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.

Theoretical Study of the Elastic and the Thermodynamic Properties of Re$_2$C under High Pressure

Hui-Ru Lei,Li-Hong Zhang,Xu Li,Xiao-Zhen Gao,Jing Li 한국물리학회 2019 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.74 No.11

The structural properties of Re$_2$C in anti-MoS$_2$ and anti-ReB$_2$ structures have been investigated by using the pseudopotential plane wave methods based on the density functional theory. The anti-ReB$_2$ structure is found to be more stable than the anti-MoS$_2$ structure. In particular, for the first time, we have studied the elastic properties of Re$_2$C in the anti-ReB$_2$ structure under high pressure. The ductile-brittle behavior and Vickers hardness for the anti-ReB$_2$ structure are also been analyzed. In addition, the Debye temperature, heat capacity and thermal expansion coefficient are discussed by using the quasiharmonic Debye model method.

Non-Benzoquinone Geldanamycin Analog, WK-88-1, Induces Apoptosis in Human Breast Cancer Cell Lines

( Yu-ru Zhao ),( Hong-mei Li ),( Meilin Zhu ),( Jing Li ),( Tao Ma ),( Qiang Huo ),( Young-soo Hong ),( Cheng-zhu Wu ) 한국미생물생명공학회(구 한국산업미생물학회) 2018 Journal of microbiology and biotechnology Vol.28 No.4

Heat shock protein 90 (Hsp90) is treated as a molecular therapeutic target for the prevention and treatment of cancer. Geldanamycin (GA) was the first identified natural Hsp90 inhibitor, but hepatotoxicity has limited its clinical application. Nevertheless, a new GA analog (WK-88- 1) with the non-benzoquinone skeleton, obtained from genetically engineered Streptomyces hygroscopicus, was found to have anticancer activity against two human breast cancer cell lines. WK-88-1 produced concentration-dependent inhibition of cell proliferation, cell cycle arrest, and apoptosis in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 cell lines. Detailed analysis showed that WK-88-1 downregulated some key cell cycle molecules (CDK1 and cyclin B1) and lead to G2/M cell cycle arrest. Further studies also showed that WK- 88-1 could induce human breast cancer cell apoptosis by downregulating Hsp90 client proteins (Akt, p-Akt, IKK, c-Raf, and Bcl-2), decreasing the ATP level, increasing reactive oxygen species production, and lowering the mitochondrial membrane potential. Meanwhile, we discovered that WK-88-1 significantly decreased the levels of Her-2 and ER-α in MCF-7 cells but not in MDA-MB-231 cells. In addition, WK-88-1 significantly increased caspase-3, -8, and -9 activities and the cleavage of PARP in a concentration-dependent manner (with the exception of caspase-3 and PARP in MCF-7 cells). Taken together, our preliminary results suggest that WK-88-1 has the potential to play a role in breast cancer therapy.

Empirical seismic vulnerability probability prediction model of RC structures considering historical field observation

Si-Qi Li,Hong-Bo Liu,Ke Du,Jia-Cheng Han,Yi-Ru Li,Li-Hui Yin 국제구조공학회 2023 Structural Engineering and Mechanics, An Int'l Jou Vol.86 No.4

To deeply probe the actual earthquake level and fragility of typical reinforced concrete (RC) structures under multiple intensity grades, considering diachronic measurement building stock samples and actual observations of representative catastrophic earth shocks in China from 1990 to 2010, RC structures were divided into traditional RC structures (TRCs) and bottom reinforced concrete frame seismic wall masonry (BFM) structures, and the empirical damage characteristics and mechanisms were analysed. A great deal of statistics and induction were developed on the historical experience investigation data of 59 typical catastrophic earthquakes in 9 provinces of China. The database and fragility matrix prediction model were established with TRCs of 4,122.5284×104 m2 and 5,844 buildings and BFMs of 5,872 buildings as empirical seismic damage samples. By employing the methods of structural damage probability and statistics, nonlinear prediction of seismic vulnerability, and numerical and applied functional analysis, the comparison matrix of actual fragility probability prediction of TRC and BFM in multiple intensity regions under the latest version of China’s macrointensity standard was established. A novel nonlinear regression prediction model of seismic vulnerability was proposed, and prediction models considering the seismic damage ratio and transcendental probability parameters were constructed. The time-varying vulnerability comparative model of the sample database was developed according to the different periods of multiple earthquakes. The new calculation method of the average fragility prediction index (AFPI) matrix parameter model has been proposed to predict the seismic fragility of an areal RC structure.

Risk Factors for Anxiety in Major Depressive Disorder Patients

Li-Min Xin,Lin Chen,Zhen-Peng Ji,Suo-Yuan Zhang,Jun Wang,Yan-Hong Liu,Da-Fang Chen,Fu-De Yang,Gang Wang,Yi-Ru Fang,Zheng Lu,Hai-Chen Yang,Jian Hu,Zhi-Yu Chen,Yi Huang,Jing Sun,Xiao-Ping Wang,Hui-Chun 대한정신약물학회 2015 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.13 No.3

Objective: To analyze the sociodemographic and clinical factors related to anxiety in patients with major depressive disorder (MDD). Methods: This study involved a secondary analysis of data obtained from the Diagnostic Assessment Service for People with Bipolar Disorders in China (DASP), which was initiated by the Chinese Society of Psychiatry (CSP) and conducted from September 1, 2010 to February 28, 2011. Based on the presence or absence of anxiety-related characteristics, 1,178 MDD patients were classified as suffering from anxious depression (n=915) or non-anxious depression (n=263), respectively. Results: Compared with the non-anxious group, the anxious-depression group had an older age at onset (t=−4.39, p<0.001), were older (t=−4.69, p<0.001), reported more lifetime depressive episodes (z=−3.24, p=0.001), were more likely to experience seasonal depressive episodes (χ2=6.896, p=0.009) and depressive episodes following stressful life events (χ2=59.350, p <0.001), and were more likely to have a family history of psychiatric disorders (χ2=6.091, p=0.014). Their positive and total scores on the Mood Disorder Questionnaire (MDQ) and the 32-item Hypomania Checklist (HCL-32) (p<0.05) were also lower. The logistic regression analysis indicated that age (odds ratio [OR]=1.03, p<0.001), a lower total MDQ score (OR=0.94, p=0.011), depressive episodes following stressful life events (OR=3.04, p<0.001), and seasonal depressive episodes (OR=1.75, p=0.039) were significantly associated with anxious depression. Conclusion: These findings indicate that older age, fewer subclinical bipolar features, an increased number of depressive episodes following stressful life events, and seasonal depressive episodes may be risk factors for anxiety-related characteristics in patients with MDD.

Genetic Variants at 6p21.1 and 7p15.3 Identified by GWASs of Multiple Cancers and Ovarian Cancer Risk: a Case-control Study in Han Chinese Women

Li, Da-Ke,Han, Jing,Liu, Ji-Bin,Jin, Guang-Fu,Qu, Jun-Wei,Zhu, Meng,Wang, Yan-Ru,Jiang, Jie,Ma, Hong-Xia Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

A recent study summarized several published genome-wide association studies (GWASs) of cancer and reported two pleiotropic loci at 6p21.1 and 7p15.3 contributing to multiple cancers including lung cancer, noncardia gastric cancer (NCGC), and esophageal squamous-cell carcinoma (ESCC) in Han Chinese. However, it is not known whether such genetic variants have similar effects on the risk of gynecologic cancers, such as ovarian cancer. Hence, we explored associations between genetic variants in 6p21.1 and 7p15.3 and ovarian cancer risk in Han Chinese women. We performed an independent case-control study by genotyping the two loci (rs2494938 A > G at 6p21.1 and rs2285947 A > G at 7p15.3) in a total of 377 ovarian cancer cases and 1,034 cancer-free controls using TaqMan allelic discrimination assay. We found that rs2285947 at 7p15.3 was significantly associated with risk of ovarian cancer with per allele odds ratio (OR) of 1.33 [95% confidence interval (CI): 1.08-1.64, P=0.008]. However, no significant association was observed between rs2494938 and ovarian cancer risk. Our results showed that rs2285947 at 7p15.3 may also contribute to the development of ovarian cancer in Han Chinese women, further suggesting pleiotropy of 7p15.3 in multiple cancers.

Advances in the Early Detection of Lung Cancer using Analysis of Volatile Organic Compounds: From Imaging to Sensors

Li, Wang,Liu, Hong-Ying,Jia, Zi-Ru,Qiao, Pan-Pan,Pi, Xi-Tian,Chen, Jun,Deng, Lin-Hong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

According to the World Health Organization (WHO), 1.37 million people died of lung cancer all around the world in 2008, occupying the first place in all cancer-related deaths. However, this number might be decreased if patients were detected earlier and treated appropriately. Unfortunately, traditional imaging techniques are not sufficiently satisfactory for early detection of lung cancer because of limitations. As one alternative, breath volatile organic compounds (VOCs) may reflect the biochemical status of the body and provide clues to some diseases including lung cancer at early stage. Early detection of lung cancer based on breath analysis is becoming more and more valued because it is non-invasive, sensitive, inexpensive and simple. In this review article, we analyze the limitations of traditional imaging techniques in the early detection of lung cancer, illustrate possible mechanisms of the production of VOCs in cancerous cells, present evidence that supports the detection of such disease using breath analysis, and summarize the advances in the study of E-noses based on gas sensitive sensors. In conclusion, the analysis of breath VOCs is a better choice for the early detection of lung cancer compared to imaging techniques. We recommend a more comprehensive technique that integrates the analysis of VOCs and non-VOCs in breath. In addition, VOCs in urine may also be a trend in research on the early detection of lung cancer.

Dextromethorphan Protect the Valproic Acid Induced Downregulation of Neutrophils in Patients with Bipolar Disorder

Ru-Band Lu,Yun-Hsuan Chang,Sheng-Yu Lee,Tzu-Yun Wang,Shu-Li Cheng,Po See Chen,Yen Kuang Yang,Jau-Shyong Hong,Shiou-Lan Chen 대한정신약물학회 2020 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.18 No.1

Objective: Valproic acid (VPA) is an anticonvulsant and commonly long term used as a mood stabilizer for patients with mood disorders. However its chronic effects on the hematological changes were noticed and need to be further evaluated. In this study, we evaluated, in Taiwanese Han Chinese patients with bipolar disorders (BD), the chronic effects of VPA or VPA plus dextromethorphan (DM) on the hematological molecules (white blood cell [WBCs], red blood cells [RBCs], hemoglobin, hematocrit, and platelets). Methods: In a 12-week, randomized, double-blind study, we randomly assigned BD patients to one of three groups: VPA plus either placebo (VPA+P, n = 57) or DM (30 mg/day, VPA+DM30, n = 56) or 60 mg/day (VPA+DM60, n = 53). The Young Mania Rating Scale and Hamilton Depression Rating Scale were used to evaluate symptom severity, and the hematological molecules were checked. Results: Paired t test showed that the WBC, neutrophils, platelets and RBCs were significantly lowered after 12 weeks of VPA+P or VPA+DM30 treatment. VPA+DM60 represented the protective effects in the WBCs, neutrophils, and RBCs but not in the platelets. We further calculated the changes of each hematological molecules after 12 weeks treatment. We found that combination use of DM60 significantly improved the decline in neutrophils induced by the long-term VPA treatment. Conclusion: Hematological molecule levels were lower after long-term treatment with VPA. VPA+DM60, which yielded the protective effect in hematological change, especially in the neutrophil counts. Thus, DM might be adjunct therapy for maintaining hematological molecules in VPA treatment.

Mutations in AP22.65 Accelerate Flowering in Arabidopsis thaliana

Ji Hong Xing,Feng Ru Wang,Jiao Jia,Jing Zhang,Li Li,Zhan Chen,Qiao Yun Weng,Ping Yang,Ye Zhang,Bin Zhao,He Long Si,Jin Gao Dong,Jian Min Han 한국식물학회 2013 Journal of Plant Biology Vol.56 No.1

Identification of the gene(s) responsible for floweringtime in Arabidopsis has significant implications. We used theT-DNA insertion library of Arabidopsis thaliana to screen anearly-flowering mutant that exhibits accelerated floweringunder short-day conditions. AP22.65, a novel flowering-timegene in that species, was isolated and identified via genomewalkingand bioinformatics analysis. The flowering time ofAP22.65-complementing plants was similar to that of theCol-0 wild type (WT). Conversely, its overexpression delayedflowering. Consistent with this phenotype, expression ofAP22.65 was decreased in the ap22.65-1 mutant, recoveredin AP22.65-complementing plants, and increased in AP22.65-overexpressing plants. Compared with the WT, expressionlevels of critical genes in different flowering pathways, i.e.,SPY, FLC, GI, CO, FT, and LFY, were down-regulated inloss-of-function mutants. Expression of AP22.65 was distributedin flowers, siliques, rosette leaves, and whole seedlings. Therefore, this gene may be a negative regulator of Arabidopsisflowering.

Distribution and using of Medicinal Plant in Mt. Jangback (Baekdu)

Hu Lin Li(이호림),Ru Zi Piao,Di Liu,Jae Han Cho(조재한),Gi Hong An(안기홍),Won Sik Kong(공원식),Yun Ji Lee(이윤지),Jin Tae Jeong(정진태),Chun Geun Park(박춘근),Jeong Hoon Lee(이정훈),한재구 한국약용작물학회 2020 한국약용작물학회 학술대회논문집 Vol.2020 No.1