Tumor vessel normalization by the PI3K inhibitor HS-173 enhances drug delivery

Kim, S.J.,Jung, K.H.,Son, M.K.,Park, J.H.,Yan, H.H.,Fang, Z.,Kang, Y.W.,Han, B.,Lim, J.H.,Hong, S.S. Elsevier 2017 Cancer letters Vol.403 No.-

Tumor vessels are leaky and immature, which causes poor oxygen and nutrient supply to tumor vessels and results in cancer cell metastasis to distant organs. This instability of tumor blood vessels also makes it difficult for anticancer drugs to penetrate and reach tumors. Numerous tumor vessel normalization approaches have been investigated for improving drug delivery into tumors. In this study, we investigated whether phosphoinositide 3-kinase (PI3K) inhibitors are able to improve vascular structure and function over the prolonged period necessary to achieve effective vessel normalization. The PI3K inhibitors, HS-173 and BEZ235 potently suppressed tumor growth and hypoxia, and increased tumor apoptosis in animal models. PI3K inhibitors also induced a regular, flat monolayer of endothelial cells (ECs) in vessels, improving stability of vessel structure, and normalized tumor vessels by increasing vascular maturity, pericyte coverage, basement membrane thickness, and tight-junctions. These effects resulted in a decrease in tumor vessel tortuosity and vessel thinning, and improved vessel function and blood flow. The tumor vessel stabilization effect of the PI3K inhibitor HS-173 also decreased the number of metastatic lung nodules in vivo metastasis model. Furthermore, HS-173 improved the delivery of doxorubicin into the tumor region, enhancing its anticancer effects. Mechanistic studies suggested that PI3K inhibitor HS-173-induced vessel normalization reflected changes in endothelial Notch signaling. Taken together, our findings indicate that vessel normalization by PI3K inhibitors restrained tumor growth and metastasis while improving chemotherapy by enhancing drug delivery into the tumor, suggesting that HS-173 may have a therapeutic value as an enhancer or an anticancer drug.

The Additivity of True or Apparent Phosphorus Digestibility Values in Some Feed Ingredients for Growing Pigs

Fang, R.J.,Li, T.J.,Yin, F.G.,Yin, Y.L.,Kong, X.F.,Wang, K.N.,Yuan, Z.,Wu, G.Y.,He, J.H.,Deng, Z.Y.,Fan, M.Z. Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.7

Two experiments were conducted to determine the additivity of apparent or true digestibility of phosphorus (P) in soybean meal (SBM), peas, faba beans, corn, oats, broken rice meal, rough rice meal, buckwheat, and sorghum for growing pigs. Chromic oxide (0.3%) was used as a digestion marker in both experiments. Each experiment lasted for 12 d, which consisted of a 7-d dietary adaptation period followed by a 5-d fecal collection period. Experiment 1 involved 6 diets: the SBM-based control diet; 4 diets with corn, oats, rough rice meal and broken rice meal substituted for SBM; and an additional diet with a representative mixture of the 5 ingredients. In Experiment 2, 6 diets were prepared similarly, except that the tested ingredients besides SBM were faba beans, peas, buckwheat, and sorghum. In each experiment, six barrows with an initial average individual BW of 20.5 kg were fed one of the six diets according to a $6{\times}6$ Latin square design. The apparent and true P digestibility values for the nine tested ingredients were determined by the substitution method. There were no differences (p>0.05) between the determined and the predicted true P digestibility values for the mixture of ingredients in Experiments 1 and 2. However, the determined and the predicted apparent P digestibility values for the mixture of ingredients differed (p = 0.059) in Experiment 1, but not in Experiment 2. These results indicate that true P digestibility values are additive in ingredients containing low levels of phytate phosphorus and anti-nutritional factors, whereas the apparent P digestibility values are not always additive in single feed ingredients for growing pigs.

Microstructure and Mechanical Properties of Nanostructured Bainite Weld with Regeneration

K. Fang,J. G. Yang,K. J. Song,X. S. Liu,Z. B. Dong,H. Y. Fang 대한금속·재료학회 2014 METALS AND MATERIALS International Vol.20 No.5

Because of the brittle martensite crystalline structure, nanostructured bainitic steel is very difficult to bewelded and easily form cracks in the welded joint, which limits the scope of their application. Regenerationtreatment can lead to nanostructured bainite formation in the welded joints, preventing further degradationof the welded joint. Detailed changes of microstructures and mechanical properties of the weld arecharacterized here. Coarse inter–dendrite structures appear in the weld due to welding segregation, and areconfirmed to be retained austenite by TEM. Moreover, an extraordinary combination of strength and ductilityof the weld is achieved. The ultimate tensile strengths are 1913MPa and 2115MPa when regenerationtemperatures are 250 °C and 230 °C. The corresponding elongations are 5.14% and 2.3%. In addition,the tension fracture behaviour and crack propagation mode of the weld are investigated.

Magnetic Microstructures of Phase-separated SmCo 2:17-type Sintered Magnets

Y. K. Fang,H. W. Chang,Z. H. Guo,T. Liu,W. Li,W. C. Chang,B. S. Han 한국자기학회 2007 한국자기학회 학술연구발표회 논문개요집 Vol.- No.-

소형 근거리 이동용 전기자동차(NEV)용 10㎾급 BLAC 구동인버터 개발

이용균(Y.K LEE),김은경(E.K KIM),김선일(S.I KIM),홍찬희(C.H Hong),방량(Liang Fang),목형수(H.S Mok) 전력전자학회 2011 전력전자학술대회 논문집 Vol.2011 No.7

This paper deals with 10㎾ BLAC drive inverter for neighborhood electric vehicle. First it introduces about hardware structure of inverter driven using 72volts battery. Then it explains motor control algorithm. Also performance of BLAC drive system is confirmed through experiments.

Friction Behavior of High Velocity Oxygen Fuel (HVOF) Thermal Spray Coating Layer of Nano WC-Co Powder

T.Y. Cho,J.H. Yoon,K.S. Kim,W. Fang,Y.K. Joo,K.O. Song,S.J. Youn,S.Y. Hwang,H.G. Chun 한국표면공학회 2007 한국표면공학회지 Vol.40 No.4

High Velocity Oxygen Fuel (HVOF) thermal spray coating of nano size WC-Co powder (nWC-Co) has been studied as one of the most promising candidate for the possible replacement of the traditional hard plating in some area which causes environmental and health problems. nWC-Co powder was coated on Inconel 718 substrates by HVOF technique. The optimal coating process obtained from the best surface properties such as hardness and porosity is the process of oxygen flow rate (FR) 38 FMR, hydrogen FR 57 FMR and feed rate 35 g/min at spray distance 6 inch for both surface temperature 25℃ and 500℃. In coating process a small portion of hard WC decomposes to less hard W₂C, Wand C at the temperature higher than its decomposition temperature 1,250°C resulting in hardness decrease and porosity increase. Friction coefficient increases with increasing coating surface temperature from 0.55-0.64 at 25℃ to 0.65-0.76 at 500℃ due to the increase of adhesion between coating and counter sliding surface. Hardness of nWC-Co is higher or comparable to those of other hard coatings, such as A1₂O₃, Cr, Cr₂O₃ and HVOF Tribaloy 400 (T400). This shows that nWC-Co is recommendable for durability improvement coating on machine components such as high speed spindle.

Betulinic acid inhibits high-fat diet-induced obesity and improves energy balance by activating AMPK

Kim, K.-D.,Jung, H.-Y.,Ryu, H.G.,Kim, B.,Jeon, J.,Yoo, H.Y.,Park, C.H.,Choi, B.-H.,Hyun, C.-K.,Kim, K.-T.,Fang, S.,Yang, S.H.,Kim, J.-B. Elsevier 2019 Nutrition, metabolism, and cardiovascular diseases Vol.29 No.4

<P><B>Abstract</B></P> <P><B>Background and aim</B></P> <P>Metabolic syndromes are prevalent worldwide and result in various complications including obesity, cardiovascular disease and type II diabetes. Betulinic acid (BA) is a naturally occurring triterpenoid that has anti-inflammatory properties. We hypothesized that treatment with BA may result in decreased body weight gain, adiposity and hepatic steatosis in a diet-induced mouse model of obesity.</P> <P><B>Methods and results</B></P> <P>Mice fed a high-fat diet and treated with BA showed less weight gain and tissue adiposity without any change in calorie intake. Gene expression profiling of mouse tissues and cell lines revealed that BA treatment increased expression of lipid oxidative genes and decreased that of lipogenesis-related genes. This modulation was mediated by increased AMP-activated protein kinase (AMPK) phosphorylation, which facilitates energy expenditure, lipid oxidation and thermogenic capacity and exerts protective effects against obesity and nonalcoholic fatty liver disease. Overall, BA markedly inhibited the development of obesity and nonalcoholic fatty liver disease in mice fed a high-fat diet, and AMPK activation in various tissues and enhanced thermogenesis are two possible mechanisms underlying the antiobesity and antisteatogenic effects of BA.</P> <P><B>Conclusions</B></P> <P>The current findings suggest that treatment with BA is a potential dietary strategy for preventing obesity and nonalcoholic fatty liver disease.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Betulinic acid (BA) decreased body weight gain, adiposity and hepatic steatosis in a diet-induced obese mouse model. </LI> <LI> BA treatment increased expression of lipid oxidative genes and decreased mRNA expression related to lipogenesis. </LI> <LI> BA treatment enhanced activation of AMPK, which facilitates energy expenditure, lipid oxidation and thermogenesis. </LI> <LI> BA intake may be a potential dietary strategy for preventing obesity and nonalcoholic fatty liver disease. </LI> </UL> </P>

A Comparable Study on Oxidation Behaviors of Inconel 718 and Incoloyl 901 in USC System

W. Fang,K.O. Song,T.Y. Cho,J.H. Yoon,S.H. Zhang,Y.K. Joo 한국표면공학회 2008 한국표면공학회 학술발표회 초록집 Vol.2008 No.-

Eugenol Inhibits Calcium Currents in Dental Afferent Neurons

Lee, M. H.,Yeon, K.-Y.,Park, C.-K.,Li, H.-Y.,Fang, Z.,Kim, M. S.,Choi, S.-Y.,Lee, S. J.,Lee, S.,Park, K.,Lee, J.-H.,Kim, J. S.,Oh, S. B. SAGE Publications 2005 Journal of dental research Vol.84 No.9

<P>Eugenol is a topical analgesic agent widely used in the dental clinic. To elucidate the molecular mechanism underlying its analgesic action, we investigated the effect of eugenol on high-voltage-activated calcium channel (HVACC) currents in dental primary afferent neurons, and with a heterologous expression system. Dental primary afferent neurons were identified by retrograde labeling with a fluorescent dye, DiI. Eugenol inhibited HVACC currents in both capsaicin-sensitive and capsaicin-insensitive dental primary afferent neurons. The HVACC inhibition by eugenol was not blocked by capsazepine, a competitive transient receptor potential vanilloid 1 (TRPV1) antagonist. Eugenol inhibited N-type calcium currents in the cell line C2D7, stably expressing the human N-type calcium channels, where TRPV1 was not endogenously expressed. Our results suggest that the HVACC inhibition by eugenol in dental primary afferent neurons, which is not mediated by TRPV1 activation, might contribute to eugenol's analgesic effect. Abbreviations: high-voltage-activated calcium channel, HVACC; transient receptor potential vanilloid 1, TRPV1; trigeminal ganglion, TG; dorsal root ganglion, DRG; capsazepine, CZP.</P>

Differential regeneration of myocardial infarction depending on the progression of disease and the composition of biomimetic hydrogel

Yoon, S.J.,Hong, S.,Fang, Y.H.,Song, M.,Son, K.H.,Son, H.S.,Kim, S.K.,Sun, K.,Park, Y. Society for Bioscience and Bioengineering, Japan ; 2014 Journal of bioscience and bioengineering Vol.118 No.4

Hydrogel has been used for regenerating myocardial infraction (MI) as a delivery vehicle for cells and growth factors. This study showed that injectable hyaluronic acid (HA)-based hydrogels alone would effectively regenerate the damaged infarcted heart tissue. We found that there are two major factors of regeneration in MI. One is molecular weight of HA and another is the progression of MI; sub-acute and chronic. Rat MI model was prepared by ligating the left anterior descending coronary artery (LAD). Four weeks after injection of hydrogel, functional analysis of the heart and histological analysis was assessed. When different molecular weight HA-based hydrogels with 50 kDa, 130 kDa, and 170 kDa were applied to the infarcted area in the sub-acute model, 50 kDa HA-based hydrogel showed the most significant regeneration of myocardium as well as functional recovery among samples. For the disease progression, 50 kDa HA-based hydrogels were injected to sub-acute and chronic MI models. The regeneration activity was significantly decreased in the chronic models reflecting that injection timing of the therapeutic agents is also major determinants in the regeneration process. These results suggest that injection time and composition of hydrogel are two major points treating MI.