Behçet's disease and genes within the major histocompatibility complex region.

Song, Yeong Wook,Kang, Eun Ha Springer-Verlag Tokyo 2012 Modern Rheumatology Vol.22 No.2

<P>The role of genetic background in the development of Behçet's disease (BD) is best reflected by the strong association between HLA-B*51 and BD that has been demonstrated across various ethnic groups. The contributions made by other HLA or non-HLA genes to disease susceptibility have been suggested by the results of a number of gene association studies, although the true associations between the genes located within the major histocompatibility complex (MHC) region and BD have often been doubted due to the possibility of linkage disequilibrium of those genes with HLA-B*51. The presence of a true susceptibility gene in the vicinity of HLA-B*51 has also been extensively investigated because of the limited evidence that directly relates HLA-B*51 to the pathogenesis of BD. However, recent genome-wide association studies have confirmed that HLA-B*51 is primarily associated with BD and that there are multiple susceptibility loci other than HLA-B*51. In this review, we discuss BD-associated genes within the MHC region and their biological roles in the pathogenesis of BD.</P>

Davallialactone protects against adriamycin-induced cardiotoxicity in vitro and in vivo.

Arunachalam, Sankarganesh,Kim, Sun Young,Lee, Sun Hwa,Lee, Young Hee,Kim, Min Sun,Yun, Bong Sik,Yi, Ho Keun,Hwang, Pyoung Han Springer-Verlag Tokyo 2012 Journal of Natural Medicines Vol.66 No.1

<P>Adriamycin (ADR) is a potent anticancer drug. Its clinical applications are limited due to its cardiotoxicity. Oxidative stress is responsible for cardiomyopathy induced by ADR. Previous studies have demonstrated that davallialactone (DAVA), extracted from mushroom Inonotus xeranticus, has potential antiplatelet aggregation activity and free radical scavenging properties. In this study, we investigated whether DAVA has protective effects against ADR-induced free radical accumulation and apoptosis in cardiac muscle cells and compared the effects of DAVA with N-acetylcysteine, a potent antioxidant. We evaluated the effect of DAVA on ADR-induced cytotoxicity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and crystal violet staining, the reactive oxygen species (ROS) production by flow cytometry, and the expression of stress-related proteins like Cu/Zn superoxide dismutase (SOD), Mn-SOD, and the involvement of mitogen-activated protein kinase pathway by Western blot analysis. Apoptosis was assessed by nuclear condensation and the expression levels of pro-apoptotic proteins, such as caspase-3 and polyadenosine diphosphate-ribose polymerase (PARP). The cardio-protective effects of DAVA were also evaluated in an in vivo study in an animal model of ADR-induced acute cardiomyopathy. Our results showed that DAVA significantly increased the viability of doxorubicin-injured H9c2 cells and inhibited ADR-induced ROS production, apoptosis, and the expression of Cu/Zn SOD and Mn-SOD. DAVA also inhibited the expression of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), which was activated by ADR. In the in vivo animal model, treatment involving DAVA significantly reduced cardiomyocyte lesions. These results suggest that DAVA is a potentially protective agent for ADR-induced cardiotoxicity in cardiomyocytes and can be a potential candidate to protect against cardiotoxicity in ADR-treated cancer patients.</P>

Effects of Galla chinensis extracts on UVB-irradiated MMP-1 production in hairless mice.

Sun, Zheng-wang,Hwang, Eunson,Lee, Hyun Ji,Lee, Tae Youp,Song, Hyun Geun,Park, Sang-Yong,Shin, Heon-Sub,Lee, Don-Gil,Yi, Tae Hoo Springer-Verlag Tokyo 2015 Journal of Natural Medicines Vol.69 No.1

<P>Galla chinensis (GAC) is a natural traditional Chinese medicine that has been widely used in folk medicine. Although GAC compounds (mainly gallic acid and methyl gallate) possess strong antiviral, antibacterial, anticancer, and antioxidant activities, there is no report regarding topical or oral administration of GAC compounds on UVB irradiation-induced photoaging in hairless mice (SKH: HR-1). In the present study, we examined cell viability, intracellular reactive oxygen species (ROS), matrix metalloproteinase-1 (MMP-1), and interleukin-6 (IL-6) in skin fibroblasts and keratinocytes induced by UVB in vitro. We also studied skin damage by measuring skin thickness, elasticity, wrinkling and levels of protein MMP-1, elastin, procollagen type I, and transforming growth factor-β1 (TGF-β1) in hairless mouse skin chronically irradiated by UVB in vivo. GAC treatment significantly prevented skin photoaging by reducing the levels of ROS, MMP-1, and IL-6 and promoting production of elastin, procollagen type I, and TGF-β1. According to the results of H&E staining and Masson's trichrome staining, GAC reduced skin thickness and wrinkle formation while it increased skin elasticity. The effects of GAC on UVB-induced skin photoaging may be due to suppressed MMP-1 expression. These findings could be referenced for the development of new agents that target UVB-induced photoaging.</P>

Coptisine inhibits RANKL-induced NF-κB phosphorylation in osteoclast precursors and suppresses function through the regulation of RANKL and OPG gene expression in osteoblastic cells.

Lee, Ji-Won,Iwahashi, Ayumi,Hasegawa, Shin-ichi,Yonezawa, Takayuki,Jeon, Won Bae,Cha, Byung-Yoon,Nagai, Kazuo,Woo, Je-Tae Springer-Verlag Tokyo 2012 Journal of Natural Medicines Vol.66 No.1

<P>Excessive receptor activator of NF-κB ligand (RANKL) signaling causes enhanced osteoclast formation and bone resorption. The downregulation of RANKL expression and its downstream signals may be an effective therapeutic approach to the treatment of bone loss diseases such as osteoporosis. Here, we found that coptisine, one of the isoquinoline alkaloids from Coptidis Rhizoma, exhibited inhibitory effects on osteoclastogenesis in vitro. Although coptisine has been studied for its antipyretic, antiphotooxidative, dampness dispelling, antidote, antinociceptive, and anti-inflammatory activities in vitro and in vivo, its effects on osteoclastogenesis have not been investigated. Therefore, we evaluated the effects of coptisine on osteoblastic cells as well as osteoclast precursors for osteoclastogenesis in vitro. The addition of coptisine to cocultures of mouse bone marrow cells and primary osteoblastic cells with 10(-8) M 1α,25(OH)(2)D(3) caused significant inhibition of osteoclast formation in a dose-dependent manner. Reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed that coptisine inhibited RANKL gene expression and stimulated the osteoprotegerin gene expression induced by 1α,25(OH)(2)D(3) in osteoblastic cells. Coptisine strongly inhibited RANKL-induced osteoclast formation when added during the early stage of bone marrow macrophage (BMM) cultures, suggesting that it acts on osteoclast precursors to inhibit RANKL/RANK signaling. Among the RANK signaling pathways, coptisine inhibited NF-κB p65 phosphorylations, which are regulated in response to RANKL in BMMs. Coptisine also inhibited the RANKL-induced expression of NFATc1, which is a key transcription factor. In addition, 10 μM coptisine significantly inhibited both the survival of mature osteoclasts and their pit-forming activity in cocultures. Thus, coptisine has potential for the treatment or prevention of several bone diseases characterized by excessive bone destruction.</P>

Second-line chemotherapy for advanced gastric cancer in Korea.

Baek, Sun Kyung,Kim, Si-Young,Jeong, Jae-heon,Cho, Kyung San,Yoon, Hwi-Joong Springer-Verlag Tokyo 2012 Gastric cancer Vol.15 No.4

<P>Stomach cancer is still one of the most prevalent malignancies and is the main cause of cancer deaths worldwide. The outcome for patients with metastasis, as well as for those with tumor recurrence, is dismal, with median survival time not greater than a year. Patients with unresectable locally advanced or metastatic lesions have been treated with systemic chemotherapy, and several randomized studies have demonstrated the benefit of chemotherapy compared with best supportive care. Recently, randomized phase III trials have presented a benefit of second-line chemotherapy compared with supportive care alone. However, it is not known at present which drug is the most effective in this setting. In Korea, the practice of offering second-line treatment to patients with advanced gastric cancer (AGC) is common, and many prospective clinical trials investigating clinical outcomes of second-line chemotherapy have been reported. Therefore, to define the potential role of second-line chemotherapy and to help to select an effective regimen, we review the published Korean prospective data concerning the use of chemotherapy in the second-line setting for the treatment of AGC. No phase III trials but 20 phase II trials were identified. The benefit of second-line chemotherapy in AGC has indirect evidence considering prolongation of progression-free survival (PFS) and improvement of the response rate. Taxanes, irinotecan, and oxaliplatin have been studied much and might be promising drugs considering cross-resistance to a 5-fluorouracil and cisplatin combination (FP). A large, prospective, multicenter, randomized phase III study is warranted to select the most effective second-line chemotherapeutic agents.</P>

Red ginseng and 20(S)-Rg3 control testosterone-induced prostate hyperplasia by deregulating androgen receptor signaling.

Bae, Jung-Soo,Park, Hyoung-Sook,Park, Jong-Wan,Li, Shan-Hua,Chun, Yang-Sook Springer-Verlag Tokyo 2012 Journal of natural medicines Vol.66 No.3

<P>Since prostate growth is governed by the androgen signaling pathway, blockade of the pathway is regarded as an appropriate strategy for the treatment of benign prostatic hyperplasia (BPH). Panax ginseng is known to have various pharmacological activities. Of several products of its root, red ginseng, having many bioactive ginsenosides, is most popularly used in Korea, and recently has been reported to control the proliferation of cancer cells. We here tested the effect of a water extract of Korean red ginseng (WKRG) on testosterone-induced prostate hyperplasia. WKRG (daily intraperitoneal injection) prevented prostate overgrowth and epithelial thickening induced by testosterone in rats, and suppressed a rat prostate kallikrein-S3. In human prostate cells, WKRG inhibited testosterone-induced cell proliferation, arrested cell cycle by inducing p21 and p27, and induced apoptosis. Testosterone-induced expression of human kallikrein-3 mRNA and activation of androgen receptor (AR) were effectively inhibited by WKRG. Of the major ginsenosides included in WKRG, 20(S)-Rg3 was identified to repress AR activity and to attenuate prostate cell growth during testosterone stimulation. Moreover, 20(S)-Rg3 downregulated AR by facilitating the degradation of AR protein. WKRG and 20(S)-Rg3 were found to have new pharmacological activities against testosterone-induced prostate overgrowth. Given that red ginseng has been used safely in Asia for 1000?years, red ginseng and 20(S)-Rg3 could be potential therapeutic regimens for treating BPH.</P>

Langerhans cell histiocytosis in endoscopic biopsy: marked pinching artifacts by endoscopy.

Noh, Songmi,Kim, Dong-Seok,Kim, Jinna,Kim, Se Hoon Springer-Verlag Tokyo 2011 Brain tumor pathology Vol.28 No.3

<P>Various diseases should be considered when evaluating a suprasellar mass. Diabetes insipidus has been reported as the primary manifestation in a patient with Langerhans cell histiocytosis involving the hypothalamopituitary axis (HPA) and can be helpful for the diagnosis. The use of endoscopic biopsy for suprasellar masses has increased. However, as it is difficult to make a diagnosis with endoscopic biopsy because of the many artifacts, pathologists must be careful. Langerhans cell histiocytosis involving the HPA as solitary lesions is rare. We report the eighth case that provides neurologists, radiologists, and pathologists with various implications.</P>