatory molecules in activated microglia.</P>