ACOX1 destabilizes p73 to suppress intrinsic apoptosis pathway and regulates sensitivity to doxorubicin in lymphoma cells

( Fei-meng Zheng ),( Wang-bing Chen ),( Tao Qin ),( Li-na Lv ),( Bi Feng ),( Yan-ling Lu ),( Zuo-quan Li ),( Xiao-chao Wang ),( Li-ju Tao ),( Hong-wen Li ),( Shu-you Li ) 생화학분자생물학회(구 한국생화학분자생물학회) 2019 BMB Reports Vol.52 No.9

Lymphoma is one of the most curable types of cancer. However, drug resistance is the main challenge faced in lymphoma treatment. Peroxisomal acyl-CoA oxidase 1 (ACOX1) is the rate-limiting enzyme in fatty acid β-oxidation. Deregulation of ACOX1 has been linked to peroxisomal disorders and carcinogenesis in the liver. Currently, there is no information about the function of ACOX1 in lymphoma. In this study, we found that upregulation of ACOX1 promoted proliferation in lymphoma cells, while downregulation of ACOX1 inhibited proliferation and induced apoptosis. Additionally, overexpression of ACOX1 increased resistance to doxorubicin, while suppression of ACOX1 expression markedly potentiated doxorubicin-induced apoptosis. Interestingly, downregulation of ACOX1 promoted mitochondrial location of Bad, reduced mitochondrial membrane potential and provoked apoptosis by activating caspase-9 and caspase-3 related apoptotic pathway. Overexpression of ACOX1 alleviated doxorubicin-induced activation of caspase-9 and caspase-3 and decrease of mitochondrial membrane potential. Importantly, downregulation of ACOX1 increased p73, but not p53, expression. p73 expression was critical for apoptosis induction induced by ACOX1 downregulation. Also, overexpression of ACOX1 significantly reduced stability of p73 protein thereby reducing p73 expression. Thus, our study indicated that suppression of ACOX1 could be a novel and effective approach for treatment of lymphoma. [BMB Reports 2019; 52(9): 566-571]

Tumor-Derived Transforming Growth Factor-β is Critical for Tumor Progression and Evasion from Immune Surveillance

Li, Zheng,Zhang, Li-Juan,Zhang, Hong-Ru,Tian, Gao-Fei,Tian, Jun,Mao, Xiao-Li,Jia, Zheng-Hu,Meng, Zi-Yu,Zhao, Li-Qing,Yin, Zhi-Nan,Wu, Zhen-Zhou Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.

Improvement of energy storage performance in PbZr0.52Ti0.48O3/PbZrO3 multilayer thin films via regulating PbZrO3 thickness

Yang Fei,Shi Yu Jia,Lin Lin,Chen Jing Yao,Hou Meng Zhe,Yu Ke Xin,Zhang Yi Han,Yuan Zheng,Li Xiao Fang,Hu Yan Chun,Shang Jun,Yin Shao Qian,Wang Xian Wei 한국물리학회 2023 Current Applied Physics Vol.50 No.-

In this work, to prepare the PbZr0.52Ti0.48O3(PZT)/PbZrO3(PZ) multilayer films, PZ films and PZT films were spin-coated on LaNiO3/SiO2/Si substrates in sequence by the sol-gel method, and the PZ films were prepared using PZ precursor solution with different concentrations. After each spin-coating, PZ layer and PZT layer were annealed with rapid thermal annealing (RTA) technique at 650 ◦C and 550 ◦C, respectively. The crystal structures, microstructures and electrical properties of the films with different PZ film thickness were comprehensively investigated. The PZ films with different thickness showed perovskite phase. The PZT films on crystallized PZ films exhibited the coexistence of pyrochlore phase and perovskite phase at the annealing temperature of 550 ◦C. The PZT/PZ multilayer films with 0.2 M PZ precursor solution exhibit typical anti-ferroelectricity with double hysteresis loops, while other multilayer films exhibit nearly linear loops. In addition, the recoverable energy storage density increases with the increase of the film thickness and reaches the maximum value 32.4 J/ cm3 in the PZT/PZ multilayer films with 0.4 M PZ precursor solution. Therefore, the ferroelectric properties of the PZT/PZ multilayer films could be regulated by different PZ film thickness, which effectively further enhances the energy storage performance.

Comparing eight types of ginsenosides in ginseng of different plant ages and regions using RRLC-Q-TOF MS/MS

Yu-Lin Dai,Meng-Dan Qiao,Peng Yu,Fei Zheng,Hao Yue,Shu-Ying Liu 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.2

Background: This article aims to compare and analyze the contents of ginsenosides in ginseng ofdifferent plant ages from different localities in China. Methods: In this study, 77 fresh ginseng samples aged 2e4 years were collected from 13 differentcultivation regions in China. The content of eight ginsenosides (Rg3, Rc, Rg1, Rf, Rb2, Rb1, Re, and Rd) wasdetermined using rapid resolution liquid chromatography coupled with quadrupoleetime-of-flighttandem mass spectrometry (RRLC-Q-TOF MS/MS) to comparatively evaluate the influences of cultivationregion and age. Results: Ginsenoside contents differed significantly depending on age and cultivation region. The contentsof ginsenosides Re, Rc, Rg1, Rg3, and Rf increased with cultivation age, whereas that of ginsenoside Rb1peaked in the third year of cultivation. Moreover, the highest ginsenoside content was obtained fromChangbai (19.36 mg/g) whereas the lowest content was obtained from Jidong (12.05 mg/g). Ginseng fromJilin Province contained greater total ginsenosides and was richer in ginsenoside Re than ginseng of thesame age group in Heilongjiang and Liaoning provinces, where Rb1 and Rg1 contents were relatively high. Conclusion: In this study, RRLC-Q-TOF MS/MS was used to analyze ginsenoside contents in 77 ginsengsamples aged 2e4 years from different cultivation regions. These patterns of variation in ginsenosidecontent, which depend on harvesting location and age, could be useful for interested parties to chooseginseng products according to their needs.

Analysis of Death Causes of In-patients with Malignant Tumors in Sichuan Cancer Hospital of China from 2002 to 2012

Wang, Xiao,Song, Zheng-Fang,Xie, Rui-Meng,Pei, Jiao,Xiang, Ming-Fei,Wang, Huan Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Objectives: To analyze underlying disease, fatality rate and the major causes of death of in-patients with malignant tumors in Sichuan Cancer Hospital. Methods: Clinical data of in-patients from 2002 to 2012 were retrospectively analyzed. Results: The top 10 tumors (82.0%of the total) of the malignant tumors of the in-patients were lung, cervical, esophagus, breast, colorectal, nasopharynx, liver and gastric cancers, lymphomas and ovarian cancers. The overall fatality rate was 2.7% during these eleven years, 3.4% and 2.0% for male and females, respectively with statistical significance for the difference (${\chi}^2$=164.737, P<0.001). The top 10 death causes were lung cancer, liver cancer, colorectal cancer, esophagus cancer, gastric cancer, lymphoma, breast cancer, pancreatic cancer, ovarian cancer and nasopharynx cancer. In-patients with pancreatic cancer had the highest fatality rate (9.6%). There were different ranks of death causes in different sex groups and age groups. Conclusion: Prevention and control work of cancer should be enhanced not only for cancers with high incidence such as lung cancer, esophageal cancer but also for the cancers which have low incidence but high fatality rate, such as pancreatic cancer and gallbladder cancer, which would help to improve the survival rate and quality of life of cancer patients in the future.

Human lactoferrin efficiently targeted into caprine beta-lactoglobulin locus with transcription activator-like effector nucleases

Yu-Guo Yuan,Shao-Zheng Song,Meng-Ming Zhu,Zheng-Yi He,Rui Lu,Ting Zhang,Fei Mi,Jin-Yu Wang,Yong Cheng 아세아·태평양축산학회 2017 Animal Bioscience Vol.30 No.8

Objective: To create genetically modified goat as a biopharming source of recombinant human lacotoferrin (hLF) with transcription activator-like effector nucleases. Methods: TALENs and targeting vector were transferred into cultured fibroblasts to insert hLF cDNA in the goat beta-lactoglobulin (BLG) locus with homology-directed repair. The gene targeted efficiency was checked using sequencing and TE7I assay. The bi-allelic gene targeted colonies were isolated and confirmed with polymerase chain reaction, and used as donor cells for somatic cell nuclear transfer (SCNT). Results: The targeted efficiency for BLG gene was approximately 10%. Among 12 Bi-allelic gene targeted colonies, five were used in first round SCNT and 4 recipients (23%) were confirmed pregnant at 30 d. In second round SCNT, 7 (53%), 4 (31%), and 3 (23%) recipients were confirmed to be pregnant by ultrasound on 30 d, 60 d, and 90 d. Conclusion: This finding signifies the combined use of TALENs and SCNT can generate bi-allelic knock-in fibroblasts that can be cloned in a fetus. Therefore, it might lay the foundation for transgenic hLF goat generation and possible use of their mammary gland as a bioreactor for large-scale production of recombinant hLF.

Comparing eight types of ginsenosides in ginseng of different plant ages and regions using RRLC-Q-TOF MS/MS

Dai, Yu-Lin,Qiao, Meng-Dan,Yu, Peng,Zheng, Fei,Yue, Hao,Liu, Shu-Ying The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.2

Background: This article aims to compare and analyze the contents of ginsenosides in ginseng of different plant ages from different localities in China. Methods: In this study, 77 fresh ginseng samples aged 2-4 years were collected from 13 different cultivation regions in China. The content of eight ginsenosides (Rg₃, Rc, Rg₁, Rf, Rb₂, Rb₁, Re, and Rd) was determined using rapid resolution liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (RRLC-Q-TOF MS/MS) to comparatively evaluate the influences of cultivation region and age. Results: Ginsenoside contents differed significantly depending on age and cultivation region. The contents of ginsenosides Re, Rc, Rg₁, Rg₃, and Rf increased with cultivation age, whereas that of ginsenoside Rb₁ peaked in the third year of cultivation. Moreover, the highest ginsenoside content was obtained from Changbai (19.36 mg/g) whereas the lowest content was obtained from Jidong (12.05 mg/g). Ginseng from Jilin Province contained greater total ginsenosides and was richer in ginsenoside Re than ginseng of the same age group in Heilongjiang and Liaoning provinces, where Rb₁ and Rg₁ contents were relatively high. Conclusion: In this study, RRLC-Q-TOF MS/MS was used to analyze ginsenoside contents in 77 ginseng samples aged 2-4 years from different cultivation regions. These patterns of variation in ginsenoside content, which depend on harvesting location and age, could be useful for interested parties to choose ginseng products according to their needs.

Is Surgical Resection Justified for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus? (A Systematic Review and Meta-Analysis)

( Liang Lei ),( Xin-fei Xu ),( Jiong-jie Yu ),( Ju-dong Li ),( Zhen-li Li ),( Jun Han ),( Han Zhang ),( Hao Xing ),( Han Wu ),( Ming-da Wang ),( Chao Li ),( Zheng Wang ),( Feng Shen ),( Meng-chao Wu ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is very poor. According to the BCLC treatment recommendations, sorafenib or other palliative treatment (PT) is recommended as the first-line therapy when it happens. In real world, however, a significant number of selected patients with HCC and PVTT suffered from surgical resection (SR). Methods: PubMed, Embase, Medline and Cochrane library were searched for studies comparing SR with PT (including TACE, sorafenib, etc.) for HCC with PVTT, which were published before September 2017. Results: 4,810 patients from 7 studies were enrolled in this meta-analysis, which divided into the SR group (n = 2,344) and the PT group (n = 2476). When compared with the PT group, the pooled hazard ratio (HR) for the 1, 3 and 5-year OS rates of the SR group were 0.56 (95% CI 0.52-0.60, P=0.03), 0.56 (95% CI 0.53-0.59, P<0.001) and 0.55 (95% CI 0.54-0.57, P<0.001). For subgroup analysis, when compared with the mere TACE group, the pooled HR for the 1, 3 and 5-year OS rates of the SR group were 0.54 (95% CI 0.43-0.67, P=0.81), 0.75 (95% CI 0.65-0.87, P=0.25) and 0.76 (95% CI 0.67-0.88, P=0.25). Conclusions: This meta-analysis demonstrated SR had better OS than TACE or other palliative therapy for HCC with PVTT. SR may be suitable as the first-line treatment for selected patients with resectable HCC and removable PVTT.