• Journal of Integrative Natural Science
• /
• v.13 no.4
• /
• pp.170-180
• /
• 2020

Abnormal regulation, hyperphosphorylation, and aggregation of the tau protein are the hallmark of several types of dementia, including Alzheimer's Disease. Increased activity of Glycogen Synthase Kinase-3β (GSK-3β) in the Central Nervous System (CNS), increased the tau hyperphosphorylation and caused the neurofibrillary tangles (NFTs) formation in the brain cells. Over the last two decades, numerous adenosine triphosphate (ATP) competitive inhibitors have been discovered that show inhibitory activity against GSK-3β. But these compounds exhibited off-target effects which motivated researchers to find new GSK-3β inhibitors. In the present study, we have collected the dataset of 31 C-Glycosylflavones derivatives that showed inhibitory activity against GSK-3β. Among the dataset, the most active compound was docked with the GSK-3β and molecular dynamics (MD) simulation was performed for 50 ns. Based on the 50 ns MD pose of the most active compound, the other dataset compounds were sketched, minimized, and aligned. The 3D-QSAR based Comparative Molecular Field Analysis (CoMFA) model was developed, which showed a reasonable value of q2=0.664 and r2=0.920. The contour maps generated based on the CoMFA model elaborated on the favorable substitutions at the R2 position. This study could assist in the future development of new GSK-3β inhibitors.

• Journal of Periodontal and Implant Science
• /
• v.50 no.5
• /
• pp.303-312
• /
• 2020

Purpose: The purpose of this study was to evaluate severe periodontitis with tooth loss as a modifiable risk factor for Alzheimer dementia (AD), vascular dementia (VaD), and mixed dementia (MD) using the National Health Insurance Service-National Health Screening Retrospective Cohort database with long-term follow-up over 14 years. Methods: Multivariate Cox hazards regression analysis was applied to a longitudinal retrospective database, which was updated in 2018, to evaluate the association between severe periodontitis with few remaining teeth and dementia after adjusting for potential risk factors, including sociodemographic factors and comorbid diseases. Results: Among 514,866 individuals in South Korea, 237,940 (46.2%) participants satisfying the inclusion criteria were selected. A total of 10,115 age- and sex-matched participants with severe periodontitis and 10,115 periodontally healthy participants were randomly selected and evenly assigned. The results showed that the risks of AD (hazard ratio [HR], 1.08), VaD (HR, 1.24), and MD (HR, 1.16) were significantly higher in patients with severe periodontitis with 1-9 remaining teeth after adjustment for sociodemographic factors, anthropomorphic measurements, lifestyle factors, and comorbidities. Conclusions: Severe periodontitis with few remaining teeth (1-9) may be considered a modifiable risk factor for the development of AD, VaD, and MD in Korean adults.

• Genomics & Informatics
• /
• v.12 no.4
• /
• pp.268-275
• /
• 2014

The harshness of legionellosis differs from mild Pontiac fever to potentially fatal Legionnaire's disease. The increasing development of drug resistance against legionellosis has led to explore new novel drug targets. It has been found that phosphoglucosamine mutase, phosphomannomutase, and phosphoglyceromutase enzymes can be used as the most probable therapeutic drug targets through extensive data mining. Phosphoglucosamine mutase is involved in amino sugar and nucleotide sugar metabolism. The purpose of this study was to predict the potential target of that specific drug. For this, the 3D structure of phosphoglucosamine mutase of Legionella pneumophila (strain Paris) was determined by means of homology modeling through Phyre2 and refined by ModRefiner. Then, the designed model was evaluated with a structure validation program, for instance, PROCHECK, ERRAT, Verify3D, and QMEAN, for further structural analysis. Secondary structural features were determined through self-optimized prediction method with alignment (SOPMA) and interacting networks by STRING. Consequently, we performed molecular docking studies. The analytical result of PROCHECK showed that 95.0% of the residues are in the most favored region, 4.50% are in the additional allowed region and 0.50% are in the generously allowed region of the Ramachandran plot. Verify3D graph value indicates a score of 0.71 and 89.791, 1.11 for ERRAT and QMEAN respectively. Arg419, Thr414, Ser412, and Thr9 were found to dock the substrate for the most favorable binding of S-mercaptocysteine. However, these findings from this current study will pave the way for further extensive investigation of this enzyme in wet lab experiments and in that way assist drug design against legionellosis.

• Genomics & Informatics
• /
• v.19 no.1
• /
• pp.6.1-6.10
• /
• 2021

Vascular endothelial growth factor (VEGF) is expressed at elevated levels by most cancer cells, which can stimulate vascular endothelial cell growth, survival, proliferation as well as trigger angiogenesis modulated by VEGF and VEGFR (a tyrosine kinase receptor) signaling. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2. Targeting this signaling molecule and its receptor is a novel approach for blocking angiogenesis. In recent years virtual high throughput screening has emerged as a widely accepted powerful technique in the identification of novel and diverse leads. The high resolution X-ray structure of VEGF has paved the way to introduce new small molecular inhibitors by structure-based virtual screening. In this study using different alkaloid molecules as potential novel inhibitors of VEGF, we proposed three alkaloid candidates for inhibiting VEGF and VEGFR mediated angiogenesis. As these three alkaloid compounds exhibited high scoring functions, which also highlights their high binding ability, it is evident that these alkaloids can be taken to further drug development pipelines for use as novel lead compounds to design new and effective drugs against cancer.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2019.10a
• /
• pp.92-92
• /
• 2019

Excessive or chronic inflammation contributes to the pathogenesis of many inflammatory diseases such as sepsis, rheumatoid arthritis, and ulcerative colitis. Hibiscus syriacus L. has been used as a medicinal plant in many Asian countries, even though its anti-inflammatory activity has been unclear. Therefore, we investigated the anti-inflammatory effect of anthocyanin fractions from the H. syriacus L. varieties Pulsae (PS) on the lipopolysaccharide (LPS)-induced expression of proinflammatory mediators and cytokines in RAW264.7 macrophages. PS suppressed LPS-induced nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) secretion concomitant with downregulation of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Furthermore, PS inhibited the production of proinflammatory cytokines such as tumor necrosis factor-alpha ($TNF-{\alpha}$), interleukin-6 (IL-6), and IL-12 in LPS-stimulated RAW264.7 macrophages. Further study showed that PS significantly decreased LPS-induced nuclear translocation of the nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) subunits, p65 and p50. Molecular docking data showed that many anthocyanins from PS fit into the hydrophobic pocket of MD2 and bound to Toll-like receptor 4 (TLR4), indicating that PS inhibits the TLR4-MD2-mediated inflammatory signaling pathway. Especially, apigenin-7-O-glucoside most powerfully bound to MD2 and TLR4 through LYS122, LYS122, and SER127 at a distance of $2.205{\AA}$, $3.098{\AA}$, and $2.844{\AA}$ and SER441 at a distance of $2.873{\AA}$ (docking score: -8.4) through hydrogen bonding, respectively. Additionally, PS inhibited LPS-induced TLR4 dimerization/expression on the cell surface, which consequently decreased MyD88 recruitment and IRAK4 phosphorylation. PS completely blocked LPS-mediated mortality in zebrafish larvae by diminishing the recruitment of neutrophil and macrophages accompanied by low levels of proinflammatory cytokines. Taken together, our results indicate that PS attenuates LPS-mediated inflammation in both in vitro and in vivo by blocking the TLR4/MD2-MyD88/IRAK4-$NF-{\kappa}B$ axis. Therefore, PS might be used as a novel modulatory candidate for effective treatment of LPS-mediated inflammatory diseases.

• Journal of Bio-Environment Control
• /
• v.21 no.4
• /
• pp.348-353
• /
• 2012

This study was conducted to figure out the possibility of non-drainage in muskmelon (Cucumis melo L.) hydroponics culture. Plants were grown under 3 different levels of drainage, standard (20~40%, SD), minimum (5~10%, MD), and non-drainage (ND). Throughout cultivation periods, constant water content and electrolyte conductivity changes in root zone were observed in SD in the range of 60~70% and $1.5{\sim}2.5dS{\cdot}m^{-1}$, respectively. ND treatment caused the fluctuation in water content and electrolyte conductivity of root zone and its change ranges were 30~50% in water content and $2{\sim}6dS{\cdot}m^{-1}$ in electrolyte conductivity, but ND treatment did not decrease fruit quality. Even if fruit fresh weight was slightly lower in ND with 1,863 g, than in SD with 1,990 g, the fruit weight in ND meets standard market size, 1,800~2,000 g. Higher soluble solids content was observed in fruit in ND than in SD and MD. Total amount of drainage per plant was 27,718, 15,769 and 2,346 mL in SD, MD and ND, respectively. SD showed $83.2m^3$ drainage, 34.5% drainage of irrigation amount whereas required total irrigation amount in ND was very low with $7m^3$.

• Proceedings of the Korean Society of Tobacco Science Conference
• /
• 2002.06a
• /
• pp.17-17
• /
• 2002

• Journal of the Korean Mathematical Society
• /
• v.53 no.2
• /
• pp.447-459
• /
• 2016

Let D be an integral domain, {$X_{\alpha}$} be a nonempty set of indeterminates over D, and $D{\mathbb{[}}\{X_{\alpha}\}{\mathbb{]}_1}$ be the first type power series ring over D. We show that if D is a t-SFT $Pr{\ddot{u}}fer$ v-multiplication domain, then $D{\mathbb{[}}\{X_{\alpha}\}{\mathbb{]}}_{1_{D-\{0\}}}$ is a Krull domain, and $D{\mathbb{[}}\{X_{\alpha}\}{\mathbb{]}}_1$ is a $Pr{\ddot{u}}fer$ v-multiplication domain if and only if D is a Krull domain.

• Journal of applied mathematics & informatics
• /
• v.5 no.3
• /
• pp.819-826
• /
• 1998

The purpose of this paper is to prove the following results; (1) Let R be a prime ring of char $(R)\neq 2$ and I a nonzero left ideal of R. The existence of a nonzero symmetric bi-derivation D : $R\timesR\;\longrightarrow\;$ such that d is sew-commuting on I where d is the trace of D forces R to be commutative (2) Let m and n be integers with $m\;\neq\;0.\;or\;n\neq\;0$. Let R be a noncommutative prime ring of char$ (R))\neq \; 2-1\; p_1 \;n_1$ where p is a prime number which is a divisor of m, and I a nonzero two-sided ideal of R. Let $D_1$ ; $R\;\times\;R\;\longrightarrow\;and\;$ $D_2\;:\;R\;\times\;R\;longrightarrow\;R$ be symmetric bi-derivations. Suppose further that there exists a symmetric bi-additive mapping B ; $R\;\times\;R\;\longrightarrow\;and\;$ such that $md_1(\chi)\chi ＋ n\chi d_2(\chi)=f(\chi$) holds for all $\chi$$\in$I, where $d_1 \;and\; d_2$ are the traces of $D_1 \;and\; D_2$ respectively and f is the trace of B. Then we have $D_1=0 \;and\; D_2=0$.

• Korean Journal of Mineralogy and Petrology
• /
• v.33 no.1
• /
• pp.19-28
• /
• 2020

Ranciéte is a hexagonal phyllomanganate mineral containing random Mn(IV) vacancies with hydrated Ca²⁺ cations charged balanced as interlayer cations. Its Mn²⁺ analogue is called takanelite, and ranciéite and takanelite are regarded as end-members of a solid solution series of (Ca²⁺,Mn²⁺)Mn₄O₉·nH₂O. Because the minerals are found as very small particles associated with other minerals, the crystal structures of the solid solution series have yet to be defined. In this research, we conducted classical molecular dynamics (MD) simulations of ranciéite and takanelite by varying the Mn²⁺/Ca²⁺ interlayer cation ratio to find relations between the interlayer cations and mineral structures. MD simulation results of chalcophanite group minerals are compared with experimental results to verify our method applied. Then, lattice parameters of ranciéite and takanelite models are presented along with detailed interlayer structures as to the distribution and coordination of cations and water molecules. This study shows the potentials of MD simulations in entangling complicated phyllomanganates structures.