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>

Effect of nano-carbon addition on color performance of polystyrene superstructure film

Ye-min ZHOU,Li-li Wang,Xiao-peng LI,Xiu-feng Wang,Hong-tao JIANG 한양대학교 세라믹연구소 2018 Journal of Ceramic Processing Research Vol.19 No.6

Polystyrene superstructure films show faint rainbow color, and this low color saturation limits its wide application. In thispaper, polystyrene superstructure films with single bright blue color were prepared by vertical deposition self-assemblymethod using polystyrene microspheres with average diameter of 310 ± 10 nm as raw material. Polystyrene superstructurefilms were modified by adding nano-carbon powder, and effect of the amount of nano-carbon powde on color performancewas studied. The results showed that without addition of nano-carbon powder, the superstructure films showed a faint rainbowcolor, while with addition of nano-carbon power, the superstructure films exhibited a single bright blue under the same naturallight source. Changing the amount of nano-carbon powder addition could adjust color saturation of the film. With increasingthe amount of nano-carbon powder addition from 0.008 wt% to 0.01 wt%, color saturation of the superstructure filmincreased gradually. Further increasing the amount of nano-carbon powder addition to 0.011wt%, color saturation of thesuperstructure film didn’t increase anymore and tended to get dark.

Probiotic supplements alleviate gestational diabetes mellitus by restoring the diversity of gut microbiota: a study based on 16S rRNA sequencing

Zheng Qing-Xiang,Jiang Xiu-Min,Wang Hai-Wei,Ge Li,Lai Yu-Ting,Jiang Xin-Yong,Chen Fan,Huang Ping-Ping 한국미생물학회 2021 The journal of microbiology Vol.59 No.9

Probiotics effectively prevent and improve metabolic diseases such as diabetes by regulating the intestinal microenvironment and gut microbiota. However, the effects of probiotics in gestational diabetes mellitus are not clear. Here, we showed that probiotic supplements significantly improved fasting blood glucose in a gestational diabetes mellitus rat model. To further understand the mechanisms of probiotics in gestational diabetes mellitus, the gut microbiota were analyzed via 16S rRNA sequencing. We found that compared with the normal pregnant group, the gestational diabetes mellitus rats had decreased diversity of gut microbiota. Moreover, probiotic supplementation restored the diversity of the gut microbiota in gestational diabetes mellitus rats, and the gut microbiota structure tended to be similar to that of normal pregnant rats. In particular, compared with gestational diabetes mellitus rats, the abundance of Firmicutes and Actinobacteria was higher after probiotic supplementation. Furthermore, activating carbohydrate metabolism and membrane transport pathways may be involved in the potential mechanisms by which probiotic supplements alleviate gestational diabetes mellitus. Overall, our results suggested that probiotic supplementation might be a novel approach to restore the gut microbiota of gestational diabetes mellitus rats and provided an experimental evidence for the use of probiotic supplements to treat gestational diabetes melitus.

Clinical Model for Predicting Hepatocellular Carcinomas in Patients with Post-Sustained Virologic Responses of Chronic Hepatitis C: A Case Control Study

( Qing-lei Zeng ),( Bing Li ),( Xue-xiu Zhang ),( Yan Chen ),( Yan-ling Fu ),( Jun Lv ),( Yan-min Liu ),( Zu-jiang Yu ) 대한소화기학회 2016 Gut and Liver Vol.10 No.6

Background/Aims: No clinical model exists to predict the occurrence of hepatocellular carcinoma in sustained virologic response-achieving (HCC after SVR) patients with chronic hepatitis C (CHC). Methods: We performed a case-control study using a clinical database to research the risk factors for HCC after SVR. A predictive model based on risk factors was established, and the area under the receiver operating characteristic curve (AUC) was calculated. Results: In the multivariate model, an initial diagnosis of compensated cirrhosis and post-SVR albumin reductions of 1 g/L were associated with 21.7-fold (95% CI, 4.2 to 112.3; p< 0.001) and 1.3-fold (95% CI, 1.1 to 1.7; p=0.004) increases in the risk of HCC after SVR, respectively. A predictive model based on an initial diagnosis of compensated cirrhosis (yes, +1; no, 0) and post- SVR albumin ≤36.0 g/L (yes, +1; not, 0) predicted the occurrence of HCC after SVR with a cutoff value of >0, an AUC of 0.880, a sensitivity of 0.833, a specificity of 0.896, and a negative predictive value of 0.956. Conclusions: An initial diagnosis of compensated cirrhosis combined with a post-SVR albumin value of ≤36.0 g/L predicts the occurrence of HCC after SVR in patients with CHC. (Gut Liver 2016;10:955-961)

Catalytic topological insulator Bi₂Se₃ nanoparticles for <i>in</i> <i>vivo</i> protection against ionizing radiation

Zhang, Xiao-Dong,Jing, Yaqi,Song, Shasha,Yang, Jiang,Wang, Jun-Ying,Xue, Xuhui,Min, Yuho,Park, Gyeongbae,Shen, Xiu,Sun, Yuan-Ming,Jeong, Unyong Elsevier 2017 Nanomedicine Vol.13 No.5

<P><B>Abstract</B></P> <P>Bi<SUB>2</SUB>Se<SUB>3</SUB> nanoparticles (NPs) have attracted wide interests in biological and medical applications. Layer-like Bi<SUB>2</SUB>Se<SUB>3</SUB> with high active surface area is promising for free radical scavenging. Here, we extended the medical applications of Bi<SUB>2</SUB>Se<SUB>3</SUB> NPs further to <I>in vivo</I> protection against ionizing radiation based on their superior antioxidant activities and electrocatalytic properties. It was found that Bi<SUB>2</SUB>Se<SUB>3</SUB> NPs can significantly increase the surviving fraction of mice after exposure of high-energy radiation of gamma ray. Additionally, the Bi<SUB>2</SUB>Se<SUB>3</SUB> NPs can help to recover radiation-lowered red blood cell counts, white blood cell counts and platelet levels. Further investigations revealed that Bi<SUB>2</SUB>Se<SUB>3</SUB> NPs behaved as functional free radical scavengers and significantly decreased the level of methylenedioxyamphetamine. <I>In vivo</I> toxicity studies showed that Bi<SUB>2</SUB>Se<SUB>3</SUB> NPs did not cause significant side effects in panels of blood chemistry, clinical biochemistry and pathology.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Bi<SUB>2</SUB>Se<SUB>3</SUB> NPs can significantly increase the surviving fraction of mice up to 70% after Gamma radiation. </LI> <LI> Bi<SUB>2</SUB>Se<SUB>3</SUB> NPs can help to recover radiation-lowered red blood cell counts, white blood cell counts and platelet levels. </LI> <LI> Bi<SUB>2</SUB>Se<SUB>3</SUB> NPs behaved as functional free radical scavengers and significantly decreased the level of methylenedioxyamphetamine. </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>Layer-like Bi<SUB>2</SUB>Se<SUB>3</SUB> with high active surface area can protect mice against ionizing radiation based on their superior antioxidant activities and electrocatalytic properties. Bi<SUB>2</SUB>Se<SUB>3</SUB> NPs can significantly increase the surviving fraction of mice up to 70% after exposure of high-energy radiation of gamma ray. Bi<SUB>2</SUB>Se<SUB>3</SUB> NPs behaved as functional free radical scavengers and significantly decreased the level of methylenedioxyamphetamine. <I>In vivo</I> toxicity studies showed that Bi<SUB>2</SUB>Se<SUB>3</SUB> NPs did not cause significant side effects in panels of blood chemistry, clinical biochemistry and pathology.</P> <P>[DISPLAY OMISSION]</P>

HMGB1 regulates autophagy through increasing transcriptional activities of JNK and ERK in human myeloid Leukemia cells

( Ming Yi Zhao ),( Ming Hua Yang ),( Liang Chun Yang ),( Yan Yu ),( Min Xie ),( Shan Zhu ),( Rui Kang ),( Dao Lin Tang ),( Zhi Gang Jiang ),( Wu Zhou Yuan ),( Xiu Shan Wu ),( Li Zhi Cao ) 생화학분자생물학회(구 한국생화학분자생물학회) 2011 BMB Reports Vol.44 No.9

HMGB1 is associated with human cancers and is an activator of autophagy which mediates chemotherapy resistance. We here show that the mRNA levels of HMGB1 are high in leukemia cells and it is involved in the progression of childhood chronic myeloid leukemia (CML). HMGB1 decreases the sensitivity of human myeloid leukemia cells K562 to anti-cancer drug induced death through up-regulating the autophagy pathway, which is confirmed by the observation with an increase in fusion of autophagosomes and autophagolysosomes. When overexpressing HMGB1, both mRNA levels of Beclin-1, VSP34 and UVRAG which are key genes involved in mammalian autophagy and protein levels of p-Bcl-2 and LC3-II are increased. Luciferase assays document that over-expression of HMGB1 increases the transcriptional activity of JNK and ERK, which may be silenced by siRNA. The results suggest that HMGB1 regulates JNK and ERK required for autophagy, which provides a potential drug target for therapeutic interventions in childhood CML. [BMB reports 2011; 44(9): 601-606]