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Interleukin-4 Induces Senescence in Human Renal Carcinoma Cell Lines through STAT6 and p38 MAPK
Kim, Hag Dong,Yu, Su-Jin,Kim, Hee Suk,Kim, Yong-Jin,Choe, Jeong Min,Park, Yun Gyu,Kim, Joon,Sohn, Jeongwon American Society for Biochemistry and Molecular Bi 2013 The Journal of biological chemistry Vol.288 No.40
<P>Interleukin (IL)-4, originally identified as a lymphocyte growth factor, can directly inhibit growth of certain tumor cell types. We reported previously that IL-4 induced cell cycle arrest in G<SUB>1</SUB> phase through an increase in p21<SUP>WAF1/CIP1</SUP> expression in human renal cell carcinoma (RCC) cell lines. In the present study, we investigated the underlying mechanism of IL-4-induced growth inhibition. In four of six human RCC cell lines, including Caki-1, A498, SNU482, and SNU228, IL-4 induced cellular senescence as demonstrated by enlarged and flattened morphology, increased granularity, and senescence-associated-β-galactosidase (SA-β-gal) staining. Signal tranducer and activator of transcription 6 (STAT6) and p38 MAPK were found to mediate IL-4-induced growth inhibition and cellular senescence. Both of these molecules were activated by 10 min after IL-4 treatment, and inhibition of their activity or expression prevented growth suppression and cellular senescence induced by IL-4. Inhibiting or silencing either STAT6 or p38 MAPK alone partially reduced the effect of IL-4, whereas inhibiting or silencing both molecules exerted an additive effect and almost completely abrogated the effect of IL-4. Thus STAT6 and p38 MAPK appeared to independently mediate IL-4-induced growth inhibition and cellular senescence. The p21<SUP>WAF1/CIP1</SUP> up-regulation that accompanied growth inhibition and cellular senescence by IL-4 was also attenuated additively when p38 MAPK and STAT6 were silenced. Taken together, these results show that IL-4 induces cellular senescence through independent signaling pathways involving STAT6 and p38 MAPK in some human RCC cell lines.</P>
Kim, Jeongwon,Gwon, Ohhun,Kwon, Ohhun,Mahmood, Javeed,Kim, Changmin,Yang, Yejin,Lee, Hansol,Lee, Jong Hoon,Jeong, Hu Young,Baek, Jong-Beom,Kim, Guntae American Chemical Society 2019 ACS NANO Vol.13 No.5
<P>Developing cost-effective, efficient bifunctional electrocatalysts for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is the heart of metal-air batteries as a renewable-energy technology. Herein, well-distributed nanopolyhedron (NP) Co<SUB>3</SUB>O<SUB>4</SUB> grown on iron (Fe) encapsulated in graphitic layers on a nitrogenated, porous two-dimensional (2D) structure, namely, a C<SUB>2</SUB>N matrix, (NP Co<SUB>3</SUB>O<SUB>4</SUB>/Fe@C<SUB>2</SUB>N), presents an outstanding bifunctional catalytic activity with a comparable overpotential and Tafel slope to those of benchmark Pt/C and IrO<SUB>2</SUB>. The rationally designed atomic configuration of Co<SUB>3</SUB>O<SUB>4</SUB> on the C<SUB>2</SUB>N matrix has a well-controlled NP morphology with a (111) plane, leading to bifunctional activities for the ORR and OER. Interestingly, the specific interaction between the NP Co<SUB>3</SUB>O<SUB>4</SUB> nanoparticles and the C<SUB>2</SUB>N matrix introduces synergistic coupling and changes the electronic configuration of Co atoms and the C<SUB>2</SUB>N framework. Benefiting from the synergistic coupling of Co<SUB>3</SUB>O<SUB>4</SUB> with the C<SUB>2</SUB>N matrix, the NP Co<SUB>3</SUB>O<SUB>4</SUB>/Fe@C<SUB>2</SUB>N electrocatalyst exhibits exceptionally high stability and an even lower charge-discharge overpotential gap of 0.85 V at 15 mA cm<SUP>-2</SUP> than that of the Pt/C+IrO<SUB>2</SUB> catalyst (1.01 V) in Zn-air batteries. This work provides insights into the rational design of a metal oxide on a C<SUB>2</SUB>N matrix for bifunctional, low-cost electrochemical catalysts.</P> [FIG OMISSION]</BR>
Ji Hyun Kim,Baek Gyu Jun,Minjong Lee,Hye Ah Lee,Tae Suk Kim,Jeongwon Heo,Da Hye Moon,Seong Hee Kang,Ki Tae Suk,Moon Young Kim,Young Don Kim,Gab Jin Cheon,Soon Koo Baik,Dong Joon Kim,Dae Hee Choi 대한간학회 2022 Clinical and Molecular Hepatology(대한간학회지) Vol.28 No.3
Background/Aims: Sepsis-3 criteria and quick Sequential Organ Failure Assessment (qSOFA) have been advocated to be used in defining sepsis in the general population. We aimed to compare the Sepsis-3 criteria and Chronic Liver Failure-SOFA (CLIF-SOFA) scores as predictors of in-hospital mortality in cirrhotic patients admitted to the emergency department (ED) for infections. Methods: A total of 1,622 cirrhosis patients admitted at the ED for infections were assessed retrospectively. We analyzed their demographic, laboratory, and microbiological data upon diagnosis of the infection. The primary endpoint was inhospital mortality rate. The predictive performances of baseline CLIF-SOFA, Sepsis-3, and qSOFA scores for in-hospital mortality were evaluated. Results: The CLIF-SOFA score proved to be significantly better in predicting in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.80; 95% confidence interval [CI], 0.78–0.82) than the Sepsis-3 (AUROC, 0.75; 95% CI, 0.72–0.77, P<0.001) and qSOFA (AUROC, 0.67; 95% CI, 0.64–0.70; P<0.001) score. The CLIF-SOFA, CLIF-C-AD scores, Sepsis-3 criteria, septic shock, and qSOFA positivity were significantly associated with in-hospital mortality (adjusted hazard ratio [aHR], 1.24; 95% CI, 1.19–1.28; aHR, 1.13; 95% CI, 1.09–1.17; aHR, 1.19; 95% CI, 1.15–1.24; aHR, 1.88; 95% CI, 1.42–2.48; aHR, 2.06; 95% CI, 1.55–2.72; respectively; all P<0.001). For CLIF-SOFA scores ≥6, in-hospital mortality was >10%; this is the cutoff point for the definition of sepsis. Conclusions: Among cirrhosis patients presenting with infections at the ED, CLIF-SOFA scores showed a better predictive performance for mortality than both Sepsis-3 criteria and qSOFA scores, and can be a useful tool of risk stratification in cirrhotic patients requiring timely intervention for infection.
Park, Geun-Ha,Lee, Seon-Eun,Kim, Young-il,Kim, Dongseon,Lee, Kitack,Kang, Jeongwon,Kim, Yeo-Hun,Kim, Haryun,Park, Seunghee,Kim, Tae-Wook Elsevier 2019 Science of the Total Environment Vol.681 No.-
<P><B>Abstract</B></P> <P>The atmospheric deposition of anthropogenic nitrogen is an increasingly important new source of nitrogen to the ocean. Coastal areas east of the Korean Peninsula are suitable for the investigation of the effects of atmospheric anthropogenic nitrogen on the ocean nutrient system because of the low riverine discharge rates and the prevailing influence of the East Asian outflow. Thus, we measured the concentrations of nitrate (NO<SUB>3</SUB> <SUP>−</SUP>) and ammonium (NH<SUB>4</SUB> <SUP>+</SUP>) in airborne particles and in precipitation from March 2014 to February 2016 at a coastal site (37.08°N, 129.41°E) on the east coast of Korea. The dry deposition of NO<SUB>3</SUB> <SUP>−</SUP> (27–30 mmol N m<SUP>−2</SUP> yr<SUP>−1</SUP>) was far greater than that of NH<SUB>4</SUB> <SUP>+</SUP> (6–8 mmol N m<SUP>−2</SUP> yr<SUP>−1</SUP>). The greater rate of dry NO<SUB>3</SUB> <SUP>−</SUP> deposition was associated with air masses traveling over northeastern China and central Korea. In contrast, the rates of wet deposition of NO<SUB>3</SUB> <SUP>−</SUP> (17–24 mmol N m<SUP>−2</SUP> yr<SUP>−1</SUP>) and NH<SUB>4</SUB> <SUP>+</SUP> (14–27 mmol N m<SUP>−2</SUP> yr<SUP>−1</SUP>) were comparable and were probably associated with in-cloud scavenging of these ions. The results indicate that the total deposition of NO<SUB>3</SUB> <SUP>−</SUP> and NH<SUB>4</SUB> <SUP>+</SUP> combined could contribute to ~2.4% and ~1.9% of the primary production in the coastal areas east of the Korean Peninsula and in the East Asian marginal seas, respectively, which would be a lower bound because the dry deposition of reactive nitrogen gas was not included. Our study shows that the atmospheric input of anthropogenic NO<SUB>3</SUB> <SUP>−</SUP> and NH<SUB>4</SUB> <SUP>+</SUP> may substantially increase phytoplankton biomass in the coastal waters of the East Sea near the Korean Peninsula.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Atmospheric Nitrogen Deposition (AND) was 64–89 mmol N m<SUP>−2</SUP> yr<SUP>−1</SUP> in the East Sea. </LI> <LI> AND was enhanced in air masses traveling over northeastern China and central Korea. </LI> <LI> AND could contribute to ~1.9% of the primary production of East Asian seas. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Plasma CRABP2 as a Novel Biomarker in Patients with Non-Small Cell Lung Cancer
Kim, Do Jun,Kim, Woo Jin,Lim, Myoungnam,Hong, Yoonki,Lee, Seung-Joon,Hong, Seok-Ho,Heo, Jeongwon,Lee, Hui-Young,Han, Seon-Sook KOREAN ACADEMY OF MEDICAL SCIENCE 2018 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.33 No.26
<P><B>Background</B></P><P>Lung cancer is the most common cause of cancer-related mortality worldwide. We previously reported the identification of a new genetic marker, cellular retinoic acid binding protein 2 (CRABP2), in lung cancer tissues. The aim of this study was to assess plasma levels of CRABP2 from patients with non-small cell lung cancer (NSCLC).</P><P><B>Methods</B></P><P>Blood samples that were collected from 122 patients with NSCLC between September 2009 and September 2013 were selected for the analysis, along with samples from age- (± 5 years), sex-, and cigarette smoking history (± 10 pack-years [PY])-matched controls from the Korea Biobank Network. The control specimens were from patients who were without malignancies or pulmonary diseases. We measured plasma levels of CRABP2 using commercially available enzyme-linked immunosorbent assay kits.</P><P><B>Results</B></P><P>The mean age of the NSCLC patients was 71.8 ± 8.9 years, and the median cigarette smoking history was 32 PY (range, 0–150 PY). Plasma CRABP2 levels were significantly higher in patients with NSCLC than in the matched controls (37.63 ± 28.71 ng/mL vs. 24.09 ± 21.09 ng/mL, <I>P</I> < 0.001). Higher plasma CRABP2 levels were also correlated with lower survival rates in NSCLC patients (<I>P</I> = 0.014).</P><P><B>Conclusion</B></P><P>Plasma CRABP2 levels might be a novel diagnostic and prognostic marker in NSCLC.</P>
Kim, Suyong,Lee, Jeongwon,Shayan, F. Lahiji,Kim, Seohyun,Huh, Inyoung,Ma, Yonghao,Yang, Huisuk,Kang, Geonwoo,Jung, Hyungil Elsevier 2018 Carbohydrate polymers Vol.180 No.-
<P><B>Abstract</B></P> <P>A dissolving microneedle (DMN) patch encapsulated with ascorbic acid 2-glucoside (AA2G) in a needle-shaped hyaluronic acid (HA) backbone was fabricated and sterilized by electron beam (e-beam, 5–40kGy) and gamma ray (γ-ray, 5–30kGy). DMN structures maintained their morphologies and fracture force regardless of e-beam and γ-ray irradiation doses. Both e-beam (40kGy) and γ-ray (20 and 30kGy) met the product sterility requirements for cosmetics and vaccines; however, γ-ray irradiation significantly degraded the encapsulated AA2G, while e-beam maintained AA2G activity. Thus, an e-beam dose of 40kGy, which satisfied the sterility requirements without loss of AA2G, is suitable for terminal sterilization of DMNs. Moreover, we confirmed that the optimized irradiation (e-beam, 40kGy) did not affect dissolution rate and drug release profile of DMNs. Further, we confirmed that HA, the backbone polymer of DMNs, could be utilized as a stabilizer that inhibits degradation of encapsulated AA2G by irradiation. This detailed analysis can be developed further to optimize various biological drugs in transdermal drug delivery systems.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Hyaluronic acid-based dissolving microneedles were fabricated and sterilized. </LI> <LI> Electron beam (e-beam) and gamma ray (γ-ray) were used for sterilization. </LI> <LI> Irradiation did not affect morphology and fracture force of dissolving microneedles. </LI> <LI> E-beam and γ-ray reduced microorganismal contamination; γ-ray degraded the drug. </LI> <LI> Hyaluronic acid stabilizes and can inhibit degradation of the encapsulated drug. </LI> </UL> </P>