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.

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]

Prevalence and Risk Factors of Cerebral Small Vessel Disease in a Chinese Population-Based Sample

Fei Han,Fei-Fei Zhai,Quan Wang,Li-Xin Zhou,Jun Ni,Ming Yao,Ming-Li Li,Shu-Yang Zhang,Li-Ying Cui,Zheng-Yu Jin,Yi-Cheng Zhu 대한뇌졸중학회 2018 Journal of stroke Vol.20 No.2

Background and Purpose Epidemiological data of cerebral small vessel disease (CSVD) in the general population of China are lacking. We report on the prevalence of lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMBs) in a community-based sample in China and compare the results with those of other studies. Methods This was a cross-sectional analysis of the population-based Shunyi Study in China. A total of 1,211 stroke-free participants (mean age, 55.6±9.3 years; 37.4% men) with available 3 Tesla (3T) magnetic resonance images were included in this analysis. Demographic information and risk factor data were assessed. The overall and age-specific prevalence of lacunes, WMH, and CMBs was evaluated. Associations between cardiovascular risk factors and the presence of these lesions were analyzed by multiple logistic regression. Results Our study showed a prevalence of 14.5% for lacunes, 72.1% for periventricular hyperintensity (PVH), 65.4% for deep white matter hyperintensity (DWMH), and 10.6% for CMBs. When compared with other community-based samples, individuals in the same age group showed a higher burden of lacunes and a relatively lower prevalence of CMBs. Advanced age was independently associated with the prevalence of these CSVD markers, while the presence of hypertension increased the risk of lacunes, PVH/DWMH, and CMBs in deep or infratentorial locations. Conclusions A higher burden of lacunes but a relatively lower prevalence of CMBs was observed in this Chinese population. This notable result highlights the challenge of CSVD prevention in China. Chinese have a risk factor profile for CSVD similar to those in other populations.

Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing

Li Shi-Dan,Xing Wei,Wang Shao-Chuan,Li You-Bin,Jiang Hao,Zheng Han-Xuan,Li Xiao-Ming,Yang Jing,Guo De-Bin,Xie Xiao-Yu,Jiang Ren-Qing,Fan Chao,Li Lei,Xu Xiang,Fei Jun 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone.

Active Compounds from Schisandra chinensis Exhibiting Tyrosinase Activity and Melanin Content Inhibition in B16 Melanoma Cells

Zheng-Fei Yan,Jian Guo,Feng-Hua Tian,Xin-Xin Mao,Yu Li,Chang-Tian Li 한국생물공학회 2015 Biotechnology and Bioprocess Engineering Vol.20 No.4

Schisandra chinensis has been used as traditional medicine. The structures of isolate active compounds (schisandrin B, deoxyschisandrin, schisandrin C) from S. chinensis were characterized by physical and spectroscopic analyses. Active compounds were tested for their potential to act as anti-melanogenesis or skin-whitening agents by their abilities to inhibit tyrosinase activity in the cell-free mushroom tyrosinase assay and cellular tyrosinase derived from B16 melanoma cells. The tyrosinase inhibitory activity was correlated to the inhibition of melanin productions in α-MSH-stimulated and unstimulated B16 cells. Cellular tyrosinase kinetics were analyzed and showed by Lineweaver- Burk plot. Schisandrin B was minimally cytotoxic (cell viability: 88.99% at 0.75 μM) and the IC50 value for suppression of mushroom tyrosinase activity was estimated as 0.6 μM. Zymography analysis demonstrated schisandrin B’s concentration-dependent effects and the kinetic analysis indicated schisandrin B’s noncompetitive-inhibitory action.

개항기 ‘支那’ 명칭의 등장과 문화적 함의

鄭立菲(Zheng, Li-Fei) 고려사학회 2017 한국사학보 Vol.- No.69

한말 기자(箕子)조선 인식에 대한 재고찰 ― 『대동력사(大東歷史)』에 나타난 기자조선 역사서술을 중심으로 ―

정립비 ( Zheng Li-fei ) 수선사학회 2018 史林 Vol.0 No.65

In Korean Empire Period, the Gija Josen was emphasized as a dynasty with legitimacy in historical books except the nationalist ones. On the first sight, this seems to be a stronger version of the classical orthodox in Joseon Dynasty. However, the history of Gija Josen was actually re-written by some historians such as Choi Kyung-Hwan(崔景焕) and Jung Gyo(鄭喬). According to them, Gija had never been invested with rank by Zhou. He became the ruler of Josen because of the abdication from the descendants of Dangun, and the election from the locals. The source of Gija’s legitimacy is not Zhou any more but Josen itself. Under these circumstances, Gija Josen could be thought had the same status as Zhou, with ability to be a strong country in the East with military, economical, cultural powers.

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.

miR-340 Reverses Cisplatin Resistance of Hepatocellular Carcinoma Cell Lines by Targeting Nrf2-dependent Antioxidant Pathway

Shi, Liang,Chen, Zhan-Guo,Wu, Li-li,Zheng, Jian-Jian,Yang, Jian-Rong,Chen, Xiao-Fei,Chen, Zeng-Qiang,Liu, Cun-Li,Chi, Sheng-Ying,Zheng, Jia-Ying,Huang, Hai-Xia,Lin, Xiang-Yang,Zheng, Fang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23

Many chemotherapeutic agents have been successfully used to treat hepatocellular carcinoma (HCC); however, the development of chemoresistance in liver cancer cells usually results in a relapse and worsening of prognosis. It has been demonstrated that DNA methylation and histone modification play crucial roles in chemotherapy resistance. Currently, extensive research has shown that there is another potential mechanism of gene expression control, which is mediated through the function of short noncoding RNAs, especially for microRNAs (miRNAs), but little is known about their roles in cancer cell drug resistance. In present study, by taking advantage of miRNA effects on the resistance of human hepatocellular carcinoma cells line to cisplatin, it has been demonstrated that miR-340 were significantly downregulated whereas Nrf2 was upregulated in HepG2/CDDP (cisplatin) cells, compared with parental HepG2 cells. Bioinformatics analysis and luciferase assays of Nrf2-3'-untranslated region-based reporter constructor indicated that Nrf2 was the direct target gene of miR-340, miR-340 mimics suppressing Nrf2-dependent antioxidant pathway and enhancing the sensitivity of HepG2/CDDP cells to cisplatin. Interestingly, transfection with miR-340 mimics combined with miR-340 inhibitors reactivated the Nrf2 related pathway and restored the resistance of HepG2/CDDP cells to CDDP. Collectively, the results first suggested that lower expression of miR-340 is involved in the development of CDDP resistance in hepatocellular carcinoma cell line, at least partly due to regulating Nrf2-dependent antioxidant pathway.

The Phytotoxic Effects of Selenium–Mercury Interactions on Root Growth in Brassica rapa (LvLing)

Zhi-Wei Bian,Jian Chen,Hui Li,Dan-Dan Liu,Li-Fei Yang,Yue-Lin Zhu,Wen-Li Zhu,Wei Liu,Zheng-Zheng Ying 한국원예학회 2016 Horticulture, Environment, and Biotechnology Vol.57 No.3

Rapid industrial and agricultural development has dramatically increased the emission of selenium (Se) and mercury (Hg) into the environment. Combined soil pollution by Se and Hg poses a potential threat to crop production. However, no toxic effects of Hg–Se interactions on plants have been reported previously. In this study, we investigated the effects of Hg–Se interactions on biochemical and physiological indices in the roots of Brassica rapa (LvLing). Seedlings were treated hydroponically with solutions of mercury chloride (1 μM), sodium selenite (4 μM), or a combination of the two. Combined Hg+Se treatment significantly inhibited root growth, reduced root biomass, and enhanced reactive oxygen species (ROS) and malondialdehyde accumulation and led to a loss of plasma membrane integrity. The combined treatment increased glutathione peroxidase, glutathione S-transferase, and peroxidase activity, reduced superoxide dismutase activity, and had no effect on catalase activity. In addition, we detected increased glutathione concentrations in root tips and reduced ascorbic acid concentrations in the presence of Hg+Se relative to individual treatments with these elements. Thus, Hg–Se interactions enhanced oxidative injury, cell death, and phytotoxicity in B. rapa roots.