Publications by authors named "Liping Yao"

69 Publications

Sox2 controls asymmetric patterning of ameloblast lineage commitment by regulation of FGF signaling in the mouse incisor.

J Mol Histol 2021 Jul 19. Epub 2021 Jul 19.

Department of Stomatology, Yantai Affiliated Hospital of Binzhou Medical University, No. 717 Jinbu Street, Yantai, 264100, Shandong, China.

Mouse incisors are covered by enamel only on the labial side and the lingual side is covered by dentin without enamel. This asymmetric distribution of enamel makes it possible to be abrased on the lingual side, generating the sharp cutting edge of incisor on the labial side. The abrasion of mouse incisors is compensated by the continuous growth throughout life. Epithelium stem cells responsible for its continuous growth are reported to localize within the labial cervical loop. The transcription factor Sox2 plays important roles in the maintenance of stem cell pluripotency and organ formation. We previously found that Sox2 mainly expressed in the dental epithelium. Besides, Sox2 has been reported to be a dental epithelium stem cell marker in the incisor. However, the exact mechanism of Sox2 controlling amelogenesis is still not quite clearly elucidated. Here we report that conditional deletion of Sox2 in the dental epithelium using Shh caused impaired ameloblast differentiation in the labial side and induced ectopic ameloblast-like cell differentiation on the lingual side. Abnormal FGF gene expression was detected by RNAscope in situ hybridization in the mutant incisor. Collectively, we speculate that asymmetric ameloblast lineage commitment of mouse incisor might be regulated by Sox2 through FGF signaling.
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http://dx.doi.org/10.1007/s10735-021-10005-1DOI Listing
July 2021

Maternal RNF114-mediated target substrate degradation regulates zygotic genome activation in mouse embryos.

Development 2021 Jul 1;148(13). Epub 2021 Jul 1.

State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing 211166, China.

Zygotic genomic activation (ZGA) is a landmark event in the maternal-to-zygotic transition (MZT), and the regulation of ZGA by maternal factors remains to be elucidated. In this study, the depletion of maternal ring finger protein 114 (RNF114), a ubiquitin E3 ligase, led to developmental arrest of two-cell mouse embryos. Using immunofluorescence and transcriptome analysis, RNF114 was proven to play a crucial role in major ZGA. To study the underlying mechanism, we performed protein profiling in mature oocytes and found a potential substrate for RNF114, chromobox 5 (CBX5), ubiquitylation and degradation of which was regulated by RNF114. The overexpression of CBX5 prevented embryonic development and impeded major ZGA. Furthermore, TAB1 was abnormally accumulated in mutant two-cell embryos, which was consistent with the result of in vitro knockdown of Rnf114. Knockdown of Cbx5 or Tab1 in maternal RNF114-depleted embryos partially rescued developmental arrest and the defect of major ZGA. In summary, our study reveals that maternal RNF114 plays a precise role in degrading some important substrates during the MZT, the misregulation of which may impede the appropriate activation of major ZGA in mouse embryos.
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http://dx.doi.org/10.1242/dev.199426DOI Listing
July 2021

Systematic analysis of the ubiquitome in mouse testis.

Proteomics 2021 May 28:e2100025. Epub 2021 May 28.

Department of Histology and Embryology, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

A growing body of evidence now supports the fact that protein ubiquitination is an important modification during the regulation of spermatogenesis. However, little is known about the ubiquitome of the testis. In this study, we created a large-scale mouse testis ubiquitome profile using di-glycine remnant antibodies and mass spectrometry and identified a total of 14,219 ubiquitination sites in 4217 proteins. Bioinformatics and phenotypic analyses showed that the ubiquitinated proteins were closely related to meiosis and spermiogenesis. And 512 ubiquitination regulatory enzymes were identified in testis that can exert regulatory functions over ubiquitination: the homologous to E6AP C-terminus (HECT) and multi-subunit RING-finger type E3 ligases were significantly enriched. In addition, we identified 22 new ubiquitination sites on testicular histones and 146 ubiquitinated epigenetic factors, thus demonstrating that ubiquitination plays an important role in epigenetic regulation. Collectively, this in-depth characterization of the ubiquitome in mouse testis could provide a rich resource for further studies of regulatory events at the protein level during spermatogenesis. All MS data are available via ProteomeXchange with the identifier PXD025866.
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http://dx.doi.org/10.1002/pmic.202100025DOI Listing
May 2021

Non-invasive high-frequency oscillatory ventilation in preterm infants after extubation: a randomized, controlled trial.

J Int Med Res 2021 Feb;49(2):300060520984915

Department of Neonatology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.

Objective: To investigate the effectiveness and safety of non-invasive high-frequency oscillatory ventilation (NHFOV) in post-extubation preterm infants.

Methods: This was a randomized, controlled trial. A total of 149 preterm infants aged between 25 to 34 weeks' gestational age with a birth weight of <1500 g who required invasive mechanical ventilation on admission were included. After extubation, they were randomized to the NHFOV group (n = 47), nasal intermittent positive pressure ventilation (NIPPV) group (n = 51), or nasal continuous positive airway pressure (NCPAP) group (n = 51). We compared the effectiveness and safety among these three groups.

Results: A total of 139 preterm infants finally completed the study. The reintubation rate was significantly lower in the NHFOV group than in the other groups. The duration of non-invasive ventilation and the length of hospital stay in the NHFOV and NIPPV groups were significantly shorter than those in the NCPAP group. The incidence of bronchopulmonary dysplasia in the NHFOV and NIPPV groups was significantly lower than that in the NCPAP group. The NHFOV group had significantly less nasal injury than the NCPAP group.

Conclusion: As post-extubation respiratory support in preterm infants, NHFOV has a lower reintubation rate compared with NCPAP and NIPPV, without increasing the rate of complications.
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http://dx.doi.org/10.1177/0300060520984915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923990PMC
February 2021

Association of systemic inflammation and body mass index with survival in patients with resectable gastric or gastroesophageal junction adenocarcinomas.

Cancer Biol Med 2021 02;18(1):283-297

State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital, Air Force Medical University of PLA, Xi'an 710032, China.

Objective: The systemic inflammation index and body mass index (BMI) are easily accessible markers that can predict mortality. However, the prognostic value of the combined use of these two markers remains unclear. The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer.

Methods: A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included. Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio (NLR). High systemic inflammation was defined as NLR ≥ 3, and underweight was defined as BMI < 18.5 kg/m.

Results: Among 2,542 patients, NLR ≥ 3 and underweight were common [627 (25%) and 349 (14%), respectively]. In the entire cohort, NLR ≥ 3 or underweight independently predicted overall survival (OS) [hazard ratio (HR): 1.236, 95% confidence interval (95% CI): 1.069-1.430; and HR: 1.600, 95% CI: 1.350-1.897, respectively] and recurrence-free survival (RFS) (HR: 1.230, 95% CI: 1.054-1.434; and HR: 1.658, 95% CI: 1.389-1.979, respectively). Patients with both NLR ≥ 3 and underweight ( neither) had much worse OS (HR: 2.445, 95% CI: 1.853-3.225) and RFS (HR: 2.405, 95% CI: 1.802-3.209). Furthermore, we observed similar results in subgroup analyses according to pathological stage, age, and postoperative chemotherapy.

Conclusions: Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival. Underweight combined with severe inflammation could enhance prognostication. Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877168PMC
February 2021

Re-labeled GX1 dimer as a novel dual-functional probe targeting TGM2 for imaging and antiangiogenic therapy of gastric cancer.

Eur J Pharm Biopharm 2020 Sep 16;154:144-152. Epub 2020 Jul 16.

State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an 710032, China. Electronic address:

Purpose: The GX1 peptide (CGNSNPKSC) can specifically bind to TGM2 and possesses the ability to target the blood vessels of gastric cancer. This study intends to develop an integrated dual-functional probe with higher affinity, specificity and targeting and to characterize it in vivo and in vitro.

Methods: The dimer and tetramer of GX1 were prepared using cross-linked PEG and labeled with Tc. The best targeting probe [PEG-(GX1)] was selected by gamma camera imaging in nude mouse models of gastric cancer. Re-PEG-(GX1) was prepared and characterized through cell binding analysis and competitive inhibition experiments, gamma camera imaging, MTT analysis and flow cytometry, BLI, immunohistochemistry, HE staining and biochemical analysis.

Results: PEG-(GX1) bound specifically to Co-HUVEC with higher affinity than GX1. Re-PEG-(GX1) had better ability to target gastric cancer in tumor-bearing nude mice and higher T/H ratios than Re-GX1. Re-PEG-(GX1) inhibited the growth of Co-HUVEC and induced apoptosis, and its effects were more robust than those of Re-GX1. BLI showed that Re-PEG-(GX1) inhibited tumor proliferation in vivo with a stronger effect than Re-GX1. Compared with Re-GX1, Re-PEG-(GX1) suppressed tumor angiogenesis and tumor cell proliferation and induced tumor cell apoptosis in vivo. The Re-PEG-(GX1) group did not cause visible changes in liver and kidney morphology and function in vivo.

Conclusion: The dimer of GX1 was synthesized by using cross-linked PEG, and then Re-PEG-(GX1) was prepared. This radiopharmaceutical played both diagnostic and therapeutic functions, and gamma camera imaging could be utilized to detect the distribution of drugs in vivo during treatment. Through a series of experiments in vitro and in vivo, the feasibility of the drug was confirmed, and these results laid the foundation for the subsequent development and application of GX1.
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http://dx.doi.org/10.1016/j.ejpb.2020.07.015DOI Listing
September 2020

TNF‑α treatment increases DKK1 protein levels in primary osteoblasts via upregulation of DKK1 mRNA levels and downregulation of miR‑335‑5p.

Mol Med Rep 2020 Aug 18;22(2):1017-1025. Epub 2020 May 18.

Department of Endodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250012, P.R. China.

Elucidation of the underlying mechanisms governing osteogenic differentiation is of significant importance to the improvement of therapeutics for bone‑related inflammatory diseases. Tumor necrosis factor‑α (TNF‑α) is regarded as one of the major agents during osteogenic differentiation in an inflammatory environment. miR‑335‑5p post‑transcriptionally downregulates the Dickkopf WNT signaling pathway inhibitor 1 (DKK1) protein level by specifically binding to the DKK1 3'UTR and activating Wnt signaling. The role of miR‑335‑5p in TNF‑α‑induced post‑transcriptional regulation of DKK1 remains to be elucidated. In the present study, the mRNA and protein levels of DKK1 and the level of miR‑335‑5p were determined in MC3T3‑E1 cells and the primary calvarial osteoblasts treated with or without TNF‑α. The role of NF‑κB signaling in TNF‑α‑induced post‑transcriptional regulation of DKK1 was also evaluated. The present study determined that although TNF‑α treatment exhibited cell‑specific effects on DKK1 mRNA expression, the stimulation of TNF‑α time‑ and concentration‑dependently upregulated the protein levels of DKK1. In primary calvarial osteoblasts, the decreased miR‑335‑5p level induced by TNF‑α‑activated NF‑κB signaling served an important role in mediating the post‑transcriptional regulation of DKK1 by TNF‑α treatment. In MC3T3‑E1 cells, the post‑transcriptional regulation of DKK1 by TNF‑α treatment was more complicated and involved other molecular signaling pathways in addition to the NF‑κB signaling. In conclusion, TNF‑α treatment served an important role in the post‑transcriptional regulation of DKK1 expression, which requires further investigation. The results of the present study not only provided new insights into the regulatory effects of miR‑335‑5p on osteogenic differentiation in an inflammatory microenvironment, but may also promote the development of potential therapeutic strategies for the treatment of bone‑related inflammatory diseases.
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http://dx.doi.org/10.3892/mmr.2020.11152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339467PMC
August 2020

Distal radial artery access in the anatomical snuffbox for coronary angiography and intervention: A single center experience.

Medicine (Baltimore) 2020 Jan;99(3):e18330

Department of Cardiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University.

Background: To explore the feasibility and safety of coronary angiography (CAG) and percutaneous coronary intervention (PCI) via the distal radial artery in the anatomical snuffbox.

Methods: Ninety two patients who underwent CAG or PCI through distal radial artery access at The Second Affiliated Hospital of Zhejiang Chinese Medical University from September 2017 to March 2018 were included in our study. We collected baseline characteristics, number, and duration of arterial punctures, procedural success rate, postoperative compression time, the numerical rating scale (NRS) scores at 3 hours after procedure, complications, hospitalization duration.

Results: The mean age was 69 ± 11years (44-92 years), and there were 57 males (62.0%). The diameter of the right distal radial artery and the more proximal right radial artery were 0.171 ± 0.05 cm, 0.213 ± 0.06 cm, respectively. On average, the number of puncture attempts was 1.52 ± 0.81, access time was 2.3 ± 1.78 minutes (0.33 - 8.72 minutes), access success was 95.7%, the postoperative compression time was 3.41 ± 0.76 hours (2-6 hours), the NRS scores at 3 hours was 1.53 ± 0.72 (1-4), and the mean hospitalization duration was 7.13 ± 4.02 days. Four patients underwent left distal radial artery access and 88 patients underwent right distal radial artery access. There were 3 local hematomas after procedure and 2 patients had vasospasm. There were no cases of major bleeding, arteriovenous fistula, radial artery occlusion, or hand numbness.

Conclusion: Cardiac catheterization through the distal radial artery in the snuffbox is safe and feasible. The right distal radial artery access can be routinely carried out.
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http://dx.doi.org/10.1097/MD.0000000000018330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220134PMC
January 2020

Fused Pyrazine- and Carbazole-Containing Azaacenes: Synthesis and Properties.

Chempluschem 2019 Sep 23;84(9):1257-1262. Epub 2019 Jul 23.

Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou, 510275, P. R. China.

A new family of azaacenes has been designed and synthesized by incorporating the electron-withdrawing sp -hybridized nitrogen of pyrazine and electron-donating nitrogen of carbazole in a molecular skeleton. Two different conjugated lengths of 8-ring aza-nonacene and 10-ring aza-undecene have been achieved by an efficient condensation reaction. The unique optoelectronic properties of these molecules were investigated using both experimental and theoretical techniques. The azaacenes show visible-region absorption and near-infrared (NIR) fluorescence. These compounds can serve as hole-transport semiconductors for solution-processed organic field-effect transistors (OFETs). Single-crystal transistor devices of one of the aza-nonacenes exhibit hole charge transport behavior with a hole mobility of 0.07 cm /Vs and an on/off current ratio of 1.3x10 .
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http://dx.doi.org/10.1002/cplu.201900383DOI Listing
September 2019

Early TIPS with covered stents versus standard treatment for acute variceal bleeding in patients with advanced cirrhosis: a randomised controlled trial.

Lancet Gastroenterol Hepatol 2019 08 29;4(8):587-598. Epub 2019 May 29.

State Key Laboratory of Cancer Biology, National Clinical Research Centre for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.

Background: The survival benefit of early placement of transjugular intrahepatic portosystemic shunts (TIPS) in patients with cirrhosis and acute variceal bleeding is controversial. We aimed to assess whether early TIPS improves survival in patients with advanced cirrhosis and acute variceal bleeding.

Methods: We did an investigator-initiated, open-label, randomised controlled trial at an academic hospital in China. Consecutive patients with advanced cirrhosis (Child-Pugh class B or C) and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy were randomly assigned (2:1) to receive either early TIPS (done within 72 h after initial endoscopy [early TIPS group]) or standard treatment (vasoactive drugs continued to day 5, followed by propranolol plus endoscopic band ligation for the prevention of rebleeding, with TIPS as rescue therapy when needed [control group]). Randomisation was done by web-based randomisation system using a Pocock and Simon's minimisation method with Child-Pugh class (B vs C) and presence or absence of active bleeding as adjustment factors. The primary outcome was transplantation-free survival, analysed in the intention-to-treat population, excluding individuals subsequently found to be ineligible for enrolment. This study is registered with ClinicalTrials.gov, number NCT01370161, and is completed.

Findings: From June 26, 2011, to Sept 30, 2017, 373 patients were screened and 132 patients were randomly assigned to the early TIPS group (n=86) or to the control group (n=46). After exclusion of three individuals subsequently found to be ineligible for enrolment (two patients in the early TIPS group with non-cirrhotic portal hypertension or hepatocellular carcinoma, and one patient in the control group due to non-cirrhotic portal hypertension), 84 patients in the early TIPS group and 45 patients in the control group were included in the intention-to-treat population. 15 (18%) patients in the early TIPS group and 15 (33%) in the control group died; two (2%) patients in the early TIPS group and one (2%) in the control group underwent liver transplantation. Transplantation-free survival was higher in the early TIPS group than in the control group (hazard ratio 0·50, 95% CI 0·25-0·98; p=0·04). Transplantation-free survival at 6 weeks was 99% (95% CI 97-100) in the early TIPS group compared with 84% (75-96; absolute risk difference 15% [95% CI 5-48]; p=0·02) and at 1 year was 86% (79-94) in the early TIPS group versus 73% (62-88) in the control group (absolute risk difference 13% [95% CI 2-28]; p=0·046). There were no significant differences between the two groups in the incidence of hepatic hydrothorax (two [2%] of 84 patients in the early TIPS group vs one [2%] of 45 in the control group; p=0·96), spontaneous bacterial peritonitis (one [1%] vs three [7%]; p=0·12), hepatic encephalopathy (29 [35%] vs 16 [36%]; p=1·00), hepatorenal syndrome (four [5%] vs six [13%]; p=0·10), and hepatocellular carcinoma (four [5%] vs one [2%]; p=0·68). There was no significant difference in the number of patients who experienced other serious adverse events (ten [12%] vs 11 [24%]; p=0·07) or non-serious adverse events (21 [25%] vs 19 [42%]; p=0·05) between groups.

Interpretation: Early TIPS with covered stents improved transplantation-free survival in selected patients with advanced cirrhosis and acute variceal bleeding and should therefore be preferred to the current standard of care.

Funding: National Natural Science Foundation of China, National Key Technology R&D Program, Optimized Overall Project of Shaanxi Province, Boost Program of Xijing Hospital.
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http://dx.doi.org/10.1016/S2468-1253(19)30090-1DOI Listing
August 2019

Ultrasonic/microwave-assisted extraction of polysaccharides from Camptotheca acuminata fruits and its antitumor activity.

Carbohydr Polym 2019 Feb 10;206:557-564. Epub 2018 Nov 10.

Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China. Electronic address:

In the present study, an efficient ultrasonic/microwave-assisted extraction (UMAE) procedure for the polysaccharides from the fruit of Camptotheca acuminata (CAFP) was investigated and optimized. Under the optimum conditions (ratio of liquid to raw material 30 mL/g, microwave irradiation time of 20 min, microwave irradiation power of 570 W and a fixed ultrasonic power of 50 W obtained by the response surface analysis with Box-Behnken design, satisfactory yields of CAFP (6.81 ± 0.04%) were achieved. The development UMAE technique produced higher yields in a shorter time than conventional hot water extraction (HWE): 20 vs. 120 min. In addition, in vivo CAFP at suitable dose is effective on H22 murine hepatoma strains, and CAFP significantly inhibited the proliferation of human oral carcinoma KB, pancreatic carcinoma BXCP-3 and gastric carcinoma SGC-7901 cells in vitro, indicating CAFP might be suitable for nature antitumor therapeutic agent development.
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http://dx.doi.org/10.1016/j.carbpol.2018.11.010DOI Listing
February 2019

Covered TIPS versus endoscopic band ligation plus propranolol for the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis: a randomised controlled trial.

Gut 2018 12 28;67(12):2156-2168. Epub 2017 Sep 28.

Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.

Objective: Limited data are available on the prevention of variceal rebleeding in cirrhotic patients with portal vein thrombosis (PVT). This study aimed to compare transjugular intrahepatic portosystemic shunt (TIPS) with covered stents versus endoscopic band ligation (EBL) plus propranolol for the prevention of variceal rebleeding among patients with cirrhosis and PVT.

Design: Consecutive cirrhotic patients (94% Child-Pugh class A or B) with PVT who had variceal bleeding in the past 6 weeks were randomly assigned to TIPS group (n=24) or EBL plus propranolol group (EBL+drug, n=25), respectively. Primary endpoint was variceal rebleeding. Secondary endpoints included survival, overt hepatic encephalopathy (OHE), portal vein recanalisation and rethrombosis, other complications of portal hypertension and adverse events.

Results: During a median follow-up of 30 months in both groups, variceal rebleeding was significantly less frequent in the TIPS group (15% vs 45% at 1 year and 25% vs 50% at 2 years, respectively; HR=0.28, 95% CI 0.10 to 0.76, p=0.008), with a significantly higher portal vein recanalisation rate (95% vs 70%; p=0.03) and a relatively lower rethrombosis rate (5% vs 33%; p=0.06) compared with the EBL+drug group. There were no statistically significant differences in survival (67% vs 84%; p=0.152), OHE (25% vs 16%; p=0.440), other complications of portal hypertension and adverse events between groups.

Conclusion: Covered TIPS placement in patients with PVT and moderately decompensated cirrhosis was more effective than EBL combined with propranolol for the prevention of rebleeding, with a higher probability of PVT resolution without increasing the risk of OHE and adverse effects, but this benefit did not translate into improved survival.

Trial Registration Number: ClinicalTrials.gov: NCT01326949.
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http://dx.doi.org/10.1136/gutjnl-2017-314634DOI Listing
December 2018

Recent advances in vitamins analysis by capillary electrophoresis.

J Pharm Biomed Anal 2018 Jan 27;147:278-287. Epub 2017 Jul 27.

Pharmaceutical Analysis, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven - University of Leuven, Belgium. Electronic address:

Vitamins are essential molecules required for human metabolism such as energy production, immune system and cell formation. Accurate vitamin analysis is critical for disease diagnosis, nutrients assessment, as well as food and drug production. This review gives an overview of the recent developments in the use of capillary electrophoresis combined with different detection techniques for the analysis of vitamins. The period covers mid-2007 until mid-2017. Different separation modes are discussed for the analysis of water-soluble vitamins and fat-soluble vitamins. On-line sample concentration for sensitive analysis is also described. The applications include the analysis of pharmaceutical, dietary supplement and biological samples.
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http://dx.doi.org/10.1016/j.jpba.2017.07.030DOI Listing
January 2018

Peroral endoscopic myotomy for the treatment of achalasia in a patient with esophageal varices. A case report.

J Gastrointestin Liver Dis 2017 Jun;26(2):189-192

State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Disease and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi' an, China.

Achalasia is very uncommon, and rarely does achalasia co-exist with esophageal varices. We present a 62-year-old woman who was diagnosed with both achalasia and esophageal varices in December 2014 and had a past history of hematemesis. The patient's achalasia symptoms' Eckardt score was 9, and her hepatic function was Child-Pugh grade A6. After comprehensive assessment of the patient's health and discussion of the pros and cons of various therapies for achalasia, the patient underwent a peroral endoscopic myotomy. She was symptom-free after the operation and had no recurrence of achalasia symptoms at 20-month follow-up. No adverse events were reported. Peroral endoscopic myotomy for achalasia with esophageal varices has not been previously reported in the English literature.
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http://dx.doi.org/10.15403/jgld.2014.1121.262.wanDOI Listing
June 2017

Constitutive heterologous overexpression of a TIR-NB-ARC-LRR gene encoding a putative disease resistance protein from wild Chinese Vitis pseudoreticulata in Arabidopsis and tobacco enhances resistance to phytopathogenic fungi and bacteria.

Plant Physiol Biochem 2017 Mar 17;112:346-361. Epub 2017 Jan 17.

State Key Laboratory of Crop Stress Biology in Arid Areas, College of Horticulture, Northwest A&F University, Yangling, Shaanxi 712100, China; Key Laboratory of Horticultural Plant Biology and Germplasm Innovation in Northwest China, Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address:

Plants use resistance (R) proteins to detect pathogen effector proteins and activate their innate immune response against the pathogen. The majority of these proteins contain an NB-ARC (nucleotide-binding adaptor shared by APAF-1, R proteins, and CED-4) domain along with a leucine-rich repeat (LRR), and some also bear a toll interleukin 1 receptor (TIR) domain. In this study, we characterized a gene encoding a TIR-NB-ARC-LRR R protein (VpTNL1) (GenBank accession number KX649890) from wild Chinese grapevine Vitis pseudoreticulata accession "Baihe-35-1", which was identified previously from a transcriptomic analysis of leaves inoculated with powdery mildew (PM; Erysiphe necator (Schw.)). The VpTNL1 transcript was found to be highly induced in V. pseudoreticulata following inoculation with E. necator, as well as treatment with salicylic acid (SA). Sequence analysis demonstrated that the deduced amino acid sequence contained a TIR domain at the N-terminus, along with an NB-ARC and four LRRs domains within the C-terminus. Constitutive expression of VpTNL1 in Arabidopsis thaliana resulted in either a wild-type or dwarf phenotype. Intriguingly, the phenotypically normal transgenic lines displayed enhanced resistance to Arabidopsis PM, Golovinomyces cichoracearum, as well as to the virulent bacterial pathogen Pseudomonas syringae pv. tomato DC3000. Similarly, constitutive expression of VpTNL1 in Nicotiana tabacum was found to confer enhanced resistance to tobacco PM, Erysiphe cichoacearum DC. Subsequent isolation of the VpTNL1 promoter and deletion analysis indicated that TC-rich repeats and TCA elements likely play an important role in its response to E. necator and SA treatment, respectively. Taken together, these results indicate that VpTNL1 contributes to PM resistance in grapevine and provide an interesting gene target for the future amelioration of grape via breeding and/or biotechnology.
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http://dx.doi.org/10.1016/j.plaphy.2017.01.017DOI Listing
March 2017

A parameterized logarithmic image processing method with Laplacian of Gaussian filtering for lung nodule enhancement in chest radiographs.

Med Biol Eng Comput 2016 Nov 25;54(11):1793-1806. Epub 2016 Mar 25.

School of Optical Electrical and Computer Engineering, University of Shanghai for Science and Technology, Shanghai, China.

The enhancement of lung nodules in chest radiographs (CXRs) plays an important role in the manual as well as computer-aided detection (CADe) lung cancer. In this paper, we proposed a parameterized logarithmic image processing (PLIP) method combined with the Laplacian of a Gaussian (LoG) filter to enhance lung nodules in CXRs. We first applied several LoG filters with varying parameters to an original CXR to enhance the nodule-like structures as well as the edges in the image. We then applied the PLIP model, which can enhance lung nodule images with high contrast and was beneficial in extracting effective features for nodule detection in the CADe scheme. Our method combined the advantages of both the PLIP algorithm and the LoG algorithm, which can enhance lung nodules in chest radiographs with high contrast. To test our nodule enhancement method, we tested a CADe scheme, with a relatively high performance in nodule detection, using a publically available database containing 140 nodules in 140 CXRs enhanced through our nodule enhancement method. The CADe scheme attained a sensitivity of 81 and 70 % with an average of 5.0 frame rate (FP) and 2.0 FP, respectively, in a leave-one-out cross-validation test. By contrast, the CADe scheme based on the original image recorded a sensitivity of 77 and 63 % at 5.0 FP and 2.0 FP, respectively. We introduced the measurement of enhancement by entropy evaluation to objectively assess our method. Experimental results show that the proposed method obtains an effective enhancement of lung nodules in CXRs for both radiologists and CADe schemes.
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http://dx.doi.org/10.1007/s11517-016-1469-xDOI Listing
November 2016

Overexpression of MsDREB6.2 results in cytokinin-deficient developmental phenotypes and enhances drought tolerance in transgenic apple plants.

Plant J 2017 02 1;89(3):510-526. Epub 2017 Feb 1.

Department of Pomology, College of Horticulture, China Agricultural University, Beijing, 100193, China.

Dehydration-responsive element binding factors (DREBs) play important roles in plant growth, development, and stress signaling pathways in model plants. However, little is known about the function of DREBs in apple (Malus × domestica), a widely cultivated crop that is frequently threatened by drought. We isolated a DREB gene from Malus sieversii (Ledeb.) Roem., MsDREB6.2, and investigated its functions using overexpression analysis and chimeric repressor gene-silencing technology (CRES-T). We identified possible target genes of the protein encoded by MsDREB6.2 using electrophoretic mobility shift assays (EMSAs) and chromatin immunoprecipitation (ChIP). Overexpression of MsDREB6.2 increased the expression of a key cytokinin (CK) catabolism gene, MdCKX4a, which led to a significant reduction in endogenous CK levels, and caused a decrease in shoot:root ratio in transgenic apple plants. Overexpression of MsDREB6.2 resulted in a decrease in stomatal aperture and density and an increase in root hydraulic conductance (L ), and thereby enhanced drought tolerance in transgenic plants. Furthermore, manipulating the level of MsDREB6.2 expression altered the expression of two aquaporin (AQP) genes. The effect of the two AQP genes on L was further characterized using the AQP inhibitor HgCl . Based on these observations, we conclude that MsDREB6.2 enhances drought tolerance and that its function may be due, at least in part, to its influence on stomatal opening, root growth, and AQP expression. These results may have applications in apple rootstock breeding programs aimed at developing drought-resistant apple varieties.
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http://dx.doi.org/10.1111/tpj.13401DOI Listing
February 2017

Endotracheal tubes positioning detection in adult portable chest radiography for intensive care unit.

Int J Comput Assist Radiol Surg 2016 Nov 14;11(11):2049-2057. Epub 2016 Jun 14.

School of Optical Electrical and Computer Engineering & Engineering Research, Center of Optical Instrument and System, Ministry of Education, University of Shanghai for Science and Technology, Shanghai, China.

Purpose: To present an automated method for detecting endotracheal (ET) tubes and marking their tips in portable chest radiography (CXR) for intensive care units (ICUs).

Methods: In this method, the lung region is first estimated and then the spine is detected between the right lung and the left lung. Because medical tubes are inserted into the body through the throat, the region of interest (ROI) is obtained across the spine. A seed point is determined in the cervical region of the ROI, and then the line path is selected from the seed point. In order to detect ET tubes, the ICU CXR image is preprocessed by contrast-limited adaptive histogram equalization. Then, a feature-based threshold method is applied to the line path to determine the tip location. A comparison to the method by use of Hough transform is also presented. The distance (error) between the detected locations and the locations annotated by a radiologist is used to evaluate the detection precision for the tip location.

Results: The proposed method is evaluated using 44 images with ET tubes and 43 images without ET tubes. The discriminant performance for detecting the existence of ET tubes in this study was 95 %, and the average of detection error for the tip location was approximately 2.5 mm.

Conclusions: The proposed method could be useful for detecting malpositioned ET tubes in ICU CXRs.
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http://dx.doi.org/10.1007/s11548-016-1430-3DOI Listing
November 2016

Improving Separability of Structures with Similar Attributes in 2D Transfer Function Design.

IEEE Trans Vis Comput Graph 2017 05 2;23(5):1546-1560. Epub 2016 Mar 2.

The 2D transfer function based on scalar value and gradient magnitude (SG-TF) is popularly used in volume rendering. However, it is plagued by the boundary-overlapping problem: different structures with similar attributes have the same region in SG-TF space, and their boundaries are usually connected. The SG-TF thus often fails in separating these structures (or their boundaries) and has limited ability to classify different objects in real-world 3D images. To overcome such a difficulty, we propose a novel method for boundary separation by integrating spatial connectivity computation of the boundaries and set operations on boundary voxels into the SG-TF. Specifically, spatial positions of boundaries and their regions in the SG-TF space are computed, from which boundaries can be well separated and volume rendered in different colors. In the method, the boundaries are divided into three classes and different boundary-separation techniques are applied to them, respectively. The complex task of separating various boundaries in 3D images is then simplified by breaking it into several small separation problems. The method shows good object classification ability in real-world 3D images while avoiding the complexity of high-dimensional transfer functions. Its effectiveness and validation is demonstrated by many experimental results to visualize boundaries of different structures in complex real-world 3D images.
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http://dx.doi.org/10.1109/TVCG.2016.2537341DOI Listing
May 2017

Enhancement of chest radiographs obtained in the intensive care unit through bone suppression and consistent processing.

Phys Med Biol 2016 Mar 1;61(6):2283-301. Epub 2016 Mar 1.

School of Optical-Electrical and Computer Engineering & Engineering Research Center of Optical Instrument and System, Ministry of Education, University of Shanghai for Science and Technology, Shanghai, People's Republic of China.

Portable chest radiographs (CXRs) are commonly used in the intensive care unit (ICU) to detect subtle pathological changes. However, exposure settings or patient and apparatus positioning deteriorate image quality in the ICU. Chest x-rays of patients in the ICU are often hazy and show low contrast and increased noise. To aid clinicians in detecting subtle pathological changes, we proposed a consistent processing and bone structure suppression method to decrease variations in image appearance and improve the diagnostic quality of images. We applied a region of interest-based look-up table to process original ICU CXRs such that they appeared consistent with each other and the standard CXRs. Then, an artificial neural network was trained by standard CXRs and the corresponding dual-energy bone images for the generation of a bone image. Once the neural network was trained, the real dual-energy image was no longer necessary, and the trained neural network was applied to the consistent processed ICU CXR to output the bone image. Finally, a gray level-based morphological method was applied to enhance the bone image by smoothing other structures on this image. This enhanced image was subtracted from the consistent, processed ICU CXR to produce a soft tissue image. This method was tested for 20 patients with a total of 87 CXRs. The findings indicated that our method suppressed bone structures on ICU CXRs and standard CXRs, simultaneously maintaining subtle pathological changes.
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http://dx.doi.org/10.1088/0031-9155/61/6/2283DOI Listing
March 2016

Ectopic Expression in Arabidopsis thaliana of an NB-ARC Encoding Putative Disease Resistance Gene from Wild Chinese Vitis pseudoreticulata Enhances Resistance to Phytopathogenic Fungi and Bacteria.

Front Plant Sci 2015 10;6:1087. Epub 2015 Dec 10.

State Key Laboratory of Crop Stress Biology in Arid Areas, College of Horticulture, Northwest A&F University Yangling, China ; Key Laboratory of Horticultural Plant Biology and Germplasm Innovation in Northwest China, Ministry of Agriculture, Northwest A&F University Yangling, China.

Plant resistance proteins mediate pathogen recognition and activate innate immune responses to restrict pathogen proliferation. One common feature of these proteins is an NB-ARC domain. In this study, we characterized a gene encoding a protein with an NB-ARC domain from wild Chinese grapevine Vitis pseudoreticulata accession "Baihe-35-1," which was identified in a transcriptome analysis of the leaves following inoculation with Erysiphe necator (Schw.), a causal agent of powdery mildew. Transcript levels of this gene, designated VpCN (GenBank accession number KT265084), increased strongly after challenge of grapevine leaves with E. necator. The deduced amino acid sequence was predicted to contain an NB-ARC domain in the C-terminus and an RxCC-like domain similar to CC domain of Rx protein in the N-terminus. Ectopic expression of VpCN in Arabidopsis thaliana resulted in either a wild-type phenotype or a dwarf phenotype. The phenotypically normal transgenic A. thaliana showed enhance resistance to A. thaliana powdery mildew Golovinomyces cichoracearum, as well as to a virulent bacterial pathogen Pseudomonas syringae pv. tomato DC3000. Moreover, promoter::GUS (β-glucuronidase) analysis revealed that powdery mildew infection induced the promoter activity of VpCN in grapevine leaves. Finally, a promoter deletion analysis showed that TC rich repeat elements likely play an important role in the response to E. necator infection. Taken together, our results suggest that VpCN contribute to powdery mildew disease resistant in grapevine.
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http://dx.doi.org/10.3389/fpls.2015.01087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674559PMC
December 2015

Quantitative Assessment of Mitral Apparatus Geometry Using Dual-Source Computed Tomography in Mitral Regurgitation.

Int Heart J 2015 24;56(4):408-14. Epub 2015 Jun 24.

Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University.

To quantitatively assess the geometric changes in mitral valve apparatus in mitral regurgitation (MR) by dualsource computed tomography (DSCT) and to analyze its impact on MR.The study subjects consisted of 20 controls, 20 patients with mild MR, and 30 patients with moderate to severe MR, all of whom underwent DSCT. The geometric parameters of the mitral valve were measured by CT and compared among the 3 groups. The correlations between DSCT measurements and MR severity were also analyzed.As regurgitation worsened, our results showed progressive enlargements of the mitral annular area, anteroposterior diameter, and mitral valve tenting area at the central level. Moreover, a higher mitral valve sphericity index and longer distance between the heads of the papillary muscles reflected a more outward displacement of the papillary muscles. The mitral annular area and tenting area at the central level had strong correlations with regurgitation severity.DSCT is available to quantitatively assess mitral valve morphology and provide additional information regarding its geometry. The mitral annular area and tenting area at the central level were the strongest determinants of MR severity.
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http://dx.doi.org/10.1536/ihj.14-337DOI Listing
September 2015

Evaluation of Tc-99 m Labeled Dimeric GX1 Peptides for Imaging of Colorectal Cancer Vasculature.

Mol Imaging Biol 2015 Oct;17(5):661-70

State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.

Purpose: This study aimed to evaluate the potential of PEGylated dimeric GX1 peptide as a radiotracer for imaging of colorectal cancer vasculature in a LoVo tumor xenografted mouse model.

Procedures: The [(99m)Tc]PEG-(GX1)2 peptide was synthesized and identified. Confocal immunofluorescence analysis, receptor binding assay, and competitive inhibition assay were performed to evaluate the binding specificity and the receptor binding affinity of PEG-(GX1)2 to Co-human umbilical vein endothelial cells (HUVECs). Single photon emission computed tomography imaging and biodistribution were performed to evaluate the targeting ability of PEG-(GX1)2 to colorectal cancer.

Results: The studies in vitro suggested that PEG-(GX1)2 co-localized with Factor VIII in the perinuclear cytoplasm of Co-HUVECs and bound specifically to Co-HUVECs with a high affinity. The studies in vivo demonstrated that the targeting efficacy of PEG-(GX1)2 was superior to GX1.

Conclusions: PEGylation improved the affinity and the targeting ability of the GX1 peptide. PEG-(GX1)2 is a more promising probe for imaging of colorectal vasculature than GX1.
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http://dx.doi.org/10.1007/s11307-015-0838-4DOI Listing
October 2015

Evaluation of 68Ga-labeled MG7 antibody: a targeted probe for PET/CT imaging of gastric cancer.

Sci Rep 2015 Mar 3;5:8626. Epub 2015 Mar 3.

State Key Laboratory of Cancer Biology &Institute of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.

MG7-Ag, a specific gastric cancer-associated antigen, can be used to non-invasively monitor gastric cancer by molecular imaging with positron emission tomography/computed tomography (PET/CT). In this study, we prepared and evaluated a (68)Ga-labeled MG7 antibody as a molecular probe for nanoPET/CT imaging of gastric cancer in a BGC-823 tumor xenografted mouse model. Macrocyclic chelator 1,4,7-triazacyclononane-N,N0,N00-triacetic acid (NOTA)-conjugated MG7 antibody was synthesized and radiolabeled with (68)Ga (t1/2 = 67.71 min). Then, (68)Ga-NOTA-MG7 was tested using in vitro cytological studies, in vivo nanoPET/CT and Cerenkov imaging studies as well as ex vivo biodistribution and histology studies. The in vitro experiments demonstrated that (68)Ga-NOTA-MG7 has an excellent radiolabeling efficiency of approximately 99% without purification, and it is stable in serum after 120 min of incubation. Cell uptake and retention studies confirmed that (68)Ga-NOTA-MG7 has good binding affinity and tumor cell retention. For the nanoPET imaging study, the predominant uptake of (68)Ga-NOTA-MG7 was visualized in tumor, liver and kidneys. The tumor uptake reached at its peak (2.53 ± 0.28%ID/g) at 60 min pi. Cherenkov imaging also confirmed the specificity of tumor uptake. Moreover, the biodistribution results were consistent with the quantification data of nanoPET/CT imaging. Histologic analysis also demonstrated specific staining of BGC-823 tumor cell lines.
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http://dx.doi.org/10.1038/srep08626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346831PMC
March 2015

Optimized extraction of polysaccharides from Taxus chinensis var. mairei fruits and its antitumor activity.

Int J Biol Macromol 2015 Apr 31;75:192-8. Epub 2015 Jan 31.

Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China.

The simultaneous ultrasonic/microwave-assisted extraction (UMAE) method is potentially useful for the extraction of polysaccharides from Taxus chinensis var. mairei fruits (TCFPs). In this study, we used a response surface methodology to identify optimal TCFPs extraction conditions. Optimal parameters were determined as follows: a liquid to raw material ratio of 33 mL/g, an extraction time of 10 min, a microwave power level of 560 W, and a fixed ultrasonic power of 50 W. Under the optimized conditions, TCFPs yields obtained by UMAE were 4.33 ± 0.15%, a 1.79-fold increase compared with conventional heating reflux extraction (HRE). In addition, the extraction time used in UMAE was shorter than that required for HRE: 10 versus 90 min. UMAE is therefore a rapid and efficient method for the extraction of TCFPs. The inhibitory effect of TCFPs on S180 tumor growth in vivo was also studied. The tumor inhibition rate of TCFPs was 76.33%, indicating a tumor-inhibiting effect. Analysis of organ weights demonstrated that TCFPs exhibited no toxicity to liver, kidney, spleen, heart, or lung relative to a positive control group. TCFPs thus show antitumor activity with no organ toxicity.
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http://dx.doi.org/10.1016/j.ijbiomac.2015.01.043DOI Listing
April 2015

Feasibility study of novel endoscopic Cerenkov luminescence imaging system in detecting and quantifying gastrointestinal disease: first human results.

Eur Radiol 2015 Jun 11;25(6):1814-22. Epub 2015 Jan 11.

State Key Laboratory of Cancer Biology, Department of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.

Objectives: Cerenkov luminescence imaging (CLI) provides potential to use clinical radiotracers for optical imaging. The goal of this study was to present a newly developed endoscopic CLI (ECLI) system and illustrate its feasibility and potential in distinguishing and quantifying cancerous lesions of the GI tract.

Methods: The ECLI system was established by integrating an electron-multiplying charge-coupled device camera with a flexible fibre endoscope. Phantom experiments and animal studies were conducted to test and illustrate the system in detecting and quantifying the presence of radionuclide in vitro and in vivo. A pilot clinical study was performed to evaluate our system in clinical settings.

Results: Phantom and mice experiments demonstrated its ability to acquire both the luminescent and photographic images with high accuracy. Linear quantitative relationships were also obtained when comparing the ECLI radiance with the radiotracer activity (r (2) = 0.9779) and traditional CLI values (r (2) = 0.9025). Imaging of patients revealed the potential of ECLI in the identification and quantification of cancerous tissue from normal, which showed good consistence with the clinical PET examination.

Conclusions: The new ECLI system shows good consistence with the clinical PET examination and has great potential for clinical translation and in aiding detection of the GI tract disease.

Key Points: • CLI preserves the characteristics of both optical and radionuclide imaging. • CLI provides great potential for clinical translation of optical imaging. • The newly developed endoscopic CLI (ECLI) has quantification and imaging capacities. • GI tract has accessible open surfaces, making ECLI a potentially suitable technique. • Cerenkov endoscopy has great clinical potential in detecting GI disease.
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http://dx.doi.org/10.1007/s00330-014-3574-2DOI Listing
June 2015

A new scoring system for spontaneous closure prediction of perimembranous ventricular septal defects in children.

PLoS One 2014 5;9(12):e113822. Epub 2014 Dec 5.

Department of Pediatric Cardiology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.

Background: Perimembranous ventricular septal defect (PMVSD) is a congenital heart aberration, which is surgically treated by patch or device closure, but also can heal without operation as spontaneous closure (SC).

Methods: We analyzed data from 1873 PMVSD patients admitted to our hospital during September 2001 and December 2009, in order to establish a Cox regression model for PMVSD SC probability prediction (derivative cohort). Initial contact age, ventricular septal defect (VSD) diameter, shunt flow, aneurysmal tissue of the ventricular membranous septum (ATVMS) development, associated complications, and left ventricular end-diastolic dimension (LVDD) were analyzed for correlations with SC. The derived scoring system based on the coefficients of the model was developed and applied to another cohort with 382 PMVSD patients to evaluate the validity for SC probability forecast (validation cohort).

Results: Multivariate Cox regression analysis revealed that SC of PMVSD was associated with age at first contact, defect size, diffuse shunt flow, ATVMS formation, associated complication, as well as increased LVDD, which were used to establish a new scoring system. The area under the receiver operating characteristic (ROC) curve of our predictive scaling was 0.831 (95% CI 0.804-0.858, p<0.001) in the derivative cohort. The scoring system also accurately predicted SC with an area under the ROC curve of 0.863 (95% CI 0.785-0.941, p<0.001) in the validation cohort.

Conclusion: Our scoring system using factors affecting SC can predict the probability of SC in PMVSD patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0113822PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257539PMC
July 2015

The biological characteristics of a novel camptothecin-artesunate conjugate.

Bioorg Med Chem Lett 2015 Jan 22;25(1):148-52. Epub 2014 Oct 22.

Key Laboratory of Forest Plant Ecology (Northeast Forestry University), Ministry of Education, 332 No. 26 Hexing Road, Harbin City, Heilongjiang Province 150040, China.

A novel conjugate of camptothecin and artesunate (C-Q) was prepared and its cytotoxicity was evaluated using the MTT assay. In addition, the antitumour activity and toxicity of C-Q were investigated in mice, and interaction between transferrin (TF) and C-Q was investigated to evaluate its interaction with biological macromolecules. In the MTT assay, C-Q showed better inhibitory activity against MCF7 breast cancer cells and SMMC-7721 liver cancer cells than camptothecin or artesunate. In vivo, C-Q showed lower toxicity and better antitumour activity compared with camptothecin. Fluorescence spectroscopy showed static quenching of TF in the presence of C-Q, and thermodynamic parameters (ΔH>0 and ΔG<0) indicated that the reaction was spontaneous and endothermic. The main binding force between C-Q and TF was hydrophobic, as indicated by thermodynamic parameters (ΔH>0 and ΔS>0). Thus, synchronous fluorescence spectra showed that C-Q had no influence on the conformation of TF. Our results indicated that C-Q represents a novel potential anticancer therapeutic vector with advantages over current methods of CPT and ART administration. This novel drug delivery system allows the use of these drugs in a manner associated with few side effects for normal tissue, and which facilitates synergistic effects of anti-tumour drugs.
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http://dx.doi.org/10.1016/j.bmcl.2014.10.048DOI Listing
January 2015

Gastric cancer cell adhesion to laminin enhances acquired chemotherapeutic drug resistance mediated by MGr1-Ag/37LRP.

Oncol Rep 2014 Jul 15;32(1):105-14. Epub 2014 May 15.

State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an 710032, P.R. China.

Adhesion of cancer cells to the extracellular matrix (ECM) causes a novel acquired chemotherapeutic drug‑resistant phenotype, referred to as cell adhesion-mediated drug resistance (CAM-DR). Our previous studies suggested that the adhesion molecule MGr1-Ag/37LRP may promote multidrug resistance in gastric cancer cells. Therefore, we investigated MGr1-Ag/37LRP binding-induced adhesion, and its role in CAM-DR. Initial studies revealed that, after adhesion to the ECM, the multidrug-resistant gastric cancer cell lines SGC7901/VCR and SGC7901/ADR showed significantly higher mean adhesive cell numbers than non‑resistant SGC7901 cells. We then investigated expression of MGr1-Ag/37LRP in gastric cancer cells adhering to laminin. Western blotting, RT-PCR and dual-luciferase reporter assays showed that laminin induced MGr1-Ag/37LRP expression and activity. In vitro and in vivo assays revealed that small interfering RNA against MGr1-Ag/37LRP significantly reduced CAM-DR in SGC7901/VCR cells. In vivo and in vitro analyses revealed that binding of MGr1-Ag/37LRP decreased intracellular drug accumulation by increasing P-glycoprotein and multidrug-associated protein expression, and inhibited drug-induced apoptosis by regulating Bcl-2 and Bax expression. These results indicate that MGr1-Ag/37LRP contributes to laminin-mediated CAM-DR in gastric cancer cells, and is a potentially effective target for reversing this phenomenon in gastric cancer.
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http://dx.doi.org/10.3892/or.2014.3184DOI Listing
July 2014
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