• Title/Summary/Keyword: Loss factor

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Inhibition of Tumoral VISTA to Overcome TKI Resistance via Downregulation of the AKT/mTOR and JAK2/STAT5 Pathways in Chronic Myeloid Leukemia

  • Kexin Ai;Mu Chen;Zhao Liang;Xiangyang Ding;Yang Gao;Honghao Zhang;Suwan Wu;Yanjie He;Yuhua Li
    • Biomolecules & Therapeutics
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    • v.32 no.5
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    • pp.582-600
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    • 2024
  • Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.

Analysis of the influence degree of each factor on the linkage affecting the lever actuating force in an implant transport device for the treatment of eye diseases (안과질환 처치를 위한 임플란트 수송장치에서 레버 작동력에 영향을 주는 연동장치에 대한 인자별 영향도 분석 )

  • Jeong-Won Lee;Joong-Seob Guk
    • Design & Manufacturing
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    • v.18 no.3
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    • pp.1-8
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    • 2024
  • Macular degeneration is a disease that damages the macula, the center of the retina, and is one of the three major eye diseases along with glaucoma and diabetic retinopathy. The optic nerve and most of the photoreceptor cells are located here, and since this is where images of objects are formed, it is the most important area for vision. The main symptom of macular degeneration is the inability to clearly distinguish the shape of objects or the inability to distinguish colors and light and dark. It is also a serious eye disease that causes black spots in the center of the field of vision. However, it is difficult to distinguish it from the form of vision loss due to presbyopia, so early diagnosis is often missed. The most common treatment for macular degeneration is antibody injection therapy. This treatment requires regular injections once every 1-2 months. When receiving antibody injection therapy, the fear of having to inject directly into the eye and the cost of long-term repeated procedures are a great burden to patients. To overcome these problems, special sustained-release formulations using drug delivery systems are being developed. Since the release speed and release time of the drug can be controlled, the number of times the drug is administered can be drastically reduced. However, the implant (Ø 0.46×6.0mm), which is a sustained-release agent, is manufactured by mixing biodegradable resin (PLGA) and therapeutic agent in a ratio of 4:6, so it is very brittle and there is a high risk of implant damage during handling. In order to safely insert the implant into the eye, a transport device that can be driven with controlled force is required. Therefore, in this study, the lever operating force was measured and analyzed to determine the influence of factors according to the cross-sectional thickness and shape of the linkage produced through injection molding as well as the post-process.

Hyaluronic Acid Synthesis Effect of Prunus yedoensis Bark Ethyl Acetate Fraction (왕벚나무 수피 에틸아세테이트 분획물의 히알루론산 합성효과)

  • Ji Hyun Song;Myong-Ki Kim;Soo Min Kwak;Yong Min Kim
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.50 no.3
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    • pp.251-259
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    • 2024
  • The skin barrier plays an important role in maintaining healthy skin by preventing external irritation and water loss in the body. In the skin, hyaluronic acid (HA) is synthesized by the enzyme hyaluronic acid synthase (HAS), which functions as a natural moisturizing factor and is involved in maintaining water retention and barrier function. Therefore, in this study, the effect of the Prunus yedoensis bark ethyl acetate fraction (PYBEAF) on HA synthesis in HaCaT cells was confirmed. Cytotoxicity evaluation was performed through MTT assay, and the amount of HA synthesis in HaCaT cells was confirmed through ELISA through PYBEAF treatment. The levels of HAS-2, HAS-3 mRNA expression were analyzed using qRT-PCR, and the protein expression level and signaling pathway were confirmed through western blotting. Consequently, PYBEAF was involved in the MAPK and CREB signaling pathways, increasing the amount of HA production through HAS-2 synthesis. This suggests that PYBEAF is effective in improving barrier function by increasing HA synthesis, which plays an important role in moisturizing and maintaining skin moisture.

Geochemical Characteristics and Heavy Metal Pollutions in the Surface Sediments of Oyster Farms in Goseong Bay, Korea (고성만 굴 양식장 표층퇴적물의 지화학적특성과 중금속 오염에 관한 연구)

  • Kang, Ju-Hyun;Lee, Sang-Jun;Jeong, Woo-Geon;Cho, Sang-Man
    • The Korean Journal of Malacology
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    • v.28 no.3
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    • pp.233-244
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    • 2012
  • Goseong bay, located in southeast sea of Korea with an area of 2,100 ha, is a semi-enclosed bay well-known for oyster farming cultured in an extended range of 148 ha. The objective of this study is to provide the fundamental data in order to manage the effective sea area. A total 26 of surface sediment were collected from Goseong bay to evaluate their sedimentary environment and heavy metals. The loss on Ignition (LOI), C/N ratio, acid volatile sulfide (AVS) and heavy metals were analyzed. loss on ignition (LOI) of surface sediment range from 1.00% to 3.03% (average 2.00%). The carbonate content ranges from 0.52% to 4.29% (average 2.37%). C/N ratio of organic matter showed that most part of organic matter comes from neighboring continent. Acid volatile sulfide (AVS) value of surface sediment from 0.02 mg/g to 1.43 mg/g (average 0.24 mg/g). A ten element of surface sediments (Al, As, Cd, Cr, Cu, Hg, Ni, Pb, V, Zn) were calculated by enrichment factor (Ef) and the results show that some areas are highly polluted with respect Cu and Hg. The correlation matrix displays the existence of remarkable levels of correlation with both positive and negative values among different variable pairs. LOI and AVS showed both positive values. LOI and AVS values falls under 2% and 1%. Therefore, Goseong bay showed good in quality of sediment.

Change of Antioxidant Activities in Carrots (Daucus carota var. sativa) with Enzyme Treatment (효소처리 가공이 당근(Daucus carota var. sativa)의 항산화 활성 변화에 미치는 영향)

  • Yoo, Jin-Kyoun;Lee, Jin-Hee;Cho, Hyung-Yong;Kim, Jung-Gook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.2
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    • pp.262-267
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    • 2013
  • The purpose of this research is to minimize the loss of nutrients in carrots (Daucus carota var. sativa). A protopectinase was used to enzymatically macerated and separate cells without damage. The enzyme modification group's collection rate was 81% (residue rate 19%), while the grinding process group's collection rate was 56% (residue rate 44%)-an over 20% of collection rate difference. Thus we predicted a big difference in transference number after the process and wastage. In comparing ingredient changes in the enzyme modification group versus the grinding process group, the content of ${\beta}$-carotene (the carrot's main ingredient) showed a change in protection factor (PF) ($2.2{\pm}0.2$ PF, $1.4{\pm}0.4$ PF, respectively), total polyphenol content ($89{\pm}3.42{\mu}g/g$, $64{\pm}4.16{\mu}g/g$, respectively), and total flavonoid content ($68{\pm}2.73{\mu}g/g$, $41{\pm}3.26{\mu}g/g$, respectively). Thus we confirmed that nutrient destruction, due to cell membrane preservation, occurred less often in the enzyme modification process than the mechanical grinding process group. We also measured DPPH radical scavenging activity, hydroxyl radical scavenging activity, and nitrite scavenging activity. DPPH radical scavenging activity was $87{\pm}0.29%$ and $74{\pm}1.56%$ in the enzymatic modification group compared to the mechanical grinding process group, respectively. Hydroxyl radical scavenging activity was $44{\pm}0.49%$ and $32{\pm}0.48%$ in the enzymatic modification group compared to the mechanical grinding process group, respectively. Nitrite scavenging activity was $59{\pm}0.53%$ and $46{\pm}0.62%$ in the enzymatic modification group compared to the mechanical grinding process group, respectively. Our results show that cell membrane preservation, via the protopectinase enzyme process, decreases the loss of nutrients and still preserves inherent antioxidants.

Recurrent Hemoptysis after Bronchial Artery Embolization (기판지동맥색전술 후 객혈의 재발에 관한 연구)

  • Kim, Soo-Ok;Oh, In-Jae;Kim, Kyu-Sik;Yu, Young-Kwon;Lim, Sung-Chul;Kim, Young-Chul;Park, Kyung-Ok;Kim, Jae-Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.4
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    • pp.364-372
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    • 2001
  • Background : To observe the immediate and long-term results of bronchial artery embolization(BAE) for hemoptysis and the factors influencing the recurrences. Methods : This study involved 75 patients with massive, or moderate and recurrent hemoptysis, who underwent bronchial artery embolization(BAE) from 1994 to 1999. The underlying diseases included pulmonary tuberculosis in 35, bronchiectasis in 22, aspergilloma in 12, lung cancer in 3, and 3 with other diseases. Results : After BAE, bleeding was controlled immediately in 61 patients(82.7%). One patient died of another medical problem, 3 patients were referred to surgery and 5 patients could not be followed-up. In the remaining 66 patients who were followed for more than one-year after BAE, 37(56.1%) patients had another hemorrhage (26 hemoptysis, 11 minor hemosputa). Among the recurred 37 subjects, 19(51.4%) experienced hemorrhage within 1 month after BAE, 31(83.8%) within 1 year, and 36(94.1%) within 3 years. The underlying lung diseases, the amount of bleeding and the extent of the involved lungs were factors affecting the outcome, especially blood loss >500cc was an important factor affecting the recurrence rate. BAE for two cases with lung malignancy was ineffective. Long-term control of bleeding (3-year cumulative non-recurrence) was achieved in 30 subjects(45.5%). Conclusion : Bronchial artery embolization(BAE) is effective as an initial treatment for moderate to massive hemoptysis. Because most of the recurrences occurred within 3 years, it is important to follow-up such patients for at least 3 years after BAE and the most significant factor affecting the prognosis was amount of blood loss.

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Antioxidant Activity and Quality Characteristics of Perilla leaves(Perilla frutescens var. japonica HARA) Cookies (들깻잎 쿠키의 항산화활성 및 품질특성)

  • Choi, Hae-Yeon;Oh, So-Yeon;Lee, Yang-Soon
    • Korean journal of food and cookery science
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    • v.25 no.5
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    • pp.521-530
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    • 2009
  • Perilla leaves powder was added to cookies to determine a practical use for the herb, which has been shown to have medical benefits and functionality. We examined the antioxidant activity and quality characteristics of cookies prepared with different amounts (as ratios of 0.5%, 1%, 3%, 5% to the total materials) of perilla leaves powder. The antioxidant activity was estimated by DPPH free radical scavenging activity and the total phenolic compound content in perilla leaves powder and cookies. The quality characteristics of the perilla leaves cookie were estimated in terms of the bulk density, pH of the dough, spread factor, loss rate, leavening rate, color, texture profile analysis, and sensory evaluations. While the bulk density and pH of the dough as well as total polyphenol contents and DPPH free radical scavenging activity of cookies significantly increased, the spread factor, loss rate, leavening rate and L value of the cookies decreased with increasing perilla leaves powder content(p<.05). The consumer acceptability scores for the $1{\sim}3%$ perilla leaves cookie groups ranked significantly(p<.05) higher than those of the other groups in appearance, taste, flavor, texture, and overall preference. This study suggests that perilla leaves powder is a good ingredient to increase the consumer acceptability and the functionality of cookies.

Dielectric/piezoelectric Properties of Mn-Doped PMN-PZT with Variations of the Sintering Temperature and Addition of B2O3 (소결온도와 B2O3첨가량에 따른 Mn첨가 PMN-PZT의 유전 및 압전특성의 변화)

  • Shin Hyo-Soon
    • Journal of the Korean Ceramic Society
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    • v.41 no.9
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    • pp.709-714
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    • 2004
  • The additive of low temperature sintering in Mn-doped PMN-PZT known as high piezoelectric materials was studied in this experiment. B$_2$O$_3$ was used for the additive of low temperature sintering. The effects of sintering temperature in dielectric, and piezoelectric properties were investigated with the amounts of B$_2$O$_3$. Sintered density was increased in comparison with no addition and under 2wt% B$_2$O$_3$ and lower sintering temperature than 100$0^{\circ}C$. Therefore, in the low sintering temperature, the densification was improved by the addition of the B$_2$O$_3$. However, the sintering density was lower than that of the main composition in the case of the sintered at over 10$50^{\circ}C$. Dielectric constant with the addition of B$_2$O$_3$ was evaluated. The dielectric constant was 1000 2 wt% of B$_2$O$_3$ and sintered at 100$0^{\circ}C$. Under 2wt% of B$_2$O$_3$, the electromechanical coupling factor and the piezoelectric constant were not so much decreased. The electromechanical coupling factor and the piezoelectric constant were 50% and 300(${\times}$10$^{-12}$ C/N) respectively. The mechanical quality factor was increased with B$_2$O$_3$. The mechanical quality factor was 1700 at 0.5wt% B$_2$O$_3$ and sintered at 110$0^{\circ}C$. Dielectric loss was less than 0.5% regardless of the amount of B$_2$O$_3$.

The Development of Vulnerable Elements and Assessment of Vulnerability of Maeul-soop Ecosystem in Korea (한국 마을숲 생태계 취약요소 발굴 및 취약성 평가)

  • Lim, Jeong-Cheol;Ryu, Tae-Bok;Ahn, Kyeong-Hwan;Choi, Byoung-Ki
    • Journal of the Korean Institute of Traditional Landscape Architecture
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    • v.34 no.4
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    • pp.57-65
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    • 2016
  • Maeul-soop(Village forest) is a key element of Korean traditional village landscape historically and culturally. However, a number of Maeul-soops have been lost or declined due to various influences since the modern age. For this Maeul-soop that has a variety of conservation values including historical, cultural and ecological ones, attention and efforts for a systematic conservation and restoration of Maeul-soop are needed. The purpose of the present study is to provide information on ecological restoration and sustainable use and management of Maeul-soops based on component plant species, habitat and location characteristics of 499 Maeul-soops spread throughout Korea. Major six categories of threat factors to Maeul-soop ecosystem were identified and the influence of each factor was evaluated. For the evaluation of weight by threat factors for the influence on the vulnerability of Maeul-soop ecosystem, more three-dimensional analysis was conducted using Analytic Hierarchy Process (AHP) analysis method. In the results of evaluation using AHP analysis method, reduction of area, among six categories, was spotted as the biggest threat to existence of Maeul-soops. Next, changes in topography and soil environment were considered as a threat factor of qualitative changes in Maeul-soop ecosystem. Influence of vegetation structure and its qualitative changes on the loss or decline of Masul-soop was evaluated to be lower than that of changes in habitat. Based on weight of each factor, the figures were converted with 100 points being the highest score and the evaluation of vulnerability of Maeul-soop was conducted with the converted figures. In the result of evaluation of vulnerability of Maeul-soops, grade III showed the highest frequency and a normal distribution was formed from low grade to high grade. 38 Maeul-soops were evaluated as grade I which showed high naturality and 10 Maeul-soops were evaluated as grade V as their maintenance was threatened. Also in the results of evaluation of vulnerability of each Maeul-soop, restoration of Maeul-soop's own area was found as top priority to guarantee the sustainability of Maeul-soops. It was confirmed that there was a need to prepare a national level ecological response strategy for each vulnerability factor of Maeul-soop, which was important national ecological resources.

Efficacy and Safety of Topical Application of Epidermal Growth Factor (EGF) for Korean Acne Patient (한국인 여드름 환자에서 표피성장인자가 함유된 외용제의 피부 적용에 대한 유효성 및 안전성 평가)

  • Suh, Joon Hyuk;Hyun, Moo Yeol;Jang, Seong Eum;Choi, Sun Young;Kim, Myeung Nam;Kim, Beom Joon
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.42 no.2
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    • pp.111-118
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    • 2016
  • Acne vulgaris is a chronic inflammatory condition characterized by comedo, papule, cyst, nodule and postinflammatory hyperpigmentation. Meanwhile, it is also induced by adverse event of drugs. Among them, acneiform folliculitis is a side effect of epidermal growth factor receptor (EGFR) inhibitor, which is an anticancer agent, and its incidence may occur in upward of 75 ~ 100% of cases. The main method of acne vulgaris treatment is oral antibiotics, retinoids, topical medication and so on. However, it is limitation that teratogenicity caused by retinoids and antibiotic resistance increased by using antibiotics. In this study, we aimed to evaluate the clinical efficacy and safety of topical recombinant human (rh) EGF in treating facial acne vulgaris. Twenty three Koreans (age: 10 ~ 29 years) with mild to moderate acne vulgar participated in the study and applied topical rhEGF cream (trouble control EGF) with 3 products (trouble control clarifying cleansing foam, trouble control all-clear filling toner, redroll calming moisture) on their face twice daily for four weeks. Several assessment methods were applied: Acne lesion counts score by investigator's global assessment, efficacy and satisfaction score by subjects. Skin sebum output level, hydration level and redness level were also measured at each visit. At the final visit, skin sebum level, transepidermal water loss, skin redness statistically decreased and acne lesions (comedone, papule) were statistically reduced. No severe side effects were observed during the study. In conclusion, topical rhEGF seems to be an effective and safe adjuvant treatment option for mild acne vulgaris.