Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy

Zhou Jing,Feng Ji,Wu Yong,Dai Hui-Qi,Zhu Guang-Zhi,Chen Pan-Hong,Wang Li-Ming,Lu Guang,Liao Xi-Wen,Lu Pei-Zhi,Su Wen-Jing,Hooi Shing Chuan,Ye Xin-Pin,Shen Han-Ming,Peng Tao,Lu Guo-Dong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.

Amperometric Determination of Nitrite at Poly(Methylene Blue)-Modified Glassy Carbon Electrode

Guang-Ri Xu,Guifang Xu,Ming-Lu Xu,Zhengqing Zhang,Yuan Tian,최한님,이원용 대한화학회 2012 Bulletin of the Korean Chemical Society Vol.33 No.2

Electrochemical characteristics of nitrite ion were investigated at a poly(methylene blue)-modified glassy carbon electrode by cyclic voltammetry and differential pulse voltammetry. The poly(methylene blue)-modified glassy carbon electrode exhibited enhanced anodic signals for nitrite. The effects of key parameters on the detection of nitrite were evaluated at the modified electrode, such as pH, accumulation time, and scan rate. Under optimum condition, the chemically modified electrode can detect nitrite in the concentration range 2.0 × 10−6 to 5.0 × 10−4 M with the detection limit of 2.0 × 10−6 M and a correlation coefficient of 0.999. The detection of nitrite using the chemically modified electrode was not affected by common ions such as Na+, K+,Ca2+, Cl−, HPO42− and H2PO4−. The modified electrode showed good stability and reproducibility. The practical application of the present method was successfully applied to the determination of nitrite ion in cabbage samples.

A FACILE SYNTHESIS OF SHAPE- AND SIZE-CONTROLLED α-Fe_2O_3 NANOPARTICLES THROUGH HYDROTHERMAL METHOD

GUANG-HUI WANG,WEN-CUI LI,KUN-MING JIA,AN-HUI LU,MATHIAS FEYEN,BERND SPLIETHOFF,FERDI SCHÜTH 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2011 NANO Vol.6 No.5

α-Fe_2O_3 nanoparticles have wide-ranging applications such as in catalysis, sensoring, painting, etc. This is the reason to study their controlled synthesis. Here we have investigated the synthesis of uniform α-Fe_2O_3nanoparticles using amino acids as morphology control agents. The products were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), thermogravimetry (TG) and differential thermal analysis (DTA). It was found that the type and the amount of amino acids as well as the reaction temperatures have significant influence on the shape and size of the obtainedα-Fe_2O_3nanoparticles. The use of acidic amino acids (always contain C=O in the side chain) typically leads to the formation of α-Fe_2O_3nanoparticles with spindle shape. However, rhombohedrally shaped α-Fe_2O_3nanoparticles were formed in presence of basic amino acids (always contain -NH_2 in the side chain). Increasing the amount of amino acid generally results in α-Fe_2O_3nanoparticles with decreasing particle sizes.

Structures, biomimetic synthesis, and anti-SARS-CoV-2 activity of two pairs of enantiomeric phenylpropanoid-conjugated protoberberine alkaloids from the rhizomes of Corydalis decumbens

Jing-Guang Lu,Yingwei Wang,Ming-Rong Yang,Cai-Yun Wang,Jieru Meng,Jiazheng Liu,Zifeng Yang,Kongsong Wu,Li-Ping Bai,Guo-Yuan Zhu,Zhi-Hong Jiang 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.9

(±)-Decumicorine A ( 1 ) and (±)- epi -decumicorine A ( 2 ), two pairs of enantiomeric isoquinoline alkaloids featuring a novel phenylpropanoid-conjugated protoberberine skeleton, were isolated and purifi ed from the rhizomes of Corydalis decumbens . The separation of (±)- 1 and (±)- 2 was achieved by chiral HPLC to produce four optically pure enantiomers. The structures and absolute confi gurations of compounds (−)- 1 , (+)- 1 , (−)- 2 , and (+)- 2 were elucidated by spectroscopic analysis, ECD calculations, and X-ray crystallographic analyses. The two racemates were generated from a Diels-Alder [4 + 2] cycloaddition between jatrorrhizine and ferulic acid in the proposed biosynthetic pathways, which were fully verifi ed by a biomimetic synthesis. Moreover, compound (+)- 1 exhibited an antiviral entry eff ect on SARS-CoV-2 pseudovirus by blocking spike binding to the ACE2 receptor on HEK-293T-ACE2 h host cells.

Double Modification of Electrode Surface for the Selective Detection of Epinephrine and Its Application to Flow Injection Amperometric Analysis

Xu, Guang-Ri,Qi, Xin-hua,Yang, Fengxia,Lee, Jae-Joon,Xu, Ming-Lu,Zhang, Yu-Ping,Kim, Sunghyun WILEY-VCH Verlag 2009 Electroanalysis Vol.21 No.22

<P>A glassy carbon electrode having two polymer layers has been applied to selectively detect epinephrine. The inner layer formed by electropolymerization of macrocyclic nickel complex functioned as an electrocatalyst for epinephrine oxidation and the outer layer composed of hydrolyzed polyurethane γ-benzyl L-glutamate as a screening layer. Differential pulse voltammetry showed almost 100% recovery of epinephrine even in 100-fold excess of interferents. When applied to a dual glassy carbon electrode as an amperometric detector in flow injection analysis, a linear response over 0.1 μM and 10 μM was obtained. Recovery tested for 5-fold diluted human urine samples was 97.5%.</P>

Amperometric Determination of Nitrite at Poly(Methylene Blue)-Modified Glassy Carbon Electrode

Xu, Guang-Ri,Xu, Guifang,Xu, Ming-Lu,Zhang, Zhengqing,Tian, Yuan,Choi, Han-Nim,Lee, Won-Yong Korean Chemical Society 2012 Bulletin of the Korean Chemical Society Vol.33 No.2

Electrochemical characteristics of nitrite ion were investigated at a poly(methylene blue)-modified glassy carbon electrode by cyclic voltammetry and differential pulse voltammetry. The poly(methylene blue)-modified glassy carbon electrode exhibited enhanced anodic signals for nitrite. The effects of key parameters on the detection of nitrite were evaluated at the modified electrode, such as pH, accumulation time, and scan rate. Under optimum condition, the chemically modified electrode can detect nitrite in the concentration range $2.0{\times}10^{-6}$ to $5.0{\times}10^{-4}$ M with the detection limit of $2.0{\times}10^{-6}$ M and a correlation coefficient of 0.999. The detection of nitrite using the chemically modified electrode was not affected by common ions such as $Na^+$, $K^+$, $Ca^{2+}$, $Cl^-$, $HPO_4^{2-}$ and $H_2PO_4^- $. The modified electrode showed good stability and reproducibility. The practical application of the present method was successfully applied to the determination of nitrite ion in cabbage samples.

High-j Proton h11/2 and g7/2 Intruder Bands in 113In

Ma Ke Yan,Lu Jing Bin,Ma Ying Jun,Li Jian,Yang Dong,Sun Wu Ji,Wang Hao,Pan Hao Nan,Wang Jia Qi,Yang Qing Yu,Zhang Da Ming,Zhu Li Hua,Wu Xiao Guang,Zheng Yun,Li Cong Bo 한국물리학회 2020 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.76 No.12

Excited states of 113In have been populated through the heavy-ion fusion evaporation reaction 110Pd(7Li, 4n)113In. A new band with the configuration of a proton d5/2 orbital is identified. Two ΔI = 2 intruder bands, built on the πh11/2 and the πg7/2 orbitals, have been extended to spins (63/2-)ħ and (55/2+)ħ, respectively. The negative-parity πh11/2 intruder band shows a smooth increase in aligned spin, which is attributed to a strong proton-neutron interaction. The properties of the positive-parity πg7/2 band are discussed based on tilted axis cranking model calculations, and the features of the antimagnetic rotation for this band are shown after backbend. Furthermore, the contributions of the two-shears-like mechanism, the neutron (gd)ν shell and the core rotation are investigated for the positive-parity πg7/2 band.

Clinical Observation on Recombinant Human Endostatin Combined with Chemotherapy for Advanced Gastrointestinal Cancer

Gao, Shao-Rong,Li, Lu-Ming,Xia, Hai-Ping,Wang, Guang-Ming,Xu, Hong-Yan,Wang, Ai-Rong Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

Objective: To explore the clinical efficacy and toxic and side effects of recombinant human endostatin (rhendostatin/endostar) combined with chemotherapy in the treatment of advanced gastric cancer. Materials and Methods: A total of 70 patients with advanced gastrointestinal adenocarcioma confirmed by histopathology and/or cytological examination were divided into group A (37 patients) and group B (33 patients). Patients in group A were given intravenous drip of 15 mg endostar added into 500 mL normal saline, once every other day until the cessation of chemotherapy or patients' maximal tolerance to chemotherapy. Patients in group B received chemotherapy alone. Two groups selected the same chemotherapy regimens. FOLFIRI scheme: 90-min intravenous drip of $180mg/m^2$ irinotecan, intravenous drip of $200mg/m^2$ calcium folinate (CF) and $400mg/m^2$ 5-fluorouracil (5-Fu) on d1, and continuous intravenous pumping of 2 $400mg/m^2$ 5-Fu for 46 h. FOLFOX4 scheme: intravenous injection of $85mg/m^2$ oxaliplatin (L-OHP), $200mg/m^2$ calcium folinate (CF) and $400mg/m^2$ 5-FU on d1 for 2 h, and then continuous intravenous pumping of 2 $400mg/m^2$ 5-Fu for 46 h. XELOX scheme: oral administration of 1 $500mg/m^2$ xeloda (or tegafur 50~60 mg) in twice during d1~14 and intravenous drip of $135mg/m^2$ L-OHP on d1 for 2 h. The modified FOLFOX scheme: intravenous injection of $135mg/m^2$ L-OHP on d1 for 2 h, $200mg/m^2$ CF and 1.0 g tegafur during d1~5. Whereas, control Group B received chemotherapy regimens which were same as Group A, but no addition of endostar. Before chemotherapy, patients were given intravenous injection of 8 mg ondansetron, intramuscular injection of 10 mg metoclopramide and 20 mg diphenhydramine for prevention of vomiting, protection of liver and stomach as well as symptomatic supportive treatment. One cycle was 21 d, 4~6 cycles in total. The efficacy was evaluated every 2 cycles. Results: 32 patients in Group A could be evaluated, and the response rate (RR) and disease control rate (DCR) were 59.38% and 78.13%, respectively. 31 patients in Groups could be evaluated, and the RR and DCR were 32.26% and 54.84%, respectively. The differences between 2 groups were significant. The toxic effects include myelosuppression, gastrointestinal reaction, fatigue, cardiotoxicity and peripheral neurotoxicity. Conclusions: Preliminary observations show that endostar (once every other day) combined with chemotherapy is effective in the treatment of advanced gastrointestinal cancer, with low toxic effects, good tolerance, deserving further study.

Synthesis and Evaluation O-Benzyl Oxime-ether Derivatives Containing β-Methoxyacrylate Moiety for Insecticidal and Fungicidal Activities

Zhi-Bin Hu,He-An Luo,Xiao-Guang Wang,Ming-Zhi Huang,Lu Huang,Huai-Lin Pang,Chun-Hui Mao,Hui Pei,Chao-Qun Huang,Jiong Sun,Ping-Le Liu,Ai-Ping Liu 대한화학회 2014 Bulletin of the Korean Chemical Society Vol.35 No.4

In attempt to lead compounds exhibiting both insecticidal and fungicidal activities, a series of O-benzyl oximeether derivatives were designed and synthesized by introducing β-methoxyacrylate pharmacophore into a scaffold. The insecticidal activity against Aphis fabae and the fungicidal activity against Erysiphe graminis were screened. The title compounds exhibited remarkable insecticidal and fungicidal activities. The most potent compound 6d was identified. Its insecticidal LC50 against A. fabae is 6.4 mg/L, which is lower than that of chlorfenapyr (19.4 mg/L) and even close to the level of imidacloprid (4.8 mg/L). Its fungicidal EC90 in preventive and curative treatment against E. graminis are 2.2 and 4.8 mg/L, respectively, which are lower than azoxystrobin (7.0 and 5.9 mg/L). These results indicate that compound 6d can be considered as a lead for further developing new O-benzyl oxime-ether typed candidates with both fungicidal and insecticidal activities.

Lobaplatin-TACE Combined with Radioactive ¹²⁵I Seed Implantation for Treatment of Primary Hepatocellular Carcinoma

Peng, Sheng,Yang, Qiu-Xia,Zhang, Tao,Lu, Ming-Jian,Yang, Guang,Liu, Zhen-Yin,Zhang, Rong,Zhang, Fu-Jun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Aim: To investigate the efficacy and safety of lobaplatin-transcatheter arterial chemoembolization (TACE) combined with radioactive $^{125}I$ seed implantation in treatment of primary hepatocellular carcinoma (HCC). Methods: 75 patients with primary HCC were enrolled in the study, among them 43 receiving lobaplatin-TACE (TACE group) and 32 lobaplatin-TACE combined with $^{125}I$ seed implantation (TACE+$^{125}I$ group). After treatment, the local remission rates and postoperative complications of two groups were compared using the Pearson Chi-square test. Overall survival in the two groups was calculated using Kaplan-Meier survival curves and the differences were tested using Log-rank test. Results: There were 7 cases of complete response (CR), 13 of partial response (PR), 6 of stable disease (SD) and 17 of progressive disease (PD) in the TACE group, with 13 cases of CR, 9 of PR, 5 of SD and 5 of PD in the TACE+$^{125}I$ group. The disease control rates of TACE and TACE+$^{125}I$ group were 60.5% (26/43) and 84.4% (27/32), respectively, with a significant difference between them (P < 0.05). The survival rates at 6, 12 and 18 months in the TACE group were 100.0%, 81.8% and 50.0%, respectively, and those in TACE+$^{125}I$ group were 100.0%, 93.8% and 65.6%. The mean survival times in the TACE and TACE+$^{125}I$ groups were 19.5 and 22.9 months, respectively. There was a significant difference in the overall survival rate between two groups (P < 0.05). No serious complications were encountered in either group. Conclusion: Lobaplatin-TACE combined with $^{125}I$ seed implantation is favorable and safe for treatment of primary HCC.