Vitamin C facilitates dopamine neuron differentiation in fetal midbrain through TET1- and JMJD3-dependent epigenetic control manner.

He, Xi-Biao,Kim, Mirang,Kim, Seon-Young,Yi, Sang-Hoon,Rhee, Yong-Hee,Kim, Taeho,Lee, Eun-Hye,Park, Chang-Hwan,Dixit, Shilpy,Harrison, Fiona E,Lee, Sang-Hun AlphaMed Press 2015 Stem Cells Vol.33 No.4

<P>Intracellular Vitamin C (VC) is maintained at high levels in the developing brain by the activity of sodium-dependent VC transporter 2 (Svct2), suggesting specific VC functions in brain development. A role of VC as a cofactor for Fe(II)-2-oxoglutarate-dependent dioxygenases has recently been suggested. We show that VC supplementation in neural stem cell cultures derived from embryonic midbrains greatly enhanced differentiation toward midbrain-type dopamine (mDA) neurons, the neuronal subtype associated with Parkinson's disease. VC induced gain of 5-hydroxymethylcytosine (5hmC) and loss of H3K27m3 in DA phenotype gene promoters, which are catalyzed by Tet1 and Jmjd3, respectively. Consequently, VC enhanced DA phenotype gene transcriptions in the progenitors by Nurr1, a transcription factor critical for mDA neuron development, to be more accessible to the gene promoters. Further mechanism studies including Tet1 and Jmjd3 knockdown/inhibition experiments revealed that both the 5hmC and H3K27m3 changes, specifically in the progenitor cells, are indispensible for the VC-mediated mDA neuron differentiation. We finally show that in Svct2 knockout mouse embryos, mDA neuron formation in the developing midbrain decreased along with the 5hmC/H3k27m3 changes. These findings together indicate an epigenetic role of VC in midbrain DA neuron development. Stem Cells2015;33:1320-1332</P>

Construction and Analysis of Food-Grade Lactobacillus kefiranofaciens β-Galactosidase Overexpression System

( Xi He ),( Mingjian Luan ),( Ning Han ),( Ting Wang ),( Xiangzhong Zhao ),( Yanyan Yao ) 한국미생물생명공학회(구 한국산업미생물학회) 2021 Journal of microbiology and biotechnology Vol.31 No.4

Lactobacillus kefiranofaciens contains two types of β-galactosidase, LacLM and LacZ, belonging to different glycoside hydrolase families. The difference in function between them has been unclear so far for practical application. In this study, LacLM and LacZ from L. kefiranofaciens ATCC51647 were cloned into constitutive lactobacillal expression vector pMG36e, respectively. Furtherly, pMG36nlacs was constructed from pMG36e-lacs by replacing erythromycin with nisin as selective marker for food-grade expressing systems in Lactobacillus plantarum WCFS1, designated recombinant LacLM and LacZ respectively. The results from hydrolysis of o-nitrophenyl-β-galactopyranoside (ONPG) showed that the β-galactosidases activity of the recombinant LacLM and LacZ was 1460% and 670% higher than that of the original L. kefiranofaciens. Moreover, the lactose hydrolytic activity of recombinant LacLM was higher than that of LacZ in milk. Nevertheless, compare to LacZ, in 25% lactose solution the galacto-oligosaccharides (GOS) production of recombinant LacLM was lower. Therefore, two β-galactopyranosides could play different roles in carbohydrate metabolism of L. kefiranofaciens. In addition, the maximal growth rate of two recombinant strains were evaluated with different temperature level and nisin concentration in fermentation assay for practical purpose. The results displayed that 37oC and 20-40 U/ml nisin were the optimal fermentation conditions for the growth of recombinant β-galactosidase strains. Altogether the food-grade Expression system of recombinant β-galactosidase was feasible for applications in the food and dairy industry.

Cloning, Purification, and Characterization of a Heterodimeric β-Galactosidase from Lactobacillus kefiranofaciens ZW3

( Xi He ),( Ning Han ),( Yan Ping Wang ) 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.1

Lactobacillus kefiranofaciens ZW3 was obtained from kefir grains, which have high lactose hydrolytic activity. In this study, a heterodimeric LacLM-type β-galactosidase gene (lacLM) from ZW3 was isolated, which was composed of two overlapping genes, lacL (1,884 bp) and lacM (960 bp) encoding large and small subunits with calculated molecular masses of 73,620 and 35,682 Da, respectively. LacLM, LacL, and LacM were expressed in Escherichia coli BL21(DE3) and these recombinant proteins were purified and characterized. The results showed that, compared with the recombinant holoenzyme, the recombinant large subunit exhibits obviously lower thermostability and hydrolytic activity. Moreover, the optimal temperature and pH of the holoenzyme and large subunit are 60oC and 7.0, and 50oC and 8.0, respectively. However, the recombinant small subunit alone has no activity. Interestingly, the activity and thermostability of the large subunit were greatly improved after mixing it with the recombinant small subunit. Therefore, the results suggest that the small subunit might play an important role in maintaining the stability of the structure of the catalytic center located in the large subunit.

Prolonged membrane depolarization enhances midbrain dopamine neuron differentiation via epigenetic histone modifications.

He, Xi-Biao,Yi, Sang-Hoon,Rhee, Yong-Hee,Kim, Hyemin,Han, Yong-Mahn,Lee, Suk-Ho,Lee, Hyunsu,Park, Chang-Hwan,Lee, Yong-Sung,Richardson, Eric,Kim, Byung-Woo,Lee, Sang-Hun AlphaMed Press 2011 Stem cells Vol.29 No.11

<P>Understanding midbrain dopamine (DA) neuron differentiation is of importance, because of physiological and clinical implications of this neuronal subtype. We show that prolonged membrane depolarization induced by KCl treatment promotes DA neuron differentiation from neural precursor cells (NPCs) derived from embryonic ventral midbrain (VM). Interestingly, the depolarization-induced increase of DA neuron yields was not abolished by L-type calcium channel blockers, along with no depolarization-mediated change of intracellular calcium level in the VM-derived NPCs (VM-NPCs), suggesting that the depolarization effect is due to a calcium-independent mechanism. Experiments with labeled DA neuron progenitors indicate that membrane depolarization acts at the differentiation fate determination stage and promotes the expression of DA phenotype genes (tyrosine hydroxylase [TH] and DA transporter [DAT]). Recruitment of Nurr1, a transcription factor crucial for midbrain DA neuron development, to the promoter of TH gene was enhanced by depolarization, along with increases of histone 3 acetylation (H3Ac) and trimethylation of histone3 on lysine 4 (H3K4m3), and decreases of H3K9m3 and H3K27m3 in the consensus Nurr1 binding regions of TH promoter. Depolarization stimuli on differentiating VM-NPCs also induced dissociation of methyl CpG binding protein 2 and related repressor complex molecules (repressor element-1 silencing transcription factor corepressor and histone deacetylase 1) from the CpG sites of TH and DAT promoters. Based on these findings, we suggest that membrane depolarization promotes DA neuron differentiation by opening chromatin structures surrounding DA phenotype genes and inhibiting the binding of corepressors, thus allowing transcriptional activators such as Nurr1 to access DA neuron differentiation gene promoter regions.</P>

A Continuous Abnormal Speech Detection Method Based on Time Domain features Weighted

He Jun,Ji-chen Yang,Qing-hua Zhang,Guo-xi Sun,Jian-bing Xiong 보안공학연구지원센터 2014 International Journal of Control and Automation Vol.7 No.12

In this brief, a novel pathological continuous speech detection method based on time domain features weighted. First, different optimal threshold for time domain features, including zero crossing ratio, short-time energy and autocorrelation, are obtained from training speech data. Second, a difference evaluation technique is proposed, and with it, the difference of the same time domain feature selected from testing speech data and training speech data were obtained. Finally, to distinguish a given speech well, a novel weighting method based on difference evaluation for each kinds of time domain is employed, respectively. Experiments were conducted on the pathological speech database to prove the power and effectiveness of the proposed method. Results obtained shown that this method outperforms other early proposed time domain feature method, creating a more reliable technique for pathological continuous speech detection.

Acupuncture and Moxibustion for Cancer-related Fatigue: a Systematic Review and Meta-analysis

He, Xi-Ran,Wang, Quan,Li, Ping-Ping Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.5

Background: Faced with highly prevalent and recalcitrant cancer-related fatigue (CRF), together with the absence of any official guidelines on management, numerous groups have been striving to seek and test alternative therapies including acupuncture and moxibustion. However, different patients have various feedbacks, and the many clinical trials have given rise to varied conclusions. In terms of the therapeutic effect of acupuncture and moxibustion, there exist vast inconsistencies. Objective: The aim of the study was to evaluate the auxiliary effectiveness of acupuncture and moxibustion in the treatment of CRF, and to provide more reliable evidence to guide clinical practice. Methods: Randomized controlled trials (RCTs) published before December 2012 were all aggregated, focusing on evaluation of acupuncture or moxibustion for CRF. The quality of the included studies was assessed basing on Cochrane handbook 5.1.0, and the available data were analyzed with RevMan software (version 5.2.0). Descriptive techniques were performed when no available data could be used. Results: A total of 7 studies involving 804 participants were eligible. With real acupuncture versus sham acupuncture, subjects receiving true acupuncture benefited more in the reduction of fatigue. With real acupuncture versus acupressure or sham acupressure, fatigue level appeared 36% improved in the acupuncture group, but 19% in the acupressure group and only 0.6% with sham acupressure. When real acupuncture plus enhanced routine care was compared with enhanced routine care, the combination group improved mean scores for general fatigue, together with physical and mental fatigue. With real acupuncture versus sham acupuncture or wait list controls, the real acupuncture group displayed significant advantages over the wait list controls at 2 weeks for fatigue improvement and better well-being effects at 6 weeks. When moxibustion plus routine care was compared with routine care alone, the meta-analyses demonstrated the combination had a relatively significant benefit in improving severe fatigue and QLQ-C30. Conclusion: Up to the search date, there exist few high quality RCTs to evaluate the effect of acupuncture and moxibustion, especially moxibustion in English. Yet acupuncture and moxibustion still appeared to be efficacious auxiliary therapeutic methods for CRF, in spite of several inherent defects of the included studies. Much more high-quality studies are urgently needed.

중국 형법상의 교통사고죄에 관한 연구

혁흥왕 ( Xi Wang He ),황찬양(역) 영남대학교 법학연구소 2009 영남법학 Vol.0 No.29

唐詩 텍스트의 테마-레마와 응집성 분석

河?蘭(He Xi-Lan) 동아인문학회 2008 동아인문학 Vol.14 No.-

Complement Receptor 1 Expression in Peripheral Blood Mononuclear Cells and the Association with Clinicopathological Features And Prognosis of Nasopharyngeal Carcinoma

He, Jian-Rong,Xi, Jing,Ren, Ze-Fang,Qin, Han,Zhang, Ying,Zeng, Yi-Xin,Mo, Hao-Yuan,Jia, Wei-Hua Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Purpose: Complement receptor 1 (CR1) is induced by Epstein-Barr virus (EBV) and may be a potential biomarker of nasopharyngeal carcinoma (NPC). We conducted the present study to evaluate the association of CR1 expression with clinicopathological features and prognosis of NPC. Methods: We enrolled 145 NPC patients and 110 controls. Expression levels of CR1 in peripheral blood mononuclear cells (PBMCs) were detected using quantitative real-time PCR and associations with clinicopathological features and prognosis were examined. Results: CR1 levels in the NPC group [3.54 (3.34, 3.79)] were slightly higher than those in the controls [3.33 (3.20, 3.47)] (P<0.001). Increased CR1 expression was associated with histology classification (type III vs. type II, P=0.002), advanced clinical stage (P=0.003), high T stage (P=0.017), and poor overall survival (HR, 4.89; 95% CI, 1.23-19.42; P=0.024). However, there were no statistically significant differences in CR1 expression among N or M stages. Conclusion: These findings indicate that CR1 expression in PBMCs may be a new biomarker for prognosis of NPC and a potential therapeutic target.

Prognostic Model Built on Blood-based Biomarkers in Patients with Metastatic Colorectal Cancer

He, Wen-Zhuo,Jiang, Chang,Yin, Chen-Xi,Guo, Gui-Fang,Rong, Ru-Ming,Qiu, Hui-Juan,Chen, Xu-Xian,Zhang, Bei,Xia, Liang-Ping Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17

Background: We had previously showed that the neutrophil lymphocyte ratio (NLR), ${\gamma}$-glutamyl transpeptidase (GGT) and carcinoembryonic antigen (CEA) are prognostic factors for metastatic colorectal cancer (mCRC) patients. In this study we developed a prognostic model based on these three indices. Materials and Methods: A total of 243 patients who were initially diagnosed as mCRC between 2005 and 2010 in the Sun Yat-sen University Cancer Center were studied. The endpoint was overall survival (OS). Results: NLR>3, elevated GGT and elevated CEA were confirmed as independent risk factors which could predict poor prognosis. Patients could be divided into three groups according to the number of risk factors they had. Those with two or three were defined as the high risk group, individuals with one risk factor as the modest risk group and patients without risk factor as the low risk group. The OS values for these three groups were 16.2 months (2.80~68.8), 24.2 months (4.07~79.0), and 37.2 months (12.6~87.8), respectively (p<0.001). Conclusions: We developed a simple but useful model based on NLR, GGT and CEA to provide prognostic information to clinical practice in highly selected mCRC patients. Further prospective and multi-center studies are warranted to test our model.