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Hwangryunhaedok-tang induces the depolarization of pacemaker potentials through 5-HT3 and 5-HT4 receptors in cultured murine small intestine interstitial cells of Cajal

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World Journal of Gastroenterology 2017年第29期23卷 5313-5323页

作者： Hyun Jung kim Guem San Lee Hyungwoo kim byung joo kim Division of Longevity and Biofunctional Medicine Healthy Aging Korean Medical Research Center School of Korean Medicine Pusan National University Wonkwang University College of Korean Medicine Division of Pharmacology School of Korean Medicine Pusan National University Division of Longevity and Biofunctional Medicine School of Korean Medicine Pusan National University

AIM To investigate the effects of a water extract of Hwangryunhaedok-tang(HHTE) on the pacemaker potentials of mouse interstitial cells of Cajal(ICCs).METHODS We dissociated ICCs from small intestines and cultured. ICCs were immunologically identified using an antic-kit antibody. We used the whole-cell patch-clamp configuration to record the pacemaker potentials generated by cultured ICCs under the current clamp mode(I = 0). All experiments were performed at 30 ℃-32 ℃RESULTS HHTE dose-dependently depolarized ICC pacemaker potentials. Pretreatment with a 5-HT_3 receptor anta-gonist(Y25130) or a 5-HT_4 receptor antagonist(RS39604) blocked HHTE-induced pacemaker potential depolarizations, whereas pretreatment with a 5-HT7 receptor antagonist(SB269970) did not. Intracellular GDPβS inhibited HHTE-induced pacemaker potential depolarization and pretreatment with a Ca^(2+)-free solution or thapsigargin abolished the pacemaker potentials. In the presence of a Ca^(2+)-free solution or thapsigargin, HHTE did not depolarize ICC pacemaker potentials. In addition, HHTE-induced pacemaker potential depolarization was unaffected by a PKC inhibitor(calphostin C) or a Rho kinase inhibitor(Y27632). Of the four ingredients of HHT, Coptidis Rhizoma and Gardeniae Fructus more effectively inhibited pacemaker potential *** These results suggest that HHTE dose-dependently depolarizes ICC pacemaker potentials through 5-HT_3 and 5-HT_4 receptors via external and internal Ca^(2+) regulation and via G protein-, PKC-and Rho kinase-independent pathways.

关键词： Hwangryunhaedok-tang Interstitial cells of Cajal Pacemaker potentials Gastrointestinal tract Motility

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Distinguished roles of static aging and strain aging in the microstructure and creep resistance of Mg-4Y-3.5Nd alloy

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Journal of Materials Science & Technology 2024年第14期181卷 20-40页

作者： Zhirou Zhang Qinghuan Huo Yuxiu Zhang byung-joo kim Hiromi Nagaumi Xuyue Yang School of Materials Science and Engineering Central South UniversityChangsha 410083China Advanced Metals Division Korea Institute of Materials ScienceChangwon 51508Republic of Korea School of Iron and Steel Soochow UniversitySuzhou 215100China

This work concerns the distinguished roles of static aging and strain aging in the creep resistance of a hot-rolled Mg-4Y-3.5Nd *** solution-treated sample is named AS while the peak-aged sample ob-tained from static aging at 220℃ is named *** strain aging(creep loading)was performed for both AS and AA samples at 220,250 and 280℃,*** results showed that the creep resistance of both samples was closely related to the width of precipitate-free zones(PFZs).Under low stress,the dislocation cross-slip was effectively delayed by the precipitates and the existing PFZs widened slowly in the AA sample,leading to its stronger creep resistance compared to the AS ***,under high stress,pyramidalslip was more frequently activated,which could not be delayed by the coars-ened ***,the widening rate of PFZs became fast and the creep resistance became weaker in the AA *** the above-mentioned results,this work provides a novel guide for using Mg alloys with rare-earth *** the temperature range of 220-280℃,static aging is positive for creep resistance under low stress,while directly performing strain aging without static aging is recom-mended for creep resistance under high stress.

关键词： Magnesium Microstructure Creep Precipitation Dislocation slip

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Effects of Lizhong Tang on gastrointestinal motility in mice

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World Journal of Gastroenterology 2016年第34期22卷 7778-7786页

作者： Min Cheol Lee Wooram Ha Jinhyeong Park Junghoon kim Yunjin Jung byung joo kim Division of Longevity and Biofunctional Medicine Healthy Aging Korean Medical Research CenterSchool of Korean MedicinePusan National UniversityYangsan 50612South Kerea Division of Pharmacology School of Korean MedicinePusan National University Yangsan 50612South Kerea College of Pharmacy Pusan National UniversityBusan 46241 South Korea

AIM To investigate the effects of Lizhong Tang,a traditional Chinese medicine formula,on gastrointestinal motility in *** The in vivo effects of Lizhong Tang on GI motility were investigated by measuring the intestinal transit rates(ITRs) and gastric emptying(GE) values in normal mice and in mice with experimentally induced GI motility dysfunction(GMD).RESULTS In normal ICR mice,the ITR and GE values were significantly and dose-dependently increased by Lizhong Tang(ITR values: 54.4% ± 1.9% vs 65.2% ± 1.8%,P < 0.01 with 0.1 g/kg Lizhong Tang and 54.4% ± 1.9% vs 83.8% ± 1.9%,P < 0.01 with 1 g/kg Lizhong Tang; GE values: 60.7% ± 1.9% vs 66.8% ± 2.1%,P < 0.05 with 0.1 g/kg Lizhong Tang and 60.7% ± 1.9% vs 72.5% ± 1.7%,P < 0.01 with 1 g/kg Lizhong Tang). The ITRs of the GMD mice were significantly reduced compared with those of the normal mice,which were significantly and dose-dependently reversed by Lizhong Tang. Additionally,in loperamide- and cisplatin-induced models of GE delay,Lizhong Tang administration reversed the GE *** These results suggest that Lizhong Tang may be a novel candidate for development as a prokinetic treatment for the GI tract.

关键词： Lizhong Tang Gastrointestinal disorders Motility Intestinal transit rate Gastric emptying

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Effects of Hwangryunhaedok-tang on gastrointestinal motility function in mice

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World Journal of Gastroenterology 2017年第15期23卷 2705-2715页

作者： Hyoyeon kim Iksung kim Min Cheol Lee Hyun Jung kim Guem San Lee Hyungwoo kim byung joo kim Division of Longevity and Biofunctional Medicine Healthy Aging Korean Medical Research CenterSchool of Korean MedicinePusan National University Wonkwang University College of Korean Medicine Division of Pharmacology School of Korean MedicinePusan National University

AIM To investigate the effects of Hwangryunhaedok-tang(HHT) on gastrointestinal(GI) motility in *** The effects of a boiling water extract of HHT(HHTE) on GI motility were investigated by calculating percent intestinal transit rates(ITR%) and gastric emptying(GE) values using Evans Blue and phenol red, respectively, in normal mice and in mice with experimentally induced GI motility dysfunction(GMD). In addition, the effects of the four components of HHT, that is, Gardeniae Fructus(GF), Scutellariae Radix(SR), Coptidis Rhizoma(CR), and Phellodendri Cortex(PC), on GI motility were also *** In normal ICR mice, ITR% and GE values were significantly and dose-dependently increased by the intragastric administration of HHTE(0.1-1 g/kg). The ITR% values of GMD mice were significantly lower than those of normal mice, and these reductions were significantly and dose-dependently inhibited by HHTE(0.1-1 g/kg). Additionally, GF, CR, and PC dosedependently increased ITR% and GE values in normal and GMD *** These results suggest that HHT is a novel candidate for the development of a gastroprokinetic agent for the GI tract.

关键词： Hwangryunhaedok-tang Gastrointestinal motility Intestinal transit rate Gastric emptying Gastroprokinetic

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Effects of Lizhong Tang on cultured mouse small intestine interstitial cells of Cajal

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World Journal of Gastroenterology 2013年第14期19卷 2249-2255页

作者： Min Woo Hwang Jung Nam kim Ho Jun Song Bora Lim Young Kyu Kwon byung joo kim Department of Sasang Constitutional Medicine College of Korean MedicineKyung-hee University School of Korean Medicine Pusan National University

AIM:To investigate the effects of Lizhong Tang,an herbal product used in traditional Chinese medicine,on mouse small intestine interstitial cells of Cajal(ICCs).METHODS:Enzymatic digestions were used to dissociate ICCs from mouse small intestine *** ICCs were morphologically distinct from other cell types in culture and were identified using phase contrast microscopy after verification with anti c-kit antibody.A whole-cell patch-clamp configuration was used to record potentials(current clamp) from cultured *** of the experiments were performed at 30-32 ℃.RESULTS:ICCs generated pacemaker potentials,and Lizhong Tang produced membrane depolarization in current-clamp *** application of flufenamic acid(a nonselective cation channel blocker) abolished the generation of pacemaker potentials by Lizhong *** with thapsigargin(a Ca 2+-ATPase inhibi-tor in the endoplasmic reticulum) also abolished the generation of pacemaker potentials by Lizhong ***,pacemaker potentials were completely abolished in the presence of an external Ca 2+-free solution,and under this condition,Lizhong Tang induced membrane ***,When GDPβ-S(1 mmol/L) was in the pipette solution,Lizhong Tang still induced membrane *** addition,membrane depolarizations were not inhibited by chelerythrine or calphostin C,which are protein kinase C inhibitors,but were inhibited by U-73122,an active phospholipase C ***:These results suggest that Lizhong Tang might affect gastrointestinal motility by modulating pacemaker activity in interstitial cells of Cajal.

关键词： Interstitial cells of Cajal Lizhong Tang Motility Gastrointestinal tract Whole-cell patch clamp configuration

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Involvement of mitochondrial Na+-Ca2+ exchange in intestinal pacemaking activity

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World Journal of Gastroenterology 2006年第5期12卷 796-799页

作者： byung joo kim Jae Yeoul Jun Insuk So Ki Whan kim Department of Physiology and Biophysics College of MedicineSeoul National UniversityRepublic of Korea Department of Physiology College of MedicineChosun UniversityRepublic of Korea

AIM： Interstitial cells of Cajal （ICCs） are the pacemaker cells that generate slow waves in the gastrointestinal （GI） tract. We have aimed to investigate the involvement of mitochondrial Na^＋-Ca^2＋ exchange in intestinal pacemaking activity in cultured interstitial cells of Cajal. METHODS： Enzymatic digestions were used to dissociate ICCs from the small intestine of a mouse. The whole-cell patch-clamp configuration was used to record membrane currents （voltage clamp） and potentials （current clamp） from cultured ICCs. RESULTS： Clonazepam and CGP37157 inhibited the pacemaking activity of ICCs in a dose-dependent manner. Clonazepam from 20 to 60 μmol/L and CGP37157 from 10 to 30 μmol/L effectively inhibited Ca^2＋ efflux from mitochondria in pacemaking activity of ICCs. The ICsos of clonazepam and CGP37157 were 37.1 and 18.2 μmol/ L, respectively. The addition of 20 μmol/L NiCl2 to the internal solution caused a ＂wax and wane＂ phenomenon of pacemaking activity of ICCs. CONCLUSION： These results suggest that mitochondria Na^＋-Ca^2＋ exchange has an important role in intestina pacemaking activity.

关键词： Mitochondrial Na^+-Ca^2+ exchange Interstitial cells of Cajal

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Effects of traditional Chinese herbal medicine San-HuangXie-Xin-Tang on gastrointestinal motility in mice

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World Journal of Gastroenterology 2015年第4期21卷 1117-1124页

作者： Min Woo Hwang Tae Seok Ahn Noo Ri Hong Han-Sol Jeong Myeong Ho Jung Ki-Tae Ha byung joo kim Department of Sasang Constitutional Medicine College of Korean MedicineKyung Hee UniversitySeoul 130-701South Korea School of Korean Medicine Pusan National UniversityYangsan 626-870South Korea

AIM: To investigate the effects of San-Huang-Xie-XinTang(SHXXT), a herbal product used in traditional Chinese medicine, on gastrointestinal(GI) motility in ***: The in vivo effects of SHXXT on GI motility were investigated by measuring the intestinal transit rates(ITRs) using Evans blue in normal mice and in mice with experimentally induced GI motility dysfunction(GMD).RESULTS: In normal ICR mice, ITRs were significantly and dose-dependently increased by SHXXT(0.1-1 g/kg). GMD was induced by injecting acetic acid or streptozotocin intraperitoneally. The ITRs of GMD mice were significantly reduced compared to normal mice, and these reductions were significantly and dose-dependently inhibited by SHXXT(0.1-1 g/kg).CONCLUSION: These results suggest that SHXXT is a novel candidate for the development of a prokinetic agent that may prevent or alleviate GMD.

关键词： Gastrointestinal disorders San-Huang-XieXin-Tang M

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Identification of TRPM7 channels in human intestinal interstitial cells of Cajal

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World Journal of Gastroenterology 2009年第46期15卷 5799-5804页

作者： byung joo kim Kyu joo Park Hyung Woo kim Seok Choi Jae Yeoul Jun In Youb Chang Ju-Hong Jeon Insuk So Seon Jeong kim School of Korean Medicine Pusan National University Department of Surgery College of MedicineSeoul National University Department of Physiology College of MedicineChosun University Department of Anatomy College of MedicineChosun University Center for Bio-Artif icial Muscle and Department of Physiology College of MedicineSeoul National University Center for Bio-Artifi cial Muscle and Depart-ment of Biomedical Engineering Hanyang University

AIM： To investigate the characteristics of slow electrical waves and the presence of transient receptor potential melastatin-type 7 （TRPM7） in the human gastrointestinal （GI） tract. METHODS： Conventional microelectrode techniques were used to record intracellular electrical responses from human GI smooth muscle tissue. Immunohistochemistry was used to identify TRPM7 channels in interstitial cells of Cajat （ICCs）. RESULTS： The human GI tract generated slow electrical waves and had ICCs which functioned as pacemak er cells. Flufenamic acid, a nonselective cation channel blocker, and 2-APB （2-aminoethoxydiphenyl borate） and La3＋, TRPM7 channel blockers, inhibited the slowwaves. Also, TRPM7 channels were expressed in ICCs in human tissue. CONCLUSION： These results suggest that the human GI tract generates slow waves and that TRPM7 channels expressed in the ICCs may be involved in the gen- eration of the slow waves.

关键词： Electrophysiology Interstitial cells of Cajal TRPM cation channels Transient receptor potential melastatin-type 7 protein Human Gastrointestinal tract

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Bio‑imitative Synergistic Color‑Changing and Shape‑Morphing Elastic Fibers with a Liquid Metal Core

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Advanced Fiber Materials 2024年第3期6卷 900-910页

作者： Seonwoo Mun Sangmin Lee Kwak Jin Bae Yejin Bae Hye‑Min Lee byung‑joo kim Jaesang Yu Sungjune Park Department of Nano Convergence Engineering Department of Polymer‑Nano Science and TechnologyJeonbuk National UniversityJeonju 54896Republic of Korea Institute of Advanced Composite Materials Korea Institute of Science and Technology(KIST)Chudong‑Ro 92Bongdong‑EupWanju‑Gun 55324JeollabukdoKorea R&BD Group 1 Industrialization DivisionKorea Carbon Industry Promotion AgencyJeonju 54853Republic of Korea Department of Advanced Materials and Chemical Engineering Jeonju UniversityJeonju 55069Republic of Korea School of Chemical Engineering Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea

The systematic integration of color-changing and shape-morphing abilities into entirely soft devices is a compelling strategy for creating adaptive camouflage,electronic skin,and wearable healthcare *** this study,we developed soft actuators capable of color change and programmable shape morphing using elastic fibers with a liquid metal *** the hollow elastic fiber with the thermochromic pigment was fabricated,liquid metal(gallium)was injected into the core of the *** has a relatively low melting point(29.8℃);thus,fluidity and metallic conductivity are preserved while *** fiber can change color by Joule heating upon applying a current through the liquid metal core and can also be actuated by the Lorentz force caused by the interaction between the external magnetic field and the magnetic field generated around the liquid metal core when a current is *** on this underlying principle,we demonstrated unique geometrical actuations,including flower-like blooming,winging butterflies,and the locomotion of coil-shaped *** color-changing and shape-morphing elastic fiber actuators presented in this study can be utilized in artificial skin,soft robotics,and actuators.

关键词： Electromagnetic actuator Liquid metal Soft electronic Thermochromic elastic fiber Bio-inspired actuator

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Comprehensive molecular characterization to predict immunotherapy response in advanced biliary tract cancer:a phase II trial of pembrolizumab

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Oncology Research 2025年第1期33卷 57-65页

作者： RYUL kim joo KYUNG PARK MINSUK KWON MINAE AN JUNG YONG HONG jooN OH PARK SUNG HEE LIM SEUNG TAE kim Division of Hematology-Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Division of Gastroenterology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Department of Hematology-Oncology Ajou University School of MedicineSuwon-siGyeonggi-doKorea Samsung Advanced Institute of Health Science and Technology Sungkyunkwan University School of MedicineSeoulKorea

Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid ***,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still *** and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line ***:All patients had microsatellite stable(MSS)type *** of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab *** analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor ***,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated ***:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.

关键词： Pembrolizumab Whole-exome sequencing Whole-transcriptome sequencing Biliary tract cancer

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