• Journal of Integrative Natural Science
• /
• v.10 no.2
• /
• pp.95-104
• /
• 2017

Proviral Integration site of Moloney (Pim) murine Leukemia virus kinases is a serine/threonine specific protein kinase. It is largely involved in cell survival and proliferation. Pim-1 phosphorylates multiple cellular substrates to inhibit apoptosis and promote cell cycle progression. Over expression of Pim-1 kinase is observed in a range of malignancies and various solid cancers. High level of Pim-1 expression is seen in myeloma, acute myeloid leukemia, prostate cancer and liver carcinomas. Hence, Pim-1 is considered as an interesting cancer target. In the present study, we have performed region-focused CoMFA study on a series of imidazopyridazine derivatives as Pim-1 kinase inhibitors. A statistically acceptable region-focused CoMFA model ($q^2=0.571$; ONC=3; $r^2=0.909$) was developed. The model was then validated using Bootsrapping and progressive sampling. The contour map highlighted the regions favorable to increase the activity. Bulky substitutions in $R^2$ position of the phenyl ring could increase the activity. Similarly, small negative substitution in the $R^1$ position of the Pyridine ring could increase the activity considerably. Our results will be useful to design novel Pim-1 kinase inhibitors of this series.

• Journal of Integrative Natural Science
• /
• v.8 no.1
• /
• pp.40-47
• /
• 2015

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that has recently emerged as a promising target in drug discovery. It is involved in multiple cellular processes and associated with the pathogenesis of several diseases. A three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed on a series of GSK-3 inhibitors to understand the structural basis for inhibitory activity. Comparative molecular field analysis (CoMFA) method was used to derive 3D-QSAR models. A reliable CoMFA model was developed using ligand-based alignment scheme. The model produced statistically acceptable results with a cross-validated correlation coefficient ($q^2$) of 0.594 and a non-cross-validated correlation coefficient ($r^2$) of 0.943. Robustness of the model was checked by bootstrapping and progressive scrambling analysis. This study could assist in the design of novel compounds with enhanced GSK-3 inhibitory activity.

• Journal of Integrative Natural Science
• /
• v.11 no.2
• /
• pp.107-112
• /
• 2018

p38 MAP kinase belongs to the Mitogen-activated protein (MAP) kinase family; a serine/threonine kinase. It plays an important role in intracellular signal transduction pathways. It is associated with the development and progression of various cancer types making it a crucial drug target. Present study involves the HQSAR analysis of recently reported imidazo[1,2-b]pyridazine derivatives as p38 MAP kinase antagonists. The model was generated with Atom (A), bond (B), chirality (Ch), and hydrogen (H) parameters and with different set of atom counts to improve the model. An acceptable HQSAR model ($q^2=0.522$, SDEP=0.479, NOC=5, $r^2=0.703$, SEE=0.378, BHL=97) was developed which exhibits good predictive ability. A contribution map for the most active compound (compound 17) illustrated that hydrogen and nitrogen atoms in the ring A and ring B, as well as nitrogen atom in ring C and the hydrogen atom in the ring D provided positive activity in inhibitory effect while, the least active compound (compound 05) possessed negative contribution to inhibitory effect. Hence, analysis of produced HQSAR model can provide insights in the designing potent and selective p38 MAP kinase antagonists.

• 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.

• Biomedical Science Letters
• /
• v.29 no.4
• /
• pp.314-320
• /
• 2023

The purpose of this study was to provide basic data on hepatitis B infection control in the community through the results of the hepatitis B surface antigen and antibody tests conducted at the Cheongyang-County Health Medical Center. From 2012 to 2020, we retrospectively analyzed the HBsAg, HBsAb, HBeAg, HBeAb, and HBV DNA results of 7,329 hepatitis B-related testers. Among 7,329 subjects, the HBsAg positivity rate was 1.7%, and the positivity rate according to age was the highest at 4.4% in their 30s, 4.2% in their 40s, 4.1% in their 50s, 2.0% in their 60s, 1.9% in their 70s and over, and 10 it was shown in the order of 0.3% from less than large. The HBsAb positivity rate was 43.1% for men, 38.2% for men, and 46.7% for women (P<0.001). To summarize the above results, for infection control of hepatitis B in Cheongyang-County, hepatitis surface antigen proton management is required for those in their 30s or older, and it is thought that efforts to acquire immunity are necessary for those in their 20s or younger.

• BMB Reports
• /
• v.38 no.6
• /
• pp.650-660
• /
• 2005

Proteins accumulated in dry, stratified Arabidopsis seeds or young seedlings, totaled 1100 to 1300 depending on the time of sampling, were analyzed by using immobilized pH gradient 2-DE gel electrophoresis. The molecular identities of 437 polypeptides, encoded by 355 independent genes, were determined by MALDI-TOF or TOF-TOF mass spectrometry. In the sum, 293 were present at all stages and 95 were accumulated during the time of radicle protrusion while another 18 appeared in later stages. Further analysis showed that 226 of the identified polypeptides could be located in different metabolic pathways. Proteins involved in carbohydrate, energy and amino acid metabolism constituted to about 1/4, and those involved in metabolism of vitamins and cofactors constituted for about 3% of the total signal intensity in gels prepared from 72 h seedlings. Enzymes related to genetic information processing increased very quickly during early imbibition and reached highest level around 30 h of germination.

• Journal of the Korean Magnetic Resonance Society
• /
• v.22 no.4
• /
• pp.119-124
• /
• 2018

Although the transcription factor CP2c has been recently validated as a promising target for development of novel anticancer therapy, its structure has not been solved yet. In the present study, the purified recombinant protein corresponding to the tetramerization domain of CP2c appeared to be well folded, whereas the Elf-1 domain showed a largely unfolded conformation. Particularly, the Elf-1 domain, which contains the putative DNA-binding region, showed a conformational equilibrium between relatively less-ordered and well-ordered conformers. Interestingly, addition of zinc shifted the equilibrium to the relatively more structured conformer, whereas zinc binding decreased the overall stability of the protein, leading to a promoted precipitation. Likewise, a dodecapeptide that has been suggested to bind to the Elf-1 domain also appeared to shift the conformational equilibrium and to destabilize the protein. These results constitute the first structural characterization of the CP2c domains and newly suggest that zinc ion might be involved in the conformational regulation of the protein.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.19
• /
• pp.8361-8366
• /
• 2014

This meta-analysis was performed to assess the implementation effects of clinical pathways in patients with gastrointestinal cancer. A comprehensive search was conducted in the Cochrane Library, PubMed, EMBASE, Web of Science and Chinese Biomedical Literature Database (from inception to May 2014). Selection of studies, assessing risk of bias and extracting data were performed by two reviewers independently. Outcomes were analyzed by fixed-effects and random-effects model meta-analysis and reported as mean difference (MD), standardized mean difference (SMD) and odds ratio (OR) with 95% confidence intervals (CI). The Jadad methodological approach was used to assess the quality of included studies and the meta-analysis was conducted with RevMan 5.1 software. Nine citations (eight trials) involving 642 patients were included. The aggregate results showed that a shorter average length of stay [MD = -4.0; 95% CI (-5.1, -2.8); P < 0.00001] was observed with the clinical pathways as compared with the usual care. A reduction in inpatient expenditure [SMD = -1.5; 95% CI (-2.3, -0.7); P = 0.0001] was also associated with clinical pathways, along with higher patient satisfaction [OR = 4.9; 95% CI (2.2, 10.6); P < 0.0001]. Clinical pathways could improve the quality of care in patients with gastrointestinal cancer, as evidenced by a significant reduction in average length of stay, a decrease in inpatient expenditure and an improvement in patient satisfaction. Therefore, indicators and mechanisms within clinical pathways should be a focus in the future.

• Journal of Integrative Natural Science
• /
• v.10 no.2
• /
• pp.85-94
• /
• 2017

Fibroblast growth factor receptor (FGFR) belongs to the family of receptor tyrosine kinase. They play important roles in cell proliferation, differentiation, development, migration, survival, wound healing, haematopoiesis and tumorigenesis. FGFRs are reported to cause several types of cancers in humans which make it an important drug target. In the current study, HQSAR analysis was performed on a series of recently reported 1H-Pyrazolo [3,4-b]pyridine derivatives as FGFR antagonists. The model was developed with Atom (A) and bond (B) connection (C), chirality (Ch), hydrogen (H) and donor/acceptor (DA) parameters and with different set of atom counts to improve the model. A reasonable HQSAR model ($q^2=0.701$, SDEP=0.654, NOC=5, $r^2=0.926$, SEE=0.325, BHL=71) was generated which showed good predictive ability. The contribution map depicted the atom contribution in inhibitory effect. A contribution map for the most active compound (compound 24) indicated that hydrogen and nitrogen atoms in the side chains of ring B as well as hydrogen atoms in the side chain of ring C and the nitrogen atom in the ring D contributed positively to the activity in inhibitory effect whereas, the lowest active compound (compound 04) showed negative contribution to inhibitory effect. Thus results of our study can provide insights in the designing potent and selective FGFR kinase inhibitors.

• Journal of Integrative Natural Science
• /
• v.9 no.3
• /
• pp.161-165
• /
• 2016

The p21-activated kinase-1 (PAK1) has emerged as a potential target for anticancer therapy. It is overexpressed in ovarian, breast and bladder cancers. This suggests that PAK1 may contribute to tumorigenesis. 4-azaindole derivatives are reported as potent PAK1 inhibitors. The present work deals with the molecular docking studies of 4-azaindoles with PAK1. Probable binding mode of these inhibitors has been identified by molecular modeling. Docking results indicated that hydrogen bonding interactions with Glu345 and Leu347 are responsible for governing inhibitor potency of the compounds. Additionally, Val284, Val328, Met344 and Leu396 were found to be accountable for hydrophobic interactions inside the active site of PAK1.