Baicalein from Scutellaria baicalensis, a Novel BACE1 and AChE Inhibitor

Jin Han,Mira Jun 한국식품영양과학회 2019 한국식품영양과학회 학술대회발표집 Vol.2019 No.10

Activation of ATP-sensitive Potassium Channels by the Predominant Metabolite of Isoflurane in Rabbit Ventricular Myocytes

Jin Han,Nari Kim,Euiyong Kim,Sungju Kim,Kanghee Cho 대한생리학회-대한약리학회 2001 The Korean Journal of Physiology & Pharmacology Vol.5 No.2

<P> Background: Recent in vivo experimental evidence suggests that isoflurane-induced cardioprotection may involve K<SUB>ATP</SUB> channel activation. However, it was demonstrated that isoflurane inhibited K<SUB>ATP</SUB> channel activities in the inside-out patch mode. To explain this discrepancy, the present investigation tested the hypothesis that a metabolite of isoflurane, trifluoroacetic acid (TFA), contributes to isoflurnae-induced cardioprotection via K<SUB>ATP</SUB> channel activation during myocardial ischemia and reperfusion. Methods: Single ventricular myocytes were isolated from rabbit hearts by an enzymatic dissociation procedure. Patch-clamp techniques were used to record single-channel currents. K<SUB>ATP</SUB> channel activities were assessed before and after the application of TFA with the inside-out patch mode. Results: TFA enhanced channel activity in a concentration-dependent fashion. The concentration of TFA for half-maximal activation and the Hill coefficient were 0.03 mM and 1.2, respectively. TFA did not affect the single channel conductance of K<SUB>ATP </SUB>channels. Analysis of open and closed time distributions showed that TFA increased burst duration and decreased the interburst interval without changes in open and closed time distributions shorter than 5 ms. TFA diminished ATP sensitivity of K<SUB>ATP</SUB> channels in a concentration-response relationship for ATP. Conclusions: TFA, a metabolite of isoflurane, enhanced K<SUB>ATP </SUB>channel activity in a concentration-dependent fashion. These results imply that TFA could mediate isoflurane-induced cardioprotection via K<SUB>ATP</SUB> channel activation during myocardial ischemia and reperfusion.

BACE1 Inhibitory Activity of Cardamonin from Boesenbergia rotunda Using Biological Assays and in Silico Molecular Docking Simulation

Jin Han,Kumju Youn,Mira Jun 한국식품영양과학회 2018 한국식품영양과학회 학술대회발표집 Vol.2018 No.10

Modulation of Ca<SUP>2⁢</SUP>-Activated Potassium Channels by cGMP- Dependent Signal Transduction Mechanism in Cerebral Arterial Smooth Muscle Cells of the Rabbit

Jin Han,Nari Kim,Kwangbok Lee,Euiyong Kim 대한생리학회-대한약리학회 2000 The Korean Journal of Physiology & Pharmacology Vol.4 No.6

<P> The present investigation tested the hypothesis that the activation of protein kinase G (PKG) leads to a phosphorylation of Ca<SUP>2⁢</SUP>-activated potassium channel (K<SUB>Ca</SUB> channel) and is involved in the activation of K<SUB>Ca</SUB> channel activity in cerebral arterial smooth muscle cells of the rabbit. Single-channel currents were recorded in cell-attached and inside-out patch configurations of patch-clamp techniques. Both molsidomine derivative 3-morpholinosydnonimine-<I>N</I>-ethylcarbamide (SIN-1, 50μM) and 8-(4-Chlorophenylthio)-guanosine-3 ,5 -cyclic monophosphate (8-pCPT-cGMP, 100μM), a membrane-permeable analogue of cGMP, increased the K<SUB>Ca</SUB> channel activity in the cell-attached patch configuration, and the effect was removed upon washout of the drugs. In inside-out patches, single-channel current amplitude was not changed by SIN-1 and 8-pCPT-cGMP. Application of ATP (100μM), cGMP (100μM), ATP⁢cGMP (100μM each), PKG (5 U/μl), ATP (100μM)⁢PKG (5 U/μl), or cGMP (100 μM)⁢PKG (5 U/μl) did not increase the channel activity. ATP (100μM)⁢cGMP (100μM)⁢PKG (5 U/μl) added directly to the intracellular phase of inside-out patches increased the channel activity with no changes in the conductance. The heat-inactivated PKG had no effect on the channel activity, and the effect of PKG was inhibited by 8-(4-Chlorophenylthio)-guanosine-3 ,5 -cyclic monophosphate, Rp-isomer (Rp-pCPT-cGMP, 100μM), a potent inhibitor of PKG or protein phosphatase 2A (PP2A, 1 U/ml). In the presence of okadaic acid (OA, 5 nM), PP2A had no effect on the channel activity. The K<SUB>Ca</SUB> channel activity spontaneously decayed to the control level upon washout of ATP, cGMP and PKG, and this was prevented by OA (5 nM) in the medium. These results suggest that the PKG-mediated phosphorylations of K<SUB>Ca</SUB> channels, or some associated proteins in the membrane patch increase the activity of the K<SUB>Ca</SUB> channel, and the activation may be associated with the vasodilating action.

Increase of L-type Calcium Current by cGMP-dependent Protein Kinase Regulates in Rabbit Ventricular Myocytes

Jin Han,Nari Kim,Euiyong Kim,Wonkyung Ho,Yung E Earm,Hankyoun Kim 대한생리학회-대한약리학회 1998 The Korean Journal of Physiology & Pharmacology Vol.2 No.6

<P> <I> </I>Background: We have previously reported that not only cGMP but also 8-Br-cGMP or 8-pCPT-cGMP, specific and potent stimulators of cGMP-dependent protein kinase (cGMP-PK), increased basal L-type calcium current (I<SUB>Ca</SUB>) in rabbit ventricular myocytes. Our findings in rabbit ventricular myocytes were entirely different from the earlier findings in different species, suggesting that the activation of cGMP-PK is involved in the facilitation of I<SUB>Ca</SUB> by cGMP. However, there is no direct evidence that cGMP-PK can stimulate I<SUB>Ca</SUB> in rabbit ventricular myocytes. In this report, we focused on the direct effect of cGMP-PK on I<SUB>Ca</SUB> in rabbit ventricular myocytes. Methods and Results: We isolated single ventricular myocytes of rabbit hearts by using enzymatic dissociation. Regulation of I<SUB>Ca</SUB> by cGMP-PK was investigated in rabbit ventricular myocytes using whole-cell voltage clamp method. I<SUB>Ca</SUB> was elicited by a depolarizing pulse to ⁢10 mV from a holding potential of ⁣40 mV. Extracellular 8-(4-Chlorophenylthio)-guanosine-3 ,5 -cyclic monophosphate (8-pCPT-cGMP), potent stimulator of cGMP-dependent protein kinase (cGMP-PK), increased basal I<SUB>Ca</SUB>. cGMP-PK also increased basal I<SUB>Ca</SUB>. The stimulation of basal I<SUB>Ca</SUB> by cGMP-PK required both 8-Br-cGMP in low concentration and intracellular ATP to be present. The stimulation of basal I<SUB>Ca</SUB> by cGMP-PK was blocked by heat inactivation of the cGMP-PK and by bath application of 8- (4-chlorophenylthio)-guanosine-3 ,5 -cyclic monophosphate, Rp-isomer (Rp-pCPT-cGMP), a phosphodiesterase-resistant cGMP-PK inhibitor. When I<SUB>Ca</SUB> was increased by internal application of cGMP-PK, IBMX resulted in an additional stimulation of I<SUB>Ca</SUB>. In the presence of cGMP-PK, already increased I<SUB>Ca</SUB> was potentiated by bath application of isoprenaline or forskolin or intracellular application of cAMP. Conclusions: We present evidence that cGMP-PK stimulated basal I<SUB>Ca</SUB> by a direct phosphorylation of L-type calcium channel or associated regulatory protein in rabbit ventricular myocytes.

Natural Products-Based Strategy for Heart Function Enhancement

Jin Han 한국식품영양과학회 2017 한국식품영양과학회 학술대회발표집 Vol.2016 No.10

Animal Models in Osteoarthritis Research: Pain Behavioral Methods and Clinical Significance

Jin Han,Donghwi Park,Seungwoo Han 대한통증연구학회 2023 International Journal of Pain Vol.14 No.2

Osteoarthritis (OA) is a leading cause of chronic pain and disability worldwide. Animal models are required to improve our understanding of the underlying pain mechanisms associated with OA and to evaluate potential therapeutics. In this review, discuss the variety of animal models used in OA research, with a focus on their relevance to human OA and the pain behavioral methods. We discuss commonly used pain behavioral assays, the technical nuances, advantages, and limitations. Moreover, we discuss how these models and methods translate into the clinic by emphasizing any interventions or findings that have guided clinical trials or drug development. Although animal models provide invaluable insight, they still have challenges and controversies, particularly with respect to their true representation of human OA pain as well as ethical considerations. We highlight the need for refining and standardizing pain assessment techniques in animal models and address emerging technologies that promise greater translational significance. This review provides insight into the role of animal models in advancing our understanding of OA pain and paves the way for future research in this field.

The Protective Effect of Melatonin Administration against Adriamycin-induced Cardiotoxicity in Rats

Jin Han,Chunghee Kim,Nari Kim,Juhee Park,Youngchurl Yang,Euiyong Kim 대한생리학회-대한약리학회 2001 The Korean Journal of Physiology & Pharmacology Vol.5 No.4

<P> Adriamycin is a commonly used chemotherapeutic agent for cancer, including acute leukemia, lymphoma, and a number of solid human tumors. However, recent studies have recognized severe cardiotoxicity after an acute dose, which are likely the result of generation of free radicals and lipid peroxidation. Therefore, the clinical uses of adriamycin have been limited. Melatonin, the pineal gland hormone known for its ability to modulate circardian rhythm, has recently been studied in its several functions, including cancer growth inhibition, stimulating the immune system, and acting as an antioxidant and radical scavenging effects. In the present study, we evaluated the effect of melatonin administration on adriamycin-induced cardiotoxicity in rat. Heart slices were prepared using a Stadie-Riggs microtome for the measurement of malondialdehyde (MDA) content used as an index of lipid peroxidation and lactate dehydrogenase (LDH) release as an indicator of lethal cell injury. Serious adriamycin-induced lethality was observed in rat by a single intraperitoneal injection in a dose-dependent manner. A single injection of adriamycin (25 mg/kg, i.p.) induced a lethality rate of 86%, with melatonin (10 mg/kg s.c. for 6 days) treatment reducing the adriamycin-induced lethality rate to 20%. The severe body weight loss caused by adriamycin was also significantly attenuated by melatonin treatment. Treatment of melatonin marked reduced adriamycin-induced the levels of MDA formation and LDH release. A cell damage indicated by the loss of myofibrils, swelling of the mitochondria as well as cytoplasmic vacuolization was seen in adriamycin-treated group. Melatonin attenuated the adriamycin-induced structural alterations. These data provide evidence that melatonin prevents adriamycin-induced cardiotoxicity and might serve as a combination with adriamycin to limit free radical-mediated cardiotoxicity.

Flexural Responses of Prestressed Hybrid Wide Flange Composite Girders

Sun?Jin Han,Deuck Hang Lee,Jae?Yuel Oh,Seung?Ho Choi,Kang Su Kim 한국콘크리트학회 2018 International Journal of Concrete Structures and M Vol.12 No.5

In this study, prestressed hybrid wide flange (PHWF) composite girders were proposed, and full-scale flexural tests were conducted to evaluate their structural performances. This new proposed girder system was developed and designed to effectively resist external loads considering the actual construction sequences. Two specimens with and without shear connectors were fabricated and tested to examine the effect of the shear connectors for achieving the fully-composite behaviors between a cast-in-place (CIP) concrete and the prefabricated prestressed steel–concrete composite girder. The test results showed that sufficient flexural strengths and deformation capacities can be obtained in both types of PHWF composite girders with and without shear connectors. To reflect the actual construction stages of the proposed PHWF composite girder, nonlinear flexural analyses were proposed considering the prestress effect and segmental effect before and after composite with the CIP concrete, respectively. The observed and analysis results of strain behaviors of the PHWF girder specimens were also compared and discussed in detail.

Evolutionary dynamics of transposable elements during silkworm domestication

Min‑Jin Han,Hong‑En Xu,Xiao‑Min Xiong,Hua‑Hao Zhang 한국유전학회 2018 Genes & Genomics Vol.40 No.10

Although there are some documented examples on population dynamics of transposable elements (TEs) in model organisms, the evolutionary dynamics of TEs in domesticated species has not been systematically investigated. The objective of this study is to understand population dynamics of TEs during silkworm domestication. In this work, using transposondisplay we examined the polymorphism of seven TE families [they represent about 59% of silkworm (Bombyx mori) total TE content] in four domesticated silkworm populations and one wild silkworm population. Maximum likelihood (ML) was used to estimate selection pressure. Population differentiation and structure were performed by using AMOVA analysis and program DISTRUCT, respectively. The results of transposon-display showed that significant differentiation occurred between the domesticated silkworm and wild silkworm. These TEs have experienced expansions and fixation in the domesticated silkworm but not in wild silkworm. Furthermore, the ML results indicated that purifying selection of TEs in the domesticated silkworm were significantly weaker than that in the wild silkworm. Interestingly, an adaptation insertion induced by BmMITE-2 was found, and this insertion can reduce the polymorphism of the flanking regions of its neighboring COQ7 gene. Our results suggested that TEs expanded and were fixed in the domesticated silkworm might result from demographic effects and artificial selection during domestication. We concluded that the data presented in this study have general implication in animal and crop improvements as well as in domestication of new species.