Anti-androgen receptor signaling and prostate cancer inhibitory effects of sucrose- and benzophenone-compounds.

Wang, Zhe,Lee, Hyo-Jeong,Wang, Lei,Jiang, Cheng,Baek, Nam-In,Kim, Sung-Hoon,L?, Junxuan Kluwer Academic/Plenum Publishers 2009 Pharmaceutical research Vol.26 No.5

<P>Novel agents that target multiple aspects of androgen receptor (AR) signaling are desirable for chemoprevention and treatment of prostate cancer (PCa). We aimed to identify compounds isolated from medicinal herbs as such drug candidates.</P>

A novel class of pyranocoumarin anti-androgen receptor signaling compounds.

Guo, Junming,Jiang, Cheng,Wang, Zhe,Lee, Hyo-Jeong,Hu, Hongbo,Malewicz, Barbara,Lee, Hyo-Jung,Lee, Jae-Ho,Baek, Nam-In,Jeong, Jin-Hyun,Kim, Dae-Keun,Kang, Kyung-Sun,Kim, Sung-Hoon,Lu, Junxuan American Association for Cancer Research 2007 Molecular Cancer Therapeutics Vol.6 No.3

<P>Androgen and the androgen receptor (AR)-mediated signaling are crucial for prostate cancer development. Novel agents that can inhibit AR signaling in ligand-dependent and ligand-independent manners are desirable for the chemoprevention of prostate carcinogenesis and for the treatment of advanced prostate cancer. We have shown recently that the pyranocoumarin compound decursin from the herb Angelica gigas possesses potent anti-AR activities distinct from the anti-androgen bicalutamide. Here, we compared the anti-AR activities and the cell cycle arrest and apoptotic effects of decursin and two natural analogues in the androgen-dependent LNCaP human prostate cancer cell culture model to identify structure-activity relationships and mechanisms. Decursin and its isomer decursinol angelate decreased prostate-specific antigen expression with IC(50) of approximately 1 mumol/L. Both inhibited the androgen-stimulated AR nuclear translocation and transactivation, decreased AR protein abundance through proteasomal degradation, and induced G(0/1) arrest and morphologic differentiation. They also induced caspase-mediated apoptosis and reactive oxygen species at higher concentrations. Furthermore, they lacked the agonist activity of bicalutamide in the absence of androgen and were more potent than bicalutamide for suppressing androgen-stimulated cell growth. Decursinol, which does not contain a side chain, lacked the reactive oxygen species induction and apoptotic activities and exerted paradoxically an inhibitory and a stimulatory effect on AR signaling and cell growth. In conclusion, decursin and decursinol angelate are members of a novel class of nonsteroidal compounds that exert a long-lasting inhibition of both ligand-dependent and ligand-independent AR signaling. The side chain is critical for sustaining the anti-AR activities and the growth arrest and apoptotic effects.</P>

Prolyl endopeptidase remodels macrophage function as a novel transcriptional coregulator and inhibits fibrosis

Lin Shuang-Zhe,Wu Wei-Jie,Cheng Yu-Qing,Zhang Jian-Bin,Jiang Dai-Xi,Ren Tian-Yi,Ding Wen-Jin,Liu Mingxi,Chen Yuan-Wen,Fan Jian-Gao 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Macrophages are immune cells crucial for host defense and homeostasis maintenance, and their dysregulation is involved in multiple pathological conditions, such as liver fibrosis. The transcriptional regulation in macrophage is indispensable for fine-tuning of macrophage functions, but the details have not been fully elucidated. Prolyl endopeptidase (PREP) is a dipeptidyl peptidase with both proteolytic and non-proteolytic functions. In this study, we found that Prep knockout significantly contributed to transcriptomic alterations in quiescent and M1/M2-polarized bone marrow-derived macrophages (BMDMs), as well as aggravated fibrosis in an experimental nonalcoholic steatohepatitis (NASH) model. Mechanistically, PREP predominantly localized to the macrophage nuclei and functioned as a transcriptional coregulator. Using CUT&Tag and co-immunoprecipitation, we found that PREP was mainly distributed in active cis-regulatory genomic regions and physically interacted with the transcription factor PU.1. Among PREP-regulated downstream genes, genes encoding profibrotic cathepsin B and D were overexpressed in BMDMs and fibrotic liver tissue. Our results indicate that PREP in macrophages functions as a transcriptional coregulator that finely tunes macrophage functions, and plays a protective role against liver fibrosis pathogenesis.

Complete mesocolic excision in right hemicolectomy

Qin-Song Sheng,Zhe Pan,Jin Chai,Xiao-Bin Cheng,Fan-Long Liu,Jin-Hai Wang,Wen-Bin Chen,Jian-Jiang Lin 대한외과학회 2017 Annals of Surgical Treatment and Research(ASRT) Vol.92 No.2

Purpose: To demonstrate the feasibility, safety, and technical strategies of hand-assisted laparoscopic complete mesocolic excision (HAL-CME) and to compare oncological outcomes between HAL-CME and the open approach (O-CME) for right colon cancers. Methods: Patients who were scheduled to undergo a right hemicolectomy were divided into HAL-CME and O-CME groups. Measured outcomes included demographic variables, perioperative parameters, and follow-up data. Demographic variables included age, sex distribution, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status classification, previous abdominal surgery, tumor localization, and potential comorbidities. Perioperative parameters included incision length, operative time, blood loss, conversion rate, postoperative pain score, postoperative first passage of flatus, duration of hospital stay, total cost, number of lymph nodes retrieved, TNM classification, and postoperative complications. Follow-up data included follow-up time, use of chemotherapy, local recurrence rate, distant metastasis rate, and short-term survival rate. Results: In total, 150 patients (HAL-CME, 78; O-CME, 72) were included. The groups were similar in age, sex distribution, BMI, ASA classification, history of previous abdominal surgeries, tumor localization, and potential comorbidities. Patients in the HAL-CME group had shorter incision lengths, longer operative times, less operative blood loss, lower pain scores, earlier first passage of flatus, shorter hospital stay, higher total costs, similar numbers of lymph nodes retrieved, similar TNM classifications, and a comparable incidence of postoperative complications. The 2 groups were also similar in local recurrence rate, distant metastasis rate, and short-term survival rate. Conclusion: The results demonstrate that the HAL-CME procedure is a safe, valid, and feasible surgical method for right hemicolon cancers.

Synergistic Immunostimulating Activity of Pidotimod and Red Ginseng Acidic Polysaccharide against Cyclophosphamide-induced Immunosuppression

Xiao Fei Du,Cheng Zhe Jiang,Chun Fu Wu,원은경,정세영 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.9

We investigated the synergistic effect of combined treatment with red ginseng acidic polysaccharide (RGAP) from Panax ginseng C.A. Meyer and pidotimod in cyclophosphamide-treated mice. The combination of pidotimod and RGAP restored concanavalin A-induced splenic T cell proliferation and LPS-stimulated B cell proliferation significantly. The production of nitric oxide from peritoneal macrophages was increased by the combinations. NK cell activity was increased by RGAP alone or in combination with pidotimod. A synergistic increase in the level of serum IL-12 and interferongamm was observed when the combination of the two was used. RGAP alone or in combination with pidotimod modulated the level of serum C-reactive protein to a near-normal level. These results indicate that combinations of pidotimod and RGAP are synergistic and suggest that combination therapy using pidotimod and RGAP for improving immune activity may provide an additional benefit over the use of the two drugs by themselves.

Effects of Phenobarbital Pretreatment on Ethyl Carbamate-induced Embryotoxicity in Rats

Chung, Moon-Koo,Jiang, Cheng-Zhe,Kim, Jong-Choon,Yun, Hyo-In,Han, Sang-Seop,Roh, Jung-Koo Korean Society of ToxicologyKorea Environmental Mu 1997 Toxicological Research Vol.13 No.1

Ethyl carbamate (EC) is a potent teratogen in rodents and is present at low concentration in fermented foods and alcohol beverages. It has been well hypothesized that some metabolic products are responsible for the teratogenic effects of the compound. In the present study, the effects of phenobarbital (PB) on EC-induced embryotoxicity were investigated in SD rats. Six groups were constructed: EC 300 (EC 300 mg/kg/day), EC 600 (EC 600 mg/kg/day), EC 600+PB (EC 600 mg/kg/day and PB 80 mg/kg/day), PB (PB 80 mg/kg/day), DR (dietary restriction, 8 g/day/rat) and a control group. Rats of the EC 600+PB group were pretreated with phenobarbital intraperitoneally for three days to induce cytochrome P450 enzymes, followed by oral administration of EC for two consecutive days. The incidence of fetal deaths in the EC 600+PB group was higher than that of the EC 600 group(42.7 vs. 14.3%). The incidence of fetal realformations in the EC 600+PB group was higher than that of the EC 600 group (external; 7.0 vs. 4.1%, visceral; 31.4 vs. 11.3%, skeletal; 11.1 vs. 6.5%). There was no embryotoxicity in the control, EC 300, PB and DR groups. These results show that the pretreatment with phenobarbital augments EC-induced embryotoxicity in rats, indicating an evidence that metabolic activation by cytochrome P450 may be the major pathway of EC to its embryotoxic forms.

Synergistic Immunostimulating Activity of Pidotimod and Red Ginseng Acidic Polysaccharide against Cyclophosphamide-induced Immunosuppression

Du, Xiao Fei,Jiang, Cheng Zhe,Wu, Chun Fu,Won, Eun-Kyung,Choung, Se-Young 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.9

We investigated the synergistic effect of combined treatment with red ginseng acidic polysaccharide (RGAP) from Panax ginseng C.A. Meyer and pidotimod in cyclophosphamide-treated mice. The combination of pidotimod and RGAP restored concanavalin A-induced splenic T cell proliferation and LPS-stimulated B cell proliferation significantly. The production of nitric oxide from peritoneal macrophages was increased by the combinations. NK cell activity was increased by RGAP alone or in combination with pidotimod. A synergistic increase in the level of serum IL-12 and interferongamm was observed when the combination of the two was used. RGAP alone or in combination with pidotimod modulated the level of serum C-reactive protein to a near-normal level. These results indicate that combinations of pidotimod and RGAP are synergistic and suggest that combination therapy using pidotimod and RGAP for improving immune activity may provide an additional benefit over the use of the two drugs by themselves.

Antibacterial Action of Norfloxacin Combined with Penicillin, Gentamicin, Amikacin, Tylosin, Trimethoprim, Tetracycline or Colistin

Yun, Hyo-in,Park, Seung-chun,Jiang, Cheng-zhe,Huh, Won,Rhee, Jae-chin,Park, Jong-myung,Choi, Sang-ho,Cho, Joon-hyoung 충남대학교 수의과대학 동물의과학연구소 1994 動物醫科學硏究誌 Vol.2 No.-

세균 감염증으로 인한 돼지 설사증의 효과적인 치료 및 예방을 위해 돼지 설사 분변으로부터 분리한 E coli 와 S typhimurium을 시험균주로 하여 norfloxacin과 국내 가축 치료에 주로 이용되고 있는 여러 항생제를 실험실적 방법으로 병용투여시 두 항생제 간의 상호작용을 checkerboard method를 이용하여 실험하였다. E coli를 시험균주로 실험한 결과, norfloxacin과 colistin의 두 항생제간의 상호작용은 상승작용을 나타내었다. 그러나 norfloxacin과 tetracycline의 병용 처치 실험에서는 길항작용을 보여주었다. S typhimurium을 시험균주로 실험한 결과, norfloxacin과 colistin의 병용 처치 실험에서는 E coli에서와 마찬가지로 상승 작용을 나타내었다. Norfloxacin과 colistin에서의 배합 비율에 따른 E coli에 대한 FIC 값은 norfloxacin이 0.08 그리고 colistin이 0.78일 때 0.38로 가장 항균 작용이 높았으며, S typhimurium에 대한 FIC 값은 E coli에서와 같은 비율에서 가장 활성이 높은 0.25를 보여주어 두 항생제의 항균력은 배합 비율에 따라서 차이가 있음을 알 수 있었다.

발생독성 검색을 위한 마우스 전배자배양법의 확립

김종춘(Jong-Choon Kim),신진영(Jin-Young Shin),신동호(Dong-Ho Shin),손우찬(Woo-Chan Son),강성철(Cheng-Zhe Jiang),정나영(Na-Young Jung),백성수(Sung-Soo Baek),정문구(Moon-Koo Chung) 한국실험동물학회 2004 Laboratory Animal Research Vol.20 No.1

The present study was carried out to establish a mouse whole embryo culture technique for detecting developmental toxicity in ICR mice. ICR mouse embryos were explanted on gestational day (GD) 8.5 and cultured for 48 hrs in the bottles containing 2 ㎖ of culture media consisting of 100% immediately centrifuged and heat-inactivated rat serum. The culture bottles with 15 ㎖ capacity were attached to a rotator drum and rotated at 35 rpm, 37.5℃ with a continuous gas flow of 5% O₂, 5% CO₂, 90% N₂ for the first 17 hrs; 20% O₂, 5% CO₂, 75% N₂ for the next 17 hrs; 40% O₂, 5% CO₂, 55% N₂ for the last 24 hrs, After 48 hrs of culture, the growth and differentiation of embryos were compared with those of embryos grown in vivo and each embryo was evaluated for the presence of any malformations. At the begining of the culture, embryos were early somite stage, and the length of whole conceptus including ectoplacental corn was about 1.8 ㎜. At the end of culture, all embryos in culture showed well-developed vascularization in the body and yolk sac. No morphological and histological defects were detected in any embryos examined. The yolk sac diameter, crown-rump length, and head length were 5.1, 4.3, and 2.3 ㎜, respectively. The number of somite pairs and morphological score were 30.0 and 67.7, respectively. The crown-rump length, head length and somite number of embryos grown for 48 hrs in vitro were slightly lower than those of embryos in vivo, respectively, but the morphology and differentiation were similar to those of embryos in vivo. These results indicated that morphology, growth and differentiation of in vitro mouse embryos are almost identical to those of in vivo embryos and suggest that the mouse whole embryo culture technique can be a useful tool for prescreening the developmental toxicity of chemicals.

Assessment of Embryotoxicity of 2-Bromopropane in ICR Mice

Kim, Jong-Choon,Shin, Dong-Ho,Kim, Sung-Ho,Oh, Ki-Seok,Kim, Hyeon-Yeong,Her, Jeong-Doo,Jiang, Cheng-Zhe,Chung, Moon-Koo Korean Society of ToxicologyKorea Environmental Mu 2003 Toxicological Research Vol.19 No.3

2-Bromopropane (2-BP), a halogenated propane analogue, is a substitute for chlorofluorocarbones (CFCs) which have a great potential to destroy the ozone layer and to warm the earth's environment. The present study was undertaken to evaluate the potential adverse effects of 2-BP on pregnant dams and embryo-fetal development after maternal exposure during the gestational days (GD) 6 through 17 in ICR mice. The test chemical was administered subcutaneously to pregnant mice at dose levels of 0, 313, 625 or 1,250 mg/kg/day. All dams were subjected to caesarean section on GD 18 and their fetuses were examined for external, visceral and skeletal abnormalities. In the 1,250 mg/kg group, maternal toxicity included an increase in the incidence of abnormal clinical signs and a decrease in the maternal body weight, body weight gain, and corrected body weight. Developmental toxicity included a decrease in the fetal body weight, a reduction in the placental weight, an increase in the fetal skeletal variation and ossification delay. There were no adverse effects on either pregnant dams or embryo-fetal development in the 313 and 625 mg/kg groups. These results suggest that a 12-day subcutaneous dose of 2-BP is embryotoxic at a maternally toxic dose (i.e., 1,250 mg/kg/day) in ICR mice. In the present experimental condition, the no-observed-adverse-effect level of 2-BP is considered to be 625 mg/kg/day for dams and embryo-fetuses, respectively.