• 대한의생명과학회지
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• 제15권3호
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• pp.257-260
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• 2009

Toll-like receptors (TLRs) recognize molecular structures derived from microbes including bacteria, viruses, yeast, and fungi. TLRs have emerged as a major signaling component of the mammalian host defense. TLR4 is a member of the Toll family that senses lipopolysaccharide (LPS), a cell wall component of gram negative bacteria. LPS recognition by TLR4 requires an additional accessory molecule, MD-2. LPS induces the activation of NF-${\kappa}B$ and IRF3 through MyD88 or TRIF-dependent pathways. The activation of NF-${\kappa}B$ leads to the induction of inflammatory gene products including cytokines and cyclooxygenase-2 (COX-2). This study was carried out to investigate the anti-inflammatory effects of oak wood vinegar. Oak wood vinegar inhibits the NF-${\kappa}B$ activation and COX-2 expression induced by LPS. These results provide new ideas to understand the mechanism of oak wood vinegar for its anti-bacterial and anti-inflammatory activities.

• 대한의생명과학회지
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• 제26권3호
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• pp.164-169
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• 2020

Atherosclerosis is a cardiovascular disease in which plaque builds up inside of an artery and can lead to various complications such as myocardial infarction, stroke, and thrombosis. Recently, hypertriglyceridemia has attracted significant attention as contributors to development of atherosclerosis. However, molecular mechanism of its contribution to atherosclerosis is poorly understood. Here we proposed a potential link between triglyceride (TG) and atherosclerosis. TG treatment promoted downregulation of certain scavenger receptor, macrophage scavenger receptor-1 (MSR-1) in phorbol myristate acetate (PMA)-derived human macrophages. TG treatment caused reduction of MSR-1 mRNA expression in a time- and dose-dependent manner. Using chemical inhibitors, we found that inhibition of signaling pathways associated with PI3K and PLC enhances TG-induced reduction of MSR-1 expression in THP-1 macrophages implying that PI3K and PLC is implicated in the expression of MSR-1 in macrophages. Since MSR-1 is associated with uptake and clearance of atherogenic lipoprotein, oxidized low density lipoprotein (oxi-LDL), our data suggest that increase of oxi-LDL due to TG-mediated reduction of its receptor MSR-1 can promote atherosclerosis.

• 대한의생명과학회지
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• 제26권1호
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• pp.42-46
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• 2020

Tuberculosis (TB) remains a major health problem worldwide. TB depends not only on the characteristics of the Mycobacterium tuberculosis (MTB) but also on the genetic susceptibility of infected patients. Recent studies have suggested that FOXO3 play an important role in the human immune associated disorder, such as TB. It was previously reported that FOXO3 genetic variants associated with a risk of TB in Chinese population. In this study, we confirm whether the genetic polymorphism of the FOXO3 gene, which was previously in Chinese, is reproduced in Korean population. Of the 154 SNPs were extracted from the FOXO3 gene, reproducibility analysis of the four SNPs performed in the previous study showed that there was a statistically significant correlation in the three SNPs (rs4946935, rs1536057, rs3800228). This study suggests that polymorphism of the FOXO3 gene in Koreans may affect the onset of tuberculosis and could be used to treat and prevent tuberculosis.

• 대한의생명과학회지
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• 제25권2호
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• pp.159-169
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• 2019

Breast cancer stem cells (BCSCs) in breast cancer cells have self-renewal ability and differentiation potential. They are also resistant to drugs after chemotherapy. To overcome this resistance, we designed negatively charged 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG)-based liposomes for drug delivery. These liposomes have enhanced the therapeutic effects of a range of antitumor therapies by increasing the cellular uptake and improving drug delivery to targets sites. In this study, we investigated whether DMPG-POPC liposomes, including the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC), can specifically bind to MCF-7 breast cancer cells and increase cellular uptake compared with that by CHOL-POPC liposomes. We also estimated the cytotoxicity of DMPG-POPC liposomes encapsulated with both metformin (Met) and sodium salicylate (Sod) against breast cancer cells and BCSCs compared with that of the free drugs. Our results demonstrated that these dual drug-encapsulated liposomes significantly enhanced the cytotoxic and anti-colony formation abilities compared with individual drug-encapsulated liposomes or free drugs in BCSCs. Overall, our results suggest that DMPG-POPC liposomes containing two drugs (Met + Sod) show promise for synergistic anti-cancer therapy of breast cancer by increasing drug delivery efficiency into breast cancer cells and BCSCs.

• 대한의생명과학회지
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• 제25권1호
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• pp.60-65
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• 2019

Toll-like receptors (TLRs) are one of the families of pattern recognition receptors (PRR) operating in the innate immunity. TLRs have the ability to recognize relatively conserved microbial components, which are generally referred to as pathogen-associated molecular patterns (PAMPs). The activation of TLRs signaling leads to the activation of $NF-{\kappa}B$ and the expression of pro-inflammatory gene products such as cytokines and inducible nitric oxide synthase (iNOS). To evaluate the therapeutic potential of pristimerin, which is a naturally occurring triterpenoid compound from Celastraceae plants, iNOS expression induced by MALP-2 (TLR2 and TLR6 agonist), Poly[I:C] (TLR3 agonist), or LPS (TLR4 agonist) were examined. Pristimerin suppressed the iNOS expression induced by MALP-2, Poly[I:C], or LPS. These results suggest that pristimerin can modulate TLRs signaling pathways leading to decreased inflammatory gene expression.

• 대한의생명과학회지
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• 제27권3호
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• pp.187-194
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• 2021

Platelets are derived from fragments formed in the cytoplasm of bone marrow megakaryocytes. Platelet count (PLT) can be altered by factors such as platelet production, destruction, and inflammation. In a previous study, the significant single nucleotide polymorphisms (SNP) were reported by the genome-wide association study (GWAS) for PLT in Koreans. In this study, it was confirmed whether significant SNPs were replicated in the HEXA (The Health Examinees) cohort. As a result, the SNPs of the THPO (rs6141), BAK1 (rs210314, rs9296095), GGNBP1 (rs75080135), ACAD10 (rs6490294), and ABCC4 (rs4148441) were significantly correlated with PLT (P < 10^-8). At the same time, it was confirmed that the direction of influence was the same according to the genotype. In conclusion, it can be seen that common SNPs are associated with the platelet count regardless of the cohort for Koreans.

• 대한의생명과학회지
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• 제27권1호
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• pp.1-11
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• 2021

Cancer stem cells, which are known to drive tumor formation and maintenance, are a major obstacle in the effective treatment of various types of cancer. Trans-membrane glycoprotein mucin 1 antigen and cell surface glycogen CD44 antigen are well-known surface markers of breast cancer cells and breast cancer stem cells, respectively. To effectively treat cancer cells and cancer stem cells, we developed a new drug-encapsulating liposome conjugated with dual-DNA aptamers specific to the surface markers of breast cancer cells and their cancer stem cells. These two aptamer (Apt)-targeted liposomes, which were prepared to encapsulate doxorubicin (Dox), were named "Dual-Apt-Dox". Dual-Apt-Dox is significantly more cytotoxic to both cancer stem cells and cancer cells compared to liposomes lacking the aptamers. Furthermore, we demonstrated the inhibitory efficacy of Dual-Apt-Dox against the experimental lung metastasis of breast cancer stem cells and cancer cells in athymic nude mice. We also showed the potent antitumor effects of dual-aptamer-conjugated liposome systems by targeting cancer cells as well as cancer stem cells. Thus, our data indicate that dual-aptamer-conjugated liposome systems can prove to be effective drug delivery vehicles for breast cancer therapy.

• 대한의생명과학회지
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• 제28권4호
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• pp.247-259
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• 2022

Immunotherapy, which uses an immune mechanism in the body, has received considerable attention for cancer treatment. Suberoylanilide hydroxamic acid (SAHA), also known as a histone deacetylase inhibitor (HDACi), is used as a cancer treatment to induce active immunity by increasing the expression of T cell-induced chemokines. However, this SAHA treatment has the disadvantage of causing PD-L1 overexpression in tumor cells. In this study, we prevented PD-L1 overexpression by blocking the PD-1/PD-L1 pathway using PD-L1 siRNA. We designed two types of liposomes, the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC) for SAHA, and 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) for siRNA. To effectively target PD-L1 in cancer cells, we conjugated PD-L1 antibody with liposomes containing SAHA or PD-L1 siRNA. These immunoliposomes were also evaluated for cytotoxicity, gene silencing, and T-cell-induced chemokine expression in human non-small cell lung cancer A549 cells. It was confirmed that the combination of the two immunoliposomes increased the cancer cell suppression efficacy through Jurkat T cell induction more than twice compared to SAHA alone treatment. In conclusion, this combination of immunoliposomes containing a drug and nucleic acid has promising therapeutic potential for non-small-cell lung carcinoma (NSCLC).

• 대한의생명과학회지
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• 제30권2호
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• pp.86-95
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• 2024

Sleep varies from individual to individual and is essential for maintaining good health, making it important for the health of individuals and societies. Sleep duration is influenced by both genetic and environmental factors, and sleep duration has been reported to be associated with obesity, metabolic syndrome, diabetes, and cardiovascular disease. In this study, we identified SNPs associated with sleep duration from the genome-wide association study (GWAS) catalog and compared them with the Korean Association Resource (KARE) cohort to find SNPs associated with sleep duration in Koreans and to identify the genes involved. The results showed that rs1553132, a SNP in the GRM5 gene, was identified as an SNP associated with sleep duration in both the GWAS catalog and the KARE cohort, and rs1504096 was the first SNP found to be associated with sleep duration in Koreans. It was found that having a minor allele tended to increase sleep duration. These results confirm the reproducibility of the association between sleep duration and the GRM5 gene in Koreans and provide a basis for using the associated SNPs as genetic determinants of sleep duration.

• 대한의생명과학회지
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• 제23권3호
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• pp.166-174
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• 2017

The bacterial cells located within the gastrointestinal tract (GIT) outnumber the host's cells by a factor of ten. These human digestive-tract microbes are referred to as the gut microbiota. During the last ten years, our understanding of gut microbiota composition and its relation with intra- and extra-intestinal diseases including risk factors of cardiovascular diseases (CVD) such as atherosclerosis and metabolic syndrome, have greatly increased. A question which frequently arises in the research community is whether one can modulate the gut microbial environment to 'control' risk factors in CVD. In this review, we summarized promising intervention methods, based on our current knowledge of intestinal microbiota in modulating CVD. Furthermore, we explore how gut microbiota can be therapeutically exploited by targeting their metabolic program to control pathologic factors of CVD.