Effects of FGF 21‐secreting adipose‐derived stem cells in thioacetamide‐induced hepatic fibrosis

Kang, Hwansu,Seo, Eunhui,Park, Jong&#x2010,Moon,Han, Na&#x2010,Young,Lee, Hookeun,Jun, Hee‐,Sook John Wiley and Sons Inc. 2018 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Vol.22 No.10

<P><B>Abstract</B></P><P>Mesenchymal stem cells (MSCs) have been investigated to treat liver diseases, but the efficiency of MSCs to treat chronic liver diseases is conflicting. FGF21 can reduce inflammation and fibrosis. We established FGF21‐secreting adipose derived stem cells (FGF21_ADSCs) to enhance the effects of ADSCs and transplanted them into thioacetamide (TAA)‐induced liver fibrosis mice via the tail vein. Transplantation of FGF21_ADSCs significantly improved liver fibrosis by decreasing serum hyaluronic acid and reducing the expression of fibrosis‐related factors such as α‐smooth muscle actin (α‐SMA), collagen and tissue inhibitor of metalloproteinase‐1 (TIMP‐1) compared with the Empty_ADSCs by inhibition of p‐JNK, NF‐κB and p‐Smad2/3 signalling. α‐lactoalbumin (LA) and lactotransferrin (LTF), secretory factors produced from FGF21_ADSCs inhibited TGF‐β1‐induced expression of α‐SMA and collagen in LX‐2 cells. These results suggest that transplantation of FGF21_ADSCs inhibited liver fibrosis more effectively than Empty_ADSCs, possibly via secretion of α‐LA and LTF.</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>

Pleural or pericardial metastasis: A significant factor affecting efficacy and adverse events in lung cancer patients treated with PD‐1/PD‐L1 inhibitors

Kang, Da Hyun,Chung, Chaeuk,Kim, Ju&#x2010,Ock,Jung, Sung Soo,Park, Hee Sun,Park, Dong Il,Jung, Sun Young,Park, Myoungrin,Lee, Jeong Eun John WileySons Australia, Ltd 2018 Thoracic cancer Vol.9 No.11

<P><B>Background</B></P><P>Immunotherapy is a new paradigm for the treatment of non‐small‐cell lung cancer (NSCLC), and targeting the PD‐1 or PD‐L1 pathway is a promising therapeutic option. Although PD‐1/PD‐L1 inhibitors are more effective than standard chemotherapy in lung cancer, clinicians are afraid to actively use them because of hyperprogression and pseudoprogression. The aim of this study was to investigate the factors associated with tumor response and serious outcomes.</P><P><B>Methods</B></P><P>We retrospectively collected the medical records of 51 patients with advanced NSCLC who received PD‐1/PD‐L1 inhibitors between January 2016 and February 2018.</P><P><B>Results</B></P><P>The mean patient age was 63.9 years, and 72.5% (37/51) were male. Most (92.2%, 47/51) had received previous systemic treatment. The overall response rate was 21.6% (11/51). The response rate was significantly lower in patients with pleural or pericardial metastasis than in patients without pleural or pericardial metastasis (4.3% vs. 35.7%; <I>P</I> = 0.007). Patients with pleural or pericardial metastasis had a significantly higher rate of adverse events of any grade (91.3% vs. 50.0%; <I>P</I> = 0.002) and grade 3–5 adverse events (52.2% vs. 25.0%; <I>P</I> = 0.046).</P><P><B>Conclusion</B></P><P>Pleural or pericardial metastasis is a significant factor affecting the efficacy and rate of adverse events in advanced NSCLC patients treated with PD‐1/PD‐L1 inhibitors. Clinicians should pay attention to the use of immune checkpoint inhibitors in lung cancer patients with pleural or pericardial metastasis.</P>

Polymer‐Stabilized Chromonic Liquid‐Crystalline Polarizer

Park, Seul&#x2010,Ki,Kim, So&#x2010,Eun,Kim, Dae&#x2010,Yoon,Kang, Shin&#x2010,Woong,Shin, Seunghan,Kuo, Shiao&#x2010,Wei,Hwang, Seok&#x2010,Ho,Lee, Seung Hee,Lee, Myong&#x2010,Hoon,Jeong, Kwang&#x201 WILEY‐VCH Verlag 2011 Advanced functional materials Vol.21 No.11

<P><B>Abstract</B></P><P>Robust coatable polarizer is fabricated by the self‐assembly of lyotropic chromonic liquid crystals and subsequent photo‐polymerizing processes. Their molecular packing structures and optical behaviors are investigated by the combined techniques of microscopy, scattering and spectroscopy. To stabilize the oriented Sunset Yellow FCF (H‐SY) films and to minimize the possible defects generated during and after the coating, acrylic acid (AA) is added to the H‐SY/H<SUB>2</SUB>O solution and photo‐polymerized. Utilizing cross‐polarized optical microscopy, phase behaviors of the H‐SY/H<SUB>2</SUB>O/AA solution are monitored by varying the compositions and temperatures of the solution. Based on the experimental results of two‐dimensional wide angle X‐ray diffraction and selected area electron diffraction, the H‐SY crystalline unit cell is determined to be a monoclinic structure with the dimensions of <I>a</I> = 1.70 nm, <I>b</I> = 1.78 nm, <I>c</I> = 0.68 nm, <I>α</I> = <I>β</I> = 90.0° and <I>γ</I> = 84.5°. The molecular arrangements in the oriented H‐SY films were further confirmed by polarized Fourier‐transform infrared spectroscopy. The polymer‐stabilized H‐SY films show good mechanical and chemical stabilities with a high polarizability. Additionally, patterned polarizers are fabricated by applying a photo‐mask during the photo‐polymerization of AA, which may open new doors for practical applications in electro‐optic devices.</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&#x2010,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>

Large‐Scale Highly Ordered Chitosan‐Core Au‐Shell Nanopatterns with Plasmonic Tunability: A Top‐Down Approach to Fabricate Core–Shell Nanostructures

Baek, Youn&#x2010,Kyoung,Yoo, Seung Min,Kang, Taejoon,Jeon, Hwan&#x2010,Jin,Kim, Kyounghwan,Lee, Ji&#x2010,Sun,Lee, Sang Yup,Kim, Bongsoo,Jung, Hee‐,Tae WILEY‐VCH Verlag 2010 Advanced functional materials Vol.20 No.24

<P><B>Abstract</B></P><P>A new strategy for fabricating highly ordered chitosan–Au core–shell nano­patterns with tunable surface plasmon resonance (SPR) properties is developed. This strategy combines fabrication of a chitosan nanopattern by using a soft‐nanoimprint technique with selective deposition of Au nanoparticles onto the patterned chitosan surface. The SPR response can be tuned by controlling the features of the resulting Au shell/polymer hybrid pattern, which makes these materials potentially useful in ultrasensitive optical sensors for molecular detection.</P>

Synthesis and Structure–Activity Relationships of Gadolinium Complexes of DO3A–Benzothiazole Conjugates as Potential Theranostic Agents

Jung, Ki&#x2010,Hye,Kang, Sun&#x2010,Hee,Kang, Min&#x2010,Kyoung,Kim, Soyeon,Kim, Hee‐,Kyung,Kim, Yeoun&#x2010,Hee,Ho Lee, Gang,Shim, Gyu&#x2010,Bo,Jung, Jae&#x2010,Chang,Chang, Yongmin,Kim, Tae WILEY‐VCH Verlag 2015 European journal of inorganic chemistry Vol.2015 No.4

<P><B>Abstract</B></P><P>The synthesis of two bifunctional chelates, 1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acid (DO3A) conjugates of benzothiazoles (H<SUB>3</SUB>L<SUP>3a</SUP> and H<SUB>3</SUB>L<SUP>3b</SUP>), and the corresponding gadolinium complexes (GdL<SUP>3a</SUP> and GdL<SUP>3b</SUP>) was achieved. The intracellular and tumor‐specific nature of GdL<SUP>3a</SUP> and GdL<SUP>3b</SUP> were confirmed by magnetic resonance images of the cytosols and nuclei of various cell lines. The two complexes displayed antitumor activities with varying degrees of growth‐inhibition and total‐growth‐inhibition values depending on the types of tumor cells. They caused morphological changes in tumor cell lines at much lower concentrations of gadolinium ([Gd] ≥ 50 μ<SMALL>M</SMALL>) than their predecessors, DO3A–(<I>p</I>‐aniline benzothiazole) conjugates (H<SUB>3</SUB>L<SUP>1</SUP>), and its Gd<SUP>III</SUP> complex (GdL<SUP>1</SUP>) required concentrations that were almost four times as high ([Gd] ≥ 200 μ<SMALL>M</SMALL>).</P>

Susceptibility to natural killer cell‐mediated lysis of colon cancer cells is enhanced by treatment with epidermal growth factor receptor inhibitors through UL16‐binding protein‐1 induction

Bae, Jae&#x2010,Ho,Kim, So&#x2010,Jung,Kim, Mi&#x2010,Ju,Oh, Sae&#x2010,Ock,Chung, Joo&#x2010,Seop,Kim, Sun&#x2010,Hee,Kang, Chi&#x2010,Dug Blackwell Publishing Ltd 2012 Cancer Science Vol.103 No.1

<P>We have previously shown that inhibition of intracellular signaling pathways by treatment with quercetin induced the expression of natural killer cell group 2D (NKG2D) ligands on cancer cells and made the cells sensitive to natural killer (NK)‐cell mediated cytotoxicity. In the present study, we investigated whether epidermal growth factor receptor (EGFR) inhibitors could induce the expression of NKG2D ligands in colon cancer cells. Treatment with EGFR inhibitors predominantly increased the levels of mRNA transcripts and surface protein of UL16‐binding protein‐1 (ULBP1) in various colon cancer cells, including KM12, Caco‐2, HCT‐15, and HT‐29, which express EGFR, and increased susceptibility of these colon cancer cells to NK‐92 cells. The expression of ULBP1 was not induced by inhibitors of nuclear factor‐κB, phosphatidylinositol 3 kinase, and MAPK, but was induced by inhibitors of PKC, and the induction of ULBP1 expression with EGFR inhibitors was prevented by treatment with PMA in colon cancer cells. A transcription factor, activator protein‐2 alpha (AP‐2α), which has a suppressive effect on <I>ULBP1</I> transcription, was prevented from binding to the <I>ULBP1</I> promoter by treatment with EGFR inhibitors. The present study suggests that EGFR inhibitors can enhance the susceptibility to NK cell‐mediated lysis of colon cancer cells by induction of ULBP1 via inhibition of the PKC pathway. (<I>Cancer Sci</I> 2012; 103: 7–16)</P>

Relaxin is up‐regulated in the rat ovary by orthodontic tooth movement

Yang, So&#x2010,Young,Ko, Hyun&#x2010,Mi,Kang, Jee&#x2010,Hae,Moon, Yeon&#x2010,Hee,Yoo, Hong&#x2010,Il,Jung, Na&#x2010,Ri,Kim, Min&#x2010,Seok,Cho, Jin&#x2010,Hyung,Oh, Won&#x2010,Mann,Kim, Sun&#x201 Blackwell Publishing Ltd 2011 European journal of oral sciences Vol.119 No.2

<P> <I>Yang S‐Y, Ko H‐M, Kang J‐H, Moon Y‐H, Yoo H‐I, Jung N‐R, Kim M‐S, Cho J‐H, Oh W‐M, Kim S‐H. Relaxin is up‐regulated in the rat ovary by orthodontic tooth movement.</I> 
 <I>Eur J Oral Sci 2011; 119: 115–120. © 2011 Eur J Oral Sci</I> </P><P>Relaxin (Rln) is an ovarian hormone that stimulates osteoclastic and osteoblastic activities and connective tissue turnover. To investigate the expression of Rln during orthodontic tooth movement, rats were implanted with orthodontic appliances that connected a spring from the upper incisors to the first molar with a 70 cN force. Rats in each group were killed 6, 48, and 144 h after activating the appliance, and the levels of <I>Rln1</I> and <I>Rln3</I> expression in the ovary were determined by real‐time RT‐PCR, northern blots, western blots, and immunofluorescence analyses. The amount of tooth movement induced by the orthodontic force increased in a time‐dependent manner. The levels of <I>Rln1</I> mRNA increased by 12‐, 41‐, and 263‐fold at 6, 48, and 144 h, respectively, after orthodontic tooth movement. The time‐dependent increase in the concentration of Rln 1 protein in the ovary was also confirmed by western blotting. Rln 1 was localized in the granulosa cells of the ovarian follicles, and the immunoreactivity against Rln 1 was increased by the movement. In contrast, the concentration of Rln 3 was below the level of detection. The results of this study suggest that local changes in periodontal tissues induced by orthodontic tooth movement may affect <I>Rln1</I> expression in the ovary. However, further studies are needed to decipher the mechanisms involved and the possible contribution of the increased level of expression of Rln 1 to the tooth movement.</P>

Identifying metabolically obese but normal‐weight (MONW) individuals in a nondiabetic Korean population: the Chungju Metabolic disease Cohort (CMC) study

Lee, Seung&#x2010,Hwan,Ha, Hee‐,Sung,Park, Young&#x2010,Jun,Lee, Jin&#x2010,Hee,Yim, Hyeon&#x2010,Woo,Yoon, Kun&#x2010,Ho,Kang, Moo&#x2010,Il,Lee, Won&#x2010,Chul,Son, Ho&#x2010,Young,Park, Yong Blackwell Publishing Ltd 2011 Clinical endocrinology Vol.75 No.4

<P><B>Summary</B></P><P><B>Objective </B> To investigate the prevalence and identify the phenotype of individuals suspected to be metabolically obese but normal weight (MONW).</P><P><B>Design and subjects </B> Eight thousand nine hundred and eighty‐seven nondiabetic subjects aged over 40 years were selected from the Chungju Metabolic disease Cohort study performed in 2003–2006 in Korea. Those within the highest quartile in the homeostasis model assessment of insulin resistance (HOMA‐IR) with a normal body mass index (BMI) between 18·5 and 23 kg/m<SUP>2</SUP> were classified as MONW.</P><P><B>Measurements </B> Data on anthropometry, lipid profiles and HOMA‐IR values were analysed.</P><P><B>Results </B> The prevalence of MONW was 14·2% for men and 12·9% for women amongst normal‐weight subjects. Multiple logistic regression analysis showed that total cholesterol (TC) levels over 5·17 m<SMALL>m</SMALL> (odds ratio, OR = 1·481; 95% confidence intervals, CI 1·086–2·021), triglyceride (TG) levels over 1·69 m<SMALL>m</SMALL> (OR = 1·507; 95% CI 1·093–2·077) and high‐density lipoprotein‐cholesterol levels lower than 1·03 m<SMALL>m</SMALL> (OR = 1·580; 95% CI 1·053–2·371) independently had higher odds of diagnosing MONW amongst men. For women, a BMI over 21·5 kg/m<SUP>2</SUP> (OR = 1·405; 95% CI 1·034–1·909), TC levels over 5·17 m<SMALL>m</SMALL> (OR = 1·524; 95% CI 1·112–2·090) and TG levels over 1·69 m<SMALL>m</SMALL> (OR = 1·799; 95% CI 1·302–2·487) were independently associated with a diagnosis of MONW.</P><P><B>Conclusions </B> More than 10% of normal‐weight subjects were classed as MONW in this cohort. Identification of these subjects based on lipid profiles could aid in the early detection of a high risk group of developing cardiometabolic diseases.</P>