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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.

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.

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

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.

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.

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

Background: The Paeonia lactiflora extract (PLE) has been reported to have neuroprotective effect against neurodegeneration that are induced by cellular stress such as oxidative stress. Its underlying mechanisms, however, remain unclear. In latest decades, emerging evidence has suggested that epigenetic mechanisms play a key role in gene regulation in response to the cellular stress. We investigated whether epigenetic modulation was involved in neuronal cell death by the neurotoxicant, 1-Methyl-4-phenylpyridinium (MPP+), and the neuroprotective effect of PLE. Methods: Differentiated SH-SY5Y, which is a well-established dopaminergic cell line model, was treated with 0 similar to 200 mu g/ml PLE for 4 h prior to MPP+ treatment. The effect of PLE on cell viability was determined by MTT assays. Gene expression levels of oxidative stress responsive genes, such as Heme oxygenase 1 (HMOX1), and histone modifiers, such as histone acetyltransferases (HATs) and deacetylases (HDACs) were measured by quantitative RT PCR. In order to investigate the changes in epigenetic modifications, the acetylated lysine 9 (H3K9ac) and lysine 27 (H3K27ac) of Histone H3 were measured by western blot using histones extracted from the cells. Results: MPP+-induced cell death in SH-SY5Y cells was significantly reduced by PLE pretreatment in a dose-dependent manner, indicating the potent neuroprotective effects of PLE. It was accompanied by induced expression of HMOX1. MPP+ treatment increased the expression of HATs and consistently increased H3K9ac and H3K27ac of Histone H3. PLE pretreatment impeded the changes in H3K9ac and H3K27ac, coincided with increased expression of HDAC5 without changes in HAT expression. Conclusions: The results suggested that MPP+-induced cell death in the dopaminergic SH-SY5Y cells was related with transcriptional induction of HATs and increased histone H3 acetylation and that PLE might prevent the cells from MPP+-induced cell death via tempering histone H3 acetylation.