Publications by authors named "Xin-Yuan Wang"

24 Publications

  • Page 1 of 1

Neo-adjuvant radiation therapy provides a survival advantage in T3-T4 nodal positive gastric and gastroesophageal junction adenocarcinoma: a SEER database analysis.

BMC Cancer 2021 Jul 3;21(1):771. Epub 2021 Jul 3.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.

Background: Due to negative results in clinical trials of postoperative chemoradiation for gastric cancer, at present, there is a tendency to move chemoradiation therapy forward in gastric and gastroesophageal junction (GEJ) adenocarcinoma. Several randomized controlled trials (RCTs) are currently recruiting subjects to investigate the effect of neo-adjuvant radiotherapy (NRT) in gastric and GEJ cancer. Large retrospective studies may be beneficial in clarifying the potential benefit of NRT, providing implications for RCTs.

Methods: We retrieved the clinicopathological and treatment data of gastric and GEJ adenocarcinoma patients who underwent surgical resection and chemotherapy between 2004 and 2015 from Surveillance, Epidemiology, and End Results (SEER) database. We compared survival between NRT and non-NRT patients among four clinical subgroups (TN, TN, TN, and TN).

Results: Overall, 5272 patients were identified, among which 1984 patients received NRT. After adjusting confounding variables, significantly improved survival between patients with and without NRT was only observed in TN subgroup [hazard ratio (HR) 0.79, 95% confidence interval (CI): 0.66-0.95; P = 0.01]. Besides, Kaplan-Meier plots showed significant cause-specific survival advantage of NRT in intestinal type (P <  0.001), but not in diffuse type (P = 0.11) for TN patients. In the multivariate competing risk model, NRT still showed survival advantage only in T N patients (subdistribution HR: 0.77; 95% CI: 0.64-0.93; P = 0.006), but not in other subgroups.

Conclusions: NRT might benefit resectable gastric and GEJ cancer patients of T3-4 stages with positive lymph nodes, particularly for intestinal-type. Nevertheless, these results should be interpreted with caution, and more data from ongoing RCTs are warranted.
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http://dx.doi.org/10.1186/s12885-021-08534-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254219PMC
July 2021

Photochemical Reactivity of Humic Substances in an Aquatic System Revealed by Excitation-Emission Matrix Fluorescence.

Front Chem 2021 28;9:679286. Epub 2021 May 28.

School of Environmental and Municipal Engineering, Qingdao University of Technology, Qingdao, China.

The photochemical reactivity of humic substances plays a critical role in the global carbon cycle, and influences the toxicity, mobility, and bioavailability of contaminants by altering their molecular structure and the mineralization of organic carbon to CO. Here, we examined the simulated irradiation process of Chinese standard fulvic acid (FA) and humic acid (HA) by using excitation-emission matrix fluorescence combined with fluorescence regional integration (FRI), parallel factor (PARAFAC) analysis, and kinetic models. Humic-like and fulvic-like materials were the main materials (constituting more than 90%) of both FA and HA, according to the FRI analysis. Four components were identified by the PARAFAC analysis: fulvic-like components composed of both carboxylic-like and phenolic-like chromophores (C1), terrestrial humic-like components primarily composed of carboxylic-like chromophores (C2), microbial humic-like overwhelming composed of phenolic-like fluorophores (C3), and protein-like components (C4). After irradiation for 72 h, the maximum fluorescence intensity ( ) of C1 and C2 of FA was reduced to 36.01-58.34%, while the of C3 of both FA and HA also decreased to 0-9.63%. By contrast, for HA, the of its C1 and C2 increased to 236.18-294.77% when irradiated for 72 h due to greater aromaticity and photorefractive tendencies. The first-order kinetic model ( = 0.908-0.990) fitted better than zero-order kinetic model ( = 0-0.754) for the C1, C2, and C3, of both FA and HA, during their photochemical reactivity. The photodegradation rate constant ( ) of C1 had values (0.105 for FA; 0.154 for HA) that surpassed those of C2 (0.059 for FA, 0.079 for HA) and C3 (0.079 for both FA and HA) based on the first-order kinetic model. The half-life times of C1, C2, and C3 ranged from 6.61-11.77 h to 4.50-8.81 h for FA and HA, respectively. Combining an excitation-emission matrix with FRI and PARAFAC analyses is a powerful approach for elucidating changes to humic substances during their irradiation, which is helpful for predicting the environmental toxicity of contaminants in natural ecosystems.
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http://dx.doi.org/10.3389/fchem.2021.679286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193985PMC
May 2021

Patterns of Lymph Node Metastasis in Patients With T1/T2 Gastroduodenal Neuroendocrine Neoplasms: Implications for Endoscopic Treatment.

Front Endocrinol (Lausanne) 2021 28;12:658392. Epub 2021 May 28.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Guidelines have differed in their opinion regarding the indications for endoscopic resection of gastric-neuroendocrine neoplasms (g-NENs) and duodenal-NENs (d-NENs). We examined the association between size and lymph node metastasis (LNM) to identify candidates most suitable for endoscopic resection. We identified 706 patients with T1/T2 g-NENs and 621 patients with T1/T2 d-NENs from the SEER database. The prevalence of LNM and risk factors associated with LNM were analyzed. LNM was present in 8.1% of patients with gastroduodenal neuroendocrine tumors (NETs) and 31.6% of patients with neuroendocrine carcinomas (NECs). Multivariate logistic regression indicated that tumor size >10mm, greater invasion depth, and poor differentiation were independently associated with LNM. In addition, the percentage of g-NETs invading submucosa with LNM increased with tumor size (≤10 mm,3.9%;11-20 mm,8.6%;>20 mm,16.1%). However, in contrast to the low LNM risk in patients with small g-NETs (≤10 mm), we found that LNM rate exceeded 5% even for patients with small submucosal-infiltrating d-NETs. Among patients with nodal-negative g-NETs, the cause specific survival (CSS) was similar for those who received surgical resection and endoscopic resection. Among patients with d-NETs, the CSS was better for those who received endoscopic resection. In conclusion, patients with d-NETs had a higher probability of LNM than those with g-NETs. Endoscopic resection can be utilized for curative treatment of submucosa-infiltrating g-NETs and intramucosal d-NETs when the size is 10 mm or less. These results reinforce the need to search for LNM in lesions that are larger than 10 mm.
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http://dx.doi.org/10.3389/fendo.2021.658392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194267PMC
May 2021

Intestinal expression of ACE2 in mice with high-fat diet-induced obesity and neonates exposed to maternal high-fat diet.

Nutrition 2021 Mar 7;90:111226. Epub 2021 Mar 7.

Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China. Electronic address:

Objective: The 2019 novel coronavirus disease (COVID-19) is threatening global health and is especially pronounced in patients with chronic metabolic syndromes. Meanwhile, a significant proportion of patients present with digestive symptoms since angiotensin-converting enzyme 2 (ACE2), which is the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the intestine. The aim of this study was to evaluate the effects of a high-fat diet (HFD) and a maternal HFD on the intestinal ACE2 levels in adults and neonates.

Methods: We examined intestinal ACE2 protein levels in mice with diet-induced obesity (DIO) and neonatal mice exposed to a maternal HFD. We also investigated Ace2 mRNA expression in intestinal macrophages.

Results: Intestinal ACE2 protein levels were increased in DIO mice but decreased in offspring exposed to a maternal HFD compared with chow-fed controls. Ace2 mRNA expression in intestinal macrophages was detected and downregulated in DIO mice. Additionally, higher intestinal ACE2 protein levels were observed in neonates than in adult mice.

Conclusions: The influence of an HFD on intestinal ACE2 protein levels is opposite in adults and neonates. Macrophages might also be involved in SARS-CoV-2 intestinal infection. These findings provide some clues for the outcomes of patients with COVID-19 with metabolic syndromes.
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http://dx.doi.org/10.1016/j.nut.2021.111226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937331PMC
March 2021

Pinocembrin ameliorates intermittent hypoxia-induced neuroinflammation through BNIP3-dependent mitophagy in a murine model of sleep apnea.

J Neuroinflammation 2020 Nov 11;17(1):337. Epub 2020 Nov 11.

Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Feng Lin Rd, Shanghai, 200032, China.

Background: Intermittent hypoxia (IH) caused by obstructive sleep apnea (OSA) leads to neuroinflammation. Pinocembrin has been shown to have neuroprotective effects, while the therapeutic functions under IH condition are still unknown.

Methods: An OSA model was established by CIH exposure inside custom-made chambers. C57BL/6 mice were intraperitoneally injected with pinocembrin (40 mg/kg, i.p.) or vehicle (PBS containing 5% povidone; i.p.), and the changes of behavior on mice were detected by the Morris water maze test. Immunohistochemical staining, western blotting, immunofluorescence assays, and immunoprecipitation were used to investigate the association between NLRP3 inflammasome and BNIP3-dependent mitophagy. The mitochondrial morphology and mitophagosomes were detected under a transmission electron microscope. The detrimental effects of IH were tested by annexin V-FITC/PI staining, Mito SOX Red staining, and JC-1 mitochondrial membrane potential assay.

Results: In this study, our observations in vivo indicated that the administration of pinocembrin can restore spatial learning and memory ability and reduce neuronal apoptosis and hippocampal inflammation. Pinocembrin treatment significantly inhibited the formation of NLRP3 inflammasome and infiltration of microglia and enhanced BNIP3-mediated mitophagy in the hippocampus of IH mice. Additionally, our in vitro results show that pinocembrin protects microglial cells against IH-induced cytotoxicity by activating BNIP3-dependent mitophagy through the JNK-ERK signaling pathway.

Conclusions: In summary, our findings demonstrated that pinocembrin can act as a potential therapeutic strategy for IH-induced neuroinflammation.
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http://dx.doi.org/10.1186/s12974-020-02014-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656728PMC
November 2020

Qualitative Transcriptional Signature for the Pathological Diagnosis of Pancreatic Cancer.

Front Mol Biosci 2020 23;7:569842. Epub 2020 Sep 23.

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

It is currently difficult for pathologists to diagnose pancreatic cancer (PC) using biopsy specimens because samples may have been from an incorrect site or contain an insufficient amount of tissue. Thus, there is a need to develop a platform-independent molecular classifier that accurately distinguishes benign pancreatic lesions from PC. Here, we developed a robust qualitative messenger RNA signature based on within-sample relative expression orderings (REOs) of genes to discriminate both PC tissues and cancer-adjacent normal tissues from non-PC pancreatitis and healthy pancreatic tissues. A signature comprising 12 gene pairs and 17 genes was built in the training datasets and validated in microarray and RNA-sequencing datasets from biopsy samples and surgically resected samples. Analysis of 1,007 PC tissues and 257 non-tumor samples from nine databases indicated that the geometric mean of sensitivity and specificity was 96.7%, and the area under receiver operating characteristic curve was 0.978 (95% confidence interval, 0.947-0.994). For 20 specimens obtained from endoscopic biopsy, the signature had a diagnostic accuracy of 100%. The REO-based signature described here can aid in the molecular diagnosis of PC and may facilitate objective differentiation between benign and malignant pancreatic lesions.
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http://dx.doi.org/10.3389/fmolb.2020.569842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538791PMC
September 2020

Pinocembrin alleviates glucocorticoid-induced apoptosis by activating autophagy via suppressing the PI3K/Akt/mTOR pathway in osteocytes.

Eur J Pharmacol 2020 Aug 26;880:173212. Epub 2020 May 26.

Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. Electronic address:

Glucocorticoids are widely used in clinical practice, but are associated with potentially severe side effects like glucocorticoid-induced osteoporosis (GIOP) and glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH). Glucocorticoid-induced osteocyte apoptosis plays critical roles in the pathological processes of both GIOP and GA-ONFH. Pinocembrin is a natural flavonoid that may exert protective effects on osteocytes. The present study investigated the effects of pinocembrin on glucocorticoid-induced apoptosis of murine long bone osteocyte Y4 (MLO-Y4) cells and sought to elucidate the underlying molecular mechanism. We found that pinocembrin attenuated glucocorticoid-induced cell viability injury and apoptosis of MLO-Y4 cells. Moreover, pinocembrin increased Beclin-1 and LC3B-II level, but decreased p62 expression, suggesting that pinocembrin activates autophagy in glucocorticoid-treated MLO-Y4 cells. The protective effects of pinocembrin on glucocorticoid-induced apoptosis of MLO-Y4 cells were mimicked by a known stimulator of autophagy but prevented by a known inhibitor of autophagy. Pinocembrin also suppressed the PI3K/Akt/mTOR signaling pathway, which regulates cell autophagy, in glucocorticoid-treated MLO-Y4 cells. In conclusion, the results indicate that pinocembrin alleviates glucocorticoid-induced osteocyte apoptosis by activating autophagy via suppressing the PI3K/Akt/mTOR pathway. Pinocembrin may represent a potential natural agent for preventing and treating GIOP and GA-ONFH.
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http://dx.doi.org/10.1016/j.ejphar.2020.173212DOI Listing
August 2020

Nucleobindin-2 enhances the epithelial-mesenchymal transition in renal cell carcinoma.

Oncol Lett 2020 Jun 10;19(6):3653-3664. Epub 2020 Apr 10.

Department of Urology, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154001, P.R. China.

Nucleobindin 2 (NUCB-2) is a multifunctional protein that contains several functional domains and is associated with a wide variety of biological processes, such as food intake and energy homeostasis. NUCB-2 has been demonstrated to be associated with worse malignant outcomes and cell migration in breast and prostate cancer. However, to the best of our knowledge, its clinical and biological significance in renal cell carcinoma remains unknown. In the present study, tissue specimens from 68 patients with renal cell carcinoma and 10 normal controls were collected for NUCB-2 mRNA and protein assays. The NUCB-2 level in the patients with renal cell cancer was significantly increased compared with the normal control patients. NUCB-2-knockout in the renal cancer cell line SK-RC-52 inhibited migration and invasion. In addition, the expression levels of molecules associated with epithelial-mesenchymal transition (EMT), including E-cadherin, β-catenin, Slug and Twist, were affected by NUCB-2 suppression and the zinc finger E-box binding to homeobox 1 (ZEB1)-dependent pathway. The AMP-dependent protein kinase (AMPK)/target of rapamycin complex (mTORC) 1 signaling pathway participates in the regulation of NUCB-2-mediated metastasis and EMT. Suppression of NUCB-2 also inhibited tumor nodule formation in a murine renal cell carcinoma tumor model. In summary, NUCB-2 increased migration, invasion and EMT in renal cell carcinoma cells through the AMPK/TORC1/ZEB1 pathway and .
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http://dx.doi.org/10.3892/ol.2020.11526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204623PMC
June 2020

DNMT3a mediates paclitaxel-induced abnormal expression of LINE-1 by increasing the intragenic methylation.

Yi Chuan 2020 Jan;42(1):100-111

Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing 211166, China.

The activation of long interspersed nuclear element-1 (LINE-1) leads to genomic instability, which promotes carcinogenesis and drug resistant. Therefore, exploring the mechanism underlying LINE-1 abnormal activation has the theoretical and clinical significance. DNA methylation is an important way to regulate gene expression. DNMT3a, one member of the DNA methyltransferase family, not only inhibits gene expression by inducing promoter hypermethylation, but also activates gene expression by increasing the intragenic DNA methylation. Our previous studies found that the expression of LINE-1 did not increase significantly in the promoter methylation in breast cancer cells treated with paclitaxel (PTX), a first-line chemotherapeutic drug for breast cancer. Here we explored whether DMNMT3a could directly mediate the drug-induced activation of LINE-1 in breast cancer cells through increasing the LINE-1 intragenic methylation. Our ChIP experiments and methyl analysis showed that treatment of breast cancer cells with PTX not only induced DNMT3a expression, but also promoted the binding of DNMT3a to the inner region of the gene to increase its methylation, resulting in upregulation of LINE-1 expression. Using expression vectors or RNA interference to alter the DNMT3a expression levels in the cells significantly changed the intragenic methylation degree and LINE-1 expression. Moreover, down-regulation of DNMT3a expression effectively inhibited the expression of LINE-1. These results indicate that DNMT3a-mediated intragenic methylation plays an important role in drug-induced abnormal activation of LINE-1, which provides a new idea for understanding the mechanism of abnormal activation of Line-1 induced by chemotherapy drug stress in breast cancer cells.
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http://dx.doi.org/10.16288/j.yczz.19-258DOI Listing
January 2020

Serum Biomarkers Related to Glucocorticoid-Induced Osteonecrosis of the Femoral Head: A Prospective Nested Case-Control Study.

J Orthop Res 2019 11 22;37(11):2348-2357. Epub 2019 Jul 22.

Department of Orthopaedics, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

Early diagnosis and prevention of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) continues to be a challenging problem for clinicians and researchers. However, the role of circulating biomarkers for GC-induced ONFH, which may reveal individual susceptibility and facilitate earlier diagnosis, remains to be determined. The aim of this study was to identify potential biomarkers that may predict early GC-induced ONFH. A total of 123 patients scheduled for initial systemic GC therapy were enrolled in this prospective nested case-control study. The serum concentrations of 13 potential biomarkers were measured in seven patients with GC-induced ONFH, diagnosed instantly after short-term use of GCs and in 20 controls who did not develop osteonecrosis despite similar GC therapy. Biomarkers were measured both before and after taking GCs to identify any differences in marker levels and the changes during GC therapy between two groups. Type I collagen cross-linked C-telopeptide (β-CTX; p = 0.000) was significantly lower, high-density lipoprotein cholesterol (p = 0.092) and apolipoprotein (apo)-B/apo-A1 (p = 0.085) tended to be lower and higher, respectively, before GC treatment in osteonecrosis group. After GC therapy, β-CTX (p = 0.014) was significantly lower and amino terminal telopeptide of procollagen type I (PINP; p = 0.068) tended to be lower in the osteonecrosis group. As secondary outcomes, we observed remarkable changes in nine potential biomarkers following short-term GC therapy in both groups. In conclusion, we found that β-CTX, could potentially be used to predict GC-induced ONFH before GC therapy. Lower β-CTX and PINP are promising biomarkers for the early diagnosis of GC-induced ONFH. These findings need to be confirmed in large-scale prospective studies. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2348-2357, 2019.
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http://dx.doi.org/10.1002/jor.24400DOI Listing
November 2019

Integrated network analysis of transcriptomic and protein-protein interaction data in taurine-treated hepatic stellate cells.

World J Gastroenterol 2019 Mar;25(9):1067-1079

School of Basic Sciences, Guangxi University of Chinese Medicine, Nanning 530200, Guangxi Zhuang Autonomous Region, China.

Background: Studies show that the antifibrotic mechanism of taurine may involve its inhibition of the activation and proliferation of hepatic stellate cells (HSCs). Since the molecular mechanism of taurine-mediated antifibrotic activity has not been fully unveiled and is little studied, it is imperative to use "omics" methods to systematically investigate the molecular mechanism by which taurine inhibits liver fibrosis.

Aim: To establish a network including transcriptomic and protein-protein interaction data to elucidate the molecular mechanism of taurine-induced HSC apoptosis.

Methods: We used microarrays, bioinformatics, protein-protein interaction (PPI) network, and sub-modules to investigate taurine-induced changes in gene expression in human HSCs (). Subsequently, all of the differentially expressed genes (DEGs) were subjected to gene ontology function and Kyoto encyclopedia of genes and genomes pathway enrichment analysis. Furthermore, the interactions of DEGs were explored in a human PPI network, and sub-modules of the DEGs interaction network were analyzed using Cytoscape software.

Results: A total of 635 DEGs were identified in taurine-treated HSCs when compared with the controls. Of these, 304 genes were statistically significantly up-regulated, and 331 down-regulated. Most of these DEGs were mainly located on the membrane and extracellular region, and are involved in the biological processes of signal transduction, cell proliferation, positive regulation of extracellular regulated protein kinases 1 (ERK1) and ERK2 cascade, extrinsic apoptotic signaling pathway and so on. Fifteen significantly enriched pathways with DEGs were identified, including mitogen-activated protein kinase (MAPK) signaling pathway, peroxisome proliferators-activated receptor signaling pathway, estrogen signaling pathway, Th1 and Th2 cell differentiation, cyclic adenosine monophosphate signaling pathway and so on. By integrating the transcriptomics and human PPI data, nine critical genes, including , , , , , , , , and , were identified in the PPI network analysis.

Conclusion: Taurine promotes the apoptosis of HSCs up-regulating and then activating the p38 MAPK-JNK-Caspase9/8/3 pathway. These findings enhance the understanding of the molecular mechanism of taurine-induced HSC apoptosis and provide references for liver disorder therapy.
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http://dx.doi.org/10.3748/wjg.v25.i9.1067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406182PMC
March 2019

Dietary flavonoid luteolin attenuates uropathogenic Escherichia. Coli invasion of the urinary bladder.

Biofactors 2016 Nov 25;42(6):674-685. Epub 2016 Jul 25.

Research Unit of Infection and Immunity, Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu, China.

Uropathogenic Escherichia coli (UPEC), the primary uropathogen, adhere to and invade bladder epithelial cells (BECs) to establish a successful urinary tract infection (UTI). Emerging antibiotic resistance requires novel nonantibiotic strategies. Our previous study indicated that luteolin attenuated adhesive and invasive abilities as well as cytotoxicity of UPEC on T24 BECs through down-regulating UPEC virulence factors. The aims of this study were to investigate the possible function of the flavonoid luteolin and the mechanisms by which luteolin functions in UPEC-induced bladder infection. Firstly, obvious reduction of UPEC invasion but not adhesion were observed in luteolin-pretreated 5637 and T24 BECs sa well as mice bladder via colony counting. The luteolin-mediated suppression of UPEC invasion was linked to elevated levels of intracellular cAMP induced by inhibiting the activity of cAMP-phosphodiesterases (cAMP-PDEs), which resulting activation of protein kinase A, thereby negatively regulating Rac1-GTPase-mediated actin polymerization. Furthermore, p38 MAPK was primarily and ERK1/2 was partially involved in luteolin-mediated suppression of UPEC invasion and actin polymerization, as confirmed with chemical activators of p38 MAPK and ERK1/2. These data suggest that luteolin can protect bladder epithelial cells against UPEC invasion. Therefore, luteolin or luteolin-rich products as dietary supplement may be beneficial to control the UPEC-related bladder infections, and cAMP-PDEs may be a therapy target for UTIs treatment. © 2016 BioFactors, 42(6):674-685, 2016.
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http://dx.doi.org/10.1002/biof.1314DOI Listing
November 2016

On-line two-dimensional countercurrent chromatography×high performance liquid chromatography system with a novel fragmentary dilution and turbulent mixing interface for preparation of coumarins from Cnidium monnieri.

J Chromatogr A 2015 Aug 22;1406:215-23. Epub 2015 Jun 22.

School of Pharmaceutical Sciences, Xiamen University, South Xiang-An Road, Xiamen, 361102, China. Electronic address:

This study describes a novel on-line two-dimensional countercurrent chromatography×high performance liquid chromatography (2D CCC×HPLC) system for one-step preparative isolation of coumarins from the fruits of Cnidium monnieri. An optimal biphasic solvent system composed of n-heptane/acetone/water (31:50:19, v/v) with suitable Kd values and a higher retention of the stationary phase was chosen to separate target compounds. In order to address the solvent incompatibility problem between CCC and RP-HPLC, a novel fragmentary dilution and turbulent mixing (FD-TM) interface was successfully developed. In detail, the eluent from the first dimensional CCC column was divided into fractions to form 'sample-dilution' stripes in the two switching sample loops, by the dilution water from the makeup pump. Following this, a long, thin tube was applied to mix the CCC eluent with water by in-tube turbulence, to reduce the solvent effect. Each CCC fraction was alternately trapped on the two holding columns for further preparative HPLC separation. This nationally designed FD-TM strategy effectively reduced post-column pressure and allowed a higher water dilution ratio at the post end of CCC, leading to improved sample recovery and a robust 2D CCC×HPLC isolation system. As a result, in a single 2D separation run (6.5h), eight target compounds (1-8) were isolated from 0.5g crude extract of C. monnieri, in overall yields of 1.3, 2.0, 0.5, 0.5, 0.8, 1.5, 8.2, and 15.0%, with HPLC purity of 90.1, 91.1, 94.7, 99.1, 99.2, 98.2, 97.9, and 91.9%, respectively. We anticipate that this improved 2D CCC×HPLC system, based on the novel FD-TM interface, has broad application for simultaneous isolation and purification of multiple components from other complex plant-derived natural products.
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http://dx.doi.org/10.1016/j.chroma.2015.06.034DOI Listing
August 2015

On-line comprehensive two-dimensional normal-phase liquid chromatography × reversed-phase liquid chromatography for preparative isolation of Peucedanum praeruptorum.

J Chromatogr A 2015 Mar 11;1387:60-8. Epub 2015 Feb 11.

School of Pharmaceutical Sciences and the Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, South Xiang-An Road, Xiamen, Fujian 361102, China. Electronic address:

A new on-line comprehensive preparative two-dimensional normal-phase liquid chromatography × reversed-phase liquid chromatography (2D NPLC × RPLC) system was developed for the separation of complicated natural products. It was based on the use of a silica gel packed medium-pressure column as the first dimension and an ODS preparative HPLC column as the second dimension. The two dimensions were connected with normal-phase (NP) and reversed-phase (RP) enrichment units, involving a newly developed airflow assisted adsorption (AAA) technique. The instrument operation and the performance of this NPLC × RPLC separation method were illustrated by gram-scale isolation of ethanol extract from the roots of Peucedanum praeruptorum. In total, 19 compounds with high purity were obtained via automated multi-step preparative separation in a short period of time using this system, and their structures were comprehensively characterized by ESI-MS, (1)H NMR, and (13)C NMR. Including two new compounds, five isomers in two groups with identical HPLC and TLC retention values were also obtained and identified by 1D NMR and 2D NMR. This is the first report of an NPLC × RPLC system successfully applied in an on-line preparative process. This system not only solved the interfacing problem of mobile-phase immiscibility caused by NP and RP separation, it also exhibited apparent advantages in separation efficiency and sample treatment capacity compared with conventional methods.
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http://dx.doi.org/10.1016/j.chroma.2015.02.003DOI Listing
March 2015

Two-dimensional countercurrent chromatography×high performance liquid chromatography with heart-cutting and stop-and-go techniques for preparative isolation of coumarin derivatives from Peucedanum praeruptorum Dunn.

J Chromatogr A 2014 Dec 26;1374:156-163. Epub 2014 Nov 26.

School of Pharmaceutical Sciences, Xiamen University, South Xiang-An Road, Xiamen 361102, China. Electronic address:

Pure compounds isolated from complex natural plants are important for drug discovery. This study describes a novel two-dimensional hyphenation of counter-current chromatography and high-performance liquid chromatography (2D CCC×HPLC) with heart-cutting and stop-and-go techniques for preparative isolation of multiple targets components from Peucedanum praeruptorum Dunn (Umbelliferae) crude extracts in a single step. The CCC and HPLC were hyphenated via a 4-port valve equipped at the post-end of the CCC column, to heart cut the impure fractions to the 2nd dimensional HPLC for further separation. Furthermore, the stop-and-go flow scheme was applied in the 1st dimensional CCC to fit with the time constraints of the 2nd dimensional preparative HPLC. Last but not least, an optimal biphasic solvent system composed of n-heptane/acetone/water (31:50:19, v/v/v) with suitable Kd values and a higher retention of the stationary phase was chosen to separate target compounds, resulting in the improvement of the CCC column efficiency. By taking the advantages of this rationally designed system, sixteen coumarins were isolated from 1.0g of P. praeruptorum crude extract, with HPLC purity from 90.1% to 99.5%, in a single 2D separation run. More interestingly, two minor linear coumarins and one angular coumarin were isolated from P. praeruptorum Dunn for the first time. As far as we known, this is the first report on the combination of heart-cutting technique and stop-and-go protocol in 2D CCC×HPLC system, by which good separations on comprehensive matrix were achieved. We expect that this approach may have broad applications for simultaneous isolation and purification of multiple components from other complex plant-derived natural products.
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http://dx.doi.org/10.1016/j.chroma.2014.11.053DOI Listing
December 2014

Luteolin decreases the attachment, invasion and cytotoxicity of UPEC in bladder epithelial cells and inhibits UPEC biofilm formation.

Food Chem Toxicol 2014 Oct 19;72:204-11. Epub 2014 Jul 19.

Research Unit of Infection and Immunity, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China; Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu 610041, China. Electronic address:

Urinary tract infection (UTI), primarily caused by uropathogenic Escherichia coli (UPEC), is one of the most common infectious diseases worldwide. Emerging antibiotic resistance requires novel treatment strategies. Luteolin, a dietary polyphenolic flavonoid, has been confirmed as a potential antimicrobial agent. Here, we evaluated the sub-MICs of luteolin for potential properties to modulate the UPEC infection. We found that luteolin significantly decreased the attachment and invasion of UPEC J96 or CFT073 in human bladder epithelial cell lines T24. Meanwhile, obvious decreased expression of type 1 fimbriae adhesin fimH gene, lower bacterial surface hydrophobicity and swimming motility, were observed in luteolin-pretreated UPEC. Furthermore, luteolin could attenuate UPEC-induced cytotoxicity in T24 cells, which manifested as decreased activity of lactate dehydrogenase (LDH). Simultaneously, the inhibition of luteolin on UPEC-induced cytotoxicity was confirmed by ethidium bromide/acridine orange staining. Finally, the luteolin-pretreated UPEC showed a lower ability of biofilm formation. Collectively, these results indicated that luteolin decreased the attachment and invasion of UPEC in bladder epithelial cells, attenuated UPEC-induced cytotoxicity and biofilm formation via down-regulating the expression of adhesin fimH gene, reducing the bacterial surface hydrophobicity and motility.
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http://dx.doi.org/10.1016/j.fct.2014.07.019DOI Listing
October 2014

[Synergistic effect of targeted inhibition of MEK/ERK and PI3K/AKT survival signaling pathways on induction of apoptosis in melanoma].

Sichuan Da Xue Xue Bao Yi Xue Ban 2014 May;45(3):355-61

Objective: The treatment of metastatic melanoma by conventional chemotherapeutic agents remains unsatisfactory. The present study was undertaken to reveal the role of co-inhibition of survival signaling pathways in apoptosis of melanoma cells.

Methods: A panel of human melanoma cell lines and fresh melanoma isolates was assessed for their sensitivity to the MEK inhibitor U0126 and/or AKT inhibitor LY294002. The proliferation and apoptosis of the cells were examined after treatment with the inhibitors.

Results: Constitutive activation of ERK1/2 and AKT was closely related to concentrations of serum in the culture medium (extracellular signals). The sensitivity of melanoma cells to apoptosis induced by inhibition of MEK/ERK was not correlated with the active BRAF mutation (BRAF(V600E)). Inhibition of MEK/ERK predominantly induced apoptosis; whereas inhibition of PI3K/AKT primarily inhibited proliferation. Co-inhibition of MEK/ERK1/2 and PI3K/AKT synergistically induced apoptosis.

Conclusion: Co-targeting MEK/ERK and PI3K/AKT pathways may further improve treatment for melanoma.
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May 2014

[Effects of environmental factors on litter decomposition in arid and semi-arid regions: A review].

Ying Yong Sheng Tai Xue Bao 2013 Nov;24(11):3300-10

Cold and Arid Regions Environmental and Engineering Research Institute, Chinese Academy of Sciences, Lanzhou 730000, China.

Litter decomposition is one of the important biochemical processes in arid and semi-arid regions, and a key component of regional nutrient turnover and carbon cycling, which is mainly affected by climate, litter quality, and decomposer community. In order to deeply understand the relationships between litter decomposition and environmental factors in arid and semi-arid regions, this paper summarized the research progress in the effects of abiotic factors (soil temperature, precipitation, and ultraviolet-B radiation) and biotic factors (litter quality, soil microbial and animal composition and community structure) on the litter decomposition in these regions. Among the factors, precipitation and ultraviolet-B radiation are considered to be the main limiting factors of litter decomposition. In arid and semi-arid regions, precipitation can significantly increase the litter decomposition rate in a short term, while the photo-degradation induced by ultraviolet-B radiation, due to the strong and long-term radiation, can increase the decomposition rate of terrestrial litter. Litter quality, soil microbial and animal composition and community structure are mainly affected by the type of ecosystems in a long term. However, the affecting mechanisms of these environmental factors on litter decomposition are still not very clear. It was suggested that the future litter ecological research should be paid more attention to the interaction of environmental factors under climate change, the variations of litter decomposition at different spatial scales, and the establishment of litter decomposition models in relation to the synergistic interactions of multiple factors.
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November 2013

Excess nicotinamide increases plasma serotonin and histamine levels.

Sheng Li Xue Bao 2013 Feb;65(1):33-8

Institute of Basic Medical Sciences, Medical College, Dalian University, China.

Methylation, a methyl group-consuming reaction, plays a key role in the degradation (i.e., inactivation) of monoamine neurotransmitters, including catecholamines, serotonin and histamine. Without labile methyl groups, the methylation-mediated degradation cannot take place. Although high niacin (nicotinic acid and nicotinamide) intake, which is very common nowadays, is known to deplete the body's methyl-group pool, its effect on monoamine-neurotransmitter degradation is not well understood. The aim of this article was to investigate the effect of excess nicotinamide on the levels of plasma serotonin and histamine in healthy subjects. Urine and venous blood samples were collected from nine healthy male volunteers before and after oral loading with 100 mg nicotinamide. Plasma N(1)-methylnicotinamide, urinary N(1)-methyl-2-pyridone-5-carboxamide (2-Py), and plasma betaine levels were measured by using high-performance liquid chromatography (HPLC). Plasma concentrations of choline, serotonin and histamine were measured using commercial kits. The results showed that the plasma N(1)-methylnicotinamide level and the urinary excretion of 2-Py significantly increased after oral loading with 100 mg nicotinamide, which was accompanied with a decrease in the methyl-group donor betaine. Compared with those before nicotinamide load, five-hour postload plasma serotonin and histamine levels significantly increased. These results suggest that excess nicotinamide can disturb monoamine-neurotransmitter metabolism. These findings may be of significance in understanding the etiology of monoamine-related mental diseases, such as schizophrenia and autism (a neurodevelopmental disorder).
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February 2013

Appropriate and inappropriate electrical therapies delivered by an implantable cardioverter-defibrillator: effect on intracardiac electrogram.

J Cardiovasc Electrophysiol 2011 May 18;22(5):554-60. Epub 2010 Nov 18.

Whiting School of Engineering, The Johns Hopkins University, Baltimore, Maryland, USA.

Introduction: Local injury current (LIC) seen after induced ventricular fibrillation rescue implantable cardioverter-defibrillator (ICD) shock predicts heart failure progression. We sought to determine the frequency of LIC after spontaneous events in patients receiving ICD therapies.

Methods And Results: Near-field (NF) right ventricular (RV) EGM during 10 seconds after delivered ICD therapy was compared with baseline EGM in 420 events that occurred in 134 patients (mean age 60.8 ± 14.8, 106 [79%] male). The magnitude of elevated or depressed potential immediately after the major fast EGM deflection was defined as LIC, and its ratio to the peak-to-peak EGM amplitude was defined as relative LIC. LIC of at least 1 mV or relative LIC of at least 15% was considered significant. LIC was observed in 121 events (28.8%) and was detected more frequently after appropriate (43 [60.6%] events) and inappropriate (56 [64.4%] events) ICD shocks, as compared with appropriate (8 [9.2%] events) and inappropriate (3 [4.7%] events) antitachycardia pacing (ATP) or nonsustained ventricular tachycardia (11 [9.9%] events) [ANOVA P < 0.0001]. Type of ICD therapy (ICD shock vs ATP) was the most significant predictor of LIC (ATP β coefficient -0.81; 95%CI-1.19 to 0.44); P < 0.0001), along with cycle length of tachycardia (β coefficient -0.0117; 95%CI -0.0167 to -0.0068, P < 0.00001) and shock energy (β coefficient 0.024; 95%CI 0.003-0.045, P = 0.025).

Conclusion: Appropriate and inappropriate ICD shocks are frequently characterized by the development of LIC in patients with structural heart disease. Type of electrical ICD therapy, shock energy and cycle length of ventricular arrhythmia are important determinants of LIC.
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http://dx.doi.org/10.1111/j.1540-8167.2010.01958.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093435PMC
May 2011

[Construction of normal human lymphocyte cDNA library].

Yi Chuan 2002 Mar;24(2):143-5

Public Health College of Xinjiang University, China.

A lymphocyte cDNA library of normal human was constructed in order to obtain specific gene and prepare lymphocyte gene chips to detect the relative genes between psychiatric diseases and immunity. The lymphocyte was abstracted from fresh normal human blood and cultured in vitro. Total RNA of lymphocyte was extracted from the cultured cells and then mRNA was extracted further. Moreover,single-strand cDNA and double-strand cDNA were synthesized in turn. The double-strand cDNAs were ligated to SalI and NotI adaptor,which were later ligated to arms of gammaZipLox. Ligated-cDNAs were packed in vitro, and then infected E. coli Y1090. Titering the phage and amplifying the library. The lymphocyte cDNA library consisted of 2.6 x 10(6) recombinants with the length of 1-5 kb and the cloning efficiency was 5 x 10(12) recombinants/g cDNA. The amplified library was 3 x 10(7) recombinants/microl in concentration and the number of bacteriophage plagues was the most suitable in density after it was diluted to 10(-6) in concentration. The constructed cDNA library of normal human lymphocyte would be helpful to further detecting target genes and preparing gene chips etc.
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March 2002

Specificity of interleukin-2 receptor gamma chain superfamily cytokines is mediated by insulin receptor substrate-dependent pathway.

J Biol Chem 2002 Mar 11;277(10):8091-8. Epub 2002 Jan 11.

Department of Pharmacology and Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4965, USA.

Interleukins 9 (IL-9) and 4 are cytokines within the IL-2 receptor gamma chain (IL-2R gamma) superfamily that possess similar and unique biological functions. The signaling mechanisms, which may determine cytokine specificity and redundancy, are not well understood. IRS proteins are tyrosine-phosphorylated following IL-9 and IL-4 stimulation, a process in part mediated by JAK tyrosine kinases (Yin, T. G., Keller, S. R., Quelle, F. W., Witthuhn, B. A., Tsang, M. L., Lienhard, G. E., Ihle, J. N., and Yang, Y. C. (1995) J. Biol. Chem. 270, 20497--20502). In the present study, we used 32D cells stably transfected with insulin receptor (32D(IR)), which do not express any IRS proteins, as a model system to study the requirement of different structural domains of IRS proteins in IL-9- and IL-4-mediated functions. Overexpression of IRS-1 and IRS-2, but not IRS-4, induced proliferation of 32D(IR) cells in response to IL-9. The pleckstrin homology (PH) domain of IRS proteins is required for IRS-mediated proliferation stimulated by IL-9. The phosphotyrosine binding and Shc and IRS-1 NPXY binding domains are interchangeable for IRS to transduce the proliferative effect of IL-4. Therefore, the PH domain plays different roles in coupling IRS proteins to activated IL-9 and IL-4 receptors. The role of IRS proteins in determining cytokine specificity was corroborated by their ability to interact with different downstream signaling molecules. Although phosphatidylinositol 3' -kinase (PI3K) and Grb-2 interact with tyrosine-phosphorylated IRS proteins, Shp-2 only binds to IRS proteins following IL-4, but not IL-9, stimulation. Although PI3K activity is necessary for the IRS-1/2-mediated proliferative effect of IL-9 and IL-4, Akt activation is only required for cell proliferation induced by IL-4, but not IL-9. These data suggest that IRS-dependent signaling pathways work by recruiting different signaling molecules to determine specificity of IL-2R gamma superfamily cytokines.
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http://dx.doi.org/10.1074/jbc.M106650200DOI Listing
March 2002
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