• Journal of Microbiology and Biotechnology
• /
• v.33 no.7
• /
• pp.864-874
• /
• 2023

Natural killer (NK) cell dysfunctions against hepatocellular carcinoma (HCC) in a hypoxic environment. Many solid tumors are present in a hypoxic condition, which changes the effector function of various immune cells. The transcription of hypoxic-inducible factors (HIFs) in cancer cells make it possible to adapt to their hypoxic environment and to escape the immune surveillance of NK cells. Recently, the correlation between the transcription of HIF-1α and pro-inflammatory cytokines has been reported. Interleukin (IL)-6 is higher in cancers with a highly invasive ability, and is closely related to the metastasis of cancers. This study showed that the expression of HIF-1α in HCC cells was associated with the presence of IL-6 in the environment of HCC-NK cells. Blocking of IL-6 by antibody in the HCC-NK interaction changed the production of several cytokines including TGF-β, IL-1, IL-18 and IL-21. Interestingly, in a co-culture of HIF-1α-expressed HCC cells and NK cells, blocking of IL-6 increased the production of IL-21 in their supernatants. In addition, the absence of IL-6 significantly enhanced the cytotoxic ability and the expression of the activating receptors (NKG2D, NKp44, and NKG2C) in NK cells to HIF-1α-expressed HCC cells. These effects might be made by the decreased expression of HIF-1α in HCC cells through the inhibited phosphorylation of STAT3. In conclusion, the absence of IL-6 in the interaction of HIF-1α-expressed HCC cells and NK cells could enhance the antitumor activity of NK cells to HCC cells.

• BMB Reports
• /
• v.56 no.8
• /
• pp.445-450
• /
• 2023

The development of atherosclerotic cardiovascular disease is associated with the phenotypic switching of vascular smooth muscle cells (SMCs) from a contractile to a synthetic state, leading to cell migration and proliferation. Platelet-derived growth factor-BB (PDGF-BB) modulates this de-differentiation by initiating a number of biological processes. In this study, we show that gene expression of hyaluronic acid (HA) and proteoglycan link protein 1 (HAPLN1) was upregulated during differentiation of human aortic SMCs (HASMCs) into a contractile state, but downregulated upon during PDGF-BB-induced dedifferentiation. This is the first study showing that the treatment of HASMCs with full-length recombinant human HAPLN1 (rhHAPLN1) significantly reversed PDGF-BB-induced decrease in the protein levels of contractile markers (SM22α, α-SMA, calponin, and SM-MHC), and inhibited the proliferation and migration of HASMCs induced by PDGF-BB. Furthermore, our results show that rhHAPLN1 significantly inhibited the phosphorylation of FAK, AKT, STAT3, p38 MAPK and Raf mediated by the binding of PDGF-BB to PDGFRβ. Together, these results indicated that rhHAPLN1 can suppress the PDGF-BB-stimulated phenotypic switching and subsequent de-differentiation of HASMCs, highlighting its potential as a novel therapeutic target for atherosclerosis and other vascular diseases.

• Journal of the Korea Convergence Society
• /
• v.13 no.1
• /
• pp.101-107
• /
• 2022

Tertomotide is a peptide vaccine developed for anti-cancer therapy. Since it has been found to ameliorate inflammatory symptoms in animal studies and clinical test, we investigated anti-inflammation activity of the tertomotide and the mechanism of action in monocyte in order to assess if tertomotide may serve as an anti-inflammatory agent by checking inflammatory cytokines and related signaling pathway following tertomotide treatment. We found that tertomotide reduced the level of pro-inflammatory cytokines such as TNF-α, IL-1β, IL-8 in LPS- or PMA-stimulated monocyte cell line and suppressed NF-κB signaling including the activation of ERK1/2 and P38 MAPK following TNF-α treatment. These results may correlate to the beneficial findings in animal studies, implicating that tertomotide may act as a potential anti-inflammatory agent. This study is an exemplary case for convergence that a computationally designed peptide for immunological purpose exerting unexpected biological activity may elicit novel anti-inflammatory drug.

• IMMUNE NETWORK
• /
• v.23 no.2
• /
• pp.15.1-15.17
• /
• 2023

Innate lymphoid cells (ILCs) are critical immune-response mediators. Although they largely reside in mucosal tissues, the kidney also bears substantial numbers. Nevertheless, kidney ILC biology is poorly understood. BALB/c and C57BL/6 mice are known to display type-2 and type-1 skewed immune responses, respectively, but it is unclear whether this extends to ILCs. We show here that indeed, BALB/c mice have higher total ILCs in the kidney than C57BL/6 mice. This difference was particularly pronounced for ILC2s. We then showed that three factors contributed to the higher ILC2s in the BALB/c kidney. First, BALB/c mice demonstrated higher numbers of ILC precursors in the bone marrow. Second, transcriptome analysis showed that compared to C57BL/6 kidneys, the BALB/c kidneys associated with significantly higher IL-2 responses. Quantitative RT-PCR also showed that compared to C57BL/6 kidneys, the BALB/c kidneys expressed higher levels of IL-2 and other cytokines known to promote ILC2 proliferation and/or survival (IL-7, IL-33, and thymic stromal lymphopoietin). Third, the BALB/c kidney ILC2s may be more sensitive to the environmental signals than C57BL/6 kidney ILC2s since they expressed their transcription factor GATA3 and the IL-2, IL-7, and IL-25 receptors at higher levels. Indeed, they also demonstrated greater responsiveness to IL-2 than C57BL/6 kidney ILC2s, as shown by their greater STAT5 phosphorylation levels after culture with IL-2. Thus, this study demonstrates previously unknown properties of kidney ILC2s. It also shows the impact of mouse strain background on ILC2 behavior, which should be considered when conducting research on immune diseases with experimental mouse models.

• The Journal of Korean Medicine
• /
• v.45 no.1
• /
• pp.114-125
• /
• 2024

Objectives: Network pharmacology is an analysis method that explores drug-centered efficacy and mechanism by constructing a compound-target-disease network based on system biology, and is attracting attention as a methodology for studying herbal medicine that has the characteristics for multi-compound therapeutics. Thus, we investigated the potential functions and pathways of Myrrha on Allergic Rhinitis (AR) via network pharmacology analysis and molecular docking. Methods: Using public databases and PubChem database, compounds of Myrrha and their target genes were collected. The putative target genes of Myrrha and known target genes of AR were compared and found the correlation. Then, the network was constructed using STRING database, and functional enrichment analysis was conducted based on the Gene Ontology (GO) Biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways. Binding-Docking stimulation was performed using CB-Dock. Results: The result showed that total 3 compounds and 55 related genes were gathered from Myrrha. 33 genes were interacted with AR gene set, suggesting that the effects of Myrrha are closely related to AR. Target genes of Myrrha are considerably associated with various pathways including 'Fc epsilon RI signaling pathway' and 'JAK-STAT signaling pathway'. As a result of blinding docking, AKT1, which is involved in both mechanisms, had high binding energies for abietic acid and dehydroabietic acid, which are components of Myrrha. Conclusion: Through a network pharmacological method, Myrrha was predicted to have high relevance with AR by regulating AKT1. This study could be used as a basis for studying therapeutic effects of Myrrha on AR.

• Journal of Microbiology and Biotechnology
• /
• v.34 no.4
• /
• pp.765-773
• /
• 2024

Ozone, a highly reactive oxidant molecule, is widely used as a complementary therapy for various skin diseases, including wound healing, pressure ulcers, diabetic foot, and infections. However, there is limited research on the effectiveness of ozone for atopic dermatitis (AD). Ozonated sunflower oil (OSO) is an active ingredient obtained from partially ozonated sunflower oil (SO). OSO markedly reduced the LPS-induced increase in IL-1β and nitric oxide (NO) levels in RAW 264.7 mouse macrophage cells. Oxazolone (OXZ) was applied to hairless mice to induce AD-like skin symptoms and immune response. OSO significantly alleviated the OXZ-induced increases in the number of infiltrating mast cells, epidermal thickness, AD symptoms, thymic stromal lymphopoietin (TSLP), and filaggrin, as well as the serum levels of NO, IgE, IL-1β, and TNF-α. Furthermore, OSO inhibited the IL-4/STAT3/MAPK pathway and the expression of NF-κB. Our results suggest that OSO treatment could relieve AD-mediated skin damage through its anti-inflammatory and antioxidant activities. Therefore, it can be used as a therapeutic agent against AD-related skin diseases.

• Clinical Endoscopy
• /
• v.57 no.4
• /
• pp.454-465
• /
• 2024

Background/Aims: Gastrointestinal bleeding is a significant and potentially lethal event. We aimed to review the efficiency and safety of self-assembling peptides for the treatment and prevention of gastrointestinal tract bleeding. Methods: We conducted a systematic search for studies describing the endoscopic use of self-assembling peptides for treatment or prevention of bleeding in the gastrointestinal tract in a parallel, independent fashion. The primary outcomes were rates of successful initial hemostasis, delayed bleeding, and rebleeding. The secondary outcomes were adverse events and ease and volume of gel used. Results: Seventeen studies were analyzed. Overall success rate of self-assembling peptides in gastrointestinal bleeding was 87.7% (38%-100%), regardless of etiology or associated treatments. Rebleeding rate ranged from 0% to 16.2%, with a mean of 4.7%, and overall delayed bleeding rate was 5% (range, 0%-15.9%). Only three adverse events were reported in a pooled number of 815 patients. The volume of gel used varied (0.43 to 3.7 mL) according to indication and type of bleeding. Conclusions: The limited available data on the use of self-assembling peptides in gastrointestinal endoscopy suggest a high efficiency and good safety profile.

• Development and Reproduction
• /
• v.12 no.1
• /
• pp.31-39
• /
• 2008

Neural tissue has limited intrinsic capacity of repair after injury, and the identification of alternate sources of neural stem cells has broad clinical potential. We isolated mesechymal-like stem cells from human adipose tissues (AT-MSCs), and studied on transdifferentiation-promoting conditions in neural cells. Dopaminergic and cholinergic neuron induction of AT-MSCs was also studied. Neural differentiation was induced by adding bFGF, EGF, dimethyl sulphoxide (DMSO) and butylated hydroxyanisole(BHA) in N2 Medium and N2 supplement. The immunoreactive cells for $\beta$-tubulin III, a neuron-specific marker, GFAP, an astrocyte marker, or Gal-C, an oligodendrocyte marker, were found. AT-MSCs treated with bFGF, SHH and FGF8 were differentiatied into dopaminergic neurons that were immunopositive for TH antibody. Differentiation of MSCs to cholinergic neurons was induced by combined treatment with basic fibroblast growth factor (bFGF), retinoic acid (RA) and sonic hedgehog (Shh). AT-MSCs treated with DMSO and BHA rapidly assumed the morphology of multipolar neurons. Both immunocytochemistry and RT-PCR analysis indicated that the expression of a number of neural markers including neuro D1, $\beta$-tubulin III, GFAP and nestinwas markedly elevated during this acute differentiation. While the stem cell markers such as SCF, C-kit, and Stat-3 were not expressed after preinduction medium culture, we confirmed the differentiation of dopaminergic and cholinergic neurons by TH/$\beta$-tubulin III or ChAT/ $\beta$-tubulin III positive cells. Conclusively, AT-MSCs can be differentiated into dopaminergic and cholinergic neuronsand these findings suggest that AT-MSCs are alternative cell source of treatment for neurodegenerative diseases.

• Journal of Korean Society of Forest Science
• /
• v.8 no.1
• /
• pp.3-10
• /
• 1968

(1) The present work is a study on the tolerance of salt concentration, salt injuries and growth, under varied conditions, of salt concentration of five kind silvicultural species. (2) Pinus thunbergii, which is tolerant of stat, has shown both low fresh leaf's pH and low gravity, while Pinus densiflora, Abies bolophylla and Pinus koraiensis have respectively shown high fresh leaf's pH and high gravity. (3) Pinus thunbergii, which is tolerant otosalt, has shown high water content ind its lead, hbile such speciesras Pinus densiflora an Abies lophylla, which are intolerant of salt have shownlow water content in their leaves. (4) A signifficance has ibeen found, in the nonreatment fresh les's pH and n gravity, among Pinusthunbergiis Pinu rigida, Pinus koraiensis, Pinus densiflora and Abies holophya. (5) The order of thetlolerance of salt among the tested species is as foohws : Pinus thunbergii, P. Korea iensis, Abies holopylla. (6) The signs of salt injuries have been observed at the tops of the trees 2~3 hours after the application of 1.5% salt solution in the case of Abiihs holop hylla which are intolerant of salt, while they have been of served at the same position 4~6 hours after the 1.5% application in the case of Pinus Koraiensis and Pinus thunbergii.

• Journal of Oral Medicine and Pain
• /
• v.21 no.2
• /
• pp.305-315
• /
• 1996

This study was performed to investigate the changes of head posture according to natural standing or sitting posture. Twenty seven healthy dental students without any signs and symptoms of temporomandibular disorders participated in this study. Cervical resting posture (CRP) of the head in sagittal plane was measured by Cervical-Range-of-Motion $^\textregistered$(CROM, U.S.A.) and lateral cephalograph was taken in natural posture. The items related to angle in cephalograph were the angles of cranial and cervical inclination to true vertical line(VER/NSL, VER/AML), the angles of cervical inclination to nasion-sella line(CVT/NSL, OPT/NSL), the angles of comical inclination to horizontal line(CVT/HOR, OPT/HOR), the angle of cervical lordosis(CVT/OPT). The items related to line measurement were the distance from subocciput to Cl(Dl), Cl to C2(D2), C2 to C3(D3), C3 to C4(D4), the upper(PNS to posterior pharyngeal wall) and the lower(tongue base to posterior pharyngeal wall) pharyngeal space, the distance from nation to mention(Na-Me), and the radius of comical curvature from the first comical vertebra(Cl ) to the fifth cervical vertebra(C5). The data were analyzed with SAS/STAT program. The obtained results were as follows : 1. Most items related to angular measurement showed significant difference between in standing and sitting posture. The angles of CRP, CVT/NSL, OPT/NSL, CVT/HOR, OPT/HOR, and CVT/OPT were high in sitting posture, but the angles of VER/NSL, VER/NSL were low in sitting posture. 2. In vertebral distance, only the distance between C3 and C4 was differed by the posture, which decreased in sitting posture. In sitting posture, the distance from nasion to menton(Na-Me) was longer, but the radius was shorter than in standing posture. 3. Correlationship in angular measurements was almost same in both postures. Ceervical resting posture(CRP) was correlated with VER/NSL, VER\ulcornerNSL was correlated with CRP, CVT/NSL, and OPT/NSL, VER/AML was correlated with CVT/HOR, OPT/HOR, CVT/OPT, and the angle of cervical lordosis(CVT/OPT) was correlated with the radius. 4. Correlationship in linear measurement was observed only in among D3, D4, and radius. And the Na-Me was not correlated with any other items. From this results, The author concluded that the head posture in sitting was mote backward extended than in standing.