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Xue‑Lian Song,Fei‑Fei Zhang,Wen‑Jing Wang,Xin‑Ning Li,Yi Dang,Ying‑Xiao Li,Qian Yang,Mei‑Jing Shi,Xiao‑Yong Qi 한국유전학회 2020 Genes & Genomics Vol.42 No.12
Background: Myocardial ischemia and reperfusion injury (MI/RI) is a complex pathophysiological process, which can lead to severe myocardial injury. The long noncoding RNA alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) has been revealed to be abnormally expressed in MI, However, its function in MI and the potential mechanism are still unclear. Objective: To evaluate the functional role of A2M-AS1 in hypoxia/reoxygenation (H/R)-induced neonatal cardiomyocytes and its potential molecular mechanism. Methods: Dataset GSE66360 was obtained from GEO database for analyzing the RNA expression of A2M-AS1 and interleukin 1 receptor type 2 (IL1R2). KEGG pathway enrichment analysis of the genes that co-expressed with A2M-AS1 was performed. Human neonatal cardiomyocytes were subjected to H/R to construct in vitro models. QRT-PCR and Western blot were adopted to test the levels of mRNA and protein. The viability and apoptosis of cardiomyocytes were tested by CCK-8 and flow cytometry assays, respectively. Results: The expression of A2M-AS1 was notably downregulated in H/R-treated cardiomyocytes. Overexpression of A2M-AS1 can notably enhance the cell viability of H/R-damaged cardiomyocytes, whereas knockdown of A2M-AS1 showed the opposite outcomes. Besides, a negative correlation was showed between A2M-AS1 and IL1R2 expression. In H/R-treated cardiomyocytes, overexpression of IL1R2 weakened the promoting proliferation and anti-apoptosis effects caused by overexpressing A2M-AS1, however, IL1R2-knockdown abolished the anti-proliferation and pro-apoptosis effects caused by silencing A2M-AS1. Conclusion: This study demonstrates the potential regulatory role of A2M-AS1/ IL1R2 axis in cardiomyocytes suffered from H/R, and provides insight into the protection of MI/RI.
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Cinnamaldehyde Derivatives Inhibit Coxsackievirus B3-Induced Viral Myocarditis
( Xiao-qiang Li ),( Xiao-xiao Liu ),( Xue-ying Wang ),( Yan-hua Xie ),( Qian Yang ),( Xin-xin Liu ),( Yuan-yuan Ding ),( Wei Cao ),( Si-wang Wang ) 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.3
The chemical property of cinnamaldehyde is unstable in vivo, although early experiments have shown its obvious therapeutic effects on viral myocarditis (VMC). To overcome this problem, we used cinnamaldehyde as a leading compound to synthesize derivatives. Five derivatives of cinnamaldehyde were synthesized: 4-methylcinnamaldehyde (1), 4-chlorocinnamaldehyde (2), 4-methoxycinnamaldehyde (3), α-bromo-4-methylcinnamaldehyde (4), and α-bromo-4-chlorocinnamaldehyde (5). Neonatal rat cardiomyocytes and HeLa cells infected by coxsackievirus B3 (CVB3) were used to evaluate their antiviral and cytotoxic effects. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. Among the derivatives, compound 4 and 5 inhibited the CVB3 in HeLa cells with the half-maximal inhibitory concentrations values of 11.38 ± 2.22 μM and 2.12 ± 0.37 μM, respectively. The 50% toxic concentrations of compound 4 and 5-treated cells were 39-fold and 87-fold higher than in the cinnamaldehyde group. Compound 4 and 5 effectively reduced the viral titers and cardiac pathological changes in a dose-dependent manner. In addition, compound 4 and 5 significantly inhibited the secretion, mRNA and protein expressions of inflammatory cytokines TNF-α, IL-1β and IL-6 in CVB3-infected cardiomyocytes, indicating that brominated cinnamaldehyde not only improved the anti-vital activities for VMC, but also had potent anti-inflammatory effects in cardiomyocytes induced by CVB3.
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Cinnamaldehyde Derivatives Inhibit Coxsackievirus B3-Induced Viral Myocarditis
Li, Xiao-Qiang,Liu, Xiao-Xiao,Wang, Xue-Ying,Xie, Yan-Hua,Yang, Qian,Liu, Xin-Xin,Ding, Yuan-Yuan,Cao, Wei,Wang, Si-Wang The Korean Society of Applied Pharmacology 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.3
The chemical property of cinnamaldehyde is unstable in vivo, although early experiments have shown its obvious therapeutic effects on viral myocarditis (VMC). To overcome this problem, we used cinnamaldehyde as a leading compound to synthesize derivatives. Five derivatives of cinnamaldehyde were synthesized: 4-methylcinnamaldehyde (1), 4-chlorocinnamaldehyde (2), 4-methoxycinnamaldehyde (3), ${\alpha}$-bromo-4-methylcinnamaldehyde (4), and ${\alpha}$-bromo-4-chlorocinnamaldehyde (5). Neonatal rat cardiomyocytes and HeLa cells infected by coxsackievirus B3 (CVB3) were used to evaluate their antiviral and cytotoxic effects. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. Among the derivatives, compound 4 and 5 inhibited the CVB3 in HeLa cells with the half-maximal inhibitory concentrations values of $11.38{\pm}2.22{\mu}M$ and $2.12{\pm}0.37{\mu}M$, respectively. The 50% toxic concentrations of compound 4 and 5-treated cells were 39-fold and 87-fold higher than in the cinnamaldehyde group. Compound 4 and 5 effectively reduced the viral titers and cardiac pathological changes in a dose-dependent manner. In addition, compound 4 and 5 significantly inhibited the secretion, mRNA and protein expressions of inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 in CVB3-infected cardiomyocytes, indicating that brominated cinnamaldehyde not only improved the anti-vital activities for VMC, but also had potent anti-inflammatory effects in cardiomyocytes induced by CVB3.
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Qing-Li Yang,Ji-Qing Shen,Yan Xue,Xiao-Bing Cheng,Zhi-Hua Jiang,Yi-Chao Yang,Ying-Dan Chen,Xiao-Nong Zhou 대한기생충학열대의학회 2015 The Korean Journal of Parasitology Vol.53 No.6
The nitric oxide (NO) formation and intrinsic nitrosation may be involved in the possible mechanisms of liver fluke-associated carcinogenesis. We still do not know much about the responses of inducible NO synthase (iNOS) induced by Clonorchis sinensis infection. This study was conducted to explore the pathological lesions and iNOS expressions in the liver of mice with different infection intensity levels of C. sinensis. Extensive periductal inflammatory cell infiltration, bile duct hyperplasia, and fibrosis were commonly observed during the infection. The different pathological responses in liver tissues strongly correlated with the infection intensity of C. sinensis. Massive acute spotty necrosis occurred in the liver parenchyma after a severe infection. The iNOS activity in liver tissues increased, and iNOS-expressing cells with morphological differences were observed after a moderate or severe infection. The iNOS-expressing cells in liver tissues had multiple origins.
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Chun-Li Lu,Ruo-Xiang Zheng,Xue Xue,Xiao-Wen Zhang,Xue-Han Liu,Xin-Yan Jin,Feng-Lan Pu,Hui-Di Lan,Min Fang,Ling-Yao Kong,Merlin Willcox,Bertrand Graz,Joelle Houriet,Xiao-Yang Hu,Jian-ping Liu 한국한의학연구원 2021 Integrative Medicine Research Vol.10 No.-
Background We aimed to investigate use of infection control behaviours, preventative and therapeutic interventions, and outcomes among respondents to an online survey during the COVID-19 pandemic in China. Methods The survey was designed by an international team, translated and adapted to simplified Chinese, including 132 kinds of traditional Chinese medicine (TCM) preparation recommended by guidelines. It was distributed and collected from February to May 2021, with data analysed by WPS spreadsheet and wjx.cn. Descriptive statistics were used to describe demographics and clinical characteristics, diagnosis, treatments, preventative behaviours and interventions, and their associated outcomes. Results The survey was accessed 503 times with 341 (67.8%) completions covering 23 provinces and four municipalities in China. Most (282/341, 82.7%) respondents reported no symptoms during the pandemic and the majority (290/341, 85.0%) reported having a SARS-CoV-2 PCR test at some point. Forty-five (13.2%) reported having a respiratory infection, among which 19 (42.2%) took one or more categories of modern medicine, e.g. painkillers, antibiotics; 16 (35.6%) used TCM interventions(s); while seven respondents combined TCM with modern medicine. All respondents reported using at least one behavioural or medical approach to prevention, with 22.3% taking TCM and 5.3% taking modern medicines. No respondents reported having a critical condition related to COVID-19. Conclusion We found evidence of widespread use of infection control behaviours, modern medicines and TCM for treatment and prevention of COVID-19 and other respiratory symptoms. Larger scale studies are warranted, including a more representative sample exploring TCM preparations recommended in clinical guidelines. Background We aimed to investigate use of infection control behaviours, preventative and therapeutic interventions, and outcomes among respondents to an online survey during the COVID-19 pandemic in China. Methods The survey was designed by an international team, translated and adapted to simplified Chinese, including 132 kinds of traditional Chinese medicine (TCM) preparation recommended by guidelines. It was distributed and collected from February to May 2021, with data analysed by WPS spreadsheet and wjx.cn. Descriptive statistics were used to describe demographics and clinical characteristics, diagnosis, treatments, preventative behaviours and interventions, and their associated outcomes. Results The survey was accessed 503 times with 341 (67.8%) completions covering 23 provinces and four municipalities in China. Most (282/341, 82.7%) respondents reported no symptoms during the pandemic and the majority (290/341, 85.0%) reported having a SARS-CoV-2 PCR test at some point. Forty-five (13.2%) reported having a respiratory infection, among which 19 (42.2%) took one or more categories of modern medicine, e.g. painkillers, antibiotics; 16 (35.6%) used TCM interventions(s); while seven respondents combined TCM with modern medicine. All respondents reported using at least one behavioural or medical approach to prevention, with 22.3% taking TCM and 5.3% taking modern medicines. No respondents reported having a critical condition related to COVID-19. Conclusion We found evidence of widespread use of infection control behaviours, modern medicines and TCM for treatment and prevention of COVID-19 and other respiratory symptoms. Larger scale studies are warranted, including a more representative sample exploring TCM preparations recommended in clinical guidelines.
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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>
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Yang Xiu,Xue Li,Xiuli Sun,Dan Xiao,Rui Miao,Huanxi Zhao,Shuying Liu 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.4
Background: Ginsenosides are not only the principal bioactive components but also the important indexes to the quality assessment of Panax ginseng Meyer. Their contents in cultivated ginseng vary with the growth environment and age. The present study aimed at evaluating the significant difference between 36 cultivated ginseng of different cultivation areas and ages based on the simultaneously determined contents of 14 ginsenosides. Methods: A high-performance liquid chromatography (HPLC) coupled with triple quadrupole mass spectrometer (MS) method was developed and used in the multiple reaction-monitoring (MRM) mode (HPLC-MRM/MS) for the quantitative analysis of ginsenosides. Multivariate statistical analysis, such as principal component analysis and partial least squares-discriminant analysis, was applied to discriminate ginseng samples of various cultivation areas and ages and to discover the differentially accumulated ginsenoside markers. Results: The developed HPLC-MRM/MS method was validated to be precise, accurate, stable, sensitive, and repeatable for the simultaneous determination of 14 ginsenosides. It was found that the 3- and 5-yrold ginseng samples were differentiated distinctly by all means of multivariate statistical analysis, whereas the 4-yr-old samples exhibited similarity to either 3- or 5-yr-old samples in the contents of ginsenosides. Among the 14 detected ginsenosides, Rg1, Rb1, Rb2, Rc, 20(S)-Rf, 20(S)-Rh1, and Rb3 were identified as potential markers for the differentiation of cultivation ages. In addition, the 5-yr-old samples were able to be classified in cultivation area based on the contents of ginsenosides, whereas the 3- and 4-yr-old samples showed little differences in cultivation area. Conclusion: This study demonstrated that the HPLC-MRM/MS method combined with multivariate statistical analysis provides deep insight into the accumulation characteristics of ginsenosides and could be used to differentiate ginseng that are cultivated in different areas and ages.
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