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Chun-Yu Liu,Tzu-Ting Huang,Pei-Yi Chu,Chun-Teng Huang,Chia-Han Lee,Wan-Lun Wang,Ka-Yi Lau,Wen-Chun Tsai,Tzu-I Chao,Jung-Chen Su,Ming-Huang Chen,Chung-Wai Shiau,Ling-Ming Tseng,Kuen-Feng Chen 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-
Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.
Chu, Jia-Qi,Jing, Kai-Peng,Gao, Xiang,Li, Peng,Huang, Rui,Niu, Yan-Ru,Yan, Shou-Quan,Kong, Jun-Chao,Yu, Cai-Yuan,Shi, Ge,Fan, Yi-Ming,Lee, Young-Ha,Zhou, Yu,Quan, Juan-Hua Landes Bioscience 2017 Cell Cycle Vol.16 No.5
<P>Autophagy and apoptosis are critical for controlling Toxoplasma gondii (T. gondii) infection. T. gondii infection during pregnancy can damage the fetus and cause birth defects; however, the molecular mechanisms of this process are poorly understood. This study aims to determine the activities of autophagy and apoptosis as well as their regulatory mechanisms during T. gondii infection by using human umbilical cord mesenchymal stem cells (hUC-MSCs) as a model of congenital diseases. LC3B, a hallmark protein of autophagy was incrementally upregulated with the infection duration, whereas p62 was downregulated in T. gondii-infected hUC-MSCs. Concurrent to this result, the invasion of T. gondii into hUC-MSCs increased in a time-dependent manner. The expression levels of Bcl-2 family proteins including Bcl-2, Bcl-xL, Bim, Bax, Bid and Bak were not altered; however, Mcl-1 levels in hUC-MSCs were dramatically decreased upon T. gondii infection. In addition, at 24h post-infection, cleaved PARP and cleaved caspase-3 protein levels were elevated in hUC-MSCs. Importantly, Mcl-1 overexpression reduced the levels of autophagy- and apoptosis-related proteins in T. gondii-infected hUC-MSCs. Mcl-1 proteins were primarily expressed in the fraction containing mitochondria and strongly interacted with Beclin-1 under normal conditions; however, these interactions were remarkably attenuated by T. gondii infection. These results suggest that mitochondrial Mcl-1 is an essential signaling mediator regulating the activation of autophagy and apoptosis during T. gondii infection.</P>
Huang, Wen-Kuan,Lin, Yung-Chang,Chiou, Meng-Jiun,Yang, Tsai-Sheng,Chang, John Wen-Cheng,Yu, Kuang-Hui,Kuo, Chang-Fu,See, Lai-Chu Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8
Background: There have been no large-scale population-based studies to estimate the subsequent risk of primary liver cancer (PLC) among patients with pyogenic liver abscess (PLA). This study aimed to provide relevant data. Materials and Methods: The Taiwan Longitudinal Health Insurance Database for the years 2000 and 2005 was used. The PLA group were adult inpatients who were newly diagnosed with PLA from 2000 to 2008. The control group was randomly selected and matched with the PLA group in terms of age, sex, and date in which medical treatment was sought other than for PLA. Results: There were 1,987 patients each in the PLA and control groups. In total, 56 had PLC, 48 (2.4%, 601.5 per 100,000 person-years) from the PLA group, and 8 from the control group. After adjusting for potential covariates, the hazard ratio of PLC for the PLA group was 3.4 times that of the control group (95% confidence interval = 1.6-7.3, p <0.001). The PLC risk for the PLA group was significantly higher within the first year after PLA diagnosis (hazard ratio: 35.4) as compared with the control group and became insignificant (hazard ratio: 2.0, 95% confidence interval = 0.8-4.9) more than one year after PLA diagnosis. Conclusions: Patients with PLA have a higher rate of PLC than matched controls, especially within the first year after the diagnosis of PLA, suggesting PLA is a warning sign for PLC.
Chu-Han Huang,Cheng-Yu Ho,Ciao-Ting Chen,Hsin-Fen Hsu,Yung-Hsiang Lin 한국식품영양과학회 2019 Preventive Nutrition and Food Science Vol.24 No.4
Lactobacillus (Lab.) is a human probiotic beneficial for the prevention and improvement of disease, yet properties of different Lab. strains are diverse. To obtain a Lab. strain that possesses greater potential against gastrointestinal dysfunction, we isolated Lactobacillus plantarum TCI378 (TCI378) from naturally fermented Korean kimchi. TCI378 has shown potential as probiotic since it can survive at pH 3.0 and in the presence of 0.3% bile acid. The bile salt hydrolase activity of TCI378 was shown by formation of opaque granular white colonies on solid de Man Rogosa Sharpe (MRS) medium supplemented with taurodeoxycholic acid, and its cholesterol-lowering ability in MRS medium supplemented with cholesterol. The metabolites of TCI378 from liquid culture in MRS medium prevented emulsification of bile salts. Moreover, both the metabolites of TCI378 and the dead bacteria reduced oil droplet accumulation in 3T3-L1, as detected by Oil red O staining. The expressions of adipocyte-specific genes perilipin 1 and glucose transporter type 4 were suppressed by the metabolites of TCI378, indicating TCI378 may have anti-obesity effects in adipocytes. These in vitro data show the potential of the prophylactic applications of TCI378 and its metabolites for reducing fat and lowering cholesterol.
Evaluation of Humic Acid and Tannic Acid Fouling in Graphene Oxide-Coated Ultrafiltration Membranes
Chu, Kyoung Hoon,Huang, Yi,Yu, Miao,Her, Namguk,Flora, Joseph R.V.,Park, Chang Min,Kim, Suhan,Cho, Jaeweon,Yoon, Yeomin American Chemical Society 2016 ACS APPLIED MATERIALS & INTERFACES Vol.8 No.34
<P>Three commercially available ultrafiltration (UF) membranes (poly(ether sulfone), PES) that have nominal molecular weight cut-offs (5, 10, and 30 kDa) were coated with graphene oxide (GO) nanosheets. Field-emission scanning electron microscopy, Fourier-transform infrared spectroscopy, confocal laser scanning microscopy, water contact angle measurements, and X-ray photoelectron spectroscopy were employed to determine the changed physicochemical properties of the membranes after GO coating. The water permeability and single-solute rejection of GO-coated (GO(c)) membranes for humic acid (HA) molecules were significantly higher by approximately 15% and S5%, respectively, compared to those of pristine UF membranes. However, the GOc membranes for single-solute tannic acid (TA) rejection showed similar trends of higher flux decline versus pristine PES membranes, because the relatively smaller TA molecules were readily adsorbed onto the membrane pores. When the mixed-solute of HA and TA rejection tests were performed, in particular, the adsorbed small TA molecules resulted in irreversible membrane fouling due to cake formation and membrane pore blocking on the membrane surface for the HA molecules. Although both membranes showed significantly higher flux declines for small molecules rejection, the GOc membranes showed better performance than the pristine UF membranes in terms of the rejection of various mixed-solute molecules, due to higher membrane recovery and antifouling capabilities.</P>