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>

Research on Transaction Security Mechanism of Mobile Commerce in Mobile Internet based on MAS

Jiang Wei-Jin,Xu Yu-Sheng,Guo Hong,Zhang Lian-Mei 보안공학연구지원센터 2015 International Journal of Security and Its Applicat Vol.9 No.12

In Mobile Internet (MI), existing uncertain factors, such as randomness, fuzziness and unpredictability, brought many security issues to on-line transactions. In on-line transactions of the mobile commerce based on mobile Internet, the trust is the premise and key which makes transactions smoothly.. Trust measurement between entities involves in trading volume, transaction time, personal income of consumer entity and its risk attitude to trust, and so on, which is difficult to be given accurately quantitative calculation. To find out the essential features of this kind of trust relationship, combined with cognitive theory and methods of social network in real life, in the research background of mobile commerce in Mobile Internet, by the research on problems in MI, such as trust, influencing factors to trust and trust mechanism, based on multi-Agent system coordination theory, a dynamic trust calculation model based on mobile Agent is given. The model can achieve the qualitative and quantitative conversion of trust. In order to effectively prevent credit speculation and fraud of malicious user, the paper presents evaluation methods of special attributes and punishment methods of. trust. To implement incentive mechanism for achieving credibility, the paper defines the time-sensitive functions, which makes dynamic attenuation of the trust. The existing trust assignment methods of new users are improved, and a new method is proposed which sets dynamically initial trust of new users based on minimum trust of the previous system, and effectively resists moral hazard of discarding reputation information. Through leading the evaluation system of trading and weighting system into the multi-factor mechanism, the model reflects better the impact of subjective factors on trust calculation, such as individual preferences, risk attitudes, enhances the sensitivity of the trust algorithm on single property of transaction. The detailed theoretical analysis and simulation results show that the mechanism can effectively reveal and resolve the trust computing problem of mobile network transactions and provides a valuable new idea to transaction security in MI.

Down-regulated serum microRNA-101 is associated with aggressive progression and poor prognosis of cervical cancer

Wei Jiang,Jia-Jia Pan,Ying-Hui Deng,Mei-Rong Liang,Li-Hua Yao 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.6

Objective: MicroRNAs (miRNAs) play a vital role in pathogenesis and progression of many cancers, including cervical cancer. However, importance of serum level of miR-101 in cervical cancer has rarely been studied. In the present study, clinical significance and prognostic value of serum miR-101 for cervical cancer was investigated. Methods: Association between miR-101 level in cervical cancer tissues and prognosis of patients was analyzed by using data retrieved from The Cancer Genome Atlas (TCGA) database, which was followed with our clinical study in which miR-101 serum level comparison between cervical cancer patients and healthy controls was conducted by real-time quantitative polymerase chain reaction (PCR). Results: TCGA database demonstrated that miR-101 was down-regulated in cervical cancer tissues compared with normal cervical tissues, and univariate Cox regression analysis indicated that decreased miR-101 expression was a highly significant negative risk factor. Similar trend was found in the serum miR-101. Serum level of miR-101 was associated with International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.003), lymph node metastasis (p=0.001), and serum squamous cell carcinoma antigen (SCC-Ag) level >4 (p=0.007). The overall survival time of cervical cancer patients with a higher level of serum miR-101 was significantly longer than that of patients with a lower level of serum miR-101. Moreover, multivariate Cox regression analysis indicated that the down-regulated serum level of miR-101 was an independent predictor for the unfavorable prognosis of cervical cancer. Conclusion: Serum level of miR-101 is closely associated with metastasis and prognosis of cervical cancer; and, hence could be a potential biomarker and prognostic predictor for cervical cancer.

A path-dependent fatigue crack propagation model under non-proportional modes I and III loading conditions

Mei, J.,Dong, P.,Kalnaus, S.,Jiang, Y.,Wei, Z. Pergamon Press 2017 Engineering fracture mechanics Vol.182 No.-

<P><B>Abstract</B></P> <P>It has been well established that fatigue damage process is load-path dependent under non-proportional multi-axial loading conditions. Most of studies to date have been focusing on interpretation of S-N based test data by constructing a path-dependent fatigue damage model. This paper presents a two-parameter mixed-mode fatigue crack growth model which takes into account of crack growth dependency on both load path traversed and a maximum effective stress intensity attained in a stress intensity factor plane ( e . g . , <SUB> K I </SUB> - <SUB> K III </SUB> plane). By taking advantage of a path-dependent maximum range (PDMR) cycle definition (Dong et al., 2010; Wei and Dong, 2010), the two parameters are formulated by introducing a moment of load path (MLP) based equivalent stress intensity factor range ( Δ <SUB> K NP </SUB> ) and a maximum effective stress intensity parameter <SUB> K Max </SUB> incorporating an interaction term <SUB> K I </SUB> · <SUB> K III </SUB> . To examine the effectiveness of the proposed model, two sets of crack growth rate test data are considered. The first set is obtained as a part of this study using 304 stainless steel disk specimens subjected to three combined non-proportional modes I and III loading conditions (i.e., with a phase angle of 0°, 90°, and 180°). The second set was obtained by Feng et al. (2007) using 1070 steel disk specimens subjected to similar types of non-proportional mixed-mode conditions. Once the proposed two-parameter non-proportional mixed-mode crack growth model is used, it is shown that a good correlation can be achieved for both sets of the crack growth rate test data.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Presented a two-parameter mixed-mode fatigue crack growth model. </LI> <LI> Both load path dependency and mean stress effect are considered. </LI> <LI> Validated by non-proportional mixed mode I and III crack growth tests on 304 steel. </LI> <LI> Good correlations are achieved both for test data obtained in this study and from others. </LI> </UL> </P>

Multiple attribute group decision making based on intuitionistic fuzzy neutral geometric operators induced by interaction coefficients

Xin Mei Wang,Zi Wen Jiang,Wei Yang 원광대학교 기초자연과학연구소 2017 ANNALS OF FUZZY MATHEMATICS AND INFORMATICS Vol.14 No.5

Various intuitionistic fuzzy aggregation operators for intuitionistic fuzzy numbers (IFNs) have been proposed and applied in the multiple attribute (group) decision making in the literature. In this paper, the neutral geometric operations are provided by an interaction coefficient, and some properties of them are investigated. Based on these, the intuitionistic fuzzy weighted neutral geometric (IFWNG) operator and the intuitionistic fuzzy ordered weighted neutral geometric (IFOWNG) operators are developed. Moreover, the approach to multiple attribute group decision making based on the proposed IFWNG operator are given. Finally, an example is given to show the feasibility and validity of the new approaches.

Efficacy and Safety of Adalimumab in Moderately to Severely Active Cases of Ulcerative Colitis: A Meta-Analysis of Published Placebo-Controlled Trials

( Zong Mei Zhang ),( Wei Li ),( Xue Liang Jiang ) 대한소화기학회 2016 Gut and Liver Vol.10 No.2

Background/Aims: To evaluate the efficacy and safety ofadalimumab (ADA) in moderately to severely active ulcerativecolitis (UC) patients who are unresponsive to traditional therapy. Methods: Electronic databases, including the PubMed, Embase, and Cochrane databases, were searched to April 20, 2014. UC-related randomized controlled trials (RCTs) that compared ADA with placebo were eligible. Review Manager 5.1 was used for data analysis. Results: This meta-analysis included three RCTs. ADA was considerably more effective compared with a placebo, and it increased the ratio of patients with clinical remission, clinical responses, mucosal healing and inflammatory bowel disease questionnaire responses in the induction and maintenance phases (p<0.05), as well as patients with steroid-free remission (p<0.05) during the maintenance phase. Clinical remission was achieved in a greater number of UC cases in the ADA 160/80/40 mg groups (0/2/4 week, every other week) compared with the placebo group at week 8 (p=0.006) and week 52 (p=0.0002), whereas the week 8 clinical remission rate was equivalent between the ADA 80/40 mg groups and the placebo group. Among the patients who received immunomodulators (IMM) at baseline, ADA was superior to the placebo in terms of inducing clinical remission (p=0.01). Between-group differences were not observed in terms of serious adverse events (p=0.61). Conclusions: ADA, particularly at doses of 160/80/40 mg (0/2/4 week, every other week), is effective and safe in patients with moderate-to-severe UC who are unresponsive to traditional treatment. Concomitant IMM therapy may improve the short-term therapeutic efficacy of ADA. (Gut Liver 2016;10:262-274)

Electrochemical Behavior of Sm(III) on the Aluminium-Gallium Alloy Electrode in LiCl-KCl Eutectic

Ye, Chang-Mei,Jiang, Shi-Lin,Liu, Ya-Lan,Xu, Kai,Yang, Shao-Hua,Chang, Ke-Ke,Ren, Hao,Chai, Zhi-Fang,Shi, Wei-Qun Korean Radioactive Waste Society 2021 방사성폐기물학회지 Vol.19 No.2

In this study, the electrochemical behavior of Sm on the binary liquid Al-Ga cathode in the LiCl-KCl molten salt system is investigated. First, the co-reduction process of Sm(III)-Al(III), Sm(III)-Ga(III), and Sm(III)-Ga(III)-Al(III) on the W electrode (inert) were studied using cyclic voltammetry (CV), square-wave voltammetry (SWV) and open circuit potential (OCP) methods, respectively. It was identified that Sm(III) can be co-reduced with Al(III) or Ga(III) to form Al_zSm_y or Ga_xSm_y intermetallic compounds. Subsequently, the under-potential deposition of Sm(III) at the Al, Ga, and Al-Ga active cathode was performed to confirm the formation of Sm-based intermetallic compounds. The X-ray diffraction (XRD) and scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) analyses indicated that Ga₃Sm and Ga₆Sm intermetallic compounds were formed on the Mo grid electrode (inert) during the potentiostatic electrolysis in LiCl-KCl-SmCl₃-AlCl₃-GaCl₃ melt, while only Ga₆Sm intermetallic compound was generated on the Al-Ga alloy electrode during the galvanostatic electrolysis in LiCl-KCl-SmCl₃ melt. The electrolysis results revealed that the interaction between Sm and Ga was predominant in the Al-Ga alloy electrode, with Al only acting as an additive to lower the melting point.

Effect of Different Cooling Rates in High Rheological Rate Forming Process on Mechanical Properties of Zr57Cu20Al10Ni8Ag5 Bulk Metallic Glass

Xiao‑Bo Mei,Bao‑Chuan Liu,Wei Jiang,Quan Xu,Qi‑Dong Zhang,Yu‑Bai Ma,Fang‑Qiu Zu 대한금속·재료학회 2020 METALS AND MATERIALS International Vol.26 No.9

The influence of cooling rates on the mechanical properties of a Zr-based bulk metallic glass prepared with high rheologicalrate forming (HRRF) was investigated and compared with traditional suction cast methods. Amorphous samples of Zr57Cu-20Ni8Al10Ag5 were prepared in copper molds with different sizes in order to obtain different cooling rates for both HRRFand traditional cast methods. These specimens were subjected to compression experiments, including microhardness testing,X-ray diffraction testing and differential scanning calorimetry analysis. The results indicate that the plasticity of the samplesformed by HRRF are higher than that of the as-cast ones at the same cooling rates, while the microhardness manifests theopposite principle. As the cooling rate increases further, the difference in plasticity further increases between two methods,indicating that the plasticity of metallic glasses is more sensitive to cooling rates during the HRRF process. At the core ofthis phenomenon is the fact that HRRF methods can introduce more free volume into glasses than traditional cast methodswith an elevated cooling rate are able to.

Relationship between the methylenetetrahydrofolate reductase (MTHFR) rs1801133 SNP and serum homocysteine levels of Zhuang hypertensive patients in the central region of Guangxi

Hu Xi-Jiang,Su Mei-Ru,Cao Bao-Wei,Ou Fa-Bang,Yin Rui-Xing,Luo An-De 대한고혈압학회 2023 Clinical Hypertension Vol.29 No.-

Background The relationship between the methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphism (SNP) and serum homocysteine (Hcy) levels or H-type hypertension in different populations is inconsistent. This study aimed to explore the association between the MTHFR rs1801133 SNP and serum Hcy levels of Zhuang hypertensive patients in the central region of Guangxi. Methods A total of 606 Zhuang inpatients with essential hypertension were recruited in our hospital from August 2016 to December 2018. The patients were divided into H-type hypertension (Hcy > 10 μmol/L, n = 528) and non–Htype hypertension (Hcy ≤ 10 μmol/L, n = 78) groups. At the same time, an age- and sex-matched group of 379 subjects with normal physical examination in our hospital were selected as the control group. Blood biochemical measurements and genotyping of the MTHFR rs1801133 SNP were performed. Results The prevalence of H-type hypertension was 87.13%. The levels of serum Hcy in patients with hypertension were higher than those in control group (14.20 ± 5.78 μmol/L vs. 11.97 ± 5.39 μmol/L, P < 0.001), especially in patients with H-type hypertension (15.08 ± 5.65 μmol/L, P < 0.001). The frequencies of TT genotype (22.73%) and T allele (46.21%) in patients with H-type hypertension were significantly higher than those in control group (11.35% and 30.47%, respectively) and non–H-type hypertension group (10.26% and 28.85%, respectively; P < 0.001 for all). Multivariate linear regression analysis showed that serum Hcy levels were significantly correlated with creatinine, lowdensity lipoprotein cholesterol, endogenous creatinine clearance rate, and the MTHFR rs1801133 genotypes in control group, while serum Hcy levels were significantly correlated with creatinine, triglyceride, low-density lipoprotein cholesterol, endogenous creatinine clearance rate, glycosylated hemoglobin, and the MTHFR rs1801133 genotypes in H-type hypertension group (P < 0.05–0.001). Serum Hcy levels in the T allele carriers were higher than those in the T allele noncarriers in both H-type hypertension and control groups. Conclusions There was closely related between the MTHFR rs1801133 SNP and serum Hcy levels in Zhuang patients with H-type hypertension in the central region of Guangxi. The MTHFR SNP may be an important reason for the increase of serum Hcy levels in Zhuang patients with H-type hypertension in this region.

Resistance to neonicotinoid insecticides and expression changes of eighteen cytochrome P450 genes in field populations of Bemisia tabaci from Xinjiang, China

Wang Qiang,Wang Mei‐Na,Jia Zun‐Zun,Ahmat Tursun,Xie Lin‐Jie,Jiang Wei‐Hua 한국곤충학회 2020 Entomological Research Vol.50 No.4

The occurrence of Bemisia tabaci poses an increasingly serious threat to cotton and vegetable crops in Xinjiang, China. Currently, neonicotinoid insecticides are commonly used to control the insect, to which resistance is inevitable due to intensive use. However, the resistance status and mechanism of B. tabaci to neonicotinoid insecticides in Xinjiang are poorly understood. Cytochrome P450 monooxygenases represent a key detoxification mechanism in the neonicotinoid resistance of B. tabaci. In this study, the resistance level to imidacloprid and thiamethoxam was investigated using the leaf dipping method in five field populations of B. tabaci from Turpan (TP, two sampling sites), Shache (SC), Hotan (HT) and Yining (YN) in northern and southern Xinjiang. The expression changes of eighteen cytochrome P450 genes from the select B. tabaci populations were determined by real-time fluorescence quantitative PCR (qPCR). The bioassay revealed that the five populations tested had developed moderate to high levels of resistance to imidacloprid (12.26–46.07- fold), while the populations remained sensitive to thiamethoxam except for HT, which had a low level of resistance. The qPCR results showed that the expression levels of five P450 genes, CYP4G68, CYP6CM1, CYP303A1-like, CYP6DZ7 and CYP6DZ4, were significantly higher in some resistant field populations than in the susceptible strain. Resistance to imidacloprid in field populations of B. tabaci might be associated with the increased expression of these five cytochrome P450 genes. The results are useful for further understanding the mechanism of neonicotinoid resistance and will contribute to the management of insecticide-resistant B. tabaci in Xinjiang.