• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.553-561
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• 2022

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia. However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

• Journal of Pharmacopuncture
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• v.15 no.4
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• pp.52-65
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• 2012

Objectives: Toad venom, called Chan-Su, is a traditional Oriental medicine secreted from the auricular and the skin glands of the Bufo bufo gargarizanz Cantor or B. melanosticus Schneider and has been widely used in China, Korea and other parts of Asia for the treatment of pain, heart conditions, and cancer. We examined the concentrations of the main chemical constituents within a commercially available toad venom product and compared the levels for different extraction methods. Methods: Toad venom was extracted using either cold or hot water, ethanol (EtOH), methanol (MeOH), or ethyl acetate (EtOAc), was fractionated using precipitation or reflux, and was then analyzed using thin layer chromatography (TLC), high-performance liquid chromatography (HTLC), and liquid chroma-tography - mass spectrometry (LC-MS). Individual components were identified by comparisons of the retention times, the ultraviolet spectra, and mass spectras and differences in chemical constituents for different solvents and extraction methods are presented. Results: Components with authentic standards, including serotonin and bufodienolides (cinobufagen, bufalin, cinobufalin, and resibufogenin), were detected. The water extract of toad venom contained the greatest amount of serotonin ($75.7{\pm}0.1$ mg/g), but very small amounts of bufodienolides ($3.8{\pm}0.0$ mg/g). In contrast, the use of MeOH or EtOH extraction solutions resulted in 5-26 times higher concentrations of bufodienolides, with only trace amounts of serotonin. The relative and the absolute concentrations of the component also varied based on the extraction method; i.e., EtOH extracts yielded the greatest total amounts of bufodienolides, and EtOAc precipitation had the lowest amounts of bufodienolides. Conclusions: Toad venom consists of serotonin and several bufodienolides, and the choice of solvent to extract chemical the constituents is important as a way to enrich the purported active components for treating different conditions.

• Journal of Pharmacopuncture
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• v.20 no.2
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• pp.100-106
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• 2017

Objectives: This study aimed to assess a Qi Blood Yin Yang evaluation method systematically and objectively and to identify the correlation between the Qi Blood Yin Yang deficiency pattern (QBYYDP) and facial color. Methods: Thirty-seven participants (17 males, 20 females) were enrolled in this study. Twenty-four (10 males, 14 females) had ages from 40 to over 60, and 13 (7 males and 6 females) were in their twenties. After sufficient rest, facial images were taken with a camera. Based on the results from a questionnaire survey, we divided the participants into five groups: the normal and the Qi-, Blood-, Yin-, and Yang-deficient groups, after which the relationships between the L, 'a', and 'b' values in the Lab color system and the characteristics of the participants in each of the deficient groups were elucidated using a facial color analysis program. Results: The color analysis for Qi-deficient (QD) participants revealed that the L value was fairly decreased in comparison with the normal participants, but the 'a' and 'b' values were almost the same. A comparison between the normal and the Yang-deficient (YaD) groups revealed that the L values were somewhat lower compared to the normal group, but the 'a' and 'b' values were not statistically different. For the Yin-deficient (YiD) group, the L value was slightly lower compared to the normal group, but the 'a' and 'b' values were almost the same and the R values were slightly increased. For the Blood-deficient (BD) group, the L values were slightly increased compared to the normal group, but the 'a' and 'b' values were decreased slightly. Conclusion: This study obtained objective, reliable data for judging the QBYYDP by using facial images and a color analysis program. However, further study with at least 10 or more subjects in each of the deficient groups is necessary to confirm our findings.

• The Journal of Internal Korean Medicine
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• v.31 no.1
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• pp.40-53
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• 2010

Background : It was not enough to apply three kinds of syndrome differentiation in our oriental medical textbook to tremor's treatment according to reports of Korea and traditional medical textbook of China. Objective : To investigate syndrome differentiations by types of diseases related to tremor through Chinese journals review and to suggest adding possible syndrome differentiations. Methods : Literature search was performed using China Academic Journal (CAJ), the search engine of China National Knowledge Infrastructure (CNKI) from January 1994 to December 2009. Searching key words were Chinese characters in combination meaning tremor, paralysis agitans, and syndrome differentiation. We included all types of articles that explained or referred to definite syndrome differentiations. The symptoms and oriental medications by syndrome differentiation in selected articles were extracted and summarized. Results : 56 Chinese journals were ultimately selected. 37 kinds of syndrome differentiations about tremor were investigated, which included dual deficiency of qi and blood (氣血兩虛) quoted 31 times, liver-kidney yin deficiency (肝腎陰虧) 23 times, liver-kidney deficiency (肝腎不足) 21 times, and phlegm-heat stirring wind (痰熱動風) 20 times. 37 kinds of syndrome differentiation could by group into eight types, such as liver-kidney yin deficiency (肝腎陰虧), dual deficiency of qi and blood (氣血兩虛), phlegm-heat stirring wind (痰熱動風), heart deficiency and spirit weakness (心虛神弱), blood stasis due to qi stagnation (氣滯血瘀), sea of marrow deficiency (髓海不足), liver qi depression (肝氣鬱結), and liver yang transforming into wind (肝陽化風). Conclusion : We suggest that the syndrome differentiations of tremor, such as heart deficiency and spirit weakness (心虛神弱), blood stasis due to qi stagnation (氣滯血瘀), sea of marrow deficiency (髓海不足), liver qi depression (肝氣鬱結), and liver yang transforming into wind (肝陽化風), can be added to liver-kidney deficiency (肝腎不足), dual deficiency of qi and blood (氣血兩虛), and phlegm-heat stirring wind (痰熱動風) of the textbook. Further systematic research will be needed on them.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.3
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• pp.241-256
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• 2023

Although chimeric antigen receptor T cell (CAR-T) is a promising immunotherapy in hematological malignancies, there remain many obstacles to CART cell therapy for solid tumors. Identifying appropriate tumor-associated antigens (TAAs) is especially critical for success. Using a bioinformatics approach, we identified common potential TAAs for CAR-T cell immunotherapy in solid tumors. We used the GEO database as a training dataset to find differentially expressed genes (DEGs) and verified candidates using the TCGA database, obtaining seven common DEGs (HM13, SDC1, MST1R, HMMR, MIF, CD24, and PDIA4). Then, we used MERAV to analyze the expression of six genes in normal tissues to determine the ideal target genes. Finally, we analyzed tumor microenvironment factors. The results of major microenvironment factor analyses showed that MDSCs, CXCL1, CXCL12, CXCL5, CCL2, CCL5, TGF- β, CTLA-4, and IFN-γ were significantly overexpressed in breast cancer. The expression of MST1R was positively correlated with TGF- β, CTLA-4, and IFN-γ. In lung adenocarcinoma, MDSCs, Tregs, CXCL12, CXCL5, CCL2, PD-L1, CTLA-4, and IFN-γ were significantly overexpressed in tumor tissues. The expression of MST1R was positively correlated with TGF- β, CTLA-4, and IFN-γ. In bladder cancer, CXCL12, CCL2, and CXCL5 were significantly overexpressed in tumor tissues. MST1R expression was positively correlated with TGF- β. Our results demonstrate that MST1R has the potential as a new target antigen for treating breast cancer, lung adenocarcinoma, and bladder cancer and may be used as a progression indicator for bladder cancer.

• The Journal of Korean Medicine
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• v.32 no.1
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• pp.164-174
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• 2011

Objective: The antiplatelet agent aspirin has been widely used for treating atherosclerosis in western medicine, and its efficacy has been proven in cardiac and extracardiac vascular diseases. On the other hand, Hyeolbuchukeo-tang has been widely used for treating blood stasis syndrome in traditional medicine. Therefore we investigated whether Hyeolbuchukeo-tang could have a synergic effect along with aspirin. Methods & Materials: Male $ApoE^{(-/-)}$ mice were randomly divided into three different experimental groups: a non-treated group(Control group), an aspirin-treated group(AP group), and an aspirin with Hyeolbuchukeo-tang-treated group(APH group). The control group was fed only an atherogenic diet, the AP group an atherogenic diet plus Aspirin 5 mg/kg, and the APH group an atherogenic diet plus Aspirin 5 mg/kg with Hyeolbuchukeo-tang 100 mg/kg. We investigated plasma lipid with liver function test, and performed the histological investigation of liver and abdominal aorta. Results: 1. We investigated photomicrographic changes of liver and abdominal aorta tissue. They showed that histological injury of aorta and lipid accumulations of the liver were lower in the AP and APH groups than in the control group. 2. In the APH group, plasma triglyceride levels were significantly lower than those in the control and AP groups. 3. There were no differences in aspartate aminotransferase and alanine aminotransferase levels among the control, AP and APH groups. Conclusion: The above results show that a combined treatment of Hyeolbuchukeo-tang and aspirin has a somewhat synergic effect in terms of inhibiting vessel injury and decreasing lipid deposits on liver cells without liver toxicity.

• The Journal of Korean Medicine
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• v.31 no.5
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• pp.124-135
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• 2010

Background and Objective: Atherosclerosis is a diffuse, systemic disease that affects the coronary, cerebral, and peripheral arterial trees. Clopidogrel is widely used antiplatelet agent and its efficacy has been proven in cardiac and extracardiac vascular diseases, but it has several side effects. Therefore we investigated whether Sopunghwalhyeoltang, which is widely used for treating the blood stasis syndrome in traditional medicine, could decrease the side effect of antiplatelets and have a synergic effect. Methods & Materials: Male $ApoE^{(-/-)}$ mice were randomly divided into three different experimental groups, non-treated group (Control group), clopidogrel-treated group (CP group) and clopidogrel with Sopunghwalhyeol-tang treated group (CPS group). The control group was fed with only an atherogenic diet, the CP group an atherogenic diet plus clopidogrel 25mg/kg and the CPS group an atherogenic diet plus clopidogrel 25mg/kg with Sopunghwalhyeol-tang 100 mg/kg. We investigated plasma lipids with liver function test, and performed a histological investigation of liver and abdominal aorta. Results: 1. Photomicrographs of liver and abdominal aorta tissue showed lower histological injury and lipid accumulation in the CP and CPS groups than those in the Control group. 2. In the CPS group, plasma triglyceride level was significantly lower than in the Control and CP groups. 3. In the CPS group, the plasma aspartate aminotransferase (AST) level was significantly lower than in the CP group. Conclusions: The above results shows that a combined treatment of Sopunghwalhyeol-tang and clopidogrel have a synergic effect through inhibiting vessel injury and decrease the side effects of clopidogrel alone.

• Journal of Korean Medicine for Obesity Research
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• v.24 no.1
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• pp.87-93
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• 2024

Objectives: Obesity is a globally prevalent public health issue. Hence, there is a need for the development of safer and more effective anti-obesity drugs. Lythrum salicaria, a traditional medicinal herb used for centuries, has been reported to improve lipid metabolism and fat accumulation. It also has a low toxicity profile. Therefore, its potential as a functional ingredient in health functional foods needs to be evaluated. Methods: In this randomized, double-blind, placebo-controlled clinical trial, 90 participants will be randomly assigned to either the experimental or control group. Each subject will orally receive L. salicaria extract (1,350 mg/day) (500 mg L. salicaria+850 mg lactose as vehicle) or lactose (1,350 mg/day) as a hard capsule formula for 84 days (12 weeks). The primary outcome will be body fat mass (kg), which will be assessed using dual-energy x-ray absorptiometry (DXA) (performed only at visits 2 and 4). Secondary outcomes include body mass index, body weight, waist-to-hip ratio, body fat percentage (%) measured using DXA, lean body mass (kg) measured using DXA (assessed only at visits 2 and 4), lipids (total cholesterol, triglyceride, high-density lipoprotein cholesterol, and calculated low-density lipoprotein cholesterol), free fatty acid, high sensitivity C-reactive protein, adiponectin, and leptin. Conclusions: This protocol will be implemented after approval of Institutional Review Board of Pusan National University Korean Medicine Hospital (approval number: PNUKHIRB-2022-08-002) and registration with the Korean National Clinical Research Information Service (CRIS) (CRIS-KCT0008060). The results of this trial will provide potential of L. salicaria as a new anti-obesity functional food with fat-reducing effects and low toxicity.

• Journal of Acupuncture Research
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• v.19 no.1
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• pp.127-134
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• 2002

Background and Purpose : Now, a lot of people are suffering from arthritis of knee joint. Western and oriental medicine, all of them are trying various methods to cure this disease, but generally the grade or level of repairing has been decided by the subjective estimation of the patients and doctors. So, we suggest the new standard for estimating the level of repair in this disease using nuclear medicine. Objective : To evalute the difference of the blood pool and delayed images in the correlation with clinical symptoms in patients with arthritis of knee joint by using acupuncture. Methods : Eight patients with arthritis of knee joint included in this study. Using Thermograph (D.I.T.I) and Radionuclide, we obtained the results. In Bone scan Tc-99m MDP, and MIBI scan was obtained at 1 minute and 3 hour after injection of 1,110 MBq Tc-99m MDP and MIBI. The analysis was carried out hurted area of joint. The Joint-to-background(J/B) ratios were obtained exclusively in the joints regions. Clinical symptoms were evaluated as pain and swelling graded from 0(no) to 5(severe) in the same joints, respectively. Results : J/B ratios on the delayed scans were higher than those on blood pool images. There was significant correlation between clinical symptoms and J/B on blood pool image in the joints =0.03). Conclusion : The results demonstrate that blood pool images of Tc-99m MDP scintigraphy correlates with clinical symptoms more than delayed images in patients with arthritis Joint.

• Journal of Preventive Medicine and Public Health
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• v.56 no.4
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• pp.319-326
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• 2023

Objectives: The coronavirus disease 2019 (COVID-19) pandemic has increased the workload of healthcare workers (HCWs), impacting their health. This study aimed to assess sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and identify factors associated with poor sleep among HCWs in Vietnam during the COVID-19 pandemic. Methods: In this cross-sectional study, 1000 frontline HCWs were recruited from various healthcare facilities in Vietnam between October 2021 and November 2021. Data were collected using a 3-part self-administered questionnaire, which covered demographics, sleep quality, and factors related to poor sleep. Poor sleep quality was defined as a total PSQI score of 5 or higher. Results: Participants' mean age was 33.20±6.81 years (range, 20.0-61.0), and 63.0% were women. The median work experience was 8.54±6.30 years. Approximately 6.3% had chronic comorbidities, such as hypertension and diabetes mellitus. About 59.5% were directly responsible for patient care and treatment, while 7.1% worked in tracing and sampling. A total of 73.8% reported poor sleep quality. Multivariate logistic regression revealed significant associations between poor sleep quality and the presence of chronic comorbidities (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.17 to 5.24), being a frontline HCW directly involved in patient care and treatment (OR, 1.59; 95% CI, 1.16 to 2.16), increased working hours (OR, 1.84; 95% CI,1.37 to 2.48), and a higher frequency of encountering critically ill and dying patients (OR, 1.42; 95% CI, 1.03 to 1.95). Conclusions: The high prevalence of poor sleep among HCWs in Vietnam during the COVID-19 pandemic was similar to that in other countries. Working conditions should be adjusted to improve sleep quality among this population.