• Journal of Ginseng Research
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• v.47 no.6
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• pp.743-754
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• 2023

Background: Myocardial fibrosis post-myocardial infarction (MI) can induce maladaptive cardiac remodeling as well as heart failure. Although 20(S)-ginsenoside Rg3 (Rg3) has been applied to cardiovascular diseases, its efficacy and specific molecular mechanism in myocardial fibrosis are largely unknown. Herein, we aimed to explore whether TGFBR1 signaling was involved in Rg3's anti-fibrotic effect post-MI. Methods: Left anterior descending (LAD) coronary artery ligation-induced MI mice and TGF-β1-stimulated primary cardiac fibroblasts (CFs) were adopted. Echocardiography, hematoxlin-eosin and Masson staining, Western-blot and immunohistochemistry, CCK8 and Edu were used to study the effects of Rg3 on myocardial fibrosis and TGFBR1 signaling. The combination mechanism of Rg3 and TGFBR1 was explored by surface plasmon resonance imaging (SPRi). Moreover, myocardial Tgfbr1-deficient mice and TGFBR1 adenovirus were adopted to confirm the pharmacological mechanism of Rg3. Results: In vivo experiments, Rg3 ameliorated myocardial fibrosis and hypertrophy and enhanced cardiac function. Rg3-TGFBR1 had the 1.78×10^-7 M equilibrium dissociation constant based on SPRi analysis, and Rg3 inhibited the activation of TGFBR1/Smads signaling dose-dependently. Cardiac-specific Tgfbr1 knockdown abolished Rg3's protection against myocardial fibrosis post-MI. In addition, Rg3 downregulated the TGF-β1-mediated CFs growth together with collagen production in vitro through TGFBR1 signaling. Moreover, TGFBR1 adenovirus partially blocked the inhibitory effect of Rg3. Conclusion: Rg3 improves myocardial fibrosis and cardiac function through suppressing CFs proliferation along with collagen deposition by inactivation of TGFBR1 pathway.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.281-292
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• 2023

Background and Objectives: Human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte (CM) hold great promise as a cellular source of CM for cardiac function restoration in ischemic heart disease. However, the use of animal-derived xenogeneic substances during the biomanufacturing of hiPSC-CM can induce inadvertent immune responses or chronic inflammation, followed by tumorigenicity. In this study, we aimed to reveal the effects of xenogeneic substances on the functional properties and potential immunogenicity of hiPSC-CM during differentiation, demonstrating the quality and safety of hiPSC-based cell therapy. Methods and Results: We successfully generated hiPSC-CM in the presence and absence of xenogeneic substances (xeno-containing (XC) and xeno-free (XF) conditions, respectively), and compared their characteristics, including the contractile functions and glycan profiles. Compared to XC-hiPSC-CM, XF-hiPSC-CM showed early onset of myocyte contractile beating and maturation, with a high expression of cardiac lineage-specific genes (ACTC1, TNNT2, and RYR2) by using MEA and RT-qPCR. We quantified N-glycolylneuraminic acid (Neu5Gc), a xenogeneic sialic acid, in hiPSC-CM using an indirect enzyme-linked immunosorbent assay and liquid chromatography-multiple reaction monitoring-mass spectrometry. Neu5Gc was incorporated into the glycans of hiPSC-CM during xeno-containing differentiation, whereas it was barely detected in XF-hiPSC-CM. Conclusions: To the best of our knowledge, this is the first study to show that the electrophysiological function and glycan profiles of hiPSC-CM can be affected by the presence of xenogeneic substances during their differentiation and maturation. To ensure quality control and safety in hiPSC-based cell therapy, xenogeneic substances should be excluded from the biomanufacturing process.

• Journal of Chest Surgery
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• v.36 no.9
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• pp.651-658
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• 2003

Since the first implanted in September 1997, the use of On-X prosthetic heart valve has been increasing around in the world. This study was designed to assess the feasibility, safety, and the postoperative hemodynamics with this new valve in clinical setting. Material and Method: The current study was carried out on 52 patients undergoing aortic valve replacement with this prosthesis between April 1999 to August 2002 at Chonnam National University Hospital to evaluate the surgical results. 52％ of the patients were male and the average age at implant was 50$\pm$13 years. The study followed the guidelines of the AATS/STS. Preoperatively, 32(61.5％) patients were in NYHA functional class III or IV and 2 patients had previous aortic valve surgery. Concomitant cardiac surgery was performed in 71.1％. The implanted valve sizes were 19 mm in 13 patients, 21 mm in 26, 23 mm in 10 and 25 mm in 3, respectively. Mean follow-up was 16.6$\pm$10.5 months (1∼39 months). Echocardiographic assessment was performed pre- and immediate postoperatively, as well as 3, 6, 12 months after surgery, evaluating pressure loss and regression of left ventricular hypertrophy. Result: Mean cardiopulmonary bypass time was 191$\pm$94.7 minutes with an aortic cross-clamp time of 142$\pm$51.7 minutes. There was no early and late mortality, Freedom from adverse events at 1 year in the study were as follows: thromboembolism, 95.6$\pm$6％; bleeding events, 90.2$\pm$4％; paravalvular leakage 92.3$\pm$4％; and overall valve-related morbidity at 1 year was 76.6$\pm$3％. There were no cases of valve thrombosis, prosthetic valve endocarditis and structural or non-structural failure. Left ventricular function at 12 months after surgery (EF=62.7$\pm$9.8％) revealed a statistically significant improvement compared to preoperative investigation (EF=55.8$\pm$15.9％, p=0.006). Left ventricular mass index was 247.3$\pm$122.3 g/$m^2$ on preoperative echocardiographic study, but regressed to 155.5$\pm$58.2 g/$m^2$ at postoperative 1 year (p=0.002). Over the follow-up period a further decrease of peak transvalvular gradients was observed in all patients: 62.5$\pm$38.0 mmHg on preoperative assessment, 18.2$\pm$6.8 mmHg at immediate postoperative period (p < 0.0001), 7.6$\pm$5.09 mmHg (p<0.0001) at 6 month, 18.0$\pm$10.8 mmHg (p<0.0001) at 1 year. Conclusion: The On-X prosthetic heart valve performs satisfactorily in the first 1 year period. Clinical outcome by examining NYHA functional classification revealed especially good results. Effective regression of left ventricular hypertrophy and statistically significant decrease of transvalvular gradient were observed over the first year, but longer-term follow-up of this patient group is needed to establish the expected rates for late valve-related events as well as the long-term clinical efficacy of this valve.

• Journal of Acupuncture Research
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• v.29 no.1
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• pp.139-150
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• 2012

Objectives : The puropse of this study was to report the availability of Hyeongsang diagnosis compensating for visceral pattern identification in applying Sa-am acupuncture therapy. Methods : Eight cases was presented to substantiate the above. Results : According to the characteristic diagnostic method of Hyeongsang medicine by feature such as face, ears, eyes, nose and mouth shape, There are 8 pattern differentiations, including essence family, Qi family, spirit family, blood family, fish type, bird type, beast(running) type and crust(crustacea) type which are correlated with essence deficiency, heat harassing the heart spirit, Qi stagnation, blood stasis, kidney essence deficiency, intense heart fire, liver blood deficiency and lung Qi deficiency in the established visceral pattern identification, respectively. Eight patients was diagnosed by the above Hyeongsang 8 pattern differentiations, of whom Sinjeonggyeok(kidney reinforcing prescription) was applied to a patient with fish type and essence family to nourish kidney essence, and Giul prescription(Qi stagnation prescription) was given to a patient with Qi family for regulating Qi, and Sanghwa priscription(ministerial fire prescription) was delivered to a patient with Spirit family to clear the heart fire and tranquilize, and Sojangjeonggyeok(small intestine reinforcing prescription) was used for a patient with blood family to nourish blood and remove blood stasis, and Sinjeonggyeok(kidney reinforcing prescription), Simhangyeok(heart heat clearing prescription), Ganjeonggyeok(liver reinforcing prescription) and Pyejeonggyeok(lung reinforcing prescription) were utilized for fish type, bird type, beast(running) type and crust(crustacea) type respectively to reinforce the relevant visceral function. Conclusions : It was suggested that characteristic diagnostic method of Hyeongsang medicine should be helpful for enhancing the accuracy of the established visceral pattern identification, applying Sa-am acupuncture therapy more appropriately.

• Journal of Chest Surgery
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• v.40 no.9
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• pp.593-599
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• 2007

Background: The correlation between levels of brain natriuretic peptide (BNP) and the effect of pulmonary resection on the right ventricle of the heart is not yet widely known. This study aims to assess the relationship between the change in hemodynamic values of the right ventricle and increased BNP levels as a compensatory mechanism for right heart failure following pulmonary resection and to evaluate the role of the BNP level as an index of right heart failure after pulmonary resection. Material and Method: In 12 non small cell lung cancer patients that had received a lobectomy or pnemonectomy, the level of NT-proBNP was measured using the immunochemical method (Elecsys $1010^{(R)}$, Roche, Germany) which was compared with hemodynamic variables determined through the use of a Swan-Garz catheter prior to and following the surgery. Echocardiography was performed prior to and following the surgery, to measure changes in right ventricular and left ventricular pressures. For statistical analysis, the Wilcoxon rank sum test and linear regression analysis were conducted using SPSSWIN (version, 11.5). Result: The level of postoperative NT-proBNP (pg/mL) significantly increased for 6 hours, then for 1 day, 2 days, 3 days and 7 days after the surgery (p=0.003, 0.002, 0.002, 0.006, 0.004). Of the hemodynamic variables measured using the Swan-Ganz catheter, the mean pulmonary artery pressure after the surgery when compared with the pressure prior to surgery significantly increased at 0 hours, 6 hours, then 1 day, 2 days, and 3 days after the surgery (p=0.002, 0,002, 0.006, 0.007, 0.008). The right ventricular pressure significantly increased at 0 hours, 6 hours, then 1 day, and 3 days after the surgery (p=0.000, 0.009, 0.044, 0.032). The pulmonary vascular resistance index [pulmonary vascular resistance index=(mean pulmonary artery pressure-mean pulmonary capillary wedge pressure)/cardiac output index] significantly increased at 6 hours, then 2 days after the surgery (p=0.008, 0.028). When a regression analysis was conducted for changes in the mean pulmonary artery pressure and NT-proBNP levels after the surgery, significance was evident after 6 hours (r=0.602, p=0.038) and there was no significance thereafter. Echocardiography displayed no significant changes after the surgery. Conclusion: There was a significant correlation between changes in the mean pulmonary artery pressure and the NT-proBNP level 6 hours after a pulmonary resection. Therefore, it can be concluded that changes in NT-proBNP level after a pulmonary resection can serve as an index that reflects early hemodynamic changes in the right ventricle after a pulmonary resection.

• Journal of Chest Surgery
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• v.40 no.1 s.270
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• pp.45-51
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• 2007

Background: Although echocardiography is usually used for quantitative assessment of left ventricular function, the recently developed 16-slice multidetector computed tomography (MDCT) is not only capable of evaluating the coronary arteries but also left ventricular function. Therefore, the objective of our study was to compare the values of left ventricular function quantified by MDCT to those by echocardiography for evaluation of its regards to clinical applications. Material and Method: From 49 patients who underwent MDCT in our hospital from November 1, 2003 to January 31, 2005, we enrolled 20 patients who underwent echocardiography during the same period for this study. Left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), stroke volume index (SVI), left ventricular mass index (LVMI), and ejection fraction (EF) were analyzed. Result: Average LVEDVI ($80.86{\pm}34.69mL$ for MDCT vs $60.23{\pm}29.06mL$ for Echocardiography, p<0.01), average LVESVI ($37.96{\pm}24.52mL$ for MDCT vs $25.68{\pm}16.57mL$ for Echocardiography, p<0.01), average SVI ($42.90{\pm}15.86mL$ for MDCT vs $34.54{\pm}17.94mL$ for Echocardiography, p<0.01), average LVMI ($72.14{\pm}25.35mL$ for MDCT vs $130.35{\pm}53.10mL$ for Echocardiography, p<0.01), and average EF ($55.63{\pm}12.91mL$ for MOCT vs $59.95{\pm}12.75ml$ for Echocardiography, p<0.05) showed significant difference between both groups. Average LVEDVI, average LVESVI, and average SVI were higher in MDCT, and average LVMI and average EF were higher in echocardiogram. Comparing correlation for each parameters between both groups, LVEDVI $(r^2=0.74,\;p<0.0001)$, LVESVI $(r^2=0.69,\;p<0.0001)$ and SVI $(r^2=0.55,\;p<0.0001)$ showed high relevance, LVMI $(r^2=0.84,\;p<0.0001)$ showed very high relevance, and $EF (r^2=0.45,\;p=0.0002)$ showed relatively high relevance. Conclusion: Quantitative assessment of left ventricular volume and function using 16-slice MDCT showed high relevance compared with echocardiography, therefore may be a feasible assessment method. However, because the average of each parameters showed significant difference, the absolute values between both studies may not be appropriate for clinical applications. Furthermore, considering the future development of MDCT, we expect to be able to easily evaluate the assessment of coronary artery stenosis along with left ventricular function in coronary artery disease patients.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1129-1136
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• 2005

The writer reports the conclusions gained from study about the cause of the hypersensitive large intestine syndrome with Dongeuibogam as the central figure through researching the disharmony among Body Essence, Vital Energy, Mentality, and Blood, mutual action of five viscera and six bowels, and external shapes. The hypersensitive large intestine syndrome is generally chronic and recurred in many cases, so it is more efficacious than symptomatic to treat according to find the contradictions of individual shapes. The shapes and cases suffering frequently the hypersensitive large intestine syndrome are Gi-kwa and Sin-kwa, having a long nose, having a bruised spot on Triple warmer, man with inclined mouth, Taeeum type, man with congested fluids, man with colic symptoms. The hypersensitive large intestine syndrome in Oriental medicine is recognized of diarrhea, constipation, abdominal pain, abdominal distention and fullness caused by seven emotions. In Dongeuibogam it can be found out the similarity in depressive symptoms due to disorder of Gi, stagnation of Gi, dysphasia due to disorder of Gi, diarrhea due to disorder of Gi, fullness of due to Gi, diarrhea due to phlegm-retention, retention of undigested food, immoderate drinking, hypo-function of the spleen, or deficiency, abdominal pain from colic symptom, and difficulty in defecation and urination, internal injury, diarrhea due to weakness and fatigue. If the Jung, Gi, Sin, and Hyul composed the human body is broken harmony, the function of large intestinal transmission would be fallen, so similar symptoms like the hypersensitive large intestine syndrome are gotten. Especially Gi-kwa suffers diarrhea, constipation abdominal pain, and abdominal distention and fullness due to depressive symptoms from disorder of Seven emotions or Seven Gi. And Sin-kwa suffers from the hypersensitive large intestine syndrome due to emotional restlessness having an influence on rhythmic movement of abdomen. Examining between five viscera and six bowels and the hypersensitive large intestine syndrome, Liver cannot disperse well having influence on mutual relation of Liver-Large intestine, Heart reduces the function of defecation and urination not to control the seven emotions, Lung having exterior and interior relation with intestine has an influence on primordial energy and let the main symptoms occur, Spleen circulating the body fluid let the main symptoms occur due to malfunction of circulation, Kidney locating in lower part of the body has deep connection with intestine, so let the disorder. Urinary bladder is connected with intestine in moisture metabolism, Stomach is connected in receive and transmission, Small intestine is connected in absorption and excretion, from small intestine pain disturbing the abdominal movement, Samcho managing the catharsis of lower heater if declined its function causes the hypersensitive large intestine syndrome. The colic symptoms of Front private parts which disorder in lower abdomen give rise to abdominal pains, difficulty in defecation and urination due to Cold are similar to the hypersensitive large intestine syndrome. The treatments of applying the shapes of colic syndrome advocated by Master Park can be efficacious cure in clinic. Researching after the clinical cases of Master Park advocating Hyungsang medicine, we came to know that plenty of prescriptions of internal injury are applied and take good effects.

• The Korean Journal of Physiology
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• v.20 no.1
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• pp.1-7
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• 1986

It has been well documented that the peripheral autonomic nervous system plays an important role in exocrine pancreatic secretion. However, the role of the central nervous system in pancreatic function is still obscure even though the central nervous system has been known to control gastrointestinal functions through the autonomic nervous system. Since the reticular formation in the mesencephalone seems to integrate the autonomic function, the present study was undertaken to investigate a possible influence of the reticular formation upon the exocrine pancreatic secretion. Twenty·two albino rats fasted for 24 hours were anesthetized by intraperitoneal injection of urethane in a dose of 1 g/kg, The pancreatic duct was cannulated to collect pancreatic juice and bile juice was diverted to the jejunum. The gastroduodenal junction was ligated to Prevent passage of gastic juice into the duodenum. A pair of electrodes were bilaterally inserted in the reticualr formation of the mesencephalone with aid of a stereotaxic apparatus. When the volume of pancreatic juice secreted for 10 min became constant, the reticular formation was electrically stimulated for 10 min. Parameters of the electical stimulation was 1.3V, 40 Hz and 2 msec. When the pancreatic secretion returned to the level before the electrical stimulation, cervical vagotomy (11 rats) or administration of propranolol (11 rats) in a dose of 0.1 mg/kg through the jugular vein was carried out. Ten minutes after the treatment, the electrical stimulation of the reticular formation was repeated. The brain was fixed by perfusion of 10% formaline solution through the heart, and then placement of the electrode tip was examined histologically. Protein concentration and amylase activity in samples of Pancreatic secretion were measured. The electrical stimulation of the reticular formation significantly increased in volume $({\mu}l/10\;min)$, Protein output $({\mu}g/10\;min)$ and amylase output (U/10 min) in the pancreatic secretion. The stimulatroy effects were not affected by the cervical vagotomy but completely abolished by propranolol. Meantime, it was also observed that both vagotomy and propranolol significantly reduced the pancreatic secretory function. These results indicate that the reticular formation in the mesencephalone may exert a stimulatory effect upon the Pancreatic secretory function not through the vagus nerve but through the sympathetic pathway in anesthetized rats.

• Journal of the Korean Applied Science and Technology
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• v.34 no.4
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• pp.827-838
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• 2017

Twenty male soccer players volunteered as the experimental subjects. The subjects were randomly assigned to the "Winter training with Cornus officinalis extract intake group"(WCI; n=10) and "Winter training group"(WT; n=10). The variables of blood fatigue substance, muscle damage and liver function where measured in all the subjects before the start of the Cornus officinalis intake after at the end of the 4 weeks winter training. Winter training program was proceeded with 6 days a week for 4 weeks. Exercise intensity was measured using the HRR(70~95%). Changes in the heart rate were also measured with the Polar. WCI group were ingested 80 mL of Cornus officinalis extract after every breakfast and dinner for 4 weeks. The test data were analyzed by paired t-test, and independent t-test(%diff), and the alpha level of p<.05 was set for all tests of significance. Lactate in WCI group had significantly decreased, and the changes between the groups were significantly lower in the WCI group than in the WT group. Ammonia in WCI group had significantly increased. CK in WCI group had significantly decreased. LDH in both group had significantly decreased. AST in WCI group had significantly decreased, and the changes between the groups were significantly lower in the WCI group than in the WT group. ALT in WCI group had significantly decreased. In conclusion, the results of this study show that Cornus officinalis extract seem to have a positive influence on blood fatigue substance, muscle damage and liver function. Therefore Cornus officinalis extract is considered to be able to contribute an ergogenic aids.

• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.418-427
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• 2003

Objects: $^{99m}-lactosylated$ human serum albumin (LSA) is a newly synthesized radiopharmaceutical that binds to asialoglycoprotein receptors, which are specifically presented on the hepatocyte membrane. Hepatic uptake and blood clearance of LSA were evaluated in rat with acute hepatic injury induced by dimethylnitrosamine (DMN) and results were compared with corresponding findings of liver enzyme profile and these of histologic changes. Materials and Methods: DMN (27 mg/kg) was injected intraperitoneally in Sprague-Dawley rat to induce acute hepatic injury. At 3(DMN-3), 8(DMN-8), and 21 (DMN-21) days after injection of DMN, LSA injected intravenously, and dynamic images of the liver and heart were recorded for 30 minutes. Time-activity curves of the heart and liver were generated from regions of interest drawn over liver and heart area. Degree of hepatic uptake and blood clearance of LSA were evaluated with visual interpretation and semiquantitative analysis using parameters (receptor index : LHL3 and index of blood clearance : HH3), analysis of time-activity curve was also performed with curve fitting using Prism program. Results: Visual assessment of LSA images revealed decreased hepatic uptake in DMN treated rat, compared to control group. In semiquantitative analysis, LHL3 was significantly lower in DMN treated rat group than control rat group (DMN-3: 0.842, DMN-8: 0.898, DMN-21: 0.91, Control: 0.96, p<0.05), whereas HH3 was significantly higher than control rat group (DMN-3: 0.731,.DMN-8: 0.654, DMN-21: 0.604, Control: 0.473, p<0.05). AST and ALT were significantly higher in DMN-3 group than those of control group. Centrilobular necrosis and infiltration of inflammatory cells were most prominent in DMN-3 group, and were decreased over time. Conclusion: The degree of hepatic uptake of LSA was inversely correlated with liver transaminase and degree of histologic liver injury in rat with acute hepatic injury.