Invited Mini Review : Stem cell maintenance by manipulating signaling pathways: past, current and future

( Xi Chen ),( Shoudong Ye ),( Qi Long Ying ) 생화학분자생물학회(구 한국생화학분자생물학회) 2015 BMB Reports Vol.48 No.12

Pluripotent stem cells only exist in a narrow window during early embryonic development, whereas multipotent stem cells are abundant throughout embryonic development and are retained in various adult tissues and organs. While pluripotent stem cell lines have been established from several species, including mouse, rat, and human, it is still challenging to establish stable multipotent stem cell lines from embryonic or adult tissues. Based on current knowledge, we anticipate that by manipulating extrinsic and intrinsic signaling pathways, most if not all types of stem cells can be maintained in a long-term culture. In this article, we summarize current culture conditions established for the long-term maintenance of authentic pluripotent and multipotent stem cells and the signaling pathways involved. We also discuss the general principles of stem cell maintenance and propose several strategies on the establishment of novel stem cell lines through manipulation of signaling pathways. [BMB Reports 2015; 48(12): 668-676]

Malignant transformation of ovarian mature cystic teratoma into squamous cell carcinoma: a Taiwanese Gynecologic Oncology Group (TGOG) study

An Jen Chiang,Min-Yu Chen,Chia-Sui Weng,Hao Lin,Chien-Hsing Lu,Peng-Hui Wang,Yu-Fang Huang,Ying-Cheng Chiang,Mu-Hsien Yu,Chih-Long Chang 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.5

Objective: The malignant transformation (MT) of ovarian mature cystic teratoma (MCT)to squamous cell carcinoma (SCC) is very rare. This study analyzed cases from multiplemedical centers in Taiwan to investigate the clinicopathologic characteristics, treatment, andprognostic factors of this disease and reviewed related literature. Methods: Pathological reports of 16,001 patients with primary ovarian cancer who weretreated at Taiwan medical centers from 1990 to 2011 were reviewed. In total, 52 patients withMT of MCT to SCC were identified. Results: Among all ovarian MCTs, the incidence of MT to SCC is 0.2%. The median age ofpatients was 52 years (range, 29–89 years), and the mean tumor size was 10.5 cm (range, 1–40cm). We analyzed the patients in our study and those in the literature and determined thatearly identification and complete surgical resection of the tumor are essential for long-termsurvival. In addition, adjuvant chemotherapy or concurrent chemoradiotherapy can be usedto treat this malignancy. Old age, large tumor size (≥15.0 cm), and solid components in MCTsare suitable indicators predicting the risk of MT of MCT to SCC. Conclusion: Similar to general epithelial ovarian cancers, the early detection of MT of MCTto SCC is critical to long-term survival. Therefore, older patients with a large tumor or those with a tumor containing a solid component in a clinically diagnosed MCT should beevaluated to exclude potential MT to SCC.

Research on Human-robot Shared Control of Throat Swab Sampling Robot Based on Intention Estimation

Ying-Long Chen,Fu-Jun Song,Peng-Yu Zhao,Yong-Jun Gong,Heng-Fei Yan 제어·로봇·시스템학회 2024 International Journal of Control, Automation, and Vol.22 No.2

With the spread and persistence of COVID-19, pharyngeal swab sampling, is an important link in nucleic acid testing, which is characterized by a high workload and susceptibility to infection. Therefore, it is necessary for medical workers to use medical robots instead of manual site sampling for collaborative sampling. However, the traditional teleoperation has difficulty ensuring the closed-loop performance due to the delay of the actual process, along with the weak control performance; Moreover, a robot cannot accurately plan and track sampling paths due to sensor accuracy and the changes in patient pharyngeal posture. The paper proposes a human-robot shared control strategy based on intention estimation, introducing the human intention as a reference, and the operator and robot work together to solve various significant problems during sampling. The human-robot negotiation based on the method includes the human judgement and perception and the robot into the invasion task. Through, the shared control based on the operator intention estimation, the robot can operate the obstacle avoidance and approach the target contact point remotely. Finally, two kinds of experiments of invasion process of throat swab sampling are implemented: a static target invasive experiment and a dynamic target invasive experiment, aiming at two different sampling conditions. Compared with the robotic independent control sampling, the time consumption in the two experiments is reduced by 34.8% and 41.6%, respectively, and the ultimate target position is basically within the scope of sampling field (where the range of the posterior pharynx wall < 20 mm). Thus, the sampling rate can reach 100%. Compared with independent control sampling by humans, the time consumption of the two experiments is respectively reduced by 15.9% and 42.3% on average, and the target position accuracy and sampling rate are quite close. Experimental results show that the control strategy improves the speed, flexibility, and intelligence of task execution compared to common sampling methods, laying the foundation for low-cost human-robot collaborative sampling.

Kinematics Modeling of Soft Manipulator Interacting with Environment Using Segmented Variable Curvature Method

Ying-Long Chen,Wen-Shuo Li,Qiang Guo,Yong-Jun Gong 제어·로봇·시스템학회 2022 International Journal of Control, Automation, and Vol.20 No.1

In this paper, a novel kinematics model based on segmented variable curvature (SVC) method is proposed to describe the deformation of soft manipulator under the condition of environmental contact. Firstly, the variable curvature (VC) framework is used to the spatial backbone curve, which is to discrete the soft manipulator into tangent arcs with different curvatures. When the contacts with surroundings occur, the contacted arcs are further divided into several separate sub-segments at the contact points. Then, combining kinematics and statics of all the segments, the model of soft manipulator is established under environmental constraints. The proposed model inherits the generality of the continuous VC method, and resolves the complex contact problem with environmental constraints. Finally, simulations and experiments are conducted to verify the effectiveness of the proposed SVC method under contact conditions. The results show that compared with the traditional VC method the proposed model can obtain higher accuracy in describing contact segment deformation under contact constraints without knowing the contact force in advance.

rs12904 Polymorphism in the 3'UTR of EFNA1 is Associated with Colorectal Cancer Susceptibility in a Chinese Population

Mao, Ying-Ying,Jing, Fang-Yuan,Jin, Ming-Juan,Li, Ying-Jun,Ding, Ye,Guo, Jing,Wang, Fen-Juan,Jiang, Long-Fang,Chen, Kun Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

Accumulated evidence has indicated that Ephrin A1 (EFNA1) is associated with angiogenesis and tumorigenesis in various types of malignancies, including colorectal cancer (CRC). In the current study, we performed an online search using the public microarray database to investigate whether EFNA1 expression might be altered in CRC tissues. We then conducted a case-control study including 306 subjects (102 cases and 204 well-matched controls) in Xiaoshan County to assess any association between genetic polymorphisms in EFNA1 and CRC susceptibility. Searches in the Oncomine expression profiling database revealed EFNA1 to be overexpressed in CRC tissue compared with adjacent normal tissue. The rs12904 G-A variant located in the 3' untranslated region (UTR) of EFNA1 was observed to be associated with CRC susceptibility. Compared with the AA homozygous genotype, those carrying GA genotype had a decreased risk of developing CRC (odds ratio (OR)=0.469, 95% confidence interval (CI): 0.225-0.977, and P=0.043). The association was stronger among smokers and tea drinkers, however, no statistical evidence of interaction between rs12904 polymorphism and smoking or tea drinking on CRC risk was found. Our results suggest that EFNA1 is involved in colorectal tumorigenesis, and rs12904 A>G polymorphism in the 3' UTR of EFNA1 is associated with CRC susceptibility. Larger studies and further mechanistic investigations are warranted to confirm our findings.

Anti-inflammatory effect of hispidin on LPS induced macrophage inflammation through MAPK and JAK1/STAT3 signaling pathways

Han Ying-Hao,Chen Dong-Qin,Jin Mei-Hua,Jin Ying-Hua,Li Jing,Shen Gui-Nan,Li Wei-Long,Gong Yi-Xi,Mao Ying-Ying,Xie Dan-Ping,Lee Dong-Seok,Yu Li-Yun,Kim Sun-Uk,김지수,권태호,Cui Yu-Dong,Sun Hu-Nan 한국응용생명화학회 2020 Applied Biological Chemistry (Appl Biol Chem) Vol.63 No.3

Severe inflammatory reactions caused by macrophage activation can trigger a systemic immune response. In the present study, we observed the anti-inflammatory properties of hispidin on LPS induced RAW264.7 macrophage cells. Our results showed that hispidin treatment significantly reduced the production of cellular NO, IL-6 and reactive oxygen species (ROS) while has not inhibitory effect on TNF-α productions. Excitingly, hispidin treatment retains the phagocytosis ability of macrophages which enabling them to perform the function of removing foreign invaders. Signaling studies showed, hispidin treatment dramatic suppressed the LPS induced mitogen activated protein kinases (MAPK) and JAK/STAT activations. In conclusion, our findings suggest that hispidin may be a new therapeutic target for clinical treatment of macrophages-mediated inflammatory responses.

Unilateral ureteral obstruction causes gut microbial dysbiosis and metabolome disorders contributing to tubulointerstitial fibrosis

Lin Chen,Dan-Qian Chen,Jing-Ru Liu,Jun Zhang,Nosratola D. Vaziri,Shougang Zhuang,Hua Chen,Ya-Long Feng,Yan Guo,Ying-Yong Zhao 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Chronic kidney disease (CKD) increases the risk and prevalence of cardiovascular disease (CVD) morbidity and mortality. Recent studies have revealed marked changes in the composition of the microbiome and the metabolome and their potential influence in renal disease and CVD via the accumulation of microbial-derived uremic toxins. However, the effect of unilateral ureteral obstruction (UUO) on the gut microbiome and circulating metabolites is unknown. Male Sprague-Dawley rats were randomized to UUO and sham-operated control groups. Renal histology, colonic microbiota, and plasma metabolites were examined two weeks later. We employed 16S rRNA sequence and untargeted metabolomic analyses to explore the changes in colonic microbiota and plasma metabolites and their relationship with tubulointerstitial fibrosis (TIF). The UUO rats exhibited tubular atrophy and dilatation, interstitial fibrosis and inflammatory cell infiltration in the obstructed kidney. UUO rats showed significant colonic enrichment and depletion of genera. Significant differences were identified in 219 plasma metabolites involved in lipid, amino acid, and bile acid metabolism, which were consistent with gut microbiota-related metabolism. Interestingly, tryptophan and its metabolites kynurenine, 5-hydroxytryptophan and 5-hydroxytryptamine levels, which were linked with TIF, correlated with nine specific genera. Plasma tryptophan level was positively correlated with Clostridium IV, Turicibacter, Pseudomonas and Lactobacillales, and negatively correlated with Oscillibacter, Blautia, and Intestinimonas, which possess the genes encoding tryptophan synthase (K16187), indoleamine 2,3-dioxygenase (K00463) and tryptophan 2,3-dioxygenase (K00453) and their corresponding enzymes (EC:1.13.11.52 and EC:1.13.11.11) that exacerbate TIF. In conclusion, UUO results in profound changes in the gut microbiome and circulating metabolites, events that contribute to the pathogenesis of inflammation and TIF.

Clinical Significance of Upregulation of mir-196a-5p in Gastric Cancer and Enriched KEGG Pathway Analysis of Target Genes

Li, Hai-Long,Xie, Shou-Pin,Yang, Ya-Li,Cheng, Ying-Xia,Zhang, Ying,Wang, Jing,Wang, Yong,Liu, Da-Long,Chen, Zhao-Feng,Zhou, Yong-Ning,Wu, Hong-Yan Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5

Background: miRNAs are relatively recently discovered cancer biomarkers which have important implications for cancer early diagnosis, treatment and estimation of prognosis. Here we focussed on expression of mir-196a-5p in gastric cancer tissues and cell lines so as to analyse its significance for clinicopathologic characteristics and generate enriched KEGG pathways clustered by target genes for exploring its potential roles as a biomarker in gastric cancer. Materials and Methods: The expression of mir-196a-5p in poorly, moderate and well differentiated gastric cancer cell lines compared with GES-1 was detected by RT-qPCR, and the expression of mir-196a-5p in gastric cancer tissues comparing with adjacent non cancer tissues of 58 cases were also assessed by RT-qPCR. Subsequently, an analysis of clinical significance of mir-196a-5p in gastric cancer and enriched KEGG pathways was executed based on the miRWalk prediction database combined with bioinformatics tools DAVID 6.7 and Mirfocus 3.0. Results: RT-qPCR showed that mir-196a-5p was up-regulated in 6 poorly and moderate differentiated gastric cancer cell lines SGC-7901, MKN-45, MKN-28, MGC-803, BGC-823, HGC-27 compared with GES-1, but down-regulated in the highly differentiated gastric cancer cell line AGS. Clinical data indicated mir-196a-5p to beup-regulated in gastric cancer tissues (47/58). Overexpression of mir-196a-5p was associated with more extensive degree of lymph node metastasis and clinical stage (P < 0.05; x2 test). Enriched KEGG pathway analyses of predicted and validated targets in miRWalk combined with DAVID 6.7 and Mirfocus 3.0 showed that the targeted genes regulated by mir-196a-5p were involved in malignancy associated biology. Conclusions: Overexpression of mir-196a-5p is associated with lymph node metastasis and clinical stage, and enriched KEGG pathway analyses showed that targeted genes regulated by mir-196a-5p may contribute to tumorgenesis, suggesting roles as an oncogenic miRNA biomarker in gastric cancer.

Cr(VI) Resistance and Removal by Indigenous Bacteria Isolated from Chromium-Contaminated Soil

( Dong Yan Long ),( Xian Jin Tang ),( Kuan Cai ),( Guang Cun Chen ),( Chao Feng Shen ),( Ji Yan Shi ),( Ling Gui Chen ),( Ying Xu Chen ) 한국미생물 · 생명공학회 2013 Journal of microbiology and biotechnology Vol.23 No.8

The removal of toxic Cr(VI) by microorganisms is a promising approach for Cr(VI) pollution remediation. In the present study, four indigenous bacteria, named LY1, LY2, LY6, and LY7, were isolated from Cr(VI)-contaminated soil. Among the four Cr(VI)-resistant isolates, strain LY6 displayed the highest Cr(VI)-removing ability, with 100 mg/l Cr(VI) being completely removed within 144 h. It could effectively remove Cr(VI) over a wide pH range from 5.5 to 9.5, with the optimal pH of 8.5. The amount of Cr(VI) removed increased with initial Cr(VI) concentration. Data from the time-course analysis of Cr(VI) removal by strain LY6 followed first-order kinetics. Based on the 16S rRNA gene sequence, strain LY6 was identified as Pseudochrobactrum asaccharolyticum, a species that had never been reported for Cr(VI) removal before. Transmission electron microscopy and energy dispersive X-ray spectroscopy analysis further confirmed that strain LY6 could accumulate chromium within the cell while conducting Cr(VI) removal. The results suggested that the indigenous bacterial strain LY6 would be a new candidate for potential application in Cr(VI) pollution bioremediation.

Potential implications of hydrogen peroxide in the pathogenesis and therapeutic strategies of gliomas

Ying Zhou,Long Wang,Chaojia Wang,Yilin Wu,Dongmei Chen,Tae Ho Lee 대한약학회 2020 Archives of Pharmacal Research Vol.43 No.2

Glioma is the most common type of primarybrain tumor, and it has a high mortality rate. Currently,there are only a few therapeutic approaches for gliomas, andtheir effects are unsatisfactory. Therefore, uncovering thepathogenesis and exploring more therapeutic strategies forthe treatment of gliomas are urgently needed to overcomethe ongoing challenges. Cellular redox imbalance has beenshown to be associated with the initiation and progression ofgliomas. Among reactive oxygen species (ROS), hydrogenperoxide (H2O2) is considered the most suitable for redoxsignaling and is a potential candidate as a key moleculethat determines the fate of cancer cells. In this review, wediscuss the potential cellular and molecular roles of H2O2in gliomagenesis and explore the potential implications ofH2O2in radiotherapy and chemotherapy and in the ongoingchallenges of current glioma treatment. Moreover, we evaluateH2O2as a potential redox sensor and potential driver molecule of nanocatalytic therapeutic strategies for gliomatreatment.