• Biomolecules & Therapeutics
• /
• v.31 no.5
• /
• pp.473-483
• /
• 2023

Many cancers arise from sites of chronic inflammation, which creates an inflammatory microenvironment surrounding the tumor. Inflammatory substances secreted by cells in the inflammatory environment can induce the proliferation and survival of cancer cells, thereby promoting cancer metastasis and angiogenesis. Therefore, it is important to identify the role of inflammatory factors in cancer progression. This review summarizes the signaling pathways and roles of C-reactive protein (CRP) in various cancer types, including breast, liver, renal, and pancreatic cancer, and the tumor microenvironment. Mounting evidence suggests the role of CRP in breast cancer, particularly in triple-negative breast cancer (TNBC), which is typically associated with a worse prognosis. Increased CRP in the inflammatory environment contributes to enhanced invasiveness and tumor formation in TNBC cells. CRP promotes endothelial cell formation and angiogenesis and contributes to the initiation and progression of atherosclerosis. In pancreatic and kidney cancers, CRP contributes to tumor progression. In liver cancer, CRP regulates inflammatory responses and lipid metabolism. CRP modulates the activity of various signaling molecules in macrophages and monocytes present in the tumor microenvironment, contributing to tumor development, the immune response, and inflammation. In the present review, we overviewed the role of CRP signaling pathways and the association between inflammation and cancer in various types of cancer. Identifying the interactions between CRP signaling pathways and other inflammatory mediators in cancer progression is crucial for understanding the complex relationship between inflammation and cancer.

• KIPS Transactions on Software and Data Engineering
• /
• v.11 no.1
• /
• pp.11-18
• /
• 2022

De novo drug design is the process of developing new drugs that can interact with biological targets such as protein receptors. Traditional process of de novo drug design consists of drug candidate discovery and drug development, but it requires a long time of more than 10 years to develop a new drug. Deep learning-based methods are being studied to shorten this period and efficiently find chemical compounds for new drug candidates. Many existing deep learning-based drug design models utilize recurrent neural networks to generate a chemical entity represented by SMILES strings, but due to the disadvantages of the recurrent networks, such as slow training speed and poor understanding of complex molecular formula rules, there is room for improvement. To overcome these shortcomings, we propose a deep learning model for SMILES string generation using variational autoencoders with self-attention mechanism. Our proposed model decreased the training time by 1/26 compared to the latest drug design model, as well as generated valid SMILES more effectively.

• Molecules and Cells
• /
• v.26 no.2
• /
• pp.206-211
• /
• 2008

HI0381 of Haemophilus influenzae was investigated by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. HI0381 is a 153-residue peptidoglycan-associated outer membrane lipoprotein, and a part of the larger Tol/Pal network. Here, we report its backbone $^1H$, $^{15}N$, and $^{13}C$ resonance assignments, and secondary structure predictions. About 97% of all of the $^1HN$, $^{15}N$, $^{13}CO$, $^{13}C{\alpha}$, and $^{13}C{\beta}$ resonances covering 131 non-proline residues of the 134 residue, mature protein, were clarified by sequential and specific assignments. CSI and TALOS analyses revealed that HI0381 contains five ${\alpha}$-helices and five ${\beta}$-strands. To characterize the structure of HI0381, the effects of pH and salt concentration were investigated by CD. In addition, the structural changes occurring when HI0381 was in a membranous environment were investigated by comparing its HSQC spectra and CD data in buffer and in DPC micelles; the results showed that helix ${\alpha}4$ and strand ${\beta}4$ became aligned with the membrane. We conclude that the conformation of HI0381 is affected by the membrane environment, implying that its folded state is directly related to its function.

• Journal of Pharmaceutical Investigation
• /
• v.35 no.2
• /
• pp.89-94
• /
• 2005

The micron or nano-sized lysozyme as a model protein drug was prepared using solution enhanced dispersion by supercritical fluid (SEDS) process at various conditions (e.g., solvent, temperature and pressure) to investigate the feasibility of pulmonary protein drug delivery. The lysozyme particles prepared were characterized by laser diffraction particle size analyzer, scanning electron microscopy (SEM) and powder X-ray diffractometry (PXRD). The biological activity of lysozyme particles after/before SEDS process was also examined. Lysozyme was precipitated as spherical particles. The precipitated particles consisted of 100 - 200 nm particles. Particle size showed the precipitates to be agglomerates with primary particles of size $1\;-\;5 \;{\mu}m$. The biological activity varied between 38 and 98% depending on the experimental conditions. There was no significant difference between untreated lysozyme and lysozyme after SEDS process in PXRD analysis. Therefore, the SEDS process could be a novel method to prepare micron or nano-sized lysozyme particles, with minimal loss of biological activity, for the pulmonary delivery of protein drug.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2018.10a
• /
• pp.101-101
• /
• 2018

Resveratrol is a polyphenolic compound, which is a naturally occurring phytochemical and is found in a variety of plants, including food such as grapes, berries and peanuts. Although several studies have demonstrated that resveratrol possesses anti-cancer activity against various types of human cancer, the molecular mechanisms of resveratrol-mediated overcome drug resistance potential are unclear. In this study, we determined whether resveratrol attenuates drug resistance responses in 5-fluorouracil-resistant colon cancer (SNUC5/5-FUR) cells. Treatment with resveratrol significantly enhanced apoptosis in a concentration-dependent manner, which was associated with the modulation of anti- and/or pro-apoptotic protein expression, activation of caspases and activation of AMP-activated protein kinase. Resveratrol treatment also increased the induction of autophagy through up-regulation of autophagy-related genes such as Microtubule-associated protein 1A/1B-light chain 3, P62 and beclin-1. However, blocking of autophagy by bafilomycin A1 reduced apoptotic cell death, suggesting that resveratrol-induced autophagy functions as a cell death mechanism in SNUC5/5-FU cells. Although the further studies are needed, these findings suggest that resveratrol may have therapeutic potential to overcome drug resistance in colon cancer patients.

• The Korean Journal of Physiology and Pharmacology
• /
• v.23 no.4
• /
• pp.231-236
• /
• 2019

In drug discovery or preclinical stages of development, potency parameters such as $IC_{50}$, $K_i$, or $K_d$ in vitro have been routinely used to predict the parameters of efficacious exposure (AUC, $C_{min}$, etc.) in humans. However, to our knowledge, the fundamental assumption that the potency in vitro is correlated with the efficacious concentration in vivo in humans has not been investigated extensively. Thus, the present review examined this assumption by comparing a wide range of published pharmacokinetic (PK) and potency data. If the drug potency in vitro and its in vivo effectiveness in humans are well correlated, the steady-state average unbound concentrations in humans [$C_{u_-ss.avg}=f_u{\cdot}F{\cdot}Dose/(CL{\cdot}{\tau})=f_u{\cdot}AUCss/{\tau}$] after treatment with approved dosage regimens should be higher than, or at least comparable to, the potency parameters assessed in vitro. We reviewed the ratios of $C_{u_-ss.avg}$/potency in vitro for a total of 54 drug entities (13 major therapeutic classes) using the dosage, PK, and in vitro potency reported in the published literature. For 54 drugs, the $C_{u_-ss.avg}$/in vitro potency ratios were < 1 for 38 (69%) and < 0.1 for 22 (34%) drugs. When the ratios were plotted against $f_u$ (unbound fraction), "ratio < 1" was predominant for drugs with high protein binding (90% of drugs with $f_u{\leq}5%$; i.e., 28 of 31 drugs). Thus, predicting the in vivo efficacious unbound concentrations in humans using only in vitro potency data and $f_u$ should be avoided, especially for molecules with high protein binding.

• Journal of Microbiology and Biotechnology
• /
• v.27 no.9
• /
• pp.1628-1638
• /
• 2017

Viola tianshanica Maxim, belonging to the Violaceae plant family, is traditionally used in Uighur medicine for treating pneumonia, headache, and fever. There is, however, a lack of basic understanding of its pharmacological activities. This study was designed to observe the effects of the ethanol extract (TSM) from Viola tianshanica Maxim on the inflammation response in acute lung injury (ALI) induced by LPS and the possible underlying mechanisms. We found that TSM (200 and 500 mg/kg) significantly decreased inflammatory cytokine production and the number of inflammatory cells, including macrophages and neutrophils, in bronchoalveolar lavage fluid. TSM also markedly inhibited the lung wet-to-dry ratio and alleviated pathological changes in lung tissues. In vitro, after TSM ($12.5-100{\mu}g/ml$) treatment to RAW 264.7 cells for 1 h, LPS ($1{\mu}g/ml$) was added and the cells were further incubated for 24 h. TSM dose-dependently inhibited the levels of proinflammatory cytokines, such as NO, $PGE_2$, $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$, and remarkably decreased the protein and mRNA expression of $TNF-{\alpha}$ and IL-6 in LPS-stimulated RAW 264.7 cells. TSM also suppressed protein expression of $p-I{\kappa}Ba$ and p-ERK1/2 and blocked nuclear translocation of $NF-{\kappa}B$ p65. The results indicate that TSM exerts anti-inflammatory effects related with inhibition on $NF-{\kappa}B$ and MAPK (p-ERK1/2) signaling pathways. In conclusion, our data demonstrate that TSM might be a potential agent for the treatment of ALI.

• Genomics & Informatics
• /
• v.20 no.3
• /
• pp.33.1-33.17
• /
• 2022

Nervous necrosis virus (NNV) is a deadly infectious disease that affects several fish species. It has been found that the NNV utilizes grouper heat shock cognate protein 70 (GHSC70) to enter the host cell. Thus, blocking the virus entry by targeting the responsible protein can protect the fishes from disease. The main objective of the study was to evaluate the inhibitory potentiality of 70 compounds of Azadirachta indica (Neem plant) which has been reported to show potential antiviral activity against various pathogens, but activity against the NNV has not yet been reported. The binding affinity of 70 compounds was calculated against the GHSC70 with the docking and molecular dynamics (MD) simulation approaches. Both the docking and MD methods predict 4 (PubChem CID: 14492795, 10134, 5280863, and 11119228) inhibitory compounds that bind strongly with the GHSC70 protein with a binding affinity of -9.7, -9.5, -9.1, and -9.0 kcal/mol, respectively. Also, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of the compounds confirmed the drug-likeness properties. As a result of the investigation, it may be inferred that Neem plant compounds may act as significant inhibitors of viral entry into the host cell. More in-vitro testing is needed to establish their effectiveness.

• YAKHAK HOEJI
• /
• v.42 no.3
• /
• pp.336-344
• /
• 1998

Effects of ochratoxin A (OTA) on embryo development were studied in cultured whole embryos from 9.5 day gestation rat for 48 h. OTA (more than $0.5{\mu}g/ml$) induced microcephaly in the cultured rat whole embryos. Protein and DNA content, and DNA synthesis were significantly inhibited by OTA. We next examined whether the microcephaly seen in cultured whole embryo partially results from inhibition of differentiation of embryonic midbrain cells. Embryonic midbrain cells were extracted from 12 day gestation rat embryos, and cultured for 96 hr. OTA ibhibited cell differentiation about 50% over control. We also tested whether OTA-induced embryotoxicity would be associated with oxidative damages. We measured the ${\gamma}$-glutamyltranspeptidase (${\gamma}$-GT) and glutathione peroxidase (GPX) activities, and glutathione (GSH) content in both cultured whole embryos and embryonic midbrain cells. OTA decreased GSH content, whereas slightly increased ${\gamma}$-GT activity, but GPX activity was not significantly changed. These results show that OTA caused the microcephaly and its effect may be partially due to the inhibition of cell differentiation of embryonic midbrain cells, but the role of oxidative damages is not clear in embryotoxicity.

• Journal of Microbiology and Biotechnology
• /
• v.29 no.10
• /
• pp.1570-1579
• /
• 2019

The fungal products dibenzodioxocinones promise a novel class of inhibitors against cholesterol ester transfer protein (CEPT). Knowledge as to their biosynthesis is scarce. In this report, we characterized four more dibenzodioxocinones, which along with a previously described member pestalotiollide B, delimit the dominant spectrum of secondary metabolites in P. microspora. Through mRNA-seq profiling in $g{\alpha}1{\Delta}$, a process that halts the production of the dibenzodioxocinones, a gene cluster harboring 21 genes including a polyketide synthase, designated as pks8, was defined. Disruption of genes in the cluster led to loss of the compounds, concluding the anticipated role in the biosynthesis of the chemicals. The biosynthetic route to dibenzodioxocinones was temporarily speculated. This study reveals the genetic basis underlying the biosynthesis of dibenzodioxocinone in fungi, and may facilitate the practice for yield improvement in the drug development arena.