Appropriate nitrogen application enhances saponin synthesis and growth mediated by optimizing root nutrient uptake ability

Wei, Wei,Ye, Chen,Huang, Hui-Chuan,Yang, Min,Mei, Xin-Yue,Du, Fei,He, Xia-Hong,Zhu, Shu-Sheng,Liu, Yi-Xiang The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.4

Background: Cultivation of medicinal crops, which synthesize hundreds of substances for curative functions, was focused on the synthesis of secondary metabolites rather than biomass accumulation. Nutrition is an important restrict factor for plant growth and secondary metabolites, but little attention has been given to the plasticity of nutrient uptake and secondary metabolites synthesis response to soil nitrogen (N) change. Methods: Two year-field experiments of Sanqi (Panax notoginseng), which can synthesize a high level of saponin in cells, were conducted to study the effects of N application on the temporal dynamics of biomass, nutrient absorption, root architecture and the relationships between these parameters and saponin synthesis. Results: Increasing N fertilizer rates could improve the dry matter yields and nutrient absorption ability through increasing the maximum daily growth (or nutrient uptake) rate. Under suitable N level (225 kg/ha N), Sanqi restricted the root length and surface and enhanced the root diameter and N uptake rate per root length (NURI) to promote nutrient absorption, but the opposite status of Sanqi root architecture and NURI was found when soil N was deficient. Furthermore, increasing N rates could promote the accumulation of saponin in roots through improving the NURI, which showed a significant positive relationship with the content of saponin in the taproots. Conclusion: Appropriate N fertilizer rates could optimize both root architecture and nutrient uptake efficiency, then promote both the accumulation of dry matter and the synthesis of saponins.

Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells Under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice

Jiang, Shu-Heng,Li, Jun,Dong, Fang-Yuan,Yang, Jian-Yu,Liu, De-Jun,Yang, Xiao-Mei,Wang, Ya-Hui,Yang, Min-Wei,Fu, Xue-Liang,Zhang, Xiao-Xin,Li, Qing,Pang, Xiu-Feng,Huo, Yan-Miao,Li, Jiao,Zhang, Jun-Feng Elsevier 2017 Gastroenterology Vol.153 No.1

<P><B>Background & Aims</B></P> <P>Desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors.</P> <P><B>Methods</B></P> <P>We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras<SUP>G12D/+</SUP>/Trp53<SUP>R172H/+</SUP>/Pdx1-Cre (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples. We also analyzed expression levels of proteins involved in 5-HT synthesis and degradation by immunohistochemical analysis of a tissue microarray containing 311 PDAC specimens, and associated expression levels with patient survival times. 5-HT level in 14 matched PDAC tumor and non-tumor tissues were analyzed by ELISA. PDAC cell lines were incubated with 5-HT and cell survival and apoptosis were measured. We analyzed expression of the 5-HT receptor HTR2B in PDAC cells and effects of receptor agonists and antagonists, as well as HTR2B knockdown with small hairpin RNAs. We determined the effects of 5-HT stimulation on gene expression profiles of BxPC-3 cells. Regulation of glycolysis by 5-HT signaling via HTR2B was assessed by immunofluorescence and immunoprecipitation analyses, as well as by determination of the extracellular acid ratio, glucose consumption, and lactate production. Primary PDACs, with or without exposure to SB204741 (a selective antagonist of HTR2B), were grown as xenograft tumors in mice, and SB204741 was administered to tumor-bearing KPC mice; tumor growth and metabolism were measured by imaging analyses.</P> <P><B>Results</B></P> <P>In immunohistochemical analysis of a tissue microarray of PDAC specimens, increased levels of TPH1 and decreased level of MAOA, which regulate 5-HT synthesis and degradation, correlated with stage and size of PDACs and shorter patient survival time. We found levels of 5-HT to be increased in human PDAC tissues compared with non-tumor pancreatic tissues, and PDAC cell lines compared with non-transformed pancreatic cells. Incubation of PDAC cell lines with 5-HT increased proliferation and prevented apoptosis. Agonists of HTR2B, but not other 5-HT receptors, promoted proliferation and prevented apoptosis of PDAC cells. Knockdown of HTR2B in PDAC cells, or incubation of cells with HTR2B inhibitors, reduced their growth as xenograft tumors in mice. We observed a correlation between 5-HT and glycolytic flux in PDAC cells; levels of metabolic enzymes involved in glycolysis, the phosphate pentose pathway, and hexosamine biosynthesis pathway increased significantly in PDAC cells following 5-HT stimulation. 5-HT stimulation led to formation of the HTR2B–LYN–p85 complex, which increased PI3K–Akt–mTOR signaling and the Warburg effect by increasing protein levels of MYC and HIF1A. Administration of SB204741 to KPC mice slowed growth and metabolism of established pancreatic tumors and prolonged survival of the mice.</P> <P><B>Conclusions</B></P> <P>Human PDACs have increased levels of 5-HT, and PDAC cells increase expression of its receptor, HTR2B. These increases allow for tumor glycolysis under metabolic stress and promote growth of pancreatic tumors and PDAC xenograft tumors in mice.</P>

Chimeric rabies glycoprotein with a transmembrane domain and cytoplasmic tail from Newcastle disease virus fusion protein incorporates into the Newcastle disease virion at reduced levels

Gui Mei Yu,Shu Long Zu,Wei Wei Zhou,Xi Jun Wang,Lei Shuai,Xue Lian Wang,Jin Ying Ge,Zhi Gao Bu 대한수의학회 2017 Journal of Veterinary Science Vol.18 No.-

Rabies remains an important worldwide health problem. Newcastle disease virus (NDV) was developed as a vaccine vector in animals by using a reverse genetics approach. Previously, our group generated a recombinant NDV (LaSota strain) expressing the complete rabies virus G protein (RVG), named rL-RVG. In this study, we constructed the variant rL-RVGTM, which expresses a chimeric rabies virus G protein (RVGTM) containing the ectodomain of RVG and the transmembrane domain (TM) and a cytoplasmic tail (CT) from the NDV fusion glycoprotein to study the function of RVG’s TM and CT. The RVGTM did not detectably incorporate into NDV virions, though it was abundantly expressed at the surface of infected BHK-21 cells. Both rL-RVG and rL-RVGTM induced similar levels of NDV virus-neutralizing antibody (VNA) after initial and secondary vaccination in mice, whereas rabies VNA induction by rL-RVGTM was markedly lower than that induced by rL-RVG. Though rL-RVG could spread from cell to cell like that in rabies virus, rL-RVGTM lost this ability and spread in a manner similar to the parental NDV. Our data suggest that the TM and CT of RVG are essential for its incorporation into NDV virions and for spreading of the recombinant virus from the initially infected cells to surrounding cells.

Antiproliferative activities of Garcinia bracteata extract and its active ingredient, isobractatin, against human tumor cell lines

Tao Shen,Wei Li,Yan-Yan Wang,Qing-Qing Zhong,Shu-Qi Wang,Xiao-Ning Wang,Dong-Mei Ren,Hongxiang Lou 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.3

In our cell based screening of antitumoringredients from plants, the EtOH extract of Garciniabracteata displayed antiproliferative effect against humanlung adenocarcinoma A549 cells, human breast cancerMCF-7 cells, and human prostate cancer PC3 cells. Phytochemicalinvestigation of this active extract producednine ingredients, and their structures were established byanalysis of MS and NMR spectra. Antiproliferative evaluationof isolated ingredients on A549, MCF-7 and PC3cells indicated that a xanthone named isobractatin (1)exhibited potent antiproliferative activity against the abovethree human cancer cell lines with IC50 values rangingfrom 2.90 to 4.15 lM. Treatment of PC3 cells with 1 led toan enhancement of the cell apoptosis, and arrested cellcycle in the G0/G1 phase. The G0/G1 phase cycle-relatedproteins analysis showed that the expressions of cyclins D1and E were reduced by 1, whereas the protein level of cyclin dependent kinase (CDK) inhibitor P21 was induced. Additionally, 1 enhanced PC3 cell apoptosis by activationsof Bax, caspases 3 and 9, and by inhibition of Bcl-2. Ourcombined data illustrated that isobractatin (1) was theantiproliferative ingredient of G. bracteata against threehuman cancer cell lines, which exerted its antiproliferatriveeffect via cell cycle arrest and induction of apoptosis.

New Triterpenoids from the Fruits of Schisandra wilsoniana and Their Biological Activities

Gao, Xue-Mei,Li, Yun-Qi,Shu, Li-Dan,Shen, Yan-Qiong,Yang, Li-Ying,Yang, Liu-Meng,Zheng, Yong-Tang,Sun, Han-Dong,Xiao, Wei-Lie,Hu, Qiu-Fen Korean Chemical Society 2013 Bulletin of the Korean Chemical Society Vol.34 No.3

Investigation of an organic extract of the fruits Schisandra wilsoniana led to the isolation of two new highly oxygenated nortriterpenoids, named schilancidilactones V-W (1-2). Their structures were elucidated by spectroscopic evidence. Compounds 1-2 feature a double bond between C-7 and C-8 compared with related known nortriterpenoids isolated from the genus Schisandra. Compounds 1 and 2 were tested for their anti-HIV-1 activities and cytotoxicity. The results revealed that compounds 1 and 2 showed moderate anti-HIV-1 activities with $EC_{50}$ 3.05 and 2.87 ${\mu}g/mL$, respectively, and compound 1 showed high cytotoxicity against KB and MDA-MB-231 cell with $IC_{50}$ values of 3.18 and 5.22 ${\mu}M$, respectively.

Causal Relations between Exposome and Stroke: A Mendelian Randomization Study

Hong-Qi Li,Yi-Wei Feng,Yu-Xiang Yang,Xin-Yi Leng,Prof Can Zhang,Shi-Dong Chen,Kevin Kuo,Shu-Yi Huang,Xue-Qing Zhang,Yi Dong,Xiang Han,Xin Cheng,Mei Cui,Lan Tan,Qiang Dong,Jin-Tai Yu 대한뇌졸중학회 2022 Journal of stroke Vol.24 No.2

Background and Purpose To explore the causal relationships of elements of the exposome with ischemic stroke and its subtypes at the omics level and to provide evidence for stroke prevention. Methods We conducted a Mendelian randomization study between exposure and any ischemic stroke (AIS) and its subtypes (large-artery atherosclerotic disease [LAD], cardioembolic stroke [CE], and small vessel disease [SVD]). The exposure dataset was the UK Biobank involving 361,194 subjects, and the outcome dataset was the MEGASTROKE consortium including 52,000 participants. Results We found that higher blood pressure (BP) (systolic BP: odds ratio [OR], 1.02; 95% confidence interval [CI], 1.01 to 1.04; diastolic BP: OR, 1.03; 95% CI, 1.01 to 1.05; pulse pressure: OR, 1.03; 95% CI, 1.00 to 1.06), atrial fibrillation (OR, 1.18; 95% CI, 1.13 to 1.25), and diabetes (OR, 1.13; 95% CI, 1.07 to 1.18) were significantly associated with ischemic stroke. Importantly, higher education (OR, 0.69; 95% CI, 0.60 to 0.79) decreased the risk of ischemic stroke. Higher systolic BP (OR, 1.06; 95% CI, 1.02 to 1.10), pulse pressure (OR, 1.08; 95% CI, 1.02 to 1.14), diabetes (OR, 1.28; 95% CI, 1.13 to 1.45), and coronary artery disease (OR, 1.58; 95% CI, 1.25 to 2.00) could cause LAD. Atrial fibrillation could cause CE (OR, 1.90; 95% CI, 1.71 to 2.11). For SVD, higher systolic BP (OR, 1.04; 95% CI, 1.00 to 1.07), diastolic BP (OR, 1.06; 95% CI, 1.01 to 1.12), and diabetes (OR, 1.22; 95% CI, 1.10 to 1.36) were causal factors. Conclusions The study revealed elements of the exposome causally linked to ischemic stroke and its subtypes, including conventional causal risk factors and novel protective factors such as higher education.

Prevalence of Enterobius vermicularis Infection among Preschool Children in Kindergartens of Taipei City, Taiwan in 2008

Tso-Kang Chang,Chien-Wei Liao,Ying-Chieh Huang,Chun-Chao Chang,Chia-Mei Chou,Hsin-Chieh Tsay,Alice Huang,Shu-Fen Guu,Ting-Chang Kao,Chia-Kwung Fan 대한기생충학열대의학회 2009 The Korean Journal of Parasitology Vol.47 No.2

Antiproliferative activities of Garcinia bracteata extract and its active ingredient, isobractatin, against human tumor cell lines

Shen, Tao,Li, Wei,Wang, Yan-Yan,Zhong, Qing-Qing,Wang, Shu-Qi,Wang, Xiao-Ning,Ren, Dong-Mei,Lou, Hong-Xiang 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.3

In our cell based screening of antitumor ingredients from plants, the EtOH extract of Garcinia bracteata displayed antiproliferative effect against human lung adenocarcinoma A549 cells, human breast cancer MCF-7 cells, and human prostate cancer PC3 cells. Phytochemical investigation of this active extract produced nine ingredients, and their structures were established by analysis of MS and NMR spectra. Antiproliferative evaluation of isolated ingredients on A549, MCF-7 and PC3 cells indicated that a xanthone named isobractatin (1) exhibited potent antiproliferative activity against the above three human cancer cell lines with $IC_{50}$ values ranging from 2.90 to $4.15{\mu}M$. Treatment of PC3 cells with 1 led to an enhancement of the cell apoptosis, and arrested cell cycle in the G0/G1 phase. The G0/G1 phase cycle-related proteins analysis showed that the expressions of cyclins D1 and E were reduced by 1, whereas the protein level of cyclin dependent kinase (CDK) inhibitor P21 was induced. Additionally, 1 enhanced PC3 cell apoptosis by activations of Bax, caspases 3 and 9, and by inhibition of Bcl-2. Our combined data illustrated that isobractatin (1) was the antiproliferative ingredient of G. bracteata against three human cancer cell lines, which exerted its antiproliferatrive effect via cell cycle arrest and induction of apoptosis.

An Optical-Density-Based Feedback Feeding Method for Ammonium Concentration Control in Spirulina platensis Cultivation

( Yi Lu Bao ),( Shu Mei Wen ),( Wei Cong ),( Xia Wu ),( Xiang Ning Zheng ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.7

Cultivation of Spirulina platensis using ammonium salts or wastewater containing ammonium as alternative nitrogen sources is considered as a commercial way to reduce the production cost. In this research, by analyzing the relationship between biomass production and ammonium- N consumption in the fed-batch culture of Spirulina platensis using ammonium bicarbonate as a nitrogen nutrient source, an online adaptive control strategy based on optical density (OD) measurements for controlling ammonium feeding was presented. The ammonium concentration was successfully controlled between the cell growth inhibitory and limiting concentrations using this OD-based feedback feeding method. As a result, the maximum biomass concentration (2.98 g/l), productivity (0.237 g/l·d), nitrogen-to-cell conversion factor (7.32 gX/gN), and contents of protein (64.1%) and chlorophyll (13.4mg/g) obtained by using the OD-based feedback feeding method were higher than those using the constant and variable feeding methods. The OD-based feedback feeding method could be recognized as an applicable way to control ammonium feeding and a benefit for Spirulina platensis cultivations.

Relationship Between the SER Treatment Period and Prognosis of Patients with Small Cell Lung Cancer

Xiao, Xiao-Guang,Wang, Shu-Jing,Hu, Li-Ya,Chu, Qian,Wei, Yao,Li, Yang,Mei, Qi,Chen, Yuan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Purpose: To explore the relationship between SER (time between the start of any treatment and the end of radiation therapy) and the survival of patients with limited-stage small cell lung cancer. Materials and Methods: Between 2008 and 2013, 135 cases of limited-stage small cell lung cancer (LS-SCLC) treated with consecutively curative chemoradiotherapy were included in this retrospective analysis. In terms of SER, patients were divided into early radiotherapy group (SER<30 days, n=76) and late radiotherapy group ($SER{\geq}30$ days, n=59) with a cut-off of SER 30 days. Outcomes of the two groups were compared for overall survival. Results: For all analyzable patients, median follow-up time was 23.8 months and median overall survival time was 16.8 months. Although there was no significant differences in distant metastasis free survival between the two groups, patients in early radiotherapy group had a significantly better PFS (p=0.003) and OS (p=0.000). Conclusions: A short SER may be a good prognostic factor for LD-SCLC patients treated with concurrent chemoradiotherapy.