Abnormal differentiation of regulatory T cells and Th17 cells induced by perinatal bisphenol A exposure in female offspring mice

You‑dan Dong,Liang Gao,Feng‑juan Wu,Ren Lin,Yuan Meng,Li‑hong Jia,Xiao‑fei Wang 대한독성 유전단백체 학회 2020 Molecular & cellular toxicology Vol.16 No.2

Background Bisphenol A (BPA) is an environmental estrogen widely exposed to human beings, and there are more studies on its reproductive toxicity, endocrine disruption and neurobehavioral disorders. Recent few studies have found that BPA has immunotoxicity, and its mechanism is not clear. Therefore, the effects of BPA on immune system have attracted extensive attention. The aim of this study was to investigate the effect and mechanism of perinatal exposure to BPA on regulatory T cells (Treg) and Th17 cells in female offspring mice. Methods Twenty-one pregnant C57BL/6 mice were randomly divided into three groups: a control group, low-dose BPA (0.2 μg/mL) and high-dose BPA (2.0 μg/mL) exposure group. All received BPA exposure via drinking water from gestational day 6 to the end of lactation. Female offspring were fed a normal diet and drinking water for 1 month. The percentages of Treg and Th17 cells, the levels of Foxp3 and RORγt protein and IL-17 and TGF-β from spleen tissue or blood were measured in female offspring. Results The percentage of Treg cells and levels of Foxp3 protein decreased, while the percentage of Th17 cells and levels of RORγt protein increased, which showed a dose–effect relationship. The levels of serum TGF-β were significantly lower and the levels of serum IL-17 were statistically higher in BPA-exposed female offspring compared with controls (P < 0.05 or P < 0.01). But there were no statistical difference in the levels of serum TGF-β and IL-17 between 0.2 μg/mL and 2.0 μg/ mL BPA groups (P > 0.05). Conclusion BPA exposure during pregnancy and lactation could cause abnormal differentiation and function of Treg and Th17 cells in female offspring mice, which was associated with down-regulated Foxp3 and up-regulated RORγt protein, respectively. Our findings indicated that BPA exposure during early development may play an important role in the development of autoimmune diseases later.

Expression Profiles of Loneliness-associated Genes for Survival Prediction in Cancer Patients

You, Liang-Fu,Yeh, Jia-Rong,Su, Mu-Chun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Influence of loneliness on human survival has been established epidemiologically, but genomic research remains undeveloped. We identified 34 loneliness-associated genes which were statistically significant for high-lonely and low-lonely individuals. With the univariate Cox proportional hazards regression model, we obtained corresponding regression coefficients for loneliness-associated genes fo individual cancer patients. Furthermore, risk scores could be generated with the combination of gene expression level multiplied by corresponding regression coefficients of loneliness-associated genes. We verified that high-risk score cancer patients had shorter mean survival time than their low-risk score counterparts. Then we validated the loneliness-associated gene signature in three independent brain cancer cohorts with Kaplan-Meier survival curves (n=77, 85 and 191), significantly separable by log-rank test with hazard ratios (HR) >1 and p-values <0.0001 (HR=2.94, 3.82, and 1.78). Moreover, we validated the loneliness-associated gene signature in bone cancer (HR=5.10, p-value=4.69e-3), lung cancer (HR=2.86, p-value=4.71e-5), ovarian cancer (HR=1.97, p-value=3.11e-5), and leukemia (HR=2.06, p-value=1.79e-4) cohorts. The last lymphoma cohort proved to have an HR=3.50, p-value=1.15e-7. Loneliness-associated genes had good survival prediction for cancer patients, especially bone cancer patients. Our study provided the first indication that expression of loneliness-associated genes are related to survival time of cancer patients.

Schumpeter and Arrow: Who Wins in Korea and Taiwan? - A Case Method Analysis of Cross Country Industrial Structure

You-liang Deng 연세대학교 동서문제연구원 2005 Global economic review Vol.34 No.1

A case study approach is applied to a cross-country comparison of Korea and Taiwan to model their developmental patterns and to examine the implications of their approach to industrialization, with specific regards to the theories of vertical integration by Schumpeter and Arrow and the theories of asset specificity by Williamson. The implications of inflation risks, external debt financing, innovation incentives, and restructuring problems from the aftermath of the 1997 Asian financial crisis will also be examined. The methodology used is a case study of two industries: bicycles and semiconductors. The results of this study are being used to create two dynamic models of industrial development for the two countries and to provide reasons for the differences in development paths and the implications associated with the undertaking of two drastically different models of industrialization.

SCHUMPETER AND ARROW : WHO WINS IN KOREA AND TAIWAN? A CASE METHOD ANALYSIS OF CROSS COUNTRY INDUSTRIAL STRUCTURE

Deng, You-liang 연세대학교 동서문제연구원 2004 Global economic review Vol.33 No.4

A case study approach is applied to a cross-country comparison of Korea and Taiwan to model their developmental patterns and to examine the implications of their approach to industrialization, with specific regard to the theories of vertical integration by Schumpeter and Arrow and the theories of asset specificity by Williamson. The implications of inflation risks, external debt financing, innovation incentives, and restructuring problems from the aftermath of the 1997 Asian financial crisis will also be examined. The methodology used is a case study of two industries: bicycles and semiconductors. The results of this study are being used to create two dynamic models of industrial development for the two countries and to provide reasons for the differences in development paths and the implications associated with the undertaking of two drastically different models of industrialization.

Detection of Rare Mutations in EGFR-ARMS-PCR-Negative Lung Adenocarcinoma by Sanger Sequencing

Chaoyue Liang,Zhuolin Wu,Xiaohong Gan,Yuanbin Liu,You You,Chenxian Liu,Chengzhi Zhou,Ying Liang,Haiyun Mo,Allen M. Chen,Jiexia Zhang 연세대학교의과대학 2018 Yonsei medical journal Vol.59 No.1

Purpose: This study aimed to identify potential epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer that went undetected by amplification refractory mutation system-Scorpion real-time PCR (ARMS-PCR). Materials and Methods: A total of 200 specimens were obtained from the First Affiliated Hospital of Guangzhou Medical University from August 2014 to August 2015. In total, 100 ARMS-negative and 100 ARMS-positive specimens were evaluated for EGFR gene mutations by Sanger sequencing. The methodology and sensitivity of each method and the outcomes of EGFR-tyrosine kinase inhibitor (TKI) therapy were analyzed. Results: Among the 100 ARMS-PCR-positive samples, 90 were positive by Sanger sequencing, while 10 cases were considered negative, because the mutation abundance was less than 10%. Among the 100 negative cases, three were positive for a rare EGFR mutation by Sanger sequencing. In the curative effect analysis of EGFR-TKIs, the progression-free survival (PFS) analysis based on ARMS and Sanger sequencing results showed no difference. However, the PFS of patients with a high abundance of EGFR mutationwas 12.4 months [95% confidence interval (CI), 11.6−12.4 months], which was significantly higher than that of patients with a low abundance of mutations detected by Sanger sequencing (95% CI, 10.7−11.3 months) (p<0.001). Conclusion: The ARMS method demonstrated higher sensitivity than Sanger sequencing, but was prone to missing mutations due to primer design. Sanger sequencing was able to detect rare EGFR mutations and deemed applicable for confirming EGFR status. A clinical trial evaluating the efficacy of EGFR-TKIs in patients with rare EGFR mutations is needed.

Evolution of ALPPS: The Simpler, Safer and Effective One---TELPP

( Shu You Peng ),( Xu An Wang ),( Cong Yun Huang ),( You Yong Zhang ),( Jiang Tao Li ),( De Fei Hong ),( Xiu Jun Cai ),( Yi Fang Wang ),( Xiao Liang ),( Jian Wei Wang ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: The characteristic of associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) carries high mortality and morbidity. There is room for improvement. We suggest Terminal Branches Portal Vein Embolization (TBPVE) as a way to compart the liver. As a result, only a single surgical operation is required.This method is termed Terminal branches portal vein Embolization Liver Partition Planned hepatectomy (TELPP). Methods: Patients with unresectable primary or metastatic liver tumor were performed with TELPP. The procedure of TELPP was that in addition to PVE, embolization agent was infused to the terminal branches of portal vein of S5,S8 or S4. CT scan was taken one or two weeks later, and standard liver volume(SLV), FLR and FLR/SLV are calculated. Two weeks later when the FLR and liver function is appropriate, open or laparoscopic hepatectomy is performed. Results: The study included 11patients including hepatocellular carcinoma: n =8, intrahepatic cholangiocarcinoma: n = 1, hilarcholangiocarcinoma: n =1, colorectal liver metastasis: n =1. After a waiting period of 14 days, the volume of theFLR had increased from 382mlto 578ml, representing a median volume increase of 51% (range =32.5%-86.7%). Of the 11patients with hepatectomy, right hemihepatectomy (n=2), extended right hemihepatectomy (n=5), right trisecmentectomy(2), extended left hemihepatectomy (n=1) and left trisecmentectomy(1). No patient died, and no serve perioperative morbidity occurred. Conclusions: ALPPS and all modifications need two-stage operations with a high morbidity and mortality rate. It seems that TELPP is very promising. It has the merit of ALPPS as extraordinarily rapid increasement of FLRvolume, yet the morbidity and mortality is much lower, owing to the fact that unlike ALPPS, there is no two liver raw surfaces left behind in the abdominal cavity to produce bile leak, as only single surgical operation is required

Composition Dependence of Structural and Magnetic Properties of Mn<SUB>3+x</SUB>Ga<SUB>1-x</SUB>C (0 ≤ x ≤ 1)

Ying-Hua Liang,Ping-Zhan Si,Ting-Ting Qi,Xin-You Wang,Fei-Yang Wang,Qiong Wu,Hong-Liang Ge,Jihoon Park,Chul-Jin Choi 한국자기학회 2024 Journal of Magnetics Vol.29 No.1

Both Mn₄C (=Mn₃MnC) and Mn₃GaC have been studied previously. However, the reports on Mn<SUB>3+x</SUB>Ga<SUB>1-x</SUB>C (0 ≤ x ≤ 1) with intermediate compositions are very rare. In this work, the structure and magnetic properties of Mn<SUB>3+x</SUB>Ga<SUB>1-x</SUB>C prepared by using solid state reaction were studied systematically. High purity anti-perovskitetype Mn<SUB>3+x</SUB>Ga<SUB>1-x</SUB>C were obtained in the composition range of 0 ≤ x ≤ 0.5, above which Mn₂₃C₆ precipitates and the fraction of Mn₂₃C₆ in the samples increases with increasing x. The structural stability, lattice parameters, and room temperature saturation magnetization of ferromagnetic Mn<SUB>3+x</SUB>Ga<SUB>1-x</SUB>C (0 ≤ x ≤ 1) decreases with increasing x. The Curie temperature of Mn<SUB>3+x</SUB>Ga<SUB>1-x</SUB>C (0 ≤ x ≤ 1) increases with increasing x. Most Mn<SUB>3+x</SUB>Ga<SUB>1-x</SUB>C with varied x exhibit near-zero coercivity and zero remanent magnetization. This work indicates that the temperature coefficient of magnetization of Mn<SUB>3+x</SUB>Ga<SUB>1-x</SUB>C may be tuned by tuning the fraction of the Ga atoms.

Apatinib Combined with Local Irradiation Leads to Systemic Tumor Control via Reversal of Immunosuppressive Tumor Microenvironment in Lung Cancer

Li-jun Liang,Chen-xi Hu,Yi-xuan Wen,Xiao-wei Geng,Ting Chen,Guo-qing Gu,Lei Wang,You-you Xia,Yong Liu,Jia-yan Fei,Jie Dong,Feng-hua Zhao,Yiliyar Ahongjiang,Kai-yuan Hui,Xiao-dong Jiang 대한암학회 2020 Cancer Research and Treatment Vol.52 No.2

Purpose This study aimed to investigate the potential systemic antitumor effects of stereotactic ablative radiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor 2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma. Materials and Methods Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor; irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grew to the touchable size, mice were randomly divided into eight treatment groups. These groups received normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200 mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not to the primary tumor. The further tumor growth/regression of mice were followed and observed. Results For the single 15 Gy modality, tumor growth delay could only be observed at the primary tumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primary and secondary tumor growth could be observed, indicated an abscopal effect was induced. Mechanism analysis suggested that programmed death-ligand 1 expression increased with SABR was counteract by additional apatinib therapy. Furthermore, when apatinib was combined with SABR, the composition of immune cells could be changed. More importantly, this two-pronged approach evoked tumor antigen–specific immune responses and the mice were resistant to another tumor rechallenge, finally, long-term survival was improved. Conclusion Our results suggested that the tumor microenvironment could be managed with apatinib, which was effective in eliciting an abscopal effect induced by SABR.

Comparison of Concurrent Chemoradiotherapy Followed by Adjuvant Chemotherapy Versus Concurrent Chemoradiotherapy Alone in Locoregionally Advanced Nasopharyngeal Carcinoma: a Meta-analysis of 793 Patients from 5 Randomized Controlled Trials

Liang, Zhong-Guo,Zhu, Xiao-Dong,Zhou, Zhi-Rui,Qu, Song,Du, You-Qin,Jiang, Yan-Ming Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

Purpose: The main objective of the present study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy followed by adjuvant chemotherapy compared with concurrent chemoradiotherapy alone in the treatment of locoregionally advanced nasopharyngeal carcinoma. Methods: The search strategy included Pubmed, Embase, the Cochrane Library, China National Knowledge Internet Web, Chinese Biomedical Database and Wanfang Database. We also searched reference lists of articles and the volumes of abstracts of scientific meetings. Randomized controlled trials (RCTs) that compared concurrent chemoradiotherapy followed by adjuvant chemotherapy with concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma were included. Meta-analysis was performed with RevMan 5.1.0. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to rate the level of evidence. Results: Five studies were included. Risk ratios of 1.02 (95%CI 0.89-1.15), 0.93 (95%CI 0.72-1.21), 1.07 (95%CI 0.87-1.32), 0.95 (95%CI 0.80-1.13) were observed for 3 years overall survival, 5 years failure-free survival, 5 years locoregional failure-free survival and 5 years distant metastasis failure-free survival. There were no treatment-related deaths in both groups of five studies. Hematologic and gastrointestinal toxicity were the most significant for patients during adjuvant chemotherapy. The level of evidence was low. Conclusion: Compared with concurrent chemoradiotherapy alone, concurrent chemotherapy followed by adjuvant chemotherapy did not improve prognosis. More toxicity was found during adjuvant chemotherapy.

Ganoderma Lucidum Polysaccharides Target a Fas/Caspase Dependent Pathway to Induce Apoptosis in Human Colon Cancer Cells

Liang, Zengenni,Guo, Yu-Tong,Yi, You-Jin,Wang, Ren-Cai,Hu, Qiu-Long,Xiong, Xing-Yao Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.9

Ganoderma lucidum polysaccharides (GLP) extracted from Ganoderma lucidum have been shown to induce cell death in some kinds of cancer cells. This study investigated the cytotoxic and apoptotic effect of GLP on HCT-116 human colon cancer cells and the molecular mechanisms involved. Cell proliferation, cell migration, lactate dehydrogenase (LDH) levels and intracellular free calcium levels ($[Ca^{2+}]i$) were determined by MTT, wound-healing, LDH release and fluorescence assays, respectively. Cell apoptosis was observed by scanning and transmission electron microscopy. For the mechanism studies, caspase-8 activation, and Fas and caspase-3 expression were evaluated. Treatment of HCT-116 cells with various concentrations of GLP (0.625-5 mg/mL) resulted in a significant decrease in cell viability (P< 0.01). This study showed that the antitumor activity of GLP was related to cell migration inhibition, cell morphology changes, intracellular $Ca^{2+}$ elevation and LDH release. Also, increase in the levels of caspase-8 activity was involved in GLP-induced apoptosis. Western blotting indicated that Fas and caspase-3 protein expression was up-regulated after exposure to GLP. This investigation demonstrated for the first time that GLP shows prominent anticancer activities against the HCT-116 human colon cancer cell line through triggering intracellular calcium release and the death receptor pathway.