Publications by authors named "Yohan Park"

62 Publications

Impact of high body mass index on allograft outcomes in kidney transplant recipients with presensitization to human leukocyte antigen.

Kidney Res Clin Pract 2021 Apr 30. Epub 2021 Apr 30.

Transplantation Research Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: This study aimed to investigate whether high body mass index (BMI) and presensitization to human leukocyte antigen (HLA) in kidney transplant recipients (KTRs) affected allograft outcomes.

Methods: From January 2010 to December 2018, 1,290 kidney transplantations (KTs) were performed at the Seoul St Mary's Hospital. Of these, 682 cases of ABO-compatible living donor KT patients were enrolled. They were divided into four groups (low BMI-non-sensitized, high BMI-non-sensitized, low BMI-sensitized, and high BMI-sensitized) according to the median BMI value (22.7 kg/m2) and HLA presensitization status (anti-HLA antibody mean fluorescence intensity > 3,000). Short-term and long-term allograft outcomes were compared between groups.

Results: In the high BMI-sensitized group, the decline in allograft function was higher than that in the other three groups. Death-censored graft loss (DCGL) rates were highest in the high BMI-sensitized group (4 of 21 [19.0%], p = 0.04). In the multivariable Cox regression hazard regression model analysis, the hazard ratio (HR) for DCGL was intensified when high BMI and presensitization statuses were combined (HR, 3.75; p = 0.03); these statuses significantly interacted with each other (p-value for interaction = 0.008).

Conclusion: Our results suggest that presensitization to HLA and high BMI might have an interactive adverse impact on allograft outcomes in KTRs.
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http://dx.doi.org/10.23876/j.krcp.20.216DOI Listing
April 2021

Clinical significance of heart rate variability for the monitoring of cardiac autonomic neuropathy in end-stage renal disease patients.

Nutr Metab Cardiovasc Dis 2021 Mar 26. Epub 2021 Mar 26.

Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Electronic address:

Background And Aims: The aim of this study is to determine whether the measurement of continuous heart rate variability (HRV) is useful in the evaluation of cardiac autonomic neuropathy (CAN) in end-stage renal disease (ESRD) patients.

Methods And Results: This cross-sectional study was performed at Seoul St. Mary's hospital between June 2017 and February 2018. Seventy-seven ESRD patients, and 29 healthy controls (HCs) were asked to wear a continuous ambulatory HRV monitor for 24 h. General cardiac function was evaluated using transthoracic echocardiogram (TTE), pulse wave velocity (PWV), coronary calcium scoring (CCS), and 24-h ambulatory blood pressure monitoring (ABPM). HRV parameters of ESRD patients and HCs, and the correlation of HRV parameters with cardiovascular screening methods were observed. All HRV parameters were significantly decreased in ESRD patients compared to HCs (P < 0.001). In the correlation analysis between TTE results and HRV parameters, 24-h standard deviation of all N-N intervals (24SDNN), 24-h standard deviation of sequential 5-min N-N interval means (24DANN) and Low Frequency Power/High Frequency Power (LF/HF) ratio showed negative correlations with E/e', LAVI and TR velocity which are representative indices for the diastolic function of the heart (P < 0.05). HRV parameters showed negative correlations with baPWV, CCS, and 24-h ABPM results as well (P < 0.05). Hemoglobin and serum albumin showed positive correlations with HRV parameters, and glucose, BUN, creatinine, and iPTH levels showed negative correlations (P < 0.05).

Conclusion: Continuous HRV monitoring may be a useful tool for the evaluation of CAN in ESRD.
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http://dx.doi.org/10.1016/j.numecd.2021.03.016DOI Listing
March 2021

Enhanced anti-angiogenic activity of novel melatonin-like agents.

J Pineal Res 2021 May 5:e12739. Epub 2021 May 5.

School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, Korea.

Hypoxia-inducible factor-1 (HIF-1) plays an important role in cellular responses to hypoxia, including the transcriptional activation of several genes involved in tumor angiogenesis. Melatonin, also known as N-acetyl-5-methopxytryptamine, is produced naturally by the pineal gland and has anti-angiogenic effects in cancer through its ability to modulate HIF-1α activity. However, the use of melatonin as a therapeutic is limited by its low oral bioavailability and short half-life. Here, we synthesized melatonin-like molecules with enhanced HIF-1α targeting activity and less toxicity and investigated their effects on tumor growth and angiogenesis, as well as the underlying molecular mechanisms. Among melatonin derivatives, N-butyryl-5-methoxytryptamine (NB-5-MT) showed the most potent HIF-1α targeting activity. This molecule was able to (a) reduce the expression of HIF-1α at the protein level, (b) reduce the transcription of HIF-1α target genes, (c) reduce reactive oxygen species (ROS) generation, (d) decrease angiogenesis in vitro and in vivo, and (e) suppress tumor size and metastasis. In addition, NB-5-MT showed improved anti-angiogenic activity compared with melatonin due to its enhanced cellular uptake. NB-5-MT is thus a promising lead for the future development of anticancer compounds with HIF-1α targeting activity. Given that HIF-1α is overexpressed in the majority of human cancers, the melatonin derivative NB-5-MT could represent a novel potent therapeutic agent for cancer.
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http://dx.doi.org/10.1111/jpi.12739DOI Listing
May 2021

Single-Step Approach toward Nitrones via Pyridinium Ylides: The DMAP-Catalyzed Reaction of Benzyl Halides with Nitrosoarenes.

J Org Chem 2021 May 23;86(9):6343-6350. Epub 2021 Apr 23.

College of Pharmacy, Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Inje-ro, Gimhae, Gyeongnam 50834, Republic of Korea.

A single-step approach is reported for the preparation of nitrones from benzyl halides and nitrosoarenes via pyridinium ylides, utilizing 4-dimethylaminopyridine (DMAP) catalyst and mild reaction conditions (LiCO, dimethylacetamide, and room temperature). The reaction provides both keto- and aldonitrones in high yields with a wide scope for benzyl halides and nitrosoarenes. In the same reaction system, 2-methyl-2-nitrosopropane, which does not have an aryl group, also affords the corresponding --butyl nitrones from primary benzyl bromides that have an electron-withdrawing group. As an application of the reaction, methyl 2-bromo-2-phenylacetate was used to prepare the corresponding isoxazolidine by a sequential one-pot synthesis.
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http://dx.doi.org/10.1021/acs.joc.1c00158DOI Listing
May 2021

A cylindrical SiC heater for an externally heated diamond anvil cell to 1500 K.

Rev Sci Instrum 2021 Jan;92(1):015119

Department of Earth and Planetary Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Semiconductor-based heaters for diamond anvil cells (DACs) have advantages over metal wire heaters in terms of repeated use and the ability to reach higher temperatures. We introduce a cylindrical SiC heater for an externally heated DAC (EHDAC) that works satisfactorily at temperatures up to 1500 K and pressures around 90 GPa. The heater is reusable and inexpensive, and only slight modifications to the DAC are required to fit the heater. Experiments on melting of NaCl and gold are conducted at ambient pressure to test the temperature accuracy of the EHDAC system, and resistance measurements on iodine at high pressures and temperatures are performed to assess the heater assembly. These test runs show that a uniform and accurate temperature can be maintained by the EHDAC assembly, which has potential applications to a variety of transport property measurements.
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http://dx.doi.org/10.1063/5.0036551DOI Listing
January 2021

Enantioselective Total Synthesis of Alkaloids: (+)-Nitramine, (+)-Isonitramine, (-)-Isonitramine, and (-)-Sibirine via Asymmetric Phase-Transfer Catalytic α-Allylations of α-Carboxylactams.

J Org Chem 2021 Mar 19;86(6):4375-4390. Epub 2021 Jan 19.

Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

Many optically active 2-azaspirocyclic structures have frequently been found in biologically active natural products. In particular, alkaloids, (+)-nitramine, (+)-isonitramine, (-)-isonitramine, and (-)-sibirine, have stereogenicity on their quaternary carbon of the 2-azaspiro[5,5]undecane-7-ol structure. To synthesize alkaloids, we developed a new enantioselective synthetic method for chiral α-quaternary lactams via the α-alkylation of α--butoxycarbonyl lactams. α-Alkylation of α--butoxycarboxylactams in the circumstances of phase-transfer catalytic (PTC) system (solid KOH, toluene, and -40 °C) by virtue of the catalytic action of (,)-NAS bromide (5 mol %) furnished the corresponding α-alkyl-α--butoxycarbonyl lactams in very high chemical (<99%) and enantioselectivity (<98% ee). Our catalytic methodology was successfully applied for the enantioselective total synthesis of alkaloids. (+)-Isonitramine was obtained in 12 steps (98% ee, 43% yield) from δ-valerolactam through enantioselective phase-transfer catalytic allylation, Dieckmann condensation, and diastereoselective reduction as the key reactions. (-)-Sibirine and (+)-nitramine were prepared from (-)-isonitramine or its intermediate. Switching the phase-transfer catalyst from (,)-NAS bromide to (,)-NAS bromide afforded (-)-isonitramine (98% ee, 41% yield). (-)-Sibirine was synthesized by -ethoxycarbonylation of (-)-isonitramine followed by reduction (98% ee, 14 steps, 32% yield). Furthermore, the diastereoselective reduction of ()-2-benzhydryl-2-azaspiro[5.5]undecane-1,7-dione [()-] followed by reductive removal of the diphenylmethyl group successfully gave (+)-nitramine (98% ee, 11 steps, 40% yield).
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http://dx.doi.org/10.1021/acs.joc.0c02573DOI Listing
March 2021

Effect of dexamethasone gargle, intravenous dexamethasone, and their combination on postoperative sore throat: a randomized controlled trial.

Anesth Pain Med (Seoul) 2020 Oct;15(4):441-450

Department of Anesthesiology and Pain Medicine, Inje University College of Medicine, Busan, Korea.

Background: Postoperative sore throat (POST) is a complication that decreases patient satisfaction and increases postoperative complaints. The present study was conducted to investigate effects of gargling with dexamethasone, intravenous dexamethasone injection and the combination of the two on the incidence and severity of POST.

Methods: Study participants were 96 patients who had undergone laparoscopic cholecystectomy, randomly allocated into three groups. Group G gargled with 0.05% dexamethasone solution and were infused intravenous 0.9% normal saline before general anesthesia; group I gargled with 0.9% normal saline and were infused intravenous 0.1 mg/kg dexamethasone; group GI gargled with 0.05% dexamethasone solution and were infused intravenous 0.1 mg/kg dexamethasone. The incidence and severity of POST, hoarseness and cough were evaluated and recorded at 1, 6, and 24 h after the surgery.

Results: There were no significant differences in the total incidence of POST up to 24 postoperative hours among Group G, Group I and Group GI (P = 0.367, Group G incidence = 34.38%, [95% confidence interval, 95% CI = 17.92-50.83], Group I incidence = 18.75%, [95% CI = 5.23-32.27], Group GI incidence = 28.13%, [95% CI = 12.55-43.70]). The other outcomes were comparable among the groups.

Conclusions: In patients who had undergone laparoscopic cholecystectomy, gargling with 0.05% dexamethasone solution demonstrated the same POST prevention effect as intravenous injection of 0.1 mg/kg dexamethasone. The incidence and severity of POST were not significantly different between the combination of gargling with 0.05% dexamethasone solution and intravenous injection of 0.1 mg/kg dexamethasone and use of each of the preventive methods alone.
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http://dx.doi.org/10.17085/apm.20057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724117PMC
October 2020

4-Dimethylaminopyridine-Catalyzed Metal-Free Aerobic Oxidation of Aryl α-Halo Esters to Aryl α-Keto Esters.

ACS Omega 2020 Sep 2;5(36):22951-22957. Epub 2020 Sep 2.

College of Pharmacy, Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Inje-ro, Gimhae, Gyeongnam 50834, Republic of Korea.

A novel, metal-free aerobic oxidation method is described. 4-Dimethylaminopyridine (DMAP) successfully catalyzed the oxidation of aryl α-halo esters to corresponding aryl α-keto esters (up to 95% yield) under mild reaction conditions (LiCO, dimethylacetamide, air, and room temperature). A mechanism has been proposed where the oxidation proceeds through a [3 + 2] cycloaddition between O in an air atmosphere and pyridinium ylides. The ylides are supposedly generated from aryl α-halo esters and DMAP in the presence of carbonates. Based on the plausible mechanism, the potential of DMAP as a catalyst in oxidation reactions was extended.
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http://dx.doi.org/10.1021/acsomega.0c02511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495759PMC
September 2020

Mortality prediction of serum neutrophil gelatinase-associated lipocalin in patients requiring continuous renal replacement therapy.

Korean J Intern Med 2021 03 7;36(2):392-400. Epub 2020 Jul 7.

Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background/aims: We investigated whether serum neutrophil gelatinase-associated lipocalin (NGAL) can predict mortality in patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT).

Methods: This study enrolled 169 patients who underwent serum NGAL testing at CRRT initiation from June 2017 to January 2019. The predictive power of serum NGAL level for 28-day mortality was compared to the Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score and Sequential Organ Failure Assessment (SOFA) score via area under the receiver operating characteristic curve (AuROC) value.

Results: There were 55 survivors and 114 non-survivors at 28 days post-CRRT initiation. Median serum NGAL level was significantly higher in the non-survivor group than in the survivor group (743.0 ng/mL vs. 504.0 ng/mL, p = 0.003). The AuROC value of serum NGAL level was 0.640, which was lower than APACHEII score and SOFA score values (0.767 and 0.715, respectively). However, in the low APACHE-II score group (< 27.5), AuROC value of serum NGAL was significantly increased (0.698), and it was an independent risk factor for 28 day-mortality (hazard ratio, 2.405; 95% confidence interval, 1.209 to 4.783; p = 0.012).

Conclusion: In patients with AKI requiring CRRT, serum NGAL levels may be useful for predicting short-term mortality in those with low APACHE-II scores.
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http://dx.doi.org/10.3904/kjim.2019.446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969065PMC
March 2021

Acute kidney injury with extreme hyperuricemia after antithymocyte globulin treatment in a kidney transplant recipient with underlying aplastic anemia: a case report.

BMC Nephrol 2020 07 2;21(1):251. Epub 2020 Jul 2.

Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, South Korea.

Background: The occurrences of hyperuricemia and acute kidney injury after antithymocyte globulin treatment are unusual in kidney transplant recipients. Here, we report a unique case of acute kidney injury with extreme hyperuricemia after antithymocyte globulin treatment in a kidney transplant recipient with underlying aplastic anemia.

Case Presentation: A 40-year-old woman with aplastic anemia who received a kidney transplant 5 years 6 months before presented to our emergency department with complaints of oliguria, generalized edema, and general weakness 6 days after receiving antithymocyte globulin treatment for acute T-cell-mediated rejection. Urinalysis revealed 100 uric acid crystal particles. The blood chemistry test results showed rapid increases in serum creatinine (from 2.86 mg/dL to 5.58 mg/dL) and uric acid levels (from 10.2 mg/dL to 32.7 mg/dL), which suggested acute uric acid nephropathy. Tumor lysis syndrome was suspected to be the cause of the acute uric acid nephropathy; hence, the patient was reevaluated for aplastic anemia. Human leukocyte antigen-DR15 was positive, and flow cytometry revealed a low percentage of glycophosphatidyl inositol-deficient granulocytes (2.9%), which suggested paroxysmal nocturnal hemoglobinuria clones. These findings indicate that the previously diagnosed aplastic anemia had either originally been hypocellular myelodysplastic syndrome (MDS) or later transformed into hypocellular MDS, which is a type of bone marrow failure syndrome.

Conclusions: Clinicians should consider unexpected tumor lysis syndrome to be the cause of complications after antithymocyte globulin treatment in kidney transplant recipients with underlying bone marrow failure syndrome.
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http://dx.doi.org/10.1186/s12882-020-01903-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330935PMC
July 2020

Design of Secure Protocol for Cloud-Assisted Electronic Health Record System Using Blockchain.

Sensors (Basel) 2020 May 21;20(10). Epub 2020 May 21.

School of Electronics Engineering, Kyungpook National University, Daegu 41566, Korea.

In the traditional electronic health record (EHR) management system, each medical service center manages their own health records, respectively, which are difficult to share on the different medical platforms. Recently, blockchain technology is one of the popular alternatives to enable medical service centers based on different platforms to share EHRs. However, it is hard to store whole EHR data in blockchain because of the size and the price of blockchain. To resolve this problem, cloud computing is considered as a promising solution. Cloud computing offers advantageous properties such as storage availability and scalability. Unfortunately, the EHR system with cloud computing can be vulnerable to various attacks because the sensitive data is sent over a public channel. We propose the secure protocol for cloud-assisted EHR system using blockchain. In the proposed scheme, blockchain technology is used to provide data integrity and access control using log transactions and the cloud server stores and manages the patient's EHRs to provide secure storage resources. We use an elliptic curve cryptosystems (ECC) to provide secure health data sharing with cloud computing. We demonstrate that the proposed EHR system can prevent various attacks by using informal security analysis and automated validation of internet security protocols and applications (AVISPA) simulation. Furthermore, we prove that the proposed EHR system provides secure mutual authentication using BAN logic analysis. We then compare the computation overhead, communication overhead, and security properties with existing schemes. Consequently, the proposed EHR system is suitable for the practical healthcare system considering security and efficiency.
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http://dx.doi.org/10.3390/s20102913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284443PMC
May 2020

Development of End Stage Renal Disease after Long-Term Ingestion of Chaga Mushroom: Case Report and Review of Literature.

J Korean Med Sci 2020 May 18;35(19):e122. Epub 2020 May 18.

Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Chaga mushrooms are widely used in folk remedies and in alternative medicine. Contrary to many beneficial effects, its adverse effect is rarely reported. We here report a case of end-stage renal disease after long-term taking Chaga mushroom. A 49-year-old Korean man with end stage renal disease (ESRD) was transferred to our hospital. Review of kidney biopsy finding was consistent with chronic tubulointerstitial nephritis with oxalate crystal deposits and drug history revealed long-term exposure to Chaga mushroom powder due to intractable atopic dermatitis. We suspected the association between Chaga mushroom and oxalate nephropathy, and measured the oxalate content of remained Chaga mushroom. The Chaga mushroom had extremely high oxalate content (14.2/100 g). Estimated daily oxalate intake of our case was 2 times for four years and 5 times for one year higher than that of usual diet. Chaga mushroom is a potential risk factor of chronic kidney disease considering high oxalate content. Nephrologist should consider oxalate nephropathy in ESRD patients exposed to Chaga mushrooms.
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http://dx.doi.org/10.3346/jkms.2020.35.e122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234858PMC
May 2020

Highly Selective Synthesis of Hydrazoarenes from Nitroarenes via Polystyrene-Supported Au-Nanoparticle-Catalyzed Reduction: Application to Azoarenes, Aminoarenes, and 4,4'-Diaminobiaryls.

ACS Omega 2020 Apr 27;5(13):7576-7583. Epub 2020 Mar 27.

College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Inje-ro, Gimhae, Gyeongnam 50834, Republic of Korea.

A selective synthesis of hydrazoarene from nitroarene and its application are reported. Using polystyrene (PS) resins as solid supports for Au nanoparticles (AuNPs), polystyrene-supported Au nanoparticles ([email protected]) were synthesized and characterized. In the presence of [email protected] (1.0 mol %) as a catalyst, nitroarenes afforded corresponding hydrazoarenes (up to 99%) with high selectivity (up to 100%) under mild reaction conditions (NaBH, 50% aq. EtOH, and room temperature). Depending on the reaction conditions (the amount of NaBH, the substituent of nitroarenes, and the sequential addition of HCl), nitroarenes were converted to corresponding azoarenes (up to 95%), aminoarenes (up to 99%), and 4,4'-diaminobiaryls (up to 99%). Our easily recyclable catalytic system using a solid-phase reaction vessel provides an attractive synthetic method in an eco-friendly and sustainable manner.
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http://dx.doi.org/10.1021/acsomega.0c00402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144144PMC
April 2020

The impact of cytomegalovirus infection on clinical severity and outcomes in kidney transplant recipients with Pneumocystis jirovecii pneumonia.

Microbiol Immunol 2020 May 25;64(5):356-365. Epub 2020 Feb 25.

Department of Internal Medicine, College of Medicine, Transplant Research Center, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.

Cytomegalovirus (CMV) infection is associated with Pneumocystis jirovecii pneumonia (PJP) in kidney transplant recipients (KTRs), but its impact on clinical severity and outcomes in KTRs with PJP is unknown. We reviewed 1994 medical records of KTRs from January 1997 to March 2019. PJP or CMV infection was diagnosed by polymerase chain reaction or culturing using blood or respiratory specimens. We divided patients into PJP and PJP+CMV groups, and evaluated the clinical severity and outcomes. Fifty two patients had PJP (2.6%) in the whole study cohort. Among patients with PJP, 38 (73.1%) had PJP alone and 14 (26.9%) had combined PJP and CMV co-infection. The PJP+CMV group showed worse laboratory findings (serum albumin and C-reactive protein, P = 0.010 for both) and higher requirement of continuous renal replacement therapy than the PJP group (P = 0.050). The pneumonia severity was worse in the PJP+CMV group than in the PJP group (P < 0.05), and CMV infection was a high risk factor of pneumonia severity (odds ratio 16.0; P = 0.002). The graft function was worse in the PJP+CMV group (P < 0.001), and the incidence of graft failure was higher in the PJP+CMV group than in the PJP group (85.7% vs 36.8%; P < 0.001). Mortality was double in the PJP+CMV group than in the PJP group, but not statistically significant (21.4% vs 10.5%; P = 0.370). Our results show that approximately one in four patients with PJP after kidney transplantation develops CMV with increased clinical severity and risk of graft failure. The possibility of increased clinical severity and worse clinical outcomes by CMV co-infection should be considered in KTRs with PJP.
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http://dx.doi.org/10.1111/1348-0421.12778DOI Listing
May 2020

Natural compounds as potential Hsp90 inhibitors for breast cancer-Pharmacophore guided molecular modelling studies.

Comput Biol Chem 2019 Dec 5;83:107113. Epub 2019 Sep 5.

Division of Life Sciences, Division of Applied Life Science (BK21 Plus), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju, 52828, Republic of Korea. Electronic address:

Breast cancer is one of the major impediments affecting women globally. The ATP-dependant heat shock protein 90 (Hsp90) forms the central component of molecular chaperone machinery that predominantly governs the folding of newly synthesized peptides and their conformational maturation. It regulates the stability and function of numerous client proteins that are frequently upregulated and/or mutated in cancer cells, therefore, making Hsp90 inhibition a promising therapeutic strategy for the development of new efficacious drugs to treat breast cancer. In the present in silico investigation, a structure-based pharmacophore model was generated with hydrogen bond donor, hydrogen bond acceptor and hydrophobic features complementary to crucial residues Ala55, Lys58, Asp93, Ile96, Met98 and Thr184 directed at inhibiting the ATP-binding activity of Hsp90. Subsequently, the phytochemical dataset of 3210 natural compounds was screened to retrieve the prospective inhibitors after rigorous validation of the model pharmacophore. The retrieved 135 phytocompounds were further filtered by drug-likeness parameters including Lipinski's rule of five and ADMET properties, then investigated via molecular docking-based scoring. Molecular interactions were assessed using Genetic Optimisation for Ligand Docking program for 95 drug-like natural compounds against Hsp90 along with two clinical drugs as reference compounds - Geldanamycin and Radicicol. Docking studies revealed three phytochemicals are better than the investigated clinical drugs. The reference and hit compounds with dock scores of 48.27 (Geldanamycin), 40.90 (Radicicol), 73.04 (Hit1), 72.92 (Hit2) and 68.12 (Hit3) were further validated for their binding stability through molecular dynamics simulations. We propose that the non-macrocyclic scaffolds of three identified phytochemicals might aid in the development of novel therapeutic candidates against Hsp90-driven cancers.
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http://dx.doi.org/10.1016/j.compbiolchem.2019.107113DOI Listing
December 2019

Synthesis of arbutin-gold nanoparticle complexes and their enhanced performance for whitening.

Arch Pharm Res 2019 Nov 29;42(11):977-989. Epub 2019 May 29.

College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Inje-ro, Gimhae, Gyungnam, 50834, South Korea.

Arbutin, a natural polyphenol, possesses numerous biological activities including whitening, anti-oxidant, anti-cancer, anti-inflammatory activities, as well as strong reducing power, making it an ideal bioactive ingredient for preparing gold nanoparticles (GNPs). Previously, we developed a novel green, mild synthetic method for GNPs using glycosides such as arbutin as reducing agents and stabilizers. Herein, we optimized the synthetic method for glycoside-GNPs using arbutin, methyl β-D-glucoside, and phenyl β-D-glucoside and validated their whitening efficacy in vitro and in vivo. The resulting glycoside-GNPs were predominantly mono-dispersed and spherical (10.30-17.13 nm diameter). Compared with arbutin itself, arbutin-GNP complexes (GNP-A1 and GNP-P2) displayed enhanced whitening capabilities. Furthermore, GNP-P2 exhibited enhanced anti-inflammatory activity and lacked the toxicity associated with arbutin. Bioactive glycoside-GNP complexes may open new directions for cosmeceuticals, and GNP-P2 may serve as a useful whitening ingredient in future cosmeceutical applications.
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http://dx.doi.org/10.1007/s12272-019-01164-7DOI Listing
November 2019

Secure Three-Factor Authentication Protocol for Multi-Gateway IoT Environments.

Sensors (Basel) 2019 May 22;19(10). Epub 2019 May 22.

School of Electronics Engineering, Kyungpook National University, Daegu 41566, Korea.

Internet of Things (IoT) environments such as smart homes, smart factories, and smart buildings have become a part of our lives. The services of IoT environments are provided through wireless networks to legal users. However, the wireless network is an open channel, which is insecure to attacks from adversaries such as replay attacks, impersonation attacks, and invasions of privacy. To provide secure IoT services to users, mutual authentication protocols have attracted much attention as consequential security issues, and numerous protocols have been studied. In 2017, Bae et al. presented a smartcard-based two-factor authentication protocol for multi-gateway IoT environments. However, we point out that Bae et al.'s protocol is vulnerable to user impersonation attacks, gateway spoofing attacks, and session key disclosure, and cannot provide a mutual authentication. In addition, we propose a three-factor mutual authentication protocol for multi-gateway IoT environments to resolve these security weaknesses. Then, we use Burrows-Abadi-Needham (BAN) logic to prove that the proposed protocol achieves secure mutual authentication, and we use the Automated Validation of Internet Security Protocols and Applications (AVISPA) tool to analyze a formal security verification. In conclusion, our proposed protocol is secure and applicable in multi-gateway IoT environments.
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http://dx.doi.org/10.3390/s19102358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566155PMC
May 2019

Pharmacotherapeutics and Molecular Mechanism of Phytochemicals in Alleviating Hormone-Responsive Breast Cancer.

Oxid Med Cell Longev 2019 4;2019:5189490. Epub 2019 Apr 4.

Division of Life Science, Division of Applied Life Science (BK21 Plus), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Republic of Korea.

Breast cancer (BC) is the leading cause of death among women worldwide devoid of effective treatment. It is therefore important to develop agents that can reverse, reduce, or slow the growth of BC. The use of natural products as chemopreventive agents provides enormous advantages. The aim of the current investigation is to determine the efficacy of the phytochemicals against BC along with the approved drugs to screen the most desirable and effective phytocompound. In the current study, 36 phytochemicals have been evaluated against aromatase to identify the potential candidate drug along with the approved drugs employing the Cdocker module accessible on the Discovery Studio (DS) v4.5 and thereafter analysing the stability of the protein ligand complex using GROningen MAchine for Chemical Simulations v5.0.6 (GROMACS). Additionally, these compounds were assessed for the inhibitory features employing the structure-based pharmacophore (SBP). The Cdocker protocol available with the DS has computed higher dock scores for the phytochemicals complemented by lower binding energies. The top-ranked compounds that have anchored with key residues located at the binding pocket of the protein were subjected to molecular dynamics (MD) simulations employing GROMACS. The resultant findings reveal the stability of the protein backbone and further guide to comprehend on the involvement of key residues Phe134, Val370, and Met374 that mechanistically inhibit BC. Among 36 compounds, curcumin, capsaicin, rosmarinic acid, and 6-shogaol have emerged as promising phytochemicals conferred with the highest Cdocker interaction energy, key residue interactions, stable MD results than reference drugs, and imbibing the key inhibitory features. Taken together, the current study illuminates the use of natural compounds as potential drugs against BC. Additionally, these compounds could also serve as scaffolds in designing and development of new drugs.
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http://dx.doi.org/10.1155/2019/5189490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476122PMC
December 2019

Discovery of Small Molecules that Target Vascular Endothelial Growth Factor Receptor-2 Signalling Pathway Employing Molecular Modelling Studies.

Cells 2019 03 21;8(3). Epub 2019 Mar 21.

Division of Life Sciences, Division of Applied Life Science (BK21 Plus), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Korea.

Angiogenesis is defined as the formation of new blood vessels and is a key phenomenon manifested in a host of cancers during which tyrosine kinases play a crucial role. Vascular endothelial growth factor receptor-2 (VEGFR-2) is pivotal in cancer angiogenesis, which warrants the urgency of discovering new anti-angiogenic inhibitors that target the signalling pathways. To obtain this objective, a structure-based pharmacophore model was built from the drug target VEGFR-2 (PDB code: 4AG8), complexed with axitinib and was subsequently validated and employed as a 3D query to retrieve the candidate compounds with the key inhibitory features. The model was escalated to molecular docking studies resulting in seven candidate compounds. The molecular docking studies revealed that the seven compounds displayed a higher dock score than the reference-cocrystallised compound. The GROningen MAchine for Chemical Simulations (GROMACS) package guided molecular dynamics (MD) results determined their binding mode and affirmed stable root mean square deviation. Furthermore, these compounds have preserved their key interactions with the residues Glu885, Glu917, Cys919 and Asp1046. The obtained findings deem that the seven compounds could act as novel anti-angiogenic inhibitors and may further assist as the prototype in designing and developing new inhibitors.
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http://dx.doi.org/10.3390/cells8030269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468367PMC
March 2019

Epidemiologic study on changes in occurrence of hemorrhagic fever with renal syndrome in Republic of Korea for 17 years according to age group: 2001-2017.

Authors:
Yohan Park

BMC Infect Dis 2019 Feb 13;19(1):153. Epub 2019 Feb 13.

Department of Internal Medicine, Yangju-si Public Health center, 1533 Buheung-ro, Yangju-si 11498, Gyeonggi-do, Republic of Korea.

Background: The potential effect of the inactivated hantavirus vaccine (IHV) remains controversial; however, it appears to be moderately effective for patients at high risk of hemorrhagic fever with renal syndrome (HFRS). This study of the epidemiology of HFRS from 2001 to 2017 aimed to examine those at high risk of HFRS in the Republic of Korea (ROK), particularly in terms of disease distribution according to age.

Methods: Raw data of HFRS patients recorded in Korea from 2001 to 2017 were obtained from the Korean Center for Disease Control and Prevention. Patients were divided into three age groups: ≤39, 40-69, and ≥ 70 years. The incidence rate per 100,000 individuals in each age group was calculated using population data. The 12-month year was divided into three-month quarters, and the number and proportion of patients corresponding to each quarter were calculated. The effects of time, sex, and quarter on HFRS incidence were assessed in a Poisson regression analysis.

Results: From 2001 to 2017, 7048 HFRS patients were recorded nationwide. Among these patients, the proportion of patients aged ≥70 years increased gradually from 16.4% in 2001 to 43.9% in 2017. Regarding the quarter-year periods, the fourth quarter contained a significantly higher proportion of patients in the ≥70 years group (69.4%) compared to the other age groups. In the Poisson regression analysis, patients aged ≥70 years had a significantly higher relative risk of HFRS incidence within each quartile compared to those in the other age groups (2.102- and 10.029-fold in the third and fourth quarters, respectively). An analysis of disease incidence revealed a more distinct pattern in seasonal variation among those aged ≥70 years compared with other age groups.

Conclusions: In this study of the incidence of HFRS in the ROK, subjects aged ≥70 years exhibited a gradual increase in incidence and a distinct pattern of seasonal variation. These results may be important to identify individuals in Korea who are at high risk of developing HFRS. In future, active immunization programs will be needed to control HFRS among these high-risk groups in Korea.
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http://dx.doi.org/10.1186/s12879-019-3794-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374896PMC
February 2019

Insulin induces phosphorylation of pyruvate dehydrogenase through RhoA activation pathway in HepG2 cells.

FASEB J 2019 02 18;33(2):2072-2083. Epub 2018 Sep 18.

Department of Biochemistry, Hallym University College of Medicine, Chuncheon, South Korea.

Insulin is a critical signaling molecule in reducing blood glucose levels, and pyruvate dehydrogenase (PDH) is an essential enzyme in regulating glucose metabolism. However, the insulin effect on PDH function has not been well established. We observed that insulin attenuated the phosphorylation (p) of Ser264 (p-Ser264) in the PDH E1α subunit (PDHA1) in normal rat hepatocyte. In contrast, insulin induced an increase of p-Ser264 PDHA1 levels in hepatocellular carcinoma HepG2 and Huh7 cells. Insulin activated RhoA and Rho-dependent coiled coil kinase, an effector protein of active RhoA, which regulated p-Ser264 PDHA1 levels, along with both p-Ser9 and p-Tyr216 forms of glycogen synthase kinase-3β (GSK-3β) in HepG2 cells. Only p-Tyr216 GSK-3β, the active form was involved in an increase of p-Ser264 PDHA1. Akt was also engaged in p-Ser9 of GSK-3β, but neither in p-Tyr216 of GSK-3β nor p-Ser264 of PDHA1 upon insulin. Reconstituted dephospho-mimic forms PDHA1 S264A and GSK-3β Y216F impaired, but wild-types PDHA1 and GSK-3β and phospho-mimic forms PDHA1 S264D and GSK-3β Y216E increased cell proliferation upon insulin through expression of c-Myc and cyclin D1. Therefore, we propose that insulin-mediated p-PDHA1 is involved in the regulation of HepG2 cell proliferation through RhoA signaling pathway.-Islam, R., Kim, J.-G., Park, Y., Cho, J.-Y., Cap, K.-C., Kho, A.-R., Chung, W.-S., Suh, S.-W., Park, J.-B. Insulin induces phosphorylation of pyruvate dehydrogenase through RhoA activation pathway in HepG2 cells.
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http://dx.doi.org/10.1096/fj.201800917RDOI Listing
February 2019

Regulation of RhoA GTPase and various transcription factors in the RhoA pathway.

J Cell Physiol 2018 09 25;233(9):6381-6392. Epub 2018 Mar 25.

Department of Biochemistry, Hallym University College of Medicine, Chuncheon, Kangwon-do, Republic of Korea.

RhoA GTPase plays a variety of functions in regulation of cytoskeletal proteins, cellular morphology, and migration along with various proliferation and transcriptional activity in cells. RhoA activity is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and the guanine nucleotide dissociation factor (GDI). The RhoA-RhoGDI complex exists in the cytosol and the active GTP-bound form of RhoA is located to the membrane. GDI displacement factors (GDFs) including IκB kinase γ (IKKγ) dissociate the RhoA-GDI complex, allowing activation of RhoA through GEFs. In addition, modifications of Tyr42 phosphorylation and Cys16/20 oxidation in RhoA and Tyr156 phosphorylation and oxidation of RhoGDI promote the dissociation of the RhoA-RhoGDI complex. The expression of RhoA is regulated through transcriptional factors such as c-Myc, HIF-1α/2α, Stat 6, and NF-κB along with several reported microRNAs. As the role of RhoA in regulating actin-filament formation and myosin-actin interaction has been well described, in this review we focus on the transcriptional activity of RhoA and also the regulation of RhoA message itself. Of interest, in the cytosol, activated RhoA induces transcriptional changes through filamentous actin (F-actin)-dependent ("actin switch") or-independent means. RhoA regulates the activity of several transcription regulators such as serum response factor (SRF)/MAL, AP-1, NF-κB, YAP/TAZ, β-catenin, and hypoxia inducible factor (HIF)-1α. Interestingly, RhoA also itself is localized to the nucleus by an as-yet-undiscovered mechanism.
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http://dx.doi.org/10.1002/jcp.26487DOI Listing
September 2018

Computational Exploration for Lead Compounds That Can Reverse the Nuclear Morphology in Progeria.

Biomed Res Int 2017 26;2017:5270940. Epub 2017 Oct 26.

Division of Applied Life Science (BK21 Plus), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Systems and Synthetic Agrobiotech Center (SSAC), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Republic of Korea.

Progeria is a rare genetic disorder characterized by premature aging that eventually leads to death and is noticed globally. Despite alarming conditions, this disease lacks effective medications; however, the farnesyltransferase inhibitors (FTIs) are a hope in the dark. Therefore, the objective of the present article is to identify new compounds from the databases employing pharmacophore based virtual screening. Utilizing nine training set compounds along with lonafarnib, a common feature pharmacophore was constructed consisting of four features. The validated Hypo1 was subsequently allowed to screen Maybridge, Chembridge, and Asinex databases to retrieve the novel lead candidates, which were then subjected to Lipinski's rule of 5 and ADMET for drug-like assessment. The obtained 3,372 compounds were forwarded to docking simulations and were manually examined for the key interactions with the crucial residues. Two compounds that have demonstrated a higher dock score than the reference compounds and showed interactions with the crucial residues were subjected to MD simulations and binding free energy calculations to assess the stability of docked conformation and to investigate the binding interactions in detail. Furthermore, this study suggests that the Hits may be more effective against progeria and further the DFT studies were executed to understand their orbital energies.
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http://dx.doi.org/10.1155/2017/5270940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684607PMC
July 2018

Regulation of RhoA GTPase and novel target proteins for ROCK.

Small GTPases 2020 03 3;11(2):95-102. Epub 2017 Dec 3.

Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, Kangwon-do, Republic of Korea.

Rho GTPases play significant roles in cellular function and their activity is regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), providing activation and inactivation of these GTPases, respectively. Active GTP-bound form of RhoA activates its effector proteins while the inactive GDP-bound form of RhoA exists in a RhoA-RhoGDI (guanine nucleotide dissociation inhibitor) complex in the cytosol. In particular, IκB kinase γ IKKγ/NF-κB essential modulator (NEMO) plays a role as a GDI displacement factor (GDF) for RhoA activation through binding to RhoA-RhoGDI complex. Meanwhile, prion protein inactivates RhoA despite RhoA/RhoGDI association. Novel target proteins for Rho-associated kinase (ROCK) such as glycogen synthase kinase (GSK)-3β and IKKβ are recently discovered. Here, we elaborate on a post-translationally modified version of RhoA, phosphorylated at Tyr42 and oxidized at Cys16/20. This form of RhoA dissociates from RhoA-RhoGDI complex and activates IKKβ on IKKγ/NEMO, thus providing possibly a critical role for tumourigenesis.
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http://dx.doi.org/10.1080/21541248.2017.1364831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053945PMC
March 2020

Single-incision endoscopic thyroidectomy for papillary thyroid cancer: A pilot study.

Int J Surg 2017 Jul 11;43:1-6. Epub 2017 May 11.

Department of Surgery, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea. Electronic address:

Background: Recently, we have reported single incision endoscopic thyroidectomy using an axillary approach with gas inflation (SIET) in cases with benign thyroid tumors to reduce post-operative pain and invasiveness of the conventional endoscopic thyroidectomy. The aim of this study was to present our experiences with SIET for papillary thyroid cancer (PTC).

Methods: Patients who were diagnosed with histologically papillary thyroid carcinoma (≤1 cm) with single, unilateral, and intra-thyroidal lesion and without clinical lymph node metastasis were included. We analyzed clinico-pathological characteristics, surgical outcomes, and oncologic adequacy of the SIET procedure.

Results: Between January 2011 and July 2012, a total of 75 patients underwent hemi-thyroidectomy with ipsilateral central lymph node dissection via SIET. The mean tumor size was 0.5 cm and 4.1 ± 2.43 central lymph nodes were removed. Of the patients, 98.3% were satisfied with their surgical wound post-operatively and no critical post-operative complications occurred during the study, except for one case of post-operative bleeding. There was one case of disease recurrence, which occurred in the contra-lateral cervical lymph node region 6 months after SIET. This patient underwent completion thyroidectomy with selective neck dissection.

Conclusion: The SIET is a safe and acceptable procedure for PTC with a reduced dissection field, less post-operative pain, and more cosmetic satisfaction than conventional endoscopic thyroid surgery.
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http://dx.doi.org/10.1016/j.ijsu.2017.05.030DOI Listing
July 2017

A synthetic Nitraria alkaloid, isonitramine protects pancreatic β-cell and attenuates postprandial hyperglycemia.

Metabolism 2017 05 10;70:107-115. Epub 2017 Feb 10.

College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 607 Obang-dong, Gimhae, Gyungnam, 621-749, South Korea; u-Healthcare & Anti-aging Research Center (u-HARC), Inje University, Gyeongnam, South Korea. Electronic address:

Objective: The extracts of Nitraria genus are composed of Nitraria alkaloids and have been used traditionally as a hypoglycemic medicine. However, the efficacy and precise mechanism of Nitraria alkaloids remain largely unknown.

Methods: Previously, we reported the total synthesis of (+)-isonitramine, one of Nitraria alkaloids. In this study, we investigated the anti-diabetic potential of isonitramine in diabetes mellitus and its underlying molecular mechanism in carbohydrate catabolism in vitro and in vivo.

Results: Isonitramine exerted significant inhibitory effect on α-glucosidases but not α-amylase in vitro. In zebrafish, isonitramine alleviated the streptozotocin (STZ)-induced postprandial hyperglycemia and protected the pancreatic damages against alloxan-induced oxidative stress in vivo. Also, isonitramine induced insulin without any toxicities and downregulated phosphoenolpyruvate carboxykinase (PEPCK), which catalyzes the first committed step in gluconeogenesis.

Conclusion: Taken together, isonitramine inhibited α-glucosidase activity and PEPCK expression, while increased insulin expression, resulting in attenuating the postprandial hyperglycemia. Also, isonitramine protected the pancreas from ROS-mediated toxicities. Therefore, isonitramine may be a new drug candidate for the treatment of diabetes mellitus.
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http://dx.doi.org/10.1016/j.metabol.2017.02.002DOI Listing
May 2017

A Selective Group Authentication Scheme for IoT-Based Medical Information System.

J Med Syst 2017 Apr 15;41(4):48. Epub 2017 Feb 15.

School of Electronics Engineering, Kyungpook National University, Daegu, South Korea.

The technology of IoT combined with medical systems is expected to support advanced medical services. However, unsolved security problems, such as misuse of medical devices, illegal access to the medical server and so on, make IoT-based medical systems not be applied widely. In addition, users have a high burden of computation to access Things for the explosive growth of IoT devices. Because medical information is critical and important, but users have a restricted computing power, IoT-based medical systems are required to provide secure and efficient authentication for users. In this paper, we propose a selective group authentication scheme using Shamir's threshold technique. The property of selectivity gives the right of choice to users to form a group which consists of things users select and access. And users can get an access authority for those Things at a time. Thus, our scheme provides an efficient user authentication for multiple Things and conditional access authority for safe IoT-based medical information system. To the best of our knowledge, our proposed scheme is the first in which selectivity is combined with group authentication in IoT environments.
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http://dx.doi.org/10.1007/s10916-017-0692-9DOI Listing
April 2017

Catalytic reduction of 4-nitrophenol with gold nanoparticles synthesized by caffeic acid.

Nanoscale Res Lett 2017 Dec 5;12(1). Epub 2017 Jan 5.

College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Inje-ro, Gimhae, Gyeongnam, 50834, Republic of Korea.

In this study, various concentrations of caffeic acid (CA) were used to synthesize gold nanoparticles (CA-AuNPs) in order to evaluate their catalytic activity in the 4-nitrophenol reduction reaction. To facilitate catalytic activity, caffeic acid was removed by centrifugation after synthesizing CA-AuNPs. The catalytic activity of CA-AuNPs was compared with that of centrifuged CA-AuNPs (cf-CA-AuNPs). Notably, cf-CA-AuNPs exhibited up to 6.41-fold higher catalytic activity compared with CA-AuNPs. The catalytic activity was dependent on the caffeic acid concentration, and the lowest concentration (0.08 mM) produced CA-AuNPs with the highest catalytic activity. The catalytic activities of both CA-AuNPs and cf-CA-AuNPs decreased with increasing caffeic acid concentration. Furthermore, a conversion yield of 4-nitrophenol to 4-aminophenol in the reaction mixture was determined to be 99.8% using reverse-phase high-performance liquid chromatography. The product, 4-aminophenol, was purified from the reaction mixture, and its structure was confirmed by H-NMR. It can be concluded that the removal of the reducing agent, caffeic acid in the present study, significantly enhanced the catalytic activity of CA-AuNPs in the 4-nitrophenol reduction reaction.
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http://dx.doi.org/10.1186/s11671-016-1776-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216008PMC
December 2017

Three-Factor User Authentication and Key Agreement Using Elliptic Curve Cryptosystem in Wireless Sensor Networks.

Sensors (Basel) 2016 Dec 14;16(12). Epub 2016 Dec 14.

School of Electronics Engineering, Kyungpook National University, Daegu 41566, Korea.

Secure communication is a significant issue in wireless sensor networks. User authentication and key agreement are essential for providing a secure system, especially in user-oriented mobile services. It is also necessary to protect the identity of each individual in wireless environments to avoid personal privacy concerns. Many authentication and key agreement schemes utilize a smart card in addition to a password to support security functionalities. However, these schemes often fail to provide security along with privacy. In 2015, Chang et al. analyzed the security vulnerabilities of previous schemes and presented the two-factor authentication scheme that provided user privacy by using dynamic identities. However, when we cryptanalyzed Chang et al.'s scheme, we found that it does not provide sufficient security for wireless sensor networks and fails to provide accurate password updates. This paper proposes a security-enhanced authentication and key agreement scheme to overcome these security weaknesses using biometric information and an elliptic curve cryptosystem. We analyze the security of the proposed scheme against various attacks and check its viability in the mobile environment.
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http://dx.doi.org/10.3390/s16122123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5191103PMC
December 2016

RhoA GTPase oxidation stimulates cell proliferation via nuclear factor-κB activation.

Free Radic Biol Med 2017 02 11;103:57-68. Epub 2016 Dec 11.

Department of Biochemistry, Hallym University College of Medicine, Chuncheon, Kangwon-do 24252, Republic of Korea; Center for Medical Science Research, Hallym University College of Medicine, Chuncheon, Kangwon-do 24252, Republic of Korea; Institute of Cell Differentiation and Ageing, Hallym University College of Medicine, Chuncheon, Kangwon-do 24252, Republic of Korea. Electronic address:

Reactive oxygen species (ROS) produced by many kinds of stimuli are essential for cellular signaling including cell proliferation. The dysregulation of ROS, therefore, is related to a variety of diseases including cancer. However, it was not clearly elucidated how ROS regulate cell proliferation and tumorigenesis. In this study, we investigated a mechanism by which the oxidation of RhoA GTPase regulates nuclear factor-κB (NF-κB) and cell proliferation. Hydrogen peroxide activated NF-κB and RhoA GTPase, but did not activate RhoA C16/20A mutant, an oxidation-resistant form. Remarkably, the oxidation of RhoA reduced its affinity towards RhoGDI, leading to the dissociation of RhoA-RhoGDI complex. Si-Vav2, a guanine nucleotide exchange factor (GEF), inhibited RhoA activation upon hydrogen peroxide. The oxidized RhoA (oxRhoA)-GTP was readily bound to IκB kinase γ (IKKγ), whereas oxidized RhoGDI did not bind to IKKγ. The oxRhoA-GTP bound to IKKγ activated IKKβ, leading to IκB phosphorylation and degradation, consequently NF-κB activation. Hydrogen peroxide induced cell proliferation, but RhoA C16/20A mutant suppressed cell proliferation and tumorigenesis. Conclusively, RhoA oxidation at Cys16/20 is critically involved in cell proliferation and tumorigenesis through NF-κB activation in response to ROS.
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http://dx.doi.org/10.1016/j.freeradbiomed.2016.12.013DOI Listing
February 2017