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Background. The purpose of this study was to evaluate the efficacy and safety of Panax ginseng extract (GS-KG9) in the treatment of hepatic dysfunction. Methods. A randomized, double-blind, placebo-controlled clinical trial was conducted from December 2017 to January 2019. The trial included 60 subjects between the ages of 19 and 70 who had higher alanine transaminase (ALT) levels than the normal upper limit. The subjects were randomly divided into two groups: GS-KG9 (n = 30) and placebo (n = 30). The former was administered three GS-KG9 capsules (3 g/day) and the latter three placebo capsules (3 g/day) twice each day orally after meals in the morning and evening for 12 weeks. The primary goal was to observe the changes in ALT and gamma-glutamyl transferase (GGT) levels. The safety of the treatment was assessed and adverse events (AEs) were recorded. Results. Out of 60 subjects, nine were excluded from the efficacy analysis because they met the exclusion criteria. Therefore, a total of 51 subjects were evaluated for the effectiveness of the treatment (26 in the GS-KG9 group and 25 in the placebo group). After 12 weeks of treatment, the ALT levels were significantly reduced in the GS-KG9 group compared to the placebo group (p=0.009). The GGT level of the GS-KG9 group was significantly lower than that of the placebo group (p=0.036). Mild AEs, such as diarrhea, occurred during the study. There were no significant differences between the two groups. Conclusion. The results of this trial suggest that GS-KG9 might be an effective and safe option for mild hepatic dysfunction. This trial is registered with KCT0004080.

Background: Cervical cancer is the fourth most common malignant tumor among women worldwide. This study aimed to evaluate the efficacy of Astragalus-containing Chinese herbal medicine (CHM) combined with chemotherapy (CT) for the treatment of cervical cancer.Methods: Ten electronic databases including PubMed, Cochrane Library, Embase, Korean databases, and Chinese medical databases, were systematically searched up to July 2020. All randomized controlled trials using Astragalus-containing CHM combined with CT to treat cervical cancer were included.Results: A total of 19 trials were included in the analysis. Compared with the control group, the Astragalus-containing CHM combined with CT group showed a significantly increased tumor response (complete and partial response (CR and PR)) (risk ratio [RR] = 1.25, 95% confidence interval [CI]: 1.17–1.33, p < 0.00001) and Karnofsky performance score (KPS) (standardized mean difference [SMD] = 1.81, 95% CI: 1.46–2.17, p < 0.00001). This group also displayed remarkably reduced CT toxicity.Conclusion: Our study suggests that Astragalus-containing CHM might be a potential option for cervical cancer to enhance the curative efficacy and reduce CT toxicity.

From 25% to 50% of adults are affected by prehypertension. Prehypertension increases the risk of hypertension and affects the heart and systemic vascular system. Food mixed tree essence of Dendropa...

Background The purpose of this study was to evaluate the efficacy and safety of Panax ginseng extract (GS-KG9) in the treatment of hepatic dysfunction. Methods A randomized, double-blind, placebo-controlled clinical trial was conducted from December 2017 to January 2019. The trial included 60 subjects between the ages of 19 and 70 who had higher alanine transaminase (ALT) levels than the normal upper limit. The subjects were randomly divided into two groups: GS-KG9 (n = 30) and placebo (n = 30). The former was administered three GS-KG9 capsules (3 g/day) and the latter three placebo capsules (3 g/day) twice each day orally after meals in the morning and evening for 12 weeks. The primary goal was to observe the changes in ALT and gamma-glutamyl transferase (GGT) levels. The safety of the treatment was assessed and adverse events (AEs) were recorded. Results Out of 60 subjects, nine were excluded from the efficacy analysis because they met the exclusion criteria. Therefore, a total of 51 subjects were evaluated for the effectiveness of the treatment (26 in the GS-KG9 group and 25 in the placebo group). After 12 weeks of treatment, the ALT levels were significantly reduced in the GS-KG9 group compared to the placebo group (p=0.009). The GGT level of the GS-KG9 group was significantly lower than that of the placebo group (p=0.036). Mild AEs, such as diarrhea, occurred during the study. There were no significant differences between the two groups. Conclusion The results of this trial suggest that GS-KG9 might be an effective and safe option for mild hepatic dysfunction. This trial is registered with KCT0004080.

Sonography is conventionally used to diagnose fractures by identifying cortical discontinuity of the bone. In this study, fracture sonography in addition to color Doppler and dynamic scanning was performed in settings with limited or no access to radiography. We describe 5 cases of ankle and foot fractures with the use of sonography to identify changes in the fractured site. The width of the fracture space increased on dynamic scanning, and the Doppler signals were generated inside the fracture space on dynamic scanning. In conclusion, color Doppler sonography accompanied by dynamic scanning is a useful adjunctive diagnostic tool in addition to previously described sonographic fracture findings.

Hyperthermia, which is a noninvasive treatment that causes tumor cells to become heated and that works in synergy with anticancer drugs and radiation therapy, is emerging as a promising treatment for patients with cancer. The purpose of this study is to report the efficacy of hyperthermia combined with chemotherapy (gemcitabine/cisplatin) for the treatment of a patient with unresectable cholangiocarcinoma. A 54-year-old man was diagnosed as hilar cholangiocarcinoma (Klatskin tumor) and was administered neoadjuvant and preoperative radiation with chemotherapy. However, because the treatment with radiation and chemotherapy was not successful, he decided to undergo hyperthermia combined with chemotherapy as a second treatment option. He was suffering from fatigue, dyspepsia, epigastralgia, and jaundice. Hyperthermia combined with chemotherapy was administered 32 times over a period of 4 months. The patient experienced no critical complications, and the patient’s condition improved, with the carbohydrate antigen 19-9 (CA 19-9) and the total bilirubin levels being relatively lowered. In addition, the computed tomography scan showed that the cholangiocarcinoma had not progressed. In conclusion, this case report suggests radiofrequency hyperthermia combined with chemotherapy may be a promising treatment option for patients with unresectable cholangiocarcinoma.

// Jong Cheon Joo 1, * , Jung Hoo Hwang 2, * , Eunbi Jo 3 , Young-Rang Kim 3 , Dae Joon Kim 4 , Kyung-Bok Lee 3 , Soo Jung Park 5 , Ik-Soon Jang 3 1 Department of Sasang Constitutional Medicine, Wonkwang University, Iksan, 54538, Republic of Korea 2 College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea 3 Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea 4 Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA 5 Department of Sasang Constitutional Medicine, Woosuk University, Wanju, Jeonbuk, 55338, Republic of Korea * These authors have contributed equally to this work Correspondence to: Ik-Soon Jang, email: jangiksn@kbsi.re.kr Soo Jung Park, email: taorgi@hanmail.net Keywords: cordycepin, CAV1, JNK, Foxo3a, apoptosis Received: June 13, 2016 Accepted: December 27, 2016 Published: January 14, 2017 ABSTRACT Forkhead transcription factor (Foxo3a) is a downstream effector of JNK-induced tumor suppression. However, it is not clear whether the caveolin-1 (CAV1)-mediated JNK/Foxo3a pathway is involved in cancer cell apoptosis. We found that cordycepin upregulates CAV1 expression, which was accompanied by JNK phosphorylation (p-JNK) and subsequent Foxo3a translocation into the nucleus, resulting in the upregulation of Bax protein expression. Furthermore, we found that CAV1 overexpression upregulated p-JNK, whereas CAV1 siRNA downregulated p-JNK. Additionally, SP600125, a specific JNK inhibitor, significantly increased Foxo3a phosphorylation, which downregulated Foxo3a translocation into the nucleus, indicating that CAV1 mediates JNK regulation of Foxo3a. Foxo3a siRNA downregulated Bax protein and attenuated A549 apoptosis, indicating that the CAV1-mediated JNK/Foxo3a pathway induces the apoptosis of A549 lung cancer cells. Cordycepin significantly decreased tumor volume in nude mice. Taken together, these results indicate that cordycepin promotes CAV1 upregulation to enhance JNK/Foxo3a signaling pathway activation, inducing apoptosis in lung cancer cells, and support its potential as a therapeutic agent for lung cancer.

Ovarian cancer is the gynecological malignancy with the poorest prognosis, in part due to its high incidence of recurrence. Platinum agents are widely used as a first-line treatment against ovarian cancer. Recurrent tumors, however, frequently demonstrate acquired chemo-resistance to platinum agent toxicity. To improve chemo-sensitivity, combination chemotherapy regimens have been investigated. This study examined anti-tumor effects and molecular mechanisms of cytotoxicity of Oldenlandia diffusa (OD) extracts on ovarian cancer cells, in particular, cells resistant to cisplatin. Six ovarian cancer cells including A2780 and cisplatin-resistant A2780 (A2780cis) as representative cell models were used. OD was extracted with water (WOD) or 50% methanol (MOD). MOD significantly induced cell death in both cisplatin-sensitive cells and cisplatin-resistant cells. The combination treatment of MOD with cisplatin reduced viability in A2780cis cells more effectively than treatment with cisplatin alone. MOD in A2780cis cells resulted in downregulation of the epigenetic modulator KDM1B and the DNA repair gene DCLRE1B. Transcriptional suppression of KDM1B and DCLRE1B induced cisplatin sensitivity. Knockdown of KDM1B led to downregulation of DCLRE1B expression, suggesting that DCLRE1B was a KDM1B downstream target. Taken together, OD extract effectively promoted cell death in cisplatin-resistant ovarian cancer cells under cisplatin treatment through modulating KDM1B and DCLRE1B.

Urokinase receptor (uPAR) is enhanced in many human cancer cells and is frequently an indicator of poor prognosis. Activation of [Formula: see text]1-integrin requires caveolin-1 and is regulated by uPAR. However, the underlying molecular mechanism responsible for the interaction between uPAR and [Formula: see text]1-integrin remains obscure. We found that modified regular Panax ginseng extract (MRGX) had a negative modulating effect on the uPAR/[Formula: see text]1-integrin interaction, disrupted the uPAR/integrin interaction by modulating caveoline-1, and caused early apoptosis in cancer cells. Additionally, we found that siRNA-mediated caveoline-1 downregulation inhibited uPAR-mediated [Formula: see text]1-integrin signaling, whereas caveoline-1 up-regulation stimulated the signaling, which suppressed p53 expression, thereby indicating negative crosstalk exists between the integrin [Formula: see text]1 and the p53 pathways. Thus, these findings identify a novel mechanism whereby the inhibition of [Formula: see text]1 integrin and the activation of p53 modulate the expression of the anti-apoptotic proteins that are crucially involved in inducing apoptosis in A549 lung cancer cells. Furthermore, MRGX causes changes in the expressions of members of the Bcl-2 family (Bax and Bcl-2) in a pro-apoptotic manner. In addition, MGRX-mediated inhibition of [Formula: see text]1 integrin attenuates ERK phosphorylation (p-ERK), which up-regulates caspase-8 and Bax. Therefore, ERK may affect mitochondria through a negative regulation of caspase-8 and Bax. Taken together, these findings reveal that MRGX is involved in uPAR-[Formula: see text]1-integrin signaling by modulating caveolin-1 signaling to induce early apoptosis in A549 lung-cancer cells and strongly indicate that MRGX might be useful as a herbal medicine and may lead to the development of new herbal medicine that would suppress the growth of lung-cancer cells.

Tongue of Fatigue by Classification of Sasang Constitution and Qi Blood Pattern Identification Na-Rae Choi ＊ , Soo-Jung Park ＊ , Jong-Cheon Joo ＊ , Young-Mi Kwon †＊ Dept. of Sasang Constitutional Medicine, College of Korean Medicine, Wonkwang University † Dept. of Radiology, College of Korean Medicine, Wonkwang UniversityObjectivesThe purpose of this study was to investigate the relevance of Sasang constitution, Qi Blood pattern identification, and tongue diagnosis in subjects complaining of fatigue.Methods Seventy-three subjects who complained of fatigue were assessed using the Chalder Fatigue Scale, tongue diagnosis, pattern identification questionnaire and Sasang constitution diagnosis. The association of tongue diagnosis with Qi Blood pattern identification and Sasang constitution was evaluated. Results1. There was no significant association between tongue diagnosis and Sasang constitution.2. Tongue color, which is one of the diagnostic indicators in tongue diagnosis, was redder in the Qi stagnation group than in the Qi deficiency and Blood deficiency groups. ConclusionsTongue diagnosis can be utilized in future if proper research regarding Sasang constitution and Sasang constitution pattern identification is conducted.Key Words

Clinical Practice Guideline for Taeyangin Disease of Sasang Constitutional Medicine Hye-Sun Park, Jong-Cheon Joo * , Eui-ju Lee † Dept. of Sasang Constitutional Medicine, College of Korean Medicine, Dongshin University, Jeollanam-do, Naju, Korea * Dept. of Sasang Constitutional Medicine, College of Korean Medicine, Wonkwang University, Jeollabuk-do, Iksan, Korea † Dept. of Sasang Constitutional Medicine, College of Korean Medicine, Kyung Hee University, Seoul, KoreaObjectivesThis research was proposed to present clinical practice guideline (CPG) for Taeyangin Disease of Sasang Constitutional Medicine (SCM). This CPG was developed by the national-wide experts committee consisting of SCM professors.Methods This guideline was performed that search and collection of literature related SCM such as 『Dongeuisusebowon󰡕,textbook of SCM, clinical guidebook of SCM and fundamental research to standardize diagnosis of Sasang ConstitutionalMedicine. Journal search related clinical trial or human complementary medicine of SCM was performed domesticand overseas. Finally, 1 article was selected and included in CPG for Taeyangin disease.Results & ConclusionsThe CPG of Taeyangin disease include classification, definition and standard symptoms of each pattern. Taeyangin disease is classified into exterior-origin lower back (EOLB) disease and interior-origin small intestine (IOSI) diseaseby region of symptom. EOLB can be replaced with Oegam-yocheok and IOSI can be replaced with Naechok-sojangthat is Korean pronuncation. EOLB disease is classified into lower back favorable symptomatology (LBFS) and lower back unfavorable symptomatology (LBUS). Lower back is to say Yocheok, so LBFS can be called Yocheok favorable symptomatology and LBUS can be called Yocheok unfavorable symptomatology. LBUS is to say paraparesissymptomatology or Haeyeok, that is Korean pronunciation, symptomatology. IOSI disease is classified into smallintestine favorable symptomatology (SIFS) and small intestine unfavorable symptomatology (SIUS). Small intestineis to say Sojang, so SIFS can be called Sojang favorable symptomatology and SIUS can be called Sojang unfavorable symptomatology. SIUS is to say regurgitation symptomatology or Yeolgeok, that is Korean pronunciation, symptomatology.Key Words: Sasang Constitutional Medicine, Clinical Practice Guideline, Taeyangin

Objectives: This study was designed to evaluate the effi cacy and the safety of constitutional herbal tea for treating chronic fatigue with no diagnosed cause, which is called Mibyeong in Korea. Methods: Males and females with ages between 40 and 59 years who had complained of fatigue for 1 month consistently or for 6 months intermittently without a definite cause were recruited. At the same time, a Chalder fatigue scale (CFS) score of 19 was essential for participation in this study. Sixty five subjects completed the entire pro cess, including blood tests and tests with medical devices. Five assessments of health status were accomplished over 8 weeks by using the CFS and the visual analogue scale (VAS). To ensure that the constitutional herbal tea was being safely used, we conducted and analyzed renal function and liver function tests. For the diagnosis of the Sasang constitution, the Sasang Constitutional Analysis Tool (SCAT) was used, and a specialist in Sasang constitutional medicine made the final diagnosis based on the SCAT result. Constitutional herbal tea was served four weeks after the first visit. The subjects took the constitutional herbal tea twice a day for one month. Results: The results are as follows: The CFS and the VAS scores were significantly improved for the subjects in the constitutional herbal tea. No abnormalities were found on the blood tests to evaluate safety after taking the constitutional herbal tea. The improvements in the CFS and the VAS scores due to the constitutional herbal tea had no significant differences according to the Sasang constitution. Conclusion: Constitutional herbal tea may be used to reduce fatigue and improve health and has no adverse effect on either the kidney or the liver.

Cellular FLICE inhibitory protein (c-FLIP) is a key anti-apoptotic regulator that associates with the signaling complex downstream of NF-κB, negatively interfering with apoptotic signaling. The role of c-FLIP downregulation by negative regulation of NF-κB signaling during apoptosis is poorly understood. Here, we demonstrate that NF-κB-mediated c-FLIPL negatively regulates the JNK signaling pathway, and that cordycepin treatment of human renal cancer cells leads to apoptosis induction through c-FLIPL inhibition. TNF-α-induced inflammatory microenvironments stimulated NF-κB signaling and the c-FLIP long form (c-FLIPL) in TK-10 cells. Specifically, cordycepin inhibited TNF-α-mediated NF-κB activation, which induced renal cancer cell apoptosis. Cordycepin downregulated GADD45B and c-FLIPL, but upregulated MKK7 and phospho-JNK, by preventing nuclear mobilization of NF-κB. Furthermore, siRNA-mediated knockdown of GADD45B in cordycepin-treated TK-10 cells considerably increased MKK7 compared to cordycepin alone. siRNA-mediated knockdown of c-FLIPL prevented TNF-α-induced JNK inactivation, whereas c-FLIPL overexpression inhibited cordycepin-mediated JNK activation. The JNK inhibitor SP600125 strongly inhibited Bax expression. In nude mice, cordycepin significantly decreased tumor volume. Taken together, the results indicate that cordycepin inhibits TNF-α-mediated NF-κB/GADD45B signaling, which activates the MKK7-JNK signaling pathway through inhibition of c-FLIPL expression, thus inducing TK-10 cell apoptosis.

Background Ovarian cancer is one of the major causes of death among females in worldwide. Cisplatin is a primary anti-cancer drug against ovarian cancer, but the recurrent tumors after treatment frequently show acquired chemoresistance. Extract of Scutellaria baicalensis (SbE) has been reported to have functional compounds including baicalin, which has anti-cancer effects. However, the anti-cancer effects of SbE in ovarian cancer and its underlying mechanisms are elusive. Methods We investigated that the effects of SbE and/or cisplatin on cell death in the cisplatin sensitive ovarian cancer cell line A2780 (CSC) and the counterpart cell line that has cisplatin resistance (CRC). Molecular mechanisms of the effects, focusing on apoptosis and autophagy, were examined. Results Treatment of cisplatin or SbE reduced cell viability significantly in CSC and too much lesser extent in CRC. Cisplatin-induced cell death in CSC was mediated by p53-induced apoptosis acompanied by expresson of damage-regulated autophagy modulator (DRAM). In CRC, decreased DRAM expression (p

Sasang Constitutional Characteristic of Amyotrophic Lateral Sclerosis Soo-Jung Park, Ho-Hyun Jeong * , Eun-Su Jang † , Sang-Hyuk Kim † , Sung-Chul Kim, Jong-Cheon JooDept. of Sasang Constitutional Medicine, Wonkwang University Jeonju Korean Medicine Hospital, * Dept. of Acupuncture and Moxibustional Medicine, Wonkwang University Gwangju Korean Medicine Hospital, † KM Health Technology Research Group, Korea Institute of Oriental MedicineObjectivesThe purpose of this study was to analyze the Sasang constitution and psychological traits of amyotrophic lateral sclerosis (ALS) patients and to utilize the results in treatment and management. MethodsThe differences of Sasang Constitution distribution, psychological characteristics, comorbid disorders between ALS group of 26 patients and general group of 1132 persons were investigated and analyzed.ResultsThere was no significant different distribution of Sasang Constitution between ALS group and general group but there was Yang-like personality tendency in ALS group than general group. In overall constitution, ALS group had the high prevalence rate of musculoskeletal disorders and diabetes than general group. In Soyangin constitution, ALS group had a high prevalence rate of musculoskeletal disorders than genral group. In Taeeumin constitution, ALS group had a high prevalence rate of diabetes and hypertension than general group.ConclusionALS patients have the Yang-like personality. It is due to the adaptation of personality on the environmental changeor coping strategy on diseases rather than the characteristics of congenital Sasang Constitution.Key Words: Amyotrophic lateral sclerosis, Sasang Constitution, Personality, Comorbid disorder

Objectives This research was proposed to present Clinical Practice Guideline(CPG) for Soeumin Disease of Sasang Constitutional Medicine(SCM): Yang Depletion Symptomatology. Methods This CPG was developed by the national-wide experts committee consisting of the society of Sasang Constitutional Medicine. it was performed by search and collection of literature related SCM, opinion of SCM experts and journal search. And it was followed by CPG`s guideline. Results & Conclusions No article was selected and included in CPG for Yang Depletion Symptomatology of Kidney Heat-based Exterior Heat disease in Soeumin disease. CPG of Yang Depletion symptomatology in Soeumin Disease include classification, definition and standard symptoms of each pattern. Yang Depletion symptomatology is classified into severe and critical pattern by severity. Yang Depletion Symptomatology severe pattern is classified into initial phase pattern and intermediate phase pattern. And Yang Depletion Symptomatology critical pattern is classified into advanced phase pattern.

Objectives: This study was designed to investigate the effects of Calculus Bovis-Fel Uris-Moschus pharmacopuncture (BUM) on the regional cerebral blood flow (rCBF) and the mean arterial blood pressure (MABP) in normal and cerebral ischemic rats and to investigate a possible pathway involved in the effects of BUM. Methods: The changes in the rCBF and the MABP fol lowing BUM into Fengfu (GV16) were determined by using a laser-Doppler flow meter and a pressure trans ducer, respectively. Results: BUM significantly increased the rCBF and de creased the MABP in normal rats in a dose-dependent manner. The effect on the rCBF was significantly inhib ited by pretreatment with methylene blue (0.01 mg/kg, intraperitoneal), an inhibitor of guanylate cyclase, but was not affected by pretreatment with indomethacin (1 mg/kg, intraperitoneal), an inhibitor of cyclooxygenase. The BUM-induced decrease of the MABP was changed neither by methylene blue nor by indomethacin pretreatment. In the cerebral ischemic rats, the rCBF was stably increased upon cerebral reperfusion in the BUM group in contrast to the rapid and marked increase in the control group. Conclusion: This study demonstrated that BUM into Fengbu (GV16) increased the rCBF in a dose-dependent manner in the normal state; furthermore, it improved the stability of the rCBF in the ischemic state upon reperfusion. Also, the effects of BUM on the rCBF were attenuated by inhibition of guanylate cyclase, suggesting that the effects involved the guanylate cy clase pathway.

Objectives The purpose of this study was to find correlations between gastrointestinal disorders, pain, sleep disorder, fatigue, and to figure out characteristics of fatigue in Sasang Constitution using medical devices data. Methods Sixty three subjects were divided into fatigue group and non-fatigue group, both groups had to undergo blood tests, questionnaire, Sasang constitutional analysis tool (SCAT), pulse wave analyzer examination, heart rate variability examination, nail fold capillary microscopic examination. Results 1) The results of questionnaire about fatigue, gastrointestinal disorder, pain, sleep disorder, quality of life had significant differences between fatigue and non-fatigue groups. 2) Soeumin had more serious gastrointestinal problem and Soyangin had more serious sleep disorder in fatigue groups than non-fatigue groups. 3) According to blood test results, there was no difference between fatigue and non-fatigue groups. 4) Elastic parameter of pulse wave analyzer and nail fold capillary microscopic examination showed significant differences between fatigue and non-fatigue groups in Soyangin. Conclusions We reach the conclusion that fatigue is usually accompanied by gastrointestinal disorder, pain, sleep disorder, deterioration in the quality of life. In Soeumin, treating gastrointestinal disorders can be helpful for treatment of fatigue. In Soyangin, improving sleep disorder may be more effective way to treat fatigue.

Houttuynia cordata Thunb ( H cordata), a medicinal plant, has anticancer activity, as it inhibits cell growth and induces cell apoptosis in cancer. However, the potential anti-cancer activity and mechanism of H cordata for human liver cancer cells is not well understood. Recently, we identified hypoxia-inducible factor (HIF)-1A, Forkhead box (FOX)O3, and MEF2A as proapoptotic factors induced by H cordata, suggesting that HIF-1A, FOXO3, and MEF2A contribute to the apoptosis of HepG2 hepatocellular carcinoma cells. FOXO3 transcription factors regulate target genes involved in apoptosis. H cordata significantly increased the mRNA and protein expression of HIF-1A and FOXO3 and stimulated MEF2A expression in addition to increased apoptosis in HepG2 cells within 24 hours. Therefore, we determined the potential role of FOXO3 on apoptosis and on H cordata–induced MEF2A in HepG2 cells. HIF-1A silencing by siRNA attenuated MEF2A and H cordata–mediated FOXO3 upregulation in HepG2 cells. Furthermore, H cordata–mediated MEF2A expression enhanced caspase-3 and caspase-7, which were abolished on silencing FOXO3 with siRNA. In addition, H cordata inhibited growth of human hepatocellular carcinoma xenografts in nude mice. Taken together, our results demonstrate that H cordata enhances HIF-1A/FOXO3 signaling, leading to MEF2A upregulation in HepG2 cells, and in parallel, it disturbs the expression of Bcl-2 family proteins (Bax, Bcl-2, and Bcl-xL), which results in apoptosis. Taken together, these findings demonstrate that H cordata promotes the activation of HIF-1A–FOXO3 and MEF2A pathways to induce apoptosis in human HepG2 hepatocellular carcinoma cells and is, therefore, a promising candidate for antitumor drug development.

Urokinase receptor (uPAR) is enhanced in many human cancer cells and is frequently an indicator of poor prognosis. Activation of [Formula: see text]1-integrin requires caveolin-1 and is regulated by uPAR. However, the underlying molecular mechanism responsible for the interaction between uPAR and [Formula: see text]1-integrin remains obscure. We found that modified regular Panax ginseng extract (MRGX) had a negative modulating effect on the uPAR/[Formula: see text]1-integrin interaction, disrupted the uPAR/integrin interaction by modulating caveoline-1, and caused early apoptosis in cancer cells. Additionally, we found that siRNA-mediated caveoline-1 downregulation inhibited uPAR-mediated [Formula: see text]1-integrin signaling, whereas caveoline-1 up-regulation stimulated the signaling, which suppressed p53 expression, thereby indicating negative crosstalk exists between the integrin [Formula: see text]1 and the p53 pathways. Thus, these findings identify a novel mechanism whereby the inhibition of [Formula: see text]1 integrin and the activation of p53 modulate the expression of the anti-apoptotic proteins that are crucially involved in inducing apoptosis in A549 lung cancer cells. Furthermore, MRGX causes changes in the expressions of members of the Bcl-2 family (Bax and Bcl-2) in a pro-apoptotic manner. In addition, MGRX-mediated inhibition of [Formula: see text]1 integrin attenuates ERK phosphorylation (p-ERK), which up-regulates caspase-8 and Bax. Therefore, ERK may affect mitochondria through a negative regulation of caspase-8 and Bax. Taken together, these findings reveal that MRGX is involved in uPAR-[Formula: see text]1-integrin signaling by modulating caveolin-1 signaling to induce early apoptosis in A549 lung-cancer cells and strongly indicate that MRGX might be useful as a herbal medicine and may lead to the development of new herbal medicine that would suppress the growth of lung-cancer cells.

Constitutive activation of extracellular signal regulated kinase (ERK)-Jun NH2-terminal kinase (JNK) signaling commonly occurs in tumors. The activation of ERK promotes cell proliferation, whereas that of JNK induces cell apoptosis. However, the apoptotic mechanism of ERK-JNK signaling in cancer is not well understood. Recently, we identified that apoptosis and activation of the JNK signaling pathway were induced after cordycepin treatment in human renal cancer, suggesting that JNK signaling might contribute to TK-10 cell apoptosis. We investigated the apoptotic effects of cordycepin by evaluating the activation of the ERK-JNK signaling pathway in renal cancer TK-10 cells. We found that cordycepin downregulated ERK and DUSP5, upregulated phosphorylated-JNK (p-JNK), and induced apoptosis. Moreover, we showed that siRNA-mediated inhibition of ERK downregulated DUSP5, whereas ERK overexpression upregulated DUSP5, and that DUSP5 knockdown by siRNA upregulated p-JNK. The JNK-specific inhibitor SP600125 upregulated nuclear translocation of β-catenin, and downregulated Dickkopf-1 (Dkk1), which has been shown to be a potent inhibitor of Wnt signaling. Dkk1 knockdown by siRNA upregulated nuclear β-catenin, suggesting the involvement of the Wnt/β-catenin signaling pathway. DUSP5 overexpression in TK-10 cells decreased p-JNK and increased nuclear β-catenin. The decreased Bax activation markedly protected against cordycepin-induced apoptosis. Bax subfamily proteins induced apoptosis through caspase-3. Taken together, we show that JNK signaling activation by cordycepin mediated ERK inhibition, which might have induced Bax translocation and caspase-3 activation via regulation of DUSP5 in TK-10 cells, thereby promoting the apoptosis of TK-10 cells. Targeting ERK-JNK signaling via the apoptotic effects of cordycepin could be a potential therapeutic strategy to treat renal cancer.

Objectives : The purpose of this study was to validate the Sasang Personality Questionnaire (SPQ), based on the diagnosis of Sasang constitutional medicine clinical specialist.

1. Objectives : In this study we derived constitutional characteristics both by using questionnaire on character and symptom and by collecting objective measurement data through face, body shape. Furthermore, by developing a program, we intend to help one`s diagnosis of Sasang constitution. 2. Methods : Through November 2007 to July 2009, we obtained questionnaire, face, and body shape data of 958 constitution confirmed subjects within the age range of 10-80 from 19 oriental medical facilities in the country. According to sex, we divided the subjects into two groups as real constitution and non-constitution group respectively. We analyzed the questionnaire through chi-square test (p

Objectives: This study was designed to investigate the effect of four pharmacopuncture drugs (scolopendrid, Calculus Bovis-Fel Uris-Moschus (BUM), bee venom 25%, and sweet bee venom 10%) on the cerebral hemodynamics, including changes in the regional cerebral blood flow (rCBF) and in the mean arterial blood pressure (MABP). Methods: The changes in the rCBF and the MABP were determined by using a laser-Doppler flowmeter and a pressure transducer, respectively. Results: Scolopendrid (0.3 ml, 1 ml/kg) caused no significant changes in the rCBF and the MABP, whereas BUM (0.3 ml, 1 ml/kg) decreased the rCBF and the MABP, bee venom 25% (0.3 ml, 1 ml/kg) increased the rCBF and lowered the MABP, and sweet bee venom 10% (0.3 ml, 1 ml/kg) increased the rCBF and had no significant effect on the MABP. Conclusions: The rCBF and the MABP were influenced differently by the administration of various pharmacopunctures. Further studies are needed to elucidate the underlying mechanism.

The ubiquitous transcription factor, NF-κB, has been reported to inhibit apoptosis and induce drug resistance in cancer cells. Cordyceps militaris extract (CME) is involved in the regulation of the NF-κB signaling pathway. However, the detailed role of CME in the suppression of the NF-κB signaling pathway is unclear. We found that CME dose-dependently inhibited tumor necrosis factor-α (TNF-α)-induced NF-κB activation in TK-10 human renal cell carcinoma. CME prevented NF-κB from translocating to the nucleus, which resulted in the downregulation of GADD45B, upregulation of MKK7, and phosphorylation of JNK (p-JNK). The increased activation of Bax led to pronounced CME-induced apoptosis, which occurred through caspase-3. Furthermore, the siRNA-mediated knockdown of GADD45B inhibited MKK7 expression, whereas the siRNA-mediated inhibition of MKK7 downregulated p-JNK and the JNK inhibitor, SP600125, inhibited Bax expression. Thus, these results indicated that CME inhibited the activation of GADD45B via the inhibition of NF-κB activation, which upregulated the MKK7-JNK signaling pathway to induce apoptosis in TK-10 cells. Thus, this study reveals a novel anticancer function of CME.

1. Objectives: To evaluate effects of bee venom acupuncture on cardiovascular system and differences according to each constitution. 2. Methods: Heart rate variability, pulse wave and the velocity of cerebral blood flow were measured before bee venom acupuncture(BVA), right after and after 30 minuets, had been applied to 20 subjects. 3. Results: 1. BVA did not have effects on measurement variables of heart rate variability. 2. BVA had effects on pulse wave, showing total time, radial augmentation index up and height of percussion wave, time to percussion wave, sum of pulse pressure down. 3. BVA did not have effects on the cerebral blood flow velocity when considering not Sasang Constitution 4. Considering Sasang Constitution, BVA demonstrates different responses in time to preincisura wave, mean blood flow velocity, peak systolic velocity and end diastolic velocity. 4.Conclusion: From those results, the following conclusions are obtained. Cause BVA alters pulse wave and makes differences in the cerebral blood flow velocity according to Sasang Constitution. Various methods of BVA treatment are needed considering Sasang Constitution.

Multidrug resistance 1 (MDR1) is a gene that expresses P-glycoprotein (P-gp), a drug transporter protein. Genetic polymorphisms ofMDR1can be associated with Sasang constitutions because Sasang constitutional medicine (SCM) prescribes different drugs according to different constitutions. A Questionnaire for Sasang Constitution Classification II (QSCC II) was used to diagnose Sasang constitutions. Two hundred and seven healthy people whose Sasang constitutions had been identified were tested. Genotype analyses, restriction fragment length polymorphism (RFLP) and pyrosequencing were used in MDR1 C1236T, and in MDR1 G2677T/A and C3435T, respectively. Significant differences inMDR1 C1236Tgenotypes were found between So-yangin and So-eumin.MDR1 G2677T/Agenotype also showed significant differences in allele distribution between So-yangin and Tae-eumin. So-yangin and So-eumin showed significant differences in the distribution of both 1236C-2677G-3435C and 1236T-2677G-3435T, haplotypes ofMDR1. The genetic polymorphism of theMDR1gene was thus shown to be an indicator that could distinguish So-yangin from other constitutions.

This study was performed to determine whether a pulse analyzer was useful 1) to characterize the variables of pulse wave of cerebral infarction patieno (CI), compared with those of healthy subjects, as well as 2) to determine Sasang Constitution in CI and healthy subjects. 1. Calibrated in Gwan, the amount of energy(Energy), height of main peak(H1), height of aorticvalley(H2), height of aortic peak(H3), total area of pulse wave(At), and area of main peak width(Aw) of the CI group were higher than those of the healthy group. 2. Calibrated in Cheek, Energy, H1, H2, H3, height of valve valley(H4), At, Aw, and main peak angle(MPA) of the CI group were higher than those of the healthy group. 3. Among the healthy (subjects) group, Taeumin showed the highest contact pressure(CP) and height of valve peak(H5) calibrated in Chon. The main peak width divided by whole time of pulse wave(MPW/T) calibrated in Gwan and Cheok, was highest in Soyangin and was lowest in Taeumin. The H3 divided by H1(H3/H1) and the time to valve valley minus the time to main peak and divided by T[(T4-T1)/T] calibrated in Cheek were highest in Soyangin. The time to main peak(T1) was longest in Soumin. 4. Among the CI group, At calibrated in Chon was widest in Taeumin and was narrowest in Soumin The time to aortic peak(T3) calibrated in Cheek was longest in Soumin and was shortest in Soyangin. The time to valve peak(T5) was shortest in Soyangin. 5. There were main effects of cerebral infarction in the area of systolic period(As) and area of diastolic period(Ad) calibrated in Chon, Energy calibrated in Cwan, and Energy, H1, H2, H3, (H4+H5)/Hl, and MPA calibrated in Cheek. 6. There were main effects of Sasang Constitution in (T4-T1)/T, area of systolic period(As), and Ad calibrated in Chon. 7. The interactions between the cerebral infarction and Sasang Constitution were observed in H5/H1 , T, At, As, Ad, and MPA calibrated in Chon, H4, T4, (T4-T1)/T, As, and Ad calibrated in Cwan, and 74,75, and MPW calibrated in Cheok. Therefore, we concluded that pulse analyzer was useful to determine the risk degree of cerebral infarction and Sasang Constitution.

Sasang constitutional medicine is a major branch of Korean traditional Oriental medicine. The differences of disease susceptibility to be shown in Sasang constitution may be due to genetic factors. Therefore, the authors examined relationship between candidate genes of cerebral infarction (CI) and Sasang constitution. The homozygous deletion allele of the angiotensin converting enzyme gene (ACE/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the e4 allele of the apolipoprotein E gene (ApoE/e4) are reported to be associated with ischemic heart disease. CI is another atherosclerotic disease; and the effects of these polymorphisms on CI have been confusing. This study investigated whether ACE/DD, AGN/TT, and ApoE/e4 genotypes are associated with CI and whether genetic risk is enhanced by Sasang constitutional classification. The authors ascertained these genotypes in patients with CI (N=211), diagnosed by brain computed tomography. Control subjects for the infarction group were randomly selected from 319 subjects matched for age, sex, and history of hypertension with patients. The ACE/DD genotype was not associated with CI. However, there was significant association between ApoE polymorphism and CI (chi2=15.089, p

Glutathione S-transferase polymorphisms (GST) were examined in 98 cases with cerebrovascular disease (CVD) to test the hypothesis that GST polymorphisms confer a risk to an individual to develop CVD. Tobacco smoke is a major cause of both cancer and vascular disease. We therefore were stratified the subjects with CVD for smoking status, and then examined whether polymorphisms in this detoxification enzyme gene, GST, influence risk of CVD. Neither GSTM1 nor GSTT1 genotypes in the CVD group was significantly different from the control group (n=230), even in smokers. We attempted the combined analyses for GSTM1 and GSTT1 genotypes in CVD for smoking status. No significant association observed between the combined genotypes and CVD. We also classified the subjects and control group into four types according to Sasang Constitutional Medicine, Korean Traditional Oriental Medicine, and investigated the association among GST genotypes, CVD, and Sasang constitutional classification. Our observations do not confirm the effect of the GSTM1 and GSTT1 genotypes as a risk factor for CVD, even in smokers. Furthermore, we first attempted to evaluate the efficacy of Sasang Constitutional Medicine, and to find an association with CVD.

The purpose of this study is to evaluate the clinical effect of Hwangryunhaedok-tang Herbal-Acupuncture. Hwangryunhaedok-tang is used in all heating diseases. Chest Heating Sensation is a unique concept in Oriental Medicine. So we applied Hwangryunhaedok-tang Herbal-Acupuncture to treat the Chest Heating Sensation. We used DITI(Digital Infrared Thermographic Imaging) to estimate the temperatures of chest surface for the outcome assessment. We came to know that the chest surface temperatures were all reduced in both cases after Herbal-Acupuncture treatment. The reduced average temperature was 1.5℃ in case 1 and 0.9℃ in case 2. The above result indicates that Hwangryunhaedok-tang Herbal-Acupuncture treatment has an effect on Chest Heating Sensation, thus continuous Hwangryunhaedok-tang Herbal-Acupuncture study will be needed for more clinical applications.

태음인의 辛丑本 新定方 처방과 약재는 甲午本과 辛丑本을 거 치면서 表病과 裏病의 구분을 비롯한 생리, 병리의 인식과 병증 적 용에 있어서 많은 변화가 있었으며, 辛丑本에서도 주치증이 생략된 처방이 있어 辛丑本만으로는 모든 처방들의 病證論적 근거를 밝히 기가 어렵다. 辛丑本의 病證 분류도 사상의학 연구자에 따라 분류 기준이나 연구 의도에 따라 다르게 구분되어 다양한 각도의 체계적 인 연구가 필요하다1-6). 사상의학에서는 병증을 기존 證治醫學과는 달리 陰陽虛實로 논하지 않고 각 체질의 保命之主가 어떤 상황에 처하느냐에 따라 升降緩束에 따라 논한 것이 기존 證治醫學의 八綱辨證, 氣血辨證, 臟腑辨證의 개념과 두드러진 차이점이라고 볼 수 있다7). 東醫壽世保元의 처방과 약재에 관한 연구는 東醫壽世保元 新 定方과 東醫四象新編을 비교한 연구8), 東醫壽世保元과 藥徵을 비 교한 연구9), 기존의학의 歸經, 性味, 效能을 사상의학적으로 재해 석한 연구10,11), 傷寒論과 金匱要略과의 비교를 통한 연구12), 八綱 의 개념에서 사상의학 처방을 분석한 연구13) 등 다수가 있으나 사 상의학적 생리, 병리를 고려한 관점에서의 연구는 비교적 적은 편 이다. 또한 東醫四象新編을 비롯한 사상의학 처방 서적은 이제마가 저술한 서적과는 달리 四象醫學의 證治醫學的 응용을 위해 실용성 과 활용성에 중심을 두어 편찬되어 四象體質 病證 運用精神과는 차이가 있다14). 이제마의 저서로는 北韓 保健省 간행 東武遺稿, 藏書閣 所藏 東武遺稿, 格致藁, 東醫壽世保元四象草本卷(이하 草本卷), 東醫壽 世保元 甲午本(이하 甲午本), 東醫壽世保元 辛丑本(이하 辛丑本)이 있으나 처방과 약재에 관한 내용은 北韓 保健省 東武遺稿, 草本卷, 甲午本, 辛丑本의 네 서적에 주로 기재되어 있다15-17). 본 연구에서 는 이제마가 저술한 네 서적에서 태음인의 생리, 병리, 병증, 처방 에 관한 내용을 수집, 정리, 요약, 분석하여 태음인의 처방을 사상 의학적으로 설명하고자 시도하여 병리와 처방에 관한 내용을 정리 하여 보고하는 바이다. 태음인 처방의 사상의학적 병리 연구