Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy

Zhou Jing,Feng Ji,Wu Yong,Dai Hui-Qi,Zhu Guang-Zhi,Chen Pan-Hong,Wang Li-Ming,Lu Guang,Liao Xi-Wen,Lu Pei-Zhi,Su Wen-Jing,Hooi Shing Chuan,Ye Xin-Pin,Shen Han-Ming,Peng Tao,Lu Guo-Dong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.

Comparative Genomics Profiling of Clinical Isolates of Helicobacter pylori in Chinese Populations Using DNA Microarray

Han, Yue-Hua,Liu, Wen-Zhong,Shi, Yao-Zhou,Lu, Li-Qiong,Xiao, Shudong,Zhang, Qing-Hua,Zhao, Guo-Ping The Microbiological Society of Korea 2007 The journal of microbiology Vol.45 No.1

In order to search for specific genotypes related to this unique phenotype, we used whole genomic DNA microarray to characterize the genomic diversity of Helicobacter pylori (H. pylori) strains isolated from clinical patients in China. The open reading frame (ORF) fragments on our microarray were generated by PCR using gene-specific primers. Genomic DNA of H. pylori 26695 and J99 were used as templates. Thirty-four H. pylori isolates were obtained from patients in Shanghai. Results were judged based on In(x) transformed and normalized Cy3/Cy5 ratios. Our microarray included 1882 DNA fragments corresponding to 1636 ORFs of both sequenced H. pylori strains. Cluster analysis, revealed two diverse regions in the H. pylori genome that were not present in other isolates. Among the 1636 genes, 1091 (66.7%) were common to all H. pylori strains, representing the functional core of the genome. Most of the genes found in the H. pylori functional core were responsible for metabolism, cellular processes, transcription and biosynthesis of amino acids, functions that are essential to H. pylori's growth and colonization in its host. In contrast, 522 (31.9%) genes were strain-specific genes that were missing from at least one strain of H. pylori. Strain-specific genes primarily included restriction modification system components, transposase genes, hypothetical proteins and outer membrane proteins. These strain-specific genes may aid the bacteria under specific circumstances during their long-term infection in genetically diverse hosts. Our results suggest 34 H. pylori clinical strains have extensive genomic diversity. Core genes and strain-specific genes both play essential roles in H. pylori propagation and pathogenesis. Our microarray experiment may help select relatively significant genes for further research on the pathogenicity of H. pylori and development of a vaccine for H. pylori.

Bidirectional Hybrid DWDM-PON for HDTV/Gigabit Ethernet/CATV Applications

Hai-Han Lu,Wen-Shing Tsai,Tzu-Shen Chien,Shih-Hung Chen,Yu-Chieh Chi,Che-Wei Liao 한국전자통신연구원 2007 ETRI Journal Vol.29 No.2

A new scheme for bi-directional HDTV/Gigabit Ethernet/CATV transmission over a hybrid densewavelength- division-multiplexing passive optical network (DWDM-PON) is proposed and demonstrated. It is based on injection-locked vertical-cavity surface-emitting lasers and distributed-feedback laser diodes as transmitters. Services with 129 HDTV channels, a 1.25 Gbps Gigabit Ethernet connection, and 77 CATV channels are successfully demonstrated over 40 km single-mode fiber links. Good performance of bit error rate, carrier-to-noise ratio, composite second order, and composite triple beat is achieved in our proposed bidirectional DWDM-PON.

Selecting and Identifying Lactic Acid Bacteria in Sourdough and Their Effect on Sourdough Physical and Chemical Properties

( Jing Han Huang ),( Syue Fong Lai ),( Wen Fu Wu ),( Chen Wei Huang ),( Ying Chen Lu ) 한국농업기계학회 2018 한국농업기계학회 학술발표논문집 Vol.23 No.1

Sourdough is traditionally used as the leavening agent for bread making and a potential source of probiotics. In this study, sourdoughs from seven restaurants in Taiwan were collected. The lactic acid bacteria strains were isolated and identified by 16S rDNA sequencing from these sourdoughs. The following lactic acid bacteria species were identified: Lactobacillus pentosus, Lactobacillus paracasei, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus sanfranciscensis. Five lactic acid bacteria strains, Lactobacillus paracasei LYC1242, Lactobacillus casei LYC1244, Lactobacillus plantarum LYC1245 and Lactobacillus casei LYC1246, were selected and singly used to ferment wheat flour. The pH value of various sourdoughs decreased to pH3 from pH5 and kelp at pH3. The titratable acidity and viscosity of various sourdoughs increased significantly compared to spontaneous fermented flour. However, there is no significant difference in titratable acidity between various sourdoughs. The sourdough fermented with L. casei LYC1244 had highest cell count. These studies provided preliminary results for choosing the best lactic acid bacteria starter strain to develop probiotic sourdough bread.

HE4 as a Serum Biomarker for ROMA Prediction and Prognosis of Epithelial Ovarian Cancer

Chen, Wen-Ting,Gao, Xiang,Han, Xiao-Dian,Zheng, Hui,Guo, Lin,Lu, Ren-Quan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Background and Purpose: Human epididymis protein 4 (HE4) has been suggested to be a novel biomarker of epithelial ovarian cancer (EOC). The present study aimed to evaluate and compare HE4 with the commonly used marker, carbohydrate antigen 125 (CA125), in prediction and therapy-monitoring of EOC. Patients and Methods: Serum HE4 concentrations from 123 ovarian cancer patients and 174 controls were measured by Roche electrochemiluminescent immunoassay (ECLIA). Risk of ovarian malignancy algorithm (ROMA) values were calculated and assessed. In addition, the prospects of HE4 detection for therapy-monitoring were evaluated in EOC patients. Results: The ROMA score could classify patients into high- and low-risk groups with malignancy. Indeed, lower serum HE4 was significantly associated with successful surgical therapy. Specifically, 38 patients with EOC exhibited a greater decline of HE4 compared with CA125. In contrast, elevation of HE4 better predicted recurrence (of 46, 11 patients developed recurrence, and with it increased HE4 serum concentrations) and a poor prognosis than CA125. Conclusions: This study suggests that serum HE4 levels are closely associated with outcome of surgical therapy and disease prognosis in Chinese EOC patients.

Stimuli-Responsive Graphene Oxide-Polymer Nanocomposites

Qi Lu,장효선,Wen Jiao Han,이진현,최형진 한국고분자학회 2019 Macromolecular Research Vol.27 No.11

Graphene oxide (GO) attracts tremendous attention for application in high-performance stimuli-responsive “smart” materials because of its unique and excellent electrical, mechanical, thermal, and optical properties, high biocompatibility, and potential application in a variety of fields, including nanocomposite-based devices. Even at an extremely small loading, the chemical, physical, and mechanical properties of GO-polymer nanocomposites can be significantly changed due to its one-atom thickness and large surface area. Therefore, GO-based filler-containing polymer nanocomposites are sensitive to various external stimuli, such as electric and magnetic fields, pH, thermal or optical excitations, and stress. This article reviews the compositions, preparations, and characteristics of a variety of external stimuli-responsive nanocomposites containing GO and other graphene-based fillers. Particularly, the electrorheological and magnetorheological behaviors of smart fluids are described with well-known models and relationships. Finally, various applications of GO-polymer nanocomposites are briefly presented.

Green Tea Powder Improves Probiotic Viability In Functional Yogurt and Provide Added Physicochemical Benefits

( Ching Han Chang ),( Yen Shiang Chen ),( Wen Fu Wu ),( Ying Chen Lu ) 한국농업기계학회 2018 한국농업기계학회 학술발표논문집 Vol.23 No.1

The purpose of this study is to investigate the effect of green tea (Camellia sinensis) powders on fermentation and survival of probiotic yogurt. Green tea powders were added to milk, sterilized, fermented with Lactobacillus reuteri LYC184 and stored at 4°C for 14 days. The quality parameters of green tea powder yogurt (TP) included bacterial number, pH, titratable acidity, color and physicochemical properties were analyzed. Results showed that the adhesiveness and pH value decrease as the storage time increases; the value of titratable acidity, viscosity and hardness are proportional to the storage time. The phenolic compounds in green tea yogurts were analyzed by HPLC. The novel yogurts showed significantly higher probiotic cell viabilities during storage at 4°C. In conclusion, adding the green tea powders to Lactobacillus reuteri LYC184 fermented yogurt is an excellent functional food that has great potential for the beneficial properties of human health.

Corpus of Eye Movements in L3 Spanish Reading: A Prediction Model

Hui-Chuan Lu,Li-Chi Kao,Zong-Han Li,Wen-Hsiang Lu,An-Chung Cheng Institute for Corpus Research 2024 Asia pacific journal of corpus research Vol.5 No.1

This research centers on the Taiwan Eye-Movement Corpus of Spanish (TECS), a specially created corpus comprising eye-tracking data from Chinese-speaking learners of Spanish as a third language in Taiwan. Its primary purpose is to explore the broad utility of TECS in understanding language learning processes, particularly the initial stages of language learning. Constructing this corpus involves gathering data on eye-tracking, reading comprehension, and language proficiency to develop a machine-learning model that predicts learner behaviors, and subsequently undergoes a predictability test for validation. The focus is on examining attention in input processing and their relationship to language learning outcomes. The TECS eye-tracking data consists of indicators derived from eye movement recordings while reading Spanish sentences with temporal references. These indicators are obtained from eye movement experiments focusing on tense verbal inflections and temporal adverbs. Chinese expresses tense using aspect markers, lexical references, and contextual cues, differing significantly from inflectional languages like Spanish. Chinese-speaking learners of Spanish face particular challenges in learning verbal morphology and tenses. The data from eye movement experiments were structured into feature vectors, with learner behaviors serving as class labels. After categorizing the collected data, we used two types of machine learning methods for classification and regression: Random Forests and the k-nearest neighbors algorithm (KNN). By leveraging these algorithms, we predicted learner behaviors and conducted performance evaluations to enhance our understanding of the nexus between learner behaviors and language learning process. Future research may further enrich TECS by gathering data from subsequent eye-movement experiments, specifically targeting various Spanish tenses and temporal lexical references during text reading. These endeavors promise to broaden and refine the corpus, advancing our understanding of language processing.

Comparative Genomics Profiling of Clinical Isolates of Helicobacter pylori in Chinese Populations Using DNA Microarray

Yue-Hua Han,Wen-Zhong Liu,Yao-Zhou Shi,Li-Qiong Lu,Shudong Xiao,Qing-Hua Zhang,Guo-Ping Zhao 한국미생물학회 2007 The journal of microbiology Vol.45 No.1

In order to search for specific genotypes related to this unique phenotype, we used whole genomic DNA microarray to characterize the genomic diversity of Helicobacter pylori (H. pylori) strains isolated from clinical patients in China.The open reading frame (ORF) fragments on our microarray were generated by PCR using gene-specific primers. Genomic DNA of H. pylori 26695 and J99 were used as templates. Thirty-four H. pylori isolates were obtained from patients in Shanghai. Results were judged based on ln(x) transformed and normalized Cy3/Cy5 ratios. Our microarray included 1882 DNA fragments corresponding to 1636 ORFs of both sequenced H. pylori strains. Cluster analysis, revealed two diverse regions in the H. pylori genome that were not present in other isolates. Among the 1636 genes, 1091 (66.7%) were common to all H. pylori strains, representing the functional core of the genome. Most of the genes found in the H. pylori functional core were responsible for metabolism, cellular processes, transcription and biosynthesis of amino acids, functions that are essential to H. pylori’s growth and colonization in its host. In contrast, 522(31.9%) genes were strain-specific genes that were missing from at least one strain of H. pylori. Strainspecific genes primarily included restriction modification system components, transposase genes, hypothetical proteins and outer membrane proteins. These strain-specific genes may aid the bacteria under specific circumstances during their long-term infection in genetically diverse hosts. Our results suggest 34 H. pylori clinical strains have extensive genomic diversity. Core genes and strain-specific genes both play essential roles in H. pylori propagation and pathogenesis. Our microarray experiment may help select relatively significant genes for further research on the pathogenicity of H. pylori and development of a vaccine for H. pylori.

Bradyrhizobium spp. and Sinorhizobium fredii are Predominant in Root Nodules of Vigna angularis, a Native Legume Crop in the Subtropical Region of China

Li Li Han,En Tao Wang,Yang Li Lu,Yong Fa Zhang,Xin Hua Sui,Wen Feng Chen,Wen Xin Chen 한국미생물학회 2009 The journal of microbiology Vol.47 No.3

Adzuki bean (Vigna angularis) is an important legume crop native to China, but its rhizobia have not been well characterized. In the present study, a total of 60 rhizobial strains isolated from eight provinces of China were analyzed with amplified 16S rRNA gene RFLP, IGS-RFLP, and sequencing analyses of 16S rRNA, atpD, recA, and nodC genes. These strains were identified as genomic species within Rhizobium, Sinorhizobium, Mesorhizobium, Bradyrhizobium, and Ochrobactrum. The most abundant groups were Bradyrhizobium species and Sinorhizobium fredii. Diverse nodC genes were found in these strains, which were mainly co-evolved with the housekeeping genes, but a possible lateral transfer of nodC from Sinorhizobium to Rhizobium was found. Analyses of the genomic and symbiotic gene backgrounds showed that adzuki bean shared the same rhizobial gene pool with soybean (legume native to China) and the exotic Vigna species. All of these data demonstrated that nodule formation is the interaction of rhizobia, host plants, and environment characters.