The tyrosine kinase inhibitor nintedanib activates SHP-1 and induces apoptosis in triple-negative breast cancer cells

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.

Development of Phalaenopsis Flowering Quality Prediction Models

( Han-chun Hsu ),( Suming Chen ),( Chao-yin Tsai ),( Yung-huei Chang ) 한국농업기계학회 2018 한국농업기계학회 학술발표논문집 Vol.23 No.1

Phalaenopsis is an important exported flower in Taiwan and its flowering quality was reported to be correlated to its leaves’ carbohydrate contents and external traits. Phalaenopsis Sogo Yukidian 'V3' was used as the experimental samples in this research. A hand-held spectrometer and a hyperspectral system were used to build the carbohydrate content prediction models (CC model) respectively first, and then combined with leaves’ external traits obtained from hyperspectral imaging to build the flowering quality prediction model (FQ model). The advantage and application of FQ models built by both devices were compared. The results showed that the CC models built with MPLSR for glucose, fructose, sucrose, total soluble sugar, starch and total carbohydrates by hyperspectral system were all better than those by hand-held spectrometer. The results of FQ models with PLSDA and SVM also showed that the performance of hyperspectral system to discriminate quality levels was better. As for the ANN models’ results to predict the total number of flowers, the errors using both devices were all lower than 0.87. The research proved that using spectral technique to predict the interior contents in Phalaenopsis leaves or flowering quality were both feasible. Although the performance of hyperspectral imaging system is better than that of hand-held spectrometer, it was expensive and not as convenient as hand-held spectrometer. We can adopt some other ways such as using multispectral imaging system or optimize the performance of hand-held spectrometer if we want to apply the results to the Phalaenopsis industry.

An Innate Bactericidal Oleic Acid Effective Against Skin Infection of Methicillin-Resistant Staphylococcus aureus: A Therapy Concordant with Evolutionary Medicine

( Chao Hsuan Chen ),( Yan Han Wang ),( Teruaki Nakatsuji ),( Yu Tsueng Liu ),( Christos C. Zouboulis ),( Richard L. Gallo ),( Liangfang Zhang ),( Ming Fa Hsieh ),( Chun Ming Huang ) 한국미생물 · 생명공학회 2011 Journal of microbiology and biotechnology Vol.21 No.4

Free fatty acids (FFAs) are known to have bacteriocidal activity and are important components of the innateimmune system. Many FFAs are naturally present in human and animal skin, breast milk, and in the bloodstream. Here, the therapeutic potential of FFAs against methicillin-resistant Staphylococcus aureus (MRSA) is demonstrated in cultures and in mice. Among a series of FFAs, only oleic acid (OA) (C18:1, cis-9) can effectively eliminate Staphylococcus aureus (S. aureus) through cell wall disruption. Lauric acid (LA, C12:0) and palmitic acid (PA, C16:0) do not have this ability. OA can inhibit growth of a number of Gram-positive bacteria, including hospital and community-associated MRSA at a dose that did not show any toxicity to human sebocytes. The bacteriocidal activities of FFAs were also demonstrated in vivo through injection of OA into mouse skin lesions previously infected with a strain of MRSA. In conclusion, our results suggest a promising therapeutic approach against MRSA through boosting the bacteriocidal activities of native FFAs, which may have been co-evolved during the interactions between microbes and their hosts.

Research on Near Infrared Spectroscopy Application for Aflatoxin Testing on Rice

( I-chun Tung ),( Tsung-hsin Wu ),( Han-chun Hsu ),( Suming Chen ),( Chao-yin Tsai ),( Yung-kun Chuang ) 한국농업기계학회 2018 한국농업기계학회 학술발표논문집 Vol.23 No.1

Rice is one of the most important staple food in the world. In many countries, environments with high temperature/humidity may provide favorable conditions for fungal propagation and production of aflatoxins during rice storage. Aflatoxin B₁ (AFB₁), one of the secondary metabolites produced by Aspergillus flavus and Aspergillus parasiticus, is particularly carcinogenic to humans. People might very likely cause severe illness once rice is contaminated by aflatoxins. Therefore, the objective of this study is to develop a nondestructive method for rapid and accurate detection of the AFB₁ content in rice. In the present study, evaluation of AFB₁ contaminated rice were conducted by using near infrared spectroscopy (NIRS) technique with chemometrics. NIR Spectra and the AFB₁ contents of the artificially contaminated rice samples were measured by FOSS NIRS 6500 spectrometer and LC-MS/MS, respectively. Modified partial least square regression (MPLSR), a commonly used multivariate analysis method was then used to build calibration models. In summary, NIRS associated with chemometrics could provide a useful tool for rapid and accurate detection of AFB₁ content in rice.

Foreword of Part 2

Hsu-Chun Yen,Han-Chieh Chao,Whai-En Chen 보안공학연구지원센터 2007 International Journal of Smart Home Vol.1 No.2

A model study for an Oceania watershed: spatio‐temporal changes of mesozooplankton in riverine and estuarine parts of the Lanyang River in Taiwan

Dahms, Hans‐,Uwe,Tseng, Li‐,Chun,Hsiao, Shih‐,Hui,Chen, Qing‐,Chao,Hwang, Jiang‐,Shiou Springer Japan 2013 Ecological research Vol.28 No.2

<P><B>Abstract</B></P><P>The mesozooplankton of a river tributary in Oceania is evaluated and is correlated against environmental, abiotic, and biological attributes of this lotic system. Abundance, distribution, and the diversity of mesozooplankton was studied at nine stations including one estuarine station during ten sampling campaigns from June 2004 to December 2005 along the Lanyang River, the largest river and estuarine ecosystem in northeastern Taiwan. Mesozooplankton was dominated by copepods, cladocerans, and fish larvae. Among all samples, the highest abundances of mesozooplankton (5,049.36 individuals m<SUP>−3</SUP>) occurred in the estuary station in August 2004, which also corresponds to the highest salinities (37.0), indicating the marine role in shaping the estuarine planktonic assemblages. The abundance of mesozooplankton and number of mesozooplankton taxa were significantly higher in samples of the estuarine station than in the riverine stations (<I>p</I> < 0.05, one‐way ANOVA). The number of mesozooplankton taxa number was affected by water temperature (<I>r</I> = 0.697; <I>p</I> = 0.025, Pearson's correlation) that was primarily influenced by the weather that was in turn affected by seasonal monsoons.</P>

Impact of Elevational Gradients and Chemical Parameters on Changes in Soil Bacterial Diversity Under Semiarid Mountain Region

Khan Salman,Han Chun,Iqbal Awais,Guan Chao,Zhao Changming 한국미생물학회 2023 The journal of microbiology Vol.61 No.10

Elevation gradients, often regarded as “natural experiments or laboratories”, can be used to study changes in the distribution of microbial diversity related to changes in environmental conditions that typically occur over small geographical scales. We obtained bacterial sequences using MiSeq sequencing and clustered them into operational taxonomic units (OTUs). The total number of reads obtained by the bacterial 16S rRNA sequencing analysis was 1,090,555, with an average of approximately 45,439 reads per sample collected from various elevations. The current study observed inconsistent bacterial diversity patterns in samples from the lowest to highest elevations. 983 OTUs were found common among all the elevations. The most unique OTUs were found in the soil sample from elevation_2, followed by elevation_1. Soil sample collected at elevation_6 had the least unique OTUs. Actinobacteria, Protobacteria, Chloroflexi were found most abundant bacterial phyla in current study. Ammonium nitrogen ( NH4 +-N), and total phosphate (TP) are the main factors influencing bacterial diversity at elevations_ 1. pH was the main factor influencing the bacterial diversity at elevations_2, elevation_3 and elevation_4. Our results provide new visions on forming and maintaining soil microbial diversity along an elevational gradient and have implications for microbial responses to environmental change in semiarid mountain ecosystems.

Kojic Acid Protects C57BL/6 Mice from Gamma-irradiation Induced Damage

Wang, Kai,Liu, Chao,Di, Chan-Juan,Ma, Cong,Han, Chun-Guang,Yuan, Mei-Ru,Li, Peng-Fei,Li, Lu,Liu, Yong-Xue Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

The radioprotective effects of a single administration of kojic acid (KA) against ionizing radiation were evaluated via assessment of 30-day survival and alterations of peripheral blood parameters of adult C57BL/6 male mice. The 30-day survival rate of mice pretreated with KA (75 or 300 mg/kg body weight, KA75 or KA300) subcutaneously 27 h prior to a lethal dose (8 Gy, 153.52 cGy/min) of gamma irradiation was higher than that of mice irradiated alone (40% or 60% vs 0%). It was observed that the white blood cell (WBC) count/the red blood cell (RBC) count, haemoglobin content, haematocrit and platelet count of mice with or without KA pretreatment as exposed to a sub-lethal dose (4 Gy, 148.14 cGy/min) of gamma irradiation decreased maximally at day 4/day 8 post-irradiation. Although the initial WBC values were low in KA300 or WR-2721 (amifostine) groups, they significantly recovered to normal at day 19, whereas in the control group they did not. The results from the cytotoxicity and cell viability assays demonstrated that KA could highly protect Chinese hamster ovary (CHO) cells against ionizing radiation with low toxicity. In summary, KA provides marked radioprotective effects both in vivo and in vitro.

A Vision-Based Collision Warning System by Surrounding Vehicles Detection

( Bing-fei Wu ),( Ying-han Chen ),( Chih-chun Kao ),( Yen-feng Li ),( Chao-jung Chen ) 한국인터넷정보학회 2012 KSII Transactions on Internet and Information Syst Vol.6 No.4

To provide active notification and enhance drivers` awareness of their surroundings, a vision-based collision warning system that detects and monitors surrounding vehicles is proposed in this paper. The main objective is to prevent possible vehicle collisions by monitoring the status of surrounding vehicles, including the distance to the other vehicles in front, behind, to the left and to the right sides. In addition, the proposed system collects and integrates this information to provide advisory warnings to drivers. To offer the correct notification, an algorithm based on features of edge and morphology to detect vehicles is also presented. The proposed system has been implemented in embedded systems and evaluated on real roads in various lighting and weather conditions. The experimental results indicate that the vehicle detection ratios were higher than 97% in the daytime, and appropriate for real road applications.

Determination of Geographical Origin of Tea using Near Infrared Spectroscopy

( Tsung-hsin Wu ),( I-chun Tung ),( Han-chun Hsu ),( Suming Chen ),( Chao-yin Tsai ),( Yung-kun Chuang ) 한국농업기계학회 2018 한국농업기계학회 학술발표논문집 Vol.23 No.1

Tea is one of the most consumed beverages in the world. Every tea has its own aroma and flavor characteristics due to geographic differences in environment and climate. Oolong tea, a very popular kind of partial fermentation tea in Taiwan, is generally more expensive and enjoyable. While tea leaves produced from the other countries are generally cheaper and not easily discernible, many stores mainly use cheaper tea leaves which are imported from Vietnam, India, and China, where adulteration and counterfeit may happen in tea market. To date, determination of geographical origin of tea is mainly depends on sensory evaluation, which lacks of objectivity in science. Therefore, determination of geographical origin of tea is necessary. Near infrared spectroscopy (NIRS) is a rapid and nondestructive analytical method which has become a powerful tool by associating with chemometrics for food industry. In the present study, the quality-related constituents of tea, including total polyphenols, total free amino acids, pH value, and water were evaluated by NIRS with modified partial least square regression (MPLSR). The calibration models built by MPLSR showed satisfied results. For total polyphenols, the results of the calibration model were Rc = 0.983 and SEC = 4.268 mg/g. The results of free amino acids were R_c = 0.913 and SEC = 3.368 mg/g. The results of pH value were R_c = 0.972 and SEC = 0.105. The results of moisture were R_c = 0.969 and SEC = 0.470 %. To identify the geographical origin of tea, the qualitative method of support vector machine (SVM) will also be applied in this study. The SVM result of identify the partially fermented tea origins was achieved and the accuracies for calibration and prediction sets were both 100%. In summary, NIRS associated with chemometrics provides a useful tool for internal quality inspection and origin identification of tea.