• Biomedical Science Letters
• /
• v.28 no.4
• /
• pp.247-259
• /
• 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).

• BMB Reports
• /
• v.50 no.11
• /
• pp.578-583
• /
• 2017

Programmed cell death-1 (PD-1) is a coinhibitory molecule and plays a pivotal role in immune regulation. Here, we demonstrate a role for PD-1 in pathogenesis of inflammatory bowel disease (IBD). Wild-type (WT) mice had severe wasting disease during experimentally induced colitis, while mice deficient for PD-1 ($PD-1^{-/-}$) did not develop colon inflammation. Interestingly, $PD-1^{-/-}$ mice cohoused with WT mice became susceptible to colitis, suggesting that resistance of $PD-1^{-/-}$ mice to colitis is dependent on their gut microbiota. 16S rRNA gene-pyrosequencing analysis showed that $PD-1^{-/-}$ mice had altered composition of gut microbiota with significant reduction in Rikenellaceae family. These altered colon bacteria of $PD-1^{-/-}$ mice induced less amount of inflammatory mediators from colon epithelial cells, including interleukin (IL)-6, and inflammatory chemokines. Taken together, our study indicates that PD-1 expression is involved in the resistance to experimental colitis through altered bacterial communities of colon.

• BMB Reports
• /
• v.51 no.11
• /
• pp.572-577
• /
• 2018

Recent studies showed that the PD-1/PD-L1 checkpoint blockade is a dramatic therapy for melanoma by enhancing antitumor immune activity. Currently, major strategies for the PD-1/PD-L1 blockade have mainly focused on the use of antibodies and compounds. Seeking an alternative approach, others employ endogenous proteins as blocking agents. The extracellular domain of PD-1 (ePD1) includes the binding site with PD-L1. Accordingly, we constructed a PD-1-based recombinantly tailored fusion protein (dFv-ePD1) that consists of bivalent variable fragments (dFv) of an MMP-2/9-targeted antibody and ePD1. The melanoma-binding intensity and antitumor activity were also investigated. We found the intense and selective binding capability of the protein dFv-ePD1 to human melanoma specimens was confirmed by a tissue microarray. In addition, dFv-ePD1 significantly suppressed the migration and invasion of mouse melanoma B16-F1 cells, and displayed cytotoxicity to cancer cells in vitro. Notably, dFv-ePD1 significantly inhibited the growth of mouse melanoma B16-F1 tumor cells in mice and in vivo fluorescence imaging showed that dFv-ePD was gradually accumulated into the B16-F1 tumor. Also the B16-F1 tumor fluorescence intensity at the tumor site was stronger than that of dFv. This study indicates that the recombinant protein dFv-ePD1 has an intensive melanoma-binding capability and exerts potent therapeutic efficacy against melanoma. The novel format of the PD-L1-blocked agent may play an active role in antitumor immunotherapy.

• Proceedings of the Korean Vacuum Society Conference
• /
• 2013.08a
• /
• pp.139.1-139.1
• /
• 2013

Graphene and graphene oxide (GO) have been modified with palladium nanoparticles (Pd NPs) to develop high performance catalysts for the Sonogashira cross coupling reaction. To understand catalytic performance of Pd NPs on graphene (Pd/G) and Pd NPs on GO (Pd/GO), we monitored their morphological and electronic structural changes before/after Sonogashira reaction using FT-IR, XRD, XPS, and XAFS. Here, we demonstrate that both Pd/G and Pd/GO show high catalytic efficiency toward the Sonogashira reaction, but only Pd/GO revealed excellent recyclability. The remarkable catalytic efficiency of both catalysts is attributed to the high degree of the Pd NP dispersions on supports and thus smaller Pd NPs can provide highly reactive low coordinated Pd atoms. However, we attributed the excellent recyclability of Pd/GO to the presence of oxygen functionalities on GO, which can provide nucleation sites for the detached Pd atoms during the Sonogashira reaction and prevent agglomeration of the Pd NPs since the oxygen functional groups are very reactive to mobile Pd adatoms.

• Tuberculosis and Respiratory Diseases
• /
• v.83 no.1
• /
• pp.51-60
• /
• 2020

Background: Programmed death-ligand 1 (PD-L1) expression is tested by immunohistochemistry (IHC)-22C3, SP263, and SP142. The aim of this study is to evaluate the correlation among the three methods of PD-L1 IHC in non-small cell lung cancer (NSCLC) and clinical significance of PD-L1 expression in lung adenocarcinoma with an epidermal growth factor receptor (EGFR)-tyrosine kinase domain mutation. Methods: The results of 230 patients who were pathologically confirmed as having NSCLC; tested using PD-L1 IHC 22C3, SP263, and SP142 methods; and evaluated via the peptide nucleic acid clamping method to confirm EGFR mutation, were analyzed in this study. Results: 164 patients underwent both the SP263 and 22C3 tests. There was a significant positive correlation between the outcomes of the two tests (Spearman correlation coefficient=0.912, p<0.001), with a derived regression equation as follows: 22C3=15.2+0.884×SP263 (R²=0.792, p<0.001). There was no relationship between the expression of PD-L1 and clinical parameters, including EGFR-tyrosine kinase inhibitor (TKI) mutation. The PD-L1 expression in patients treated with EGFR-TKI yielded a 2-month-shorter progression period than that in the PD-L1-negative group. However, this did not reach statistical significance (PD-L1<1% vs. PD-L1≥1%, 10 months vs. 8 months). Conclusion: The results of the 22C3 and those of SP263 methods were in good correlation with one another. Since the PD-L1 expression is not influenced by the EGFR mutation, it is necessary to perform a PD-L1 test to set the treatment direction in the patients with EGFR-mutant NSCLC.

• KSBB Journal
• /
• v.23 no.5
• /
• pp.413-418
• /
• 2008

The production of 1,3.propanediol (1,3-PD) was investigated with Klebsiella pneumoniae DSM2026 and K. pneumoniae DSM4799 using crude glycerol obtained from biodiesel industry. Crude glycerol was used without prior purification to investigate effects of impurities in crude glycerol on 1,3-PD production. In the batch cultures, 1,3-PD production with crude glycerol was $1.1{\sim}2.5$ times higher than that with pure glycerol, indicating that crude glycerol is even a better substrate than pure glycerol for 1,3-PD fermentation. When glucose was added, 1,3-PD production and yield decreased in spite of enhanced cell growth. Furthermore, the addition of glucose was found to increase 2,3-butanediol, a by-product, significantly because of the change in metabolism in the presence of glucose. In semi-batch cultures without glucose addition, 26 g/L 1,3-PD was produced with crude glycerol, which was $2{\sim}3$ times higher than that with pure glycerol. Based on our results, it was clearly shown that crude glycerol is an effective substrate for biological 1,3-PD production, making it more feasible to produce 1,3-PD at a lower price.

• Journal of Ginseng Research
• /
• v.10 no.1
• /
• pp.101-107
• /
• 1986

Relationships among ginsenosides, panaxadiol(PD), panaxatriol(PT), and total saponin(TS) in Panax ginseng root (2nd Year) grown with culture solotion different in nitrogen, phosphorus and potassium level were analyzed by simple correlation, multiple regression and standard partial regression coefficient. The closeness between ginsenosides by simple correlation was closely related with the similarity of molecular structure. The content of PT was much attributed to Re and Rg1. The contribution order of ginsenosides for PD was Rb1>Rb2$\geq$Rd>Rc. There was significant positive correlation between PT and PD but PD increased more rapidly than PT. Thus total saponin depended much on PD and PT/PD decreased with the increase of total saponin content. All ginsenosides, especially Re showed decreasing tendency with the increase of root weight.

• The Journal of Korean Medicine
• /
• v.30 no.4
• /
• pp.79-92
• /
• 2009

Objectives: The aim of the present study was to explore the neuroprotective effect and the possible mechanism of the PD-1 extracts on 1-methyl-4-phenyl-1,2,3,6-tetrahydrophridine (MPTP)-lesioned C57BL/6 mouse model of Parkinson's disease (PD). Methods: The mice were supplemented (or not) with 50 or 100 mg/kg/day of PD-1 for 2 weeks, after which MPTP was injected intraperitoneally. We observed that daily administration of PD-1 prevented MPTP-induced depletion of striatal DA, and maintained striatal and nigral tyrosine hydroxylase (TH) protein levels. Results: Our results demonstrated that mice treated with PD-1 prior to MPTP administration showed more abundant TH-immunopositive (TH-ir) fibers and neurons than mice given only MPTP, indicating that PD-1 protects dopaminergic striatal fibers and nigral neurons from MPTP insults. Possible neuroprotective effect of PD-1 was further studied by the detection of antiapoptotic protein (bcl-2) and proapoptotic protein (Bax). In this assay, MPTP elevated the Bax protein and decreased the bcl-2 protein, while these expressions were prevented by PD-1 pre-treatment. Conclusions: The present results suggest that PD-1 is able to protect dopaminergic neurons from MPTP-induced neuronal injury with anti-apoptotic activity being one of the possible mechanisms.

• Journal of the Mineralogical Society of Korea
• /
• v.8 no.1
• /
• pp.13-22
• /
• 1995

Phase relations of the Pd-Sb system were investigated using the sealed-capsule technique; the quenched run products were studied by reflected light microscopy, X-ray diffraction, and electron microprobe analysis. Eight binary phases were confirmed to exist in the system: Pd20Sb7, Pd31Sb12, Pd8Sb3 (mertieite II), Pd5Sb2, Pd2Sb, Pd5Sb3, PdSb (sudburyite), and PdSb2, (unnamed PdSb2), The X-ray powder diffraction data of all the phases, except for Pd5Sb3, however, may be indexable on an orthorhombic cell, space group Cmc2, with a=3.362(1), b=17.484(7), c=6.934(2)$\AA$. Some physical properties as well as re-determined cell parameters are newly established. A revised phase relations of the Pd-Sb system are presented.

• Korean Journal of Metals and Materials
• /
• v.50 no.10
• /
• pp.711-720
• /
• 2012

In this study, the effect of aging treatment on the microstructure and tensile properties of AZ61-xPd (x = 0, 1 and 2 wt%) alloys were investigated. The microstructure of as-cast AZ61-xPd alloys mainly consisted of ${\alpha}-Mg$, $Mg_{17}Al_{12}$ and $Al_4Pd$ phases. After solution treatment, most of the $Mg_{17}Al_{12}$ phases were dissolved into the Mg matrix. Thereafter, $Mg_{17}Al_{12}$ phases were finely formed and distributed near thermally stable $Al_4Pd$ phases and inside the grains through aging treatment at $220^{\circ}C$ during 88 hours. With the aging at $220^{\circ}C$, the peak aged AZ61-xPd alloys showed higher hardness than as-cast and solution treated AZ61-xPd alloys. In particular, the AZ61-1Pd alloy was optimized due to refined $Mg_{17}Al_{12}$ and $Al_4Pd$ phases. Further, the peak aging time was reduced with increasing Pd addition (>1 wt%). Tensile strength was increased by Pd addition at $25^{\circ}C$, $150^{\circ}C$, both as-cast and peak aged AZ61-xPd alloys. After aging treatment, room and high temperature tensile strength were increased more than the as-cast specimens. The AZ61-1Pd alloy especially showed the largest strength increase range. Elongation was decreased with addition Pd at $25^{\circ}C$ and $150^{\circ}C$.