• Biomolecules & Therapeutics
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• v.3 no.4
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• pp.316-321
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• 1995

All the pharmacological studies of LB17522 described here were carried out with high doses (fifteen to sixty times of the therapeutic dose) to determine an indication of potential side effects in clinical use in terms of the acute clinical signs, cardiovascular and central nervous system. LB10522 does not produce any observable clinical signs except for the symptoms such as moist eye, skin rash, slight salivation, vomitting, and slightly reduced activity. The effects of LB10522 on the hemodynamics and cardiac function of anesthetized beagle dogs are as follows; heart rates and mean arterial blood pressure had a tendency to increase mildly, which is a normal finding in anesthetized dogs. All the animals except for one showed relatively stable respiratory rates throughout the observation period. Each animal treated with LB10522 showed slight increase in the left cardiac work and left ventricular stroke work which are mainly related to corresponding increases in cardiac output. Femoral blood flow were shown to be increased in some animals treated with LB10522. The epileptogenic activities of various cephalosporins were assessed by a direct intracerebral injection of appropriate concentration of test articles. The CD$_{50}$ values (nmol) obtained from the analysis of the dose-response data are as follows; 78.2, 175.3, 156.3, and 53.5 for cefazolin, cephaloridine, ceftazidime, and LB 10522, respectively. LB10522 seems to be equipotent with cefazolin or to be three times more potent than cephaloridine and ceftazidime in causing adverse CNS stimulation. Taken into consideration all the information obtained, LB10522 is not supposed to induce much changes in the functions examined in these studies in man at therapeutic doses.s.

• Transactions of the Korean Society of Mechanical Engineers B
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• v.38 no.12
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• pp.971-974
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• 2014

A ventricular assist device (VAD) is used for bridge to heart transplantation and heart diseases. Knowing the status of a pneumatic pulsatile VAD when implanting it into the body is important: when the velocity of blood flow through the VAD is slow, a thrombus may occur, and thrombosis can be fatal to a patient. In order to determine the state of a VAD, various sensors need to be implanted. Because this introduces the risk of infection and difficulties with sensor management, we developed a method for estimating the state of a VAD indirectly via the pressure in an air tube that can be measured in vitro. We compared the measured values to in vitro experimental results. The estimated and measured values showed some errors, but the accuracy can be improved by refining the estimation process to minimize the risk of infection.

• Journal of Chest Surgery
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• v.54 no.5
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• pp.383-388
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• 2021

Background: Achieving external access to and manual occlusion of the left atrial appendage (LAA) during minimally invasive mitral valve surgery (MIMVS) through a small right thoracotomy is difficult. Occlusion of the LAA using an epicardial closure device seems quite useful compared to other surgical techniques. Methods: Fourteen patients with atrial fibrillation underwent MIMVS with concomitant surgical occlusion of the LAA using double-layered endocardial closure stitches (n=6, endocardial suture group) or the AtriClip Pro closure device (n=8, AtriClip group) at our institution. The primary safety endpoint was any device-related adverse event, and the primary efficacy endpoint was successful complete occlusion of blood flow into the LAA as assessed by transthoracic echocardiography at hospital discharge. The primary efficacy endpoint for stroke reduction was the occurrence of ischemic or hemorrhagic neurologic events. Results: All patients underwent LAA occlusion as scheduled. The cardiopulmonary bypass and aortic cross-clamp times in the endocardial suture group and the AtriClip group were 202±39 and 128±41 minutes, and 213±53 and 136±44 minutes, respectively (p=0.68, p=0.73). No patients in either group experienced any device-related serious adverse events, incomplete LAA occlusion, early postoperative stroke, or neurologic complication. Conclusion: Epicardial LAA occlusion using the AtriClip Pro during MIMVS in patients with mitral valve disease and atrial fibrillation is a simple, safe, and effective adjunctive procedure.

• Journal of Applied Biological Chemistry
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• v.62 no.2
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• pp.129-135
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• 2019

Salvia miltiorrhiza Radix is cultivated in Korea and China and is traditionally used to treat cardiovascular diseases. In this study, we developed and validated a quantitative analysis method for S. miltiorrhiza Radix using high-performance liquid chromatography (HPLC). Identification was performed using ultra performance liquid chromatography-tandem mass spectrometry. For quantitative analysis, we used seven marker compounds. Separation conditions for HPLC were optimized using an ODS column with gradient conditions of 1% formic acid in distilled water and 1% formic acid in acetonitrile, with a flow rate of 0.8 mL/min and a detection wavelength of 280 nm. This method showed good linearity ($R^2=0.9998$), precision (relative standard deviation ${\leq}3.3%$), accuracy (recovery of 94.16-102.89%), limit of detection ($7.53{\mu}g/mL$), and limit of quantification ($23.71{\mu}g/mL$). This approach successfully quantified marker compounds in S. miltiorrhiza Radix. The individual marker compounds were identified by comparing the molecular masses and retention times with does standard compounds. Marker compound contents of S. miltiorrhiza Radix were investigated with different cultivation regions. Seven marker compounds were detected and quantified in all samples. Among them, salvianolic acid B showed the highest contents and it ranged from 4.13 to 7.15%. The salvianolic acid B content (7.15%) of marker compound was the highest in Bonghwa, and the tanshinone IIA content (1.90%) was the highest in Pohang. The results of marker compounds and developed method were intended to provide a favorable reference for the study of S. miltiorrhiza Radix from different regions of Korea.

• Toxicological Research
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• v.35 no.1
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• pp.83-91
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• 2019

Nanoparticles (NPs) have been recognized as both useful tools and potentially toxic materials in various industrial and medicinal fields. Previously, we found that zinc oxide (ZnO) NPs that are neurotoxic to human dopaminergic neuroblastoma SH-SY5Y cells are mediated by lipoxygenase (LOX), not cyclooxygenase-2 (COX-2). Here, we examined whether human bone marrow-derived mesenchymal stem cells (MSCs), which are different from neuroblastoma cells, might exhibit COX-2- and/or LOX-dependent cytotoxicity of ZnO NPs. Additionally, changes in annexin V expression, caspase-3/7 activity, and mitochondrial membrane potential (MMP) induced by ZnO NPs and ZnO were compared at 12 hr and 24 hr after exposure using flow cytometry. Cytotoxicity was measured based on lactate dehydrogenase activity and confirmed by trypan blue staining. Rescue studies were executed using zinc or iron chelators. ZnO NPs and ZnO showed similar dose-dependent and significant cytotoxic effects at concentrations ${\geq}15{\mu}g/mL$, in accordance with annexin V expression, caspase-3/7 activity, and MMP results. Human MSCs exhibited both COX-2 and LOX-mediated cytotoxicity after exposure to ZnO NPs, which was different from human neuroblastoma cells. Zinc and iron chelators significantly attenuated ZnO NPs-induced toxicity. Conclusively, these results suggest that ZnO NPs exhibit both COX-2- and LOX-mediated apoptosis by the participation of mitochondrial dysfunction in human MSC cultures.

• Journal of Ginseng Research
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• v.45 no.4
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• pp.490-497
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• 2021

Background and objective: Synthetic ginsenoside compounds G-Rp (1,3, and 4) and natural ginsenosides in Panax ginseng 20(S)-Rg3, Rg6, F4 and Ro have inhibitory actions on human platelets. However, the inhibitory mechanism of ginsenoside Rk1 (G-Rk1) is still unclear thus, we initiated investigation of the anti-platelet mechanism by G-Rk1 from Panax ginseng. Methodology: Our study focused to investigate the action of G-Rk1 on agonist-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding with integrin α_IIbβ₃ using flow cytometry, intracellular calcium mobilization, fibronectin adhesion, dense granule secretion, and thromboxane B2 secretion. Thrombin-induced clot retraction was also observed in human platelets. Key Results: Collagen, thrombin, and U46619-stimulated human platelet aggregation were dose-dependently inhibited by G-Rk1, while it demonstrated a more effective suppression on collagen-stimulated platelet aggregation using human platelets. Moreover, G-Rk1 suppressed collagen-induced elevation of Ca²⁺ release from endoplasmic reticulum, granule release, and α_IIbβ₃ activity without any cytotoxicity. Conclusions and implications: These results indicate that G-Rk1 possess strong anti-platelet effect, proposing a new drug candidate for treatment and prevention of platelet-mediated thrombosis in cardiovascular disease.

• Journal of radiological science and technology
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• v.45 no.3
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• pp.225-232
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• 2022

Fine dust threatens human health in various forms, depending on the particle size, such as by causing respiratory, cardiovascular, and brain diseases, after entering the body via the lungs. The aim of this study was to correlate fine dust exposure with changes in brain blood flow in Sprague Dawley rats by using micro-positron emission tomography and elucidate the possibility of developing cerebrovascular diseases caused by fine dust. The subjects were exposured to an average fine dust (particulate matter 2.5) of 206.2 ± 7.74 to ten rats four times a day, twice a day for 90 min. Before the experiment, they were maintained at NPO to the maximize the intake of ¹⁸F-fluorodeoxy glucose(¹⁸F-FDG) and minimize changes in the ¹⁸F-FDG biomass depending on the ambient environment and body temperature of the rats. PET images were acquired in the list mode 40 min after injecting ¹⁸F-FDG 44.4 MBq into the rats tail vein using a micro-PET scanner pre and post exposure to fine dust. We found that the whole brain level of ¹⁸F-FDG standardized uptake value in rats averaged 5.21 ± 0.52 g/mL pre and 4.22 ± 0.48 g/mL post exposure to fine dust, resulting in a statistically significant difference. Fine dust was able to alter brain activity after entering the body via the lungs in various forms depending on the particle size.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.61-73
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• 2023

Esophageal squamous cell carcinoma (ESCC) is a kind of malignant tumor with high incidence and mortality in the digestive system. The aim of this study is to explore the function of lnc-ABCA12-3 in the development of ESCC and its unique mechanisms. RT-PCR was applied to detect gene transcription levels in tissues or cell lines like TE-1, EC9706, and HEEC cells. Western blot was conducted to identify protein expression levels of mitochondrial apoptosis and toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway. CCK-8 and EdU assays were carried out to measure cell proliferation, and cell apoptosis was examined by flow cytometry. ELISA was used for checking the changes in glycolysis-related indicators. Lnc-ABCA12-3 was highly expressed in ESCC tissues and cells, which preferred it to be a candidate target. The TE-1 and EC9706 cells proliferation and glycolysis were obviously inhibited with the downregulation of lnc-ABCA12-3, while apoptosis was promoted. TLR4 activator could largely reverse the apoptosis acceleration and relieved the proliferation and glycolysis suppression caused by lnc-ABCA12-3 downregulation. Moreover, the effect of lnc-ABCA12-3 on ESCC cells was actualized by activating the TLR4/NF-κB signaling pathway under the mediation of exosome. Taken together, the lnc-ABCA12-3 could promote the proliferation and glycolysis of ESCC, while repressing its apoptosis probably by regulating the TLR4/NF-κB signaling pathway under the mediation of exosome.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.706-713
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• 2023

Background and objective: The ability to inhibit aggregation has been demonstrated with synthetically derived ginsenoside compounds G-Rp (1, 3, and 4) and ginsenosides naturally found in Panax ginseng 20(S)-Rg3, Rg6, F4, and Ro. Among these compounds, Rk3 (G-Rk3) from Panax ginseng needs to be further explored in order to reveal the mechanisms of action during inhibition. Methodology: Our study focused to investigate the action of G-Rk3 on agonist-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding with integrin α_IIbβ₃ using flow cytometry, intracellular calcium mobilization, dense granule secretion, and thromboxane B₂ secretion. In addition, we checked the regulation of phosphorylation on PI3K/MAPK pathway, and thrombin-induced clot retraction was also observed in platelets rich plasma. Key Results: G-Rk3 significantly increased amounts of cyclic adenosine monophosphate (cAMP) and led to significant phosphorylation of cAMP-dependent kinase substrates vasodilator-stimulated phosphoprotein (VASP) and inositol 1,4,5-trisphosphate receptor (IP₃R). In the presence of G-Rk3, dense tubular system Ca²⁺ was inhibited, and platelet activity was lowered by inactivating the integrin αIIb/β₃ and reducing the binding of fibrinogen. Furthermore, the effect of G-Rk3 extended to the inhibition of MAPK and PI3K/Akt phosphorylation resulting in the reduced secretion of intracellular granules and reduced production of TXA₂. Lastly, G-Rk3 inhibited platelet aggregation and thrombus formation via fibrin clot. Conclusions and implications: These results suggest that when dealing with cardiovascular diseases brought upon by faulty aggregation among platelets or through the formation of a thrombus, the G-Rk3 compound can play a role as an effective prophylactic or therapeutic agent.

• Journal of the Korean Society of Radiology
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• v.82 no.2
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• pp.447-454
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• 2021

The authors report a successful thrombectomy using the AngioJet Rheolytic Thrombectomy System (AngioJet) and an embolic protection device in a patient with femorofemoral bypass graft occlusion. Lower extremity CT angiograms showed occlusion in the left-to-right femorofemoral bypass graft. A rheolytic thrombectomy using the AngioJet and balloon angioplasty restored blood flow to the right lower extremity, and distal embolization may be effectively prevented by placing an embolic protection device within the right superficial femoral artery during the procedure.