Publications by authors named "Juanjuan Yan"

35 Publications

Establishment of a homogeneous immunoassay-light-initiated chemiluminescence assay for detecting anti-Müllerian hormone in human serum.

J Immunol Methods 2021 Jul 22;494:113059. Epub 2021 Apr 22.

School of Medical Laboratory, Tianjin Medical University, Tianjin 300203, China. Electronic address:

Anti-Müllerian hormone (AMH) is known as a reliable marker of ovarian reserve (OR). The determination of AMH is of great importance and most existed AMH detection methods are heterogeneous immunoassay. In this study, a novel homogeneous sandwich immunoassay-light-initiated chemiluminescence assay (LICA) for detecting AMH serum level was developed. This AMH-LICA was performed by incubating serum samples with AMH mouse monoclonal antibody coated with chemibeads, streptavidin-coated sensibeads, and biotinylated AMH mouse monoclonal antibody. Sensitivity, precision, accuracy and cross-reactivity of this assay were evaluated. Besides, a regression analysis showed a high correlation between AMH-LICA and Roche Elecsys® AMH assay (y = 0.9851x + 0.07147, R = 0.9569). As a homogeneous immunoassay, this AMH-LICA could accurately and rapidly determine the serum level of AMH with high-throughput. Thus, this new developed assay may be a new useful analytical tool for the determination of AMH.
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http://dx.doi.org/10.1016/j.jim.2021.113059DOI Listing
July 2021

The clinical course of critically ill COVID-19 patients receiving invasive mechanical ventilation with subsequent terminal weaning: Primary data from 11 cases.

Medicine (Baltimore) 2021 Apr;100(16):e25619

Department of Critical Care Medicine.

Abstract: The coronavirus disease (COVID-19) outbreak was first reported in December 2019 in Wuhan, China. Specific information about critically ill COVID-19 patients receiving invasive mechanical ventilation (IMV) is rare.To describe the clinical course and complications of critically ill patients with COVID-19 who received IMV and were successfully weaned from it.This retrospective study included patients admitted to 3 intensive care units (ICUs) and 1 sub-ICU of Renmin Hospital of Wuhan University and Wuhan Jin Yin-tan Hospital between December 24, 2019, and March 12, 2020. Eleven patients who had been diagnosed with critically ill COVID-19 according to the World Health Organization interim guidance, received invasive ventilation, and were finally successfully weaned from it, were enrolled in our study. Their presenting symptoms, comorbidity conditions, laboratory values, ICU course, ventilator parameters, treatments, and relative complications were recorded.Of 108 critically ill COVID-19 patients who received invasive ventilation, 11 patients who underwent tracheal extubation or terminal weaning were included. The mean age of the 11 patients was 52.8 years (range, 38-70 years), 8 (72.7%) were male, and 2 were health care workers. The median time from onset of symptoms to dyspnea was 6.6 days (range, 3-13 days), and the median duration of IMV was 15.7 days (range, 6-29 days). All 11 patients presented with acute severe hypoxemic respiratory failure and received IMV, and 1 patient switched to extracorporeal membrane oxygenation assistance. A lung-protective strategy with lower tidal volume ventilation and proper driving pressure is the main strategy of IMV. All patients had extrapulmonary manifestations, including acute kidney injury, hepatic dysfunction, myocardial damage, and/or lymphopenia. Hospital-acquired infections occurred in 7 (63.6%) patients.Critical COVID-19 illness is characterized by acute hypoxemic respiratory failure and subsequent dysfunction of other organs with a high mortality rate. Correct ventilation strategies and other clinical strategies to improve oxygenation based on the skilled trained group and the availability of equipment are the key methods to rescue lives.
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http://dx.doi.org/10.1097/MD.0000000000025619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078419PMC
April 2021

Recent advances in chemistry and bioactivity of Sargentodoxa cuneata.

J Ethnopharmacol 2021 Apr 15;270:113840. Epub 2021 Jan 15.

Department of Emergency, LongHua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address:

Ethnopharmacological Relevance: The genus Sargentodoxa comprises only one species, Sargentodoxa cuneata (Oliv.) Rehd et al., widely distributed in the subtropical zone of China. The plant is extensively used in traditional medicine for treating arthritis, joint pains, amenorrhea, acute appendicitis and inflammatory intestinal obstruction. Pharmacological studies show anti-inflammatory, antioxidant, antitumor, antimicrobial, and anti-sepsis activities.

Aim Of The Review: This review aims to summarize the information about distribution, traditional uses, chemical constituents and pharmacological activities of S. cuneata, as an attempt to provide a scientific basis for its traditional uses and to support its application and development for new drug development.

Methodology: Scientific information of S. cuneata was retrieved from the online bibliographic databases, including Web of Science, Google Scholar, PubMed, Springer Link, the Wiley online library, SciFinder, Baidu Scholar, China national knowledge infrastructure (CNKI) and WANFANG DATA (up to March 2020). We also search doctoral dissertations, master dissertations conference papers and published books. The keywords were used: "Sargentodoxa", "Da Xue Teng", "Hong Teng", "Xue Teng", "secondary metabolites", "chemical components", "biological activity", "pharmacology", "traditional uses".

Observations And Results: S. cuneata is utilized as valuable herbal medicines to treat various diseases in China. Over 110 chemical constituents have been isolated and identified from the stem of S. cuneata, including phenolic acids, phenolic glycosides, lignans, flavones, triterpenoids and other compounds. The extract and compounds of S. cuneata have a wide spectrum of pharmacological activities, including antitumor, anti-inflammatory, antioxidant, antimicrobial, anti-sepsis and anti-arthritis effects, as well as protective activity against cerebrovascular diseases.

Conclusion: S. cuneata has a rich legacy for the treatment of many diseases, especially arthritis and sepsis, which is reinforced by current investigations. However, the present studies about bioactive chemical constituents and detail pharmacological mechanisms of S. cuneata were insufficient. Further studies should focus on these aspects in relation to its clinical applications. This review has systematically summarized the traditional uses, phytochemical constituents and pharmacological effects of S. cuneata, providing references for the therapeutic potential of new drug development.
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http://dx.doi.org/10.1016/j.jep.2021.113840DOI Listing
April 2021

Lipid peroxidation of kidney of the turtle Mauremys reevesii caused by cadmium.

Environ Sci Pollut Res Int 2021 Feb 3;28(6):6811-6817. Epub 2020 Oct 3.

Shanxi Key Laboratory of Chinese Medicine Encephalopathy, Shanxi University of Chinese Medicine, Taiyuan, Shanxi Province, China.

This research was designed to investigate lipid peroxidation of the kidney of turtle (Mauremys reevesii) caused by cadmium. Turtles were injected intraperitoneally with cadmium at the concentration of 0 (control), 7.5, 15, and 30 mg/kg, and 5 turtles were taken from each group after exposure for 1 week (1 w), 2 weeks (2 w), and 3 weeks (3 w). Superoxide dismutase (SOD) and catalase (CAT) activities as well as glutathione (GSH) and malonyldialdehyde (MDA) contents in the homogenate of kidney tissue were analyzed. The results demonstrated that a short time of low dose of cadmium could stimulate the increase of SOD activity in the kidney of turtles, but a long time of high dose of cadmium could induce the decrease of SOD activity in the kidney of turtles. Cadmium could decrease CAT activity and GSH content in turtle kidney, but increased MDA content in turtle kidney. There were some other effects on the turtles, such as depression and diarrhea. The experimental results indicate that cadmium causes temporary oxidative stress on the kidney of turtles.
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http://dx.doi.org/10.1007/s11356-020-11054-xDOI Listing
February 2021

Oxidative stress in liver of turtle Mauremys reevesii caused by cadmium.

Environ Sci Pollut Res Int 2021 Feb 29;28(6):6405-6410. Epub 2020 Sep 29.

Bureau of agriculture and rural affairs of Qianan, Tangshan, Hebei Province, China.

The research was designed to examine oxidative stress of the liver of turtle Mauremys reevesii caused by cadmium (Cd). Turtles were injected intraperitoneally with cadmium at the concentration of 7.5, 15, and 30 mg/kg, and 5 turtles were taken from each group after exposure for 1 week (1 w), 2 weeks (2 w), and 3 weeks (3 w). The activities of SOD and CAT as well as the contents of GSH and MDA in liver tissues were detected by using a kit. The results showed that the difference between the control group and the Cd-treated group was statistically significant with the increase of Cd concentration and the prolongation of exposure time, which suggested that Cd caused oxidative stress on the liver of turtles.
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http://dx.doi.org/10.1007/s11356-020-11017-2DOI Listing
February 2021

Effects of cadmium on the activities of ALT and AST as well as the content of TP in plasma of freshwater turtle Mauremys reevesii.

Environ Sci Pollut Res Int 2020 May 13;27(15):18025-18028. Epub 2020 Mar 13.

Bureau of Agriculture and Rural Affairs of Qianan, Tangshan, Hebei Province, China.

Cadmium (Cd) is one of the toxic metals in the aquatic environment. This study was designed to examine the effects of Cd on the activities of ALT and AST and the concentrations of TP in plasma of freshwater turtle Mauremys reevesii. Experiment turtles were exposed to Cd at the concentration of 15 mg/kg by intraperitoneal injection. The activities of ALT and AST and the concentrations of TP were investigated. Compared with the controls, the activities of ALT and AST in plasma of the treated turtles significantly increased. The concentrations of TP were comparable between the treated turtles and the controls except that were higher than the control turtles in 14 days (14 d) and 56 days (56 d). As a result that turtles exposed to Cd were led to liver function damage.
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http://dx.doi.org/10.1007/s11356-020-08338-7DOI Listing
May 2020

Effects of cadmium on the gene transcription of the liver in the freshwater turtle (Chinemys reevesii).

Environ Sci Pollut Res Int 2020 Mar 4;27(8):8431-8438. Epub 2020 Jan 4.

Qianan Agriculture Animal Husbandry and Fishery Bureau, Tangshan, Hebei Province, China.

This study investigated the related gene transcription of liver in freshwater turtle Chinemys reevesii exposed to cadmium (Cd). After acclimation, healthy turtles were selected for experiments. They were randomly divided into four experimental groups and each group had 5 animals. The turtles were treated with 0 mg/kg, 7.5 mg/kg, 15 mg/kg, and 30 mg/kg Cd chloride separately by intraperitoneal injection. Liver samples were collected for examination of the transcription of related genes at 2 weeks after Cd exposure. The transcription of mRNA of MT, SOD, CAT, PNKP, and GPX4 genes in turtle liver cells were analyzed. Results showed that Cd promoted MT mRNA transcription in turtle's liver at low dose (7.5 mg/kg) and inhibited MT mRNA transcription in turtle's liver at middle dose (15 mg/kg) and high dose (30 mg/kg). Cd inhibited the transcription of SOD, CAT, and PNKP mRNA in turtle's liver, and the inhibition was obvious at high dose (30 mg/kg). Cd promoted GPX4 mRNA transcription in turtle's liver, especially at low dose (7.5 mg/kg). In conclusion, Cd had different effects on the mRNA transcription of liver cells in the freshwater turtle Chinemys reevesii exposed to Cd.
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http://dx.doi.org/10.1007/s11356-019-07432-9DOI Listing
March 2020

Hollow Mesoporous FeO Nanospindles/CNTs Composite: An Efficient Catalyst for High-Performance Li-O Batteries.

Front Chem 2019 25;7:511. Epub 2019 Jul 25.

Jiangsu Key Laboratory of Materials and Technology for Energy Conversion, College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, China.

The design of mesoporous or hollow transition metal oxide/carbon hybrid catalysts is very important for rechargeable Li-O batteries. Here, spindle-like FeO with hollow mesoporous structure on CNTs backbones ([email protected]) are prepared by a facile hydrolysis process combined with low temperature calcination. Within this hybrid structure, the hollow interior and mesoporous shell of the FeO nanospindles provide high specific surface area and abundant catalytical active sites, which is also beneficial to facilitating the electrolyte infiltration and oxygen diffusion. Furthermore, the crisscrossed CNTs form a three-dimensional (3D) conductive network to accelerate and stabilize the electron transport, which leads to the decreasing internal resistance of electrode. As a cathodic catalyst for Li-O batteries, the [email protected] composite exhibits high specific capacity and excellent cycling stability (more than 100 cycles).
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http://dx.doi.org/10.3389/fchem.2019.00511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6672713PMC
July 2019

Biocompatible Iodine-Starch-Alginate Hydrogel for Tumor Photothermal Therapy.

ACS Biomater Sci Eng 2019 Jul 7;5(7):3654-3662. Epub 2019 Jun 7.

School of Medical Imaging, Tianjin Medical University, No. 1, Guangdong Rong, Hexi District, Tianjin 300203, China.

Photothermal therapy (PTT) with the advantages of high efficiency and minimal invasiveness is a promising technique for tumor therapy, but clinical application of PTT agents has been stifled by the great safety concerns. Herein, a deep blue iodine-starch-alginate (ALG) hydrogel is elegantly fabricated based on the classic and simple "iodine-starch test" for in vivo tumor PTT in a facile and mild way. The iodine-starch-ALG hydrogel composed of clinically used agents is fabricated by dispersing blue iodine-starch complex into alginate-Ca hydrogel, which guarantees the good chemical stability of iodine-starch complex via separating them from surrounding reductive environment. The iodine-starch-ALG hydrogel possesses favorable biocompatibility derived from the biosafe and degradable components and possesses good photothermal heating ability based on iodine-starch chromophore. The proposed iodine-starch-ALG hydrogel is successfully applied in tumor PTT in vitro and in vivo for the first time. This work lays down a novel way for the development of high-performance and biocompatible biomaterials via teaching old drugs new tricks.
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http://dx.doi.org/10.1021/acsbiomaterials.9b00280DOI Listing
July 2019

Low phase noise optoelectronic oscillator based on an electroabsorption modulated laser.

Appl Opt 2019 Jun;58(16):4512-4517

An optoelectronic oscillator (OEO) scheme based on an electroabsorption modulated laser (EML) is proposed and experimentally demonstrated. The oscillation conditions and a complete phase noise model for the EML-based OEO are detailed. A 20-GHz microwave signal with a side-mode suppression ratio of 42 dB is generated and evaluated. The corresponding single sideband phase noise with a 1-km and 4-km fiber used in the loop is respectively measured to be -110.2  dBc/Hz and -114.8  dBc/Hz at 10 kHz offset frequency. The experimental phase noise results agree well with the theoretical results in an offset frequency range from 100 Hz to 10 MHz.
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http://dx.doi.org/10.1364/AO.58.004512DOI Listing
June 2019

Development of a light-initiated chemiluminescent assay for the quantitation of sIgE against egg white allergens based on component-resolved diagnosis.

Anal Bioanal Chem 2018 Feb 15;410(5):1501-1510. Epub 2017 Dec 15.

Department of Clinical Laboratory, School of Medical Laboratory, Tianjin Medical University, Tianjin, 300203, China.

The determination of specific IgE (sIgE) level is of great importance in IgE-mediated food allergies. Our aim was to develop a homogeneous immunoassay-light-initiated chemiluminescent assay (LICA)-for measuring allergen sIgE of a single component in egg white, thus evaluating the LICA-sIgE assay as a useful tool in the diagnosis of food allergy. The LICA-sIgE assay was performed by incubating serum sample with anti-human IgE antibody coated with chemiluminescer beads, streptavidin-coated sensitizer beads, and biotinylated antigens, which consist of four components in egg white. Serum samples from egg allergic patients (n = 70) and healthy volunteers (n = 30) were collected. For calibration, purified human IgE was used as the calibrator. Working conditions of this homogeneous immunoassay were optimized, analytical performance was determined, and correlation of the results between LICA and ImmunoCAP was evaluated. The assays were performed in 8-well plates with a sample volume diluted to 1:10 of 25 μl. Intra-assay precision (% coefficient of variation) ranged from 1.83 to 4.13%, and inter-assay precision ranged from 2.70 to 8.70%. It exhibited excellent sensitivity, which could distinguish between positive samples and negative samples even at a large dilution level. The sIgE-LICA and ImmunoCAP correlated well in patients allergic to single component (r  = 0.929). Also, the components ovomucoid and ovalbumin were best at predicting ImmunoCAP results, with the same area under the ROC curve (AUC) of 0.81, and a specificity of 90.0 and 93.3%, respectively. Our data show effective performance characteristics of LICA to detect sIgE in human serum based on component-resolved diagnostic tests (CRD). The homogeneous sIgE-LICA assay has the following key advantages: requires no washing, simplicity and rapidity, reproducibility, high-throughput, good performance in a liquid phase assay, and good suitability for sIgE diagnosis in food allergy based on CRD. Graphical abstract A light-initiated chemiluminescent assay was developed for the quantitation of sIgE against egg white allergens based on component-resolved diagnosis. Components Gal d 1 and Gal d 2 with the highest AUC values of 0.81 were considered the best at predicting egg allergy.
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http://dx.doi.org/10.1007/s00216-017-0791-yDOI Listing
February 2018

Tpeak-Tend dispersion as a predictor for malignant arrhythmia events in patients with vasospastic angina.

Int J Cardiol 2017 Dec;249:61-65

Department of Cardiology, People's Hospital of Zhengzhou University, Institute of Cardiovascular Epidemiology of Henan Province, Zhengzhou, Henan Province, China. Electronic address:

Background: Tpeak-Tend interval (Tp-e interval) in electrocardiogram (ECG) has been reported to predict malignant arrhythmia events (MAE) in ST-segment elevation myocardial infarction and ion channelopathy. Tp-e interval and other ECG parameters as predictors for MAE was evaluated in patients with vasospastic angina (VA).

Methods And Results: Sixty-two patients with VA (Non-MAE group) and 20 patients with VA complicated by MAE (MAE group) were enrolled in our Division of Cardiology between January 2010 and December 2015. Continuous variables were analyzed by t-test and categorical variables by Chi-square analysis. Patients with MAE showed greater QTc (corrected QT interval) dispersion (P=0.005), Tp-ec (corrected Tp-e) interval (P=0.001), Tp-ec dispersion (P<0.001) and Tp-e/QT ratio (P<0.001) than those in non-MAE groups when ST-segment elevated. After elevated ST-segment returned, there were no significant differences in these ECG parameters between two groups (All P>0.05). At univariate binary logistic regression analysis QTc dispersion (odds ratio(OR)=1.133; P=0.013), Tp-ec (OR=1.058; P=0.003), Tp-e/QT (OR=1.403; P=0.001), and Tp-ec dispersion (OR=1.497; P=0.004) were significantly associated with MAE. At multivariable logistic regression analysis, Tp-ec dispersion remained a predictor of MAE. Receiver operating characteristic (ROC) curve analysis showed that only AUC (Area under curve) of Tp-ec dispersion had significant difference with those in QTc dispersion (P<0.001), Tp-ec (P=0.003), and Tp-e/QT ratio (P=0.012), respectively.

Conclusions: QTc dispersion, Tp-ec, Tp-e/QT and Tp-ec dispersion were significantly increased in VA patients with MAE than those without MAE when coronary spasm was onset. Prolonged Tp-ec dispersion was the best discriminators and a strong independent predictor of MAE in VA patients.
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http://dx.doi.org/10.1016/j.ijcard.2017.07.093DOI Listing
December 2017

Cadmium toxicokinetics in the freshwater turtle, Chinemys reevesii.

Chemosphere 2017 Sep 4;182:392-398. Epub 2017 May 4.

School of Life Science, Shanxi University, Taiyuan, Shanxi Province, China. Electronic address:

This study was designed to investigate the toxicokinetics of Cadmium (Cd) in Chinemys reevesii. The animals were exposed to 15 mg/kg Cd chloride by intraperitoneal injection, and the Cd absorption, distribution, and excretion in different organs were determined. The results showed that Cd absorption reached its peak in the blood at 3 h after treatment. The accumulation of Cd was the highest in the liver and the second highest in the pancreas. All other tissues also accumulated Cd, such as spleen, kidney, intestine, lung, stomach, heart, brain, muscle. A small amount of Cd was found in the faeces. The urine and bile had low concentrations of Cd. In conclusion, absorbance of Cd reaches its peak at 3 h in blood. The liver and pancreas are the major organs of Cd accumulation, and the major excretion route of Cd is through feaces.
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http://dx.doi.org/10.1016/j.chemosphere.2017.05.029DOI Listing
September 2017

Comparison of coronary plaque, coronary artery calcification and major adverse cardiac events in Chinese outpatients with and without type 2 diabetes.

Springerplus 2016 29;5(1):1678. Epub 2016 Sep 29.

Department of Cardiology, Zhengzhou University People's Hospital, 7 Wei Wu Road, Zhengzhou, 450003 China.

Objective: Diabetes substantially increases the risk of cardiovascular disease (CAD) and is associated with an increased risk of CAD mortality. The purpose of this study was to investigate the differences in coronary artery plaque, coronary artery calcification (CAC) measured in outpatients with and without type 2 diabetes, and the occurrence rate of a major adverse cardiac event (MACE) throughout follow-up with the same patients.

Methods: Five hundred eighty-eight outpatients with suspected CAD comprising 208 diabetic and 380 non-diabetic patients were enrolled in this study. Coronary artery plaque and CAC scores were detected and measured by dual-source computed tomography. The major MACE during the follow-up period (4.0-20 months) was recorded and its relationship to type 2 diabetes and CAC was investigated.

Results: The diabetes group had higher CAC scores in the left anterior descending, left circumflex, and right coronary arteries and total CAC burden than the group without diabetes. The diabetes group had more diseased coronary segments and more obstructed vessels than the non-diabetes group. Logistic regression analysis demonstrated that diabetes is positively associated with mixed coronary plaque and non-calcified plaque. All patients in the diabetes group and all patients with higher CACs in both groups had a higher incidence rate of MACEs.

Conclusion: Patients with type 2 diabetes have a higher prevalence of obstructive CAD, higher CAC scores, and a higher incidence rate of MACEs than those without diabetes. Diabetes and higher CAC scores were the important predictors of the occurrence of MACEs throughout follow-up with patients.
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http://dx.doi.org/10.1186/s40064-016-3373-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042911PMC
September 2016

Identification and characterization of ovary development-related protein EJO1 (Eri s 2) from the ovary of Eriocheir sinensis as a new food allergen.

Mol Nutr Food Res 2016 10 23;60(10):2275-2287. Epub 2016 Jun 23.

School of Medical Laboratory, Tianjin Medical University, Tianjin, China.

Scope: Crab is a major source of shellfish allergens. Most studies have focused on allergens in crab muscle (CM) rather than on allergens in crab ovary (CO). This study aimed to identify potential allergens in CO from Eriocheir sinensis.

Methods And Results: Dot blot and immunoblotting results revealed the differential reactivity of CM and CO extracts to positive sera from patients allergic to crabs. Four CO proteins showed good specific IgE-binding activities in 2-DE/immunoblotting analysis; mass spectrometry identified the proteins as hemocyanin, vitellogenin, ovary development-related protein EJO1and EJO2. The recently identified allergen EJO1 is named 'Eri s 2' in the World Health Organization and International Union of Immunological Societies (WHO/IUIS) allergen nomenclature database. Recombinant Eri s 2 exhibited good reactivity to positive sera, and pre-incubation with recombinant Eri s 2 abrogated the reactivity of positive sera from two patients to CO in a dose-dependent manner. Moreover, co-incubation of recombinant Eri s 2 with patient basophils dose-dependently promoted basophil activation, confirming the biological activity of Eri s 2.

Conclusion: CO tissue is an important allergen source, and Eri s 2 is a new crab allergen. This study provides insights that will be useful for component-resolved diagnostics for crab allergy.
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http://dx.doi.org/10.1002/mnfr.201600144DOI Listing
October 2016

Identification of the major allergenic epitopes of Eriocheir sinensis roe hemocyanin: A novel tool for food allergy diagnoses.

Mol Immunol 2016 06 18;74:125-32. Epub 2016 May 18.

School of Medical Laboratory, Tianjin Medical University, 1 Guangdong Road, Hexi District, Tianjin 300203, China. Electronic address:

Crab meat and roe are highly nutritious delicacies in China. While extensive research has been conducted for allergens derived from crab-meat, data relevant to the allergenic potential of crab roe derived proteins, of which hemocyanin is a principal contender, are almost entirely absent. Using bioinformatics prediction and IgE-binding assays, the three principal immunodominant epitopes of hemocyanin were identified and then combined as a single recombinant fusion protein (rHc). This together with the full-length recombinant protein (Hc) were expressed in Escherichia coli and subsequently identified by SDS-PAGE and immunoblotting. Ninety-five percent of our patients were found to carry rHc-specific IgE antibodies by ELISA. Dot-blot inhibition, together with ELISA inhibition studies, showed that pre-incubation of patient sera with the recombinant epitope protein could inhibit26% to 63% (mean: 50%) of IgE binding to immobilized, full-length Hc and the dose-response curve represents as a sigmoid shape. The recombinant protein (rHc) represents a versatile biologic tool with which to diagnose and investigate therapies for E. sinensis allergy.
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http://dx.doi.org/10.1016/j.molimm.2016.05.003DOI Listing
June 2016

An overview of the molecular mechanisms and novel roles of Nrf2 in neurodegenerative disorders.

Cytokine Growth Factor Rev 2015 Feb 16;26(1):47-57. Epub 2014 Sep 16.

Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. Electronic address:

Recently, growing evidence has demonstrated that nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal regulator of endogenous defense systems that function via the activation of a set of protective genes, and this is particularly clear in the central nervous system (CNS). Therefore, it is highly useful to summarize the current literature on the molecular mechanisms and role of Nrf2 in the CNS. In this review, we first briefly introduce the molecular features of Nrf2. We then discuss the regulation, cerebral actions, upstream modulators and downstream targets of Nrf2 pathway. Following this background, we expand our discussion to the role of Nrf2 in several major neurodegenerative disorders (NDDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis. Lastly, we discuss some potential future directions. The information reviewed here may be significant in the design of further experimental research and increase the potential of Nrf2 as a therapeutic target in the future.
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http://dx.doi.org/10.1016/j.cytogfr.2014.09.002DOI Listing
February 2015

Novel role of silent information regulator 1 in acute endothelial cell oxidative stress injury.

Biochim Biophys Acta 2014 Nov 14;1842(11):2246-56. Epub 2014 Aug 14.

Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. Electronic address:

Silent information regulator 1 (SIRT1), a class III histone deacetylase, retards aging and plays roles in cellular oxidative stress injury (OSI). However, the biological context in which SIRT1 promotes oxidative injury is not fully understood. Here, we show that SIRT1 essentially mediates hydrogen peroxide (H2O2)-induced cytotoxicity in human umbilical vein endothelial cell (HUVEC). In HUVECs, SIRT1 protein expression was significantly increased in a dose-dependent manner after H2O2 treatment, whereas the acetylation levels of the NF-κB p65 subunit and p53 were decreased. EX527 (a specific SIRT1 inhibitor) conferred protection to the HUVECs against H2O2, as indicated by an improved cell viability, adhesion, an enhanced migratory ability, a decreased apoptotic index, decreased reactive oxygen species (ROS) production and reductions in several biochemical parameters. Immunofluorescence and Western blot analyses demonstrated that H2O2 treatment up-regulated SIRT1, phosphorylated-JNK (p-JNK), p-p38MAPK, and p-ERK expression. EX527 pretreatment reversed these effects on SIRT1, p-JNK, and p-p38MAPK but further increased the p-ERK levels. Similar results were confirmed in SIRT1 siRNA experiments. In summary, SIRT1 signaling pathway inhibition imparts protection against acute endothelial OSI, and modulation of MAPKs (JNK, p38MAPK, and ERK) may be involved in the protective effect of SIRT1 inhibition.
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http://dx.doi.org/10.1016/j.bbadis.2014.08.003DOI Listing
November 2014

A review of melatonin in hepatic ischemia/reperfusion injury and clinical liver disease.

Ann Med 2014 Nov 18;46(7):503-11. Epub 2014 Jul 18.

Department of Neurosurgery, Xijing Hospital, The Fourth Military Medical University , Xi'an , China.

Ischemia/reperfusion injury (IRI) can lead to cellular and, eventually, organ dysfunction, with the liver being one of the most frequently affected organs. Melatonin, a molecule that has notable antioxidant and anti-inflammatory properties, has been shown to protect against hepatic IRI. The purpose of this review is to summarize the protective effects of melatonin on hepatic IRI. The review initially summarizes the antioxidant properties of melatonin. We then discuss the protective effects of melatonin against endothelial and mitochondrial dysfunction. Thereafter, we introduce some information covering melatonin-related signaling pathways, including heme oxygenase-1 (HO-1), toll-like receptor (TLR), c-Jun N-terminal kinase (JNK), and so on. Furthermore, the clinical application of melatonin to hepatic diseases is considered. Finally, the safety of melatonin is evaluated. Taken together, the information compiled in this review will serve as a comprehensive reference regarding the pharmacological benefits of melatonin on hepatic IRI, aid in the design of future experimental research, and promote melatonin as a new therapeutic target.
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http://dx.doi.org/10.3109/07853890.2014.934275DOI Listing
November 2014

Inhibition of SIRT1 signaling sensitizes the antitumor activity of silybin against human lung adenocarcinoma cells in vitro and in vivo.

Mol Cancer Ther 2014 Jul 5;13(7):1860-72. Epub 2014 May 5.

Authors' Affiliations: Department of Cardiovascular Surgery, Xijing Hospital;

Although silybin, a natural flavonolignan, has been shown to exhibit potent antitumor activities against various types of cancers, including lung cancer, the molecular mechanisms behind these activities remain unclear. Silent information regulator 1 (SIRT1) is a conserved NAD(+)-dependent deacetylase that has been implicated in the modulation of transcriptional silencing and cell survival. Furthermore, it plays a key role in carcinogenesis through the deacetylation of important regulatory proteins, including p53. In this study, we investigated the antitumor activity of silybin towards human lung adenocarcinoma cells in vitro and in vivo and explored the role of the SIRT1 signaling pathway in this process. Silybin treatment resulted in a dose- and time-dependent decrease in lung adenocarcinoma A549 cell viability. In addition, silybin exhibited strong antitumor activity illustrated by reductions in tumor cell adhesion, migratory capability, and glutathione levels and by increased apoptotic indices and reactive oxygen species levels. Silybin treatment also downregulated SIRT1 and upregulated p53 acetylation. SIRT1 siRNA (in vitro) or cambinol (a known SIRT1 inhibitor used for in vivo studies) further enhanced the antitumor activity of silybin. In summary, silybin is a potent inhibitor of lung adenocarcinoma cell growth that interferes with SIRT1 signaling, and this inhibition is a novel mechanism of silybin action that may be used for therapeutic intervention in lung adenocarcinoma treatment.
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http://dx.doi.org/10.1158/1535-7163.MCT-13-0942DOI Listing
July 2014

Silybin-mediated inhibition of Notch signaling exerts antitumor activity in human hepatocellular carcinoma cells.

PLoS One 2013 27;8(12):e83699. Epub 2013 Dec 27.

Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an City, China.

Hepatocellular carcinoma (HCC) is a global health burden that is associated with limited treatment options and poor patient prognoses. Silybin (SIL), an antioxidant derived from the milk thistle plant (Silybum marianum), has been reported to exert hepatoprotective and antitumorigenic effects both in vitro and in vivo. While SIL has been shown to have potent antitumor activity against various types of cancer, including HCC, the molecular mechanisms underlying the effects of SIL remain largely unknown. The Notch signaling pathway plays crucial roles in tumorigenesis and immune development. In the present study, we assessed the antitumor activity of SIL in human HCC HepG2 cells in vitro and in vivo and explored the roles of the Notch pathway and of the apoptosis-related signaling pathway on the activity of SIL. SIL treatment resulted in a dose- and time-dependent inhibition of HCC cell viability. Additionally, SIL exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration, intracellular glutathione (GSH) levels and total antioxidant capability (T-AOC) but also by increases in the apoptotic index, caspase3 activity, and reactive oxygen species (ROS). Furthermore, SIL treatment decreased the expression of the Notch1 intracellular domain (NICD), RBP-Jκ, and Hes1 proteins, upregulated the apoptosis pathway-related protein Bax, and downregulated Bcl2, survivin, and cyclin D1. Notch1 siRNA (in vitro) or DAPT (a known Notch1 inhibitor, in vivo) further enhanced the antitumor activity of SIL, and recombinant Jagged1 protein (a known Notch ligand in vitro) attenuated the antitumor activity of SIL. Taken together, these data indicate that SIL is a potent inhibitor of HCC cell growth that targets the Notch signaling pathway and suggest that the inhibition of Notch signaling may be a novel therapeutic intervention for HCC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083699PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3873967PMC
September 2014

Novel role of silent information regulator 1 in myocardial ischemia.

Circulation 2013 Nov;128(20):2232-40

Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China (Y.Y., W.D., Z.J., S.Y., D.Y.); Team 10, School of Stomatology, The Fourth Military Medical University, Xi'an, China (Y.L.); and Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi'an, China (J.Y.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.113.002480DOI Listing
November 2013

SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury.

Free Radic Biol Med 2013 Dec 20;65:667-679. Epub 2013 Jul 20.

Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. Electronic address:

Ischemia reperfusion (IR) injury (IRI) is harmful to the cardiovascular system and causes mitochondrial oxidative stress. Silent information regulator 1 (SIRT1), a type of histone deacetylase, contributes to IRI. Curcumin (Cur) is a strong natural antioxidant and is the active component in Curcuma longa; Cur has protective effects against IRI and may regulate the activity of SIRT1. This study was designed to investigate the protective effect of Cur pretreatment on myocardial IRI and to elucidate this potential mechanism. Isolated and in vivo rat hearts and cultured neonatal rat cardiomyocytes were subjected to IR. Prior to this procedure, the hearts or cardiomyocytes were exposed to Cur in the absence or presence of the SIRT1 inhibitor sirtinol or SIRT1 siRNA. Cur conferred a cardioprotective effect, as shown by improved postischemic cardiac function, decreased myocardial infarct size, decreased myocardial apoptotic index, and several biochemical parameters, including the up-regulation of the antiapoptotic protein Bcl2 and the down-regulation of the proapoptotic protein Bax. Sirtinol and SIRT1 siRNA each blocked the Cur-mediated cardioprotection by inhibiting SIRT1 signaling. Cur also resulted in a well-preserved mitochondrial redox potential, significantly elevated mitochondrial superoxide dismutase activity, and decreased formation of mitochondrial hydrogen peroxide and malondialdehyde. These observations indicated that the IR-induced mitochondrial oxidative damage was remarkably attenuated. However, this Cur-elevated mitochondrial function was reversed by sirtinol or SIRT1 siRNA treatment. In summary, our results demonstrate that Cur pretreatment attenuates IRI by reducing IR-induced mitochondrial oxidative damage through the activation of SIRT1 signaling.
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http://dx.doi.org/10.1016/j.freeradbiomed.2013.07.007DOI Listing
December 2013

New role of silent information regulator 1 in cerebral ischemia.

Neurobiol Aging 2013 Dec 12;34(12):2879-88. Epub 2013 Jul 12.

Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.

Silent information regulator 1 (SIRT1) is a type of histone deacetylase whose activity is dependent on nicotinamide adenine dinucleotide. SIRT1 plays a key role in the longevity effects elicited by calorie restriction. Recently, a neuroprotective effect of SIRT1 was reported for neurological diseases. The focus of this review is to summarize the protective effects of SIRT1 in cerebral ischemia. First, the posttranslational modifications of SIRT1 are illustrated; then, we discuss the roles of SIRT1 in cerebral immune homeostasis. Next, we introduce the deacetylase activity of SIRT1 in cerebral ischemia and provide some examples of relevant studies. In addition, we discuss several activated mediators of SIRT1, such as resveratrol, caloric restriction, ischemic preconditioning, and other proteins and compounds. Finally, we highlight a few SIRT1-related signaling pathways, such as the peroxisome proliferator-activated receptor γ coactivator 1α, nuclear transcription factor κB, uncoupling protein 2, and forkhead box O pathways. Taken together, the information compiled in this article will serve as a comprehensive reference for the actions of SIRT1 in the nervous system and will help in the design of future experimental research and promote SIRT1 as a new therapeutic target.
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http://dx.doi.org/10.1016/j.neurobiolaging.2013.06.008DOI Listing
December 2013

JAK2/STAT3 activation by melatonin attenuates the mitochondrial oxidative damage induced by myocardial ischemia/reperfusion injury.

J Pineal Res 2013 Oct 25;55(3):275-86. Epub 2013 Jun 25.

Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.

Ischemia/reperfusion injury (IRI) is harmful to the cardiovascular system and causes mitochondrial oxidative stress. Numerous data indicate that the JAK2/STAT3 signaling pathway is specifically involved in preventing myocardial IRI. Melatonin has potent activity against IRI and may regulate JAK2/STAT3 signaling. This study investigated the protective effect of melatonin pretreatment on myocardial IRI and elucidated its potential mechanism. Perfused isolated rat hearts and cultured neonatal rat cardiomyocytes were exposed to melatonin in the absence or presence of the JAK2/STAT3 inhibitor AG490 or JAK2 siRNA and then subjected to IR. Melatonin conferred a cardio-protective effect, as shown by improved postischemic cardiac function, decreased infarct size, reduced apoptotic index, diminished lactate dehydrogenase release, up-regulation of the anti-apoptotic protein Bcl2, and down-regulation of the pro-apoptotic protein Bax. AG490 or JAK2 siRNA blocked melatonin-mediated cardio-protection by inhibiting JAK2/STAT3 signaling. Melatonin exposure also resulted in a well-preserved mitochondrial redox potential, significantly elevated mitochondrial superoxide dismutase (SOD) activity, and decreased formation of mitochondrial hydrogen peroxide (H2 O2 ) and malondialdehyde (MDA), which indicates that the IR-induced mitochondrial oxidative damage was significantly attenuated. However, this melatonin-induced effect on mitochondrial function was reversed by AG490 or JAK2 siRNA treatment. In summary, our results demonstrate that melatonin pretreatment can attenuate IRI by reducing IR-induced mitochondrial oxidative damage via the activation of the JAK2/STAT3 signaling pathway.
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http://dx.doi.org/10.1111/jpi.12070DOI Listing
October 2013

Pterostilbene exerts antitumor activity via the Notch1 signaling pathway in human lung adenocarcinoma cells.

PLoS One 2013 3;8(5):e62652. Epub 2013 May 3.

Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an City, China.

Although pterostilbene (PTE) has been shown to have potent antitumor activities against various cancer types, the molecular mechanisms of these activities remain unclear. In this study, we investigated the antitumor activity of PTE against human lung adenocarcinoma in vitro and in vivo and explored the role of the Notch1 signaling pathway in this process. PTE treatment resulted in a dose- and time-dependent decrease in the viability of A549 cells. Additionally, PTE exhibited strong antitumor activity, as evidenced not only by a reduced mitochondrial membrane potential (MMP) and a decreased intracellular glutathione content but also by increases in the apoptotic index and the level of reactive oxygen species (ROS). Furthermore, PTE treatment induced the activation of the Notch1 Intracellular Domain (NICD) protein and activated Hes1. DAPT (a gamma secretase inhibitor) and Notch1 siRNA prevented the induction of NICD and Hes1 activation by PTE treatment and sensitized the cells to PTE treatment. The down-regulation of Notch signaling also prevented the activation of pro-survival pathways (most notably the PI3K/Akt pathway) after PTE treatment. In summary, lung adenocarcinoma cells may enhance Notch1 activation as a protective mechanism in response to PTE treatment. Combining a gamma secretase inhibitor with PTE treatment may represent a novel approach for treating lung adenocarcinoma by inhibiting the survival pathways of cancer cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0062652PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3643961PMC
February 2014

A correlational study of scoliosis and trunk balance in adult patients with mandibular deviation.

PLoS One 2013 29;8(3):e59929. Epub 2013 Mar 29.

Department of Orthodontics, The 161th Hospital of PLA, Wuhan, China.

Previous studies have confirmed that patients with mandibular deviation often have abnormal morphology of their cervical vertebrae. However, the relationship between mandibular deviation, scoliosis, and trunk balance has not been studied. Currently, mandibular deviation is usually treated as a single pathology, which leads to poor clinical efficiency. We investigated the relationship of spine coronal morphology and trunk balance in adult patients with mandibular deviation, and compared the finding to those in healthy volunteers. 35 adult patients with skeletal mandibular deviation and 10 healthy volunteers underwent anterior X-ray films of the head and posteroanterior X-ray films of the spine. Landmarks and lines were drawn and measured on these films. The axis distance method was used to measure the degree of scoliosis and the balance angle method was used to measure trunk balance. The relationship of mandibular deviation, spine coronal morphology and trunk balance was evaluated with the Pearson correlation method. The spine coronal morphology of patients with mandibular deviation demonstrated an "S" type curve, while a straight line parallel with the gravity line was found in the control group (significant difference, p<0.01). The trunk balance of patients with mandibular deviation was disturbed (imbalance angle >1°), while the control group had a normal trunk balance (imbalance angle <1°). There was a significant difference between the two groups (p<0.01). The degree of scoliosis and shoulder imbalance correlated with the degree of mandibular deviation, and presented a linear trend. The direction of mandibular deviation was the same as that of the lateral bending of thoracolumbar vertebrae, which was opposite to the direction of lateral bending of cervical vertebrae. Our study shows the degree of mandibular deviation has a high correlation with the degree of scoliosis and trunk imbalance, all the three deformities should be clinically evaluated in the management of mandibular deviation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059929PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612109PMC
January 2014

New role of JAK2/STAT3 signaling in endothelial cell oxidative stress injury and protective effect of melatonin.

PLoS One 2013 6;8(3):e57941. Epub 2013 Mar 6.

Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an City, Shanxi Province, China.

Previous studies have shown that the JAK2/STAT3 signaling pathway plays a regulatory role in cellular oxidative stress injury (OSI). In this study, we explored the role of the JAK2/STAT3 signaling pathway in hydrogen peroxide (H2O2)-induced OSI and the protective effect of melatonin against (H2O2)-induced injury in human umbilical vein endothelial cells (HUVECs). AG490 (a specific inhibitor of the JAK2/STAT3 signaling pathway) and JAK2 siRNA were used to manipulate JAK2/STAT3 activity, and the results showed that AG490 and JAK2 siRNA inhibited OSI and the levels of p-JAK2 and p-STAT3. HUVECs were then subjected to H2O2 in the absence or presence of melatonin, the main secretory product of the pineal gland. Melatonin conferred a protective effect against H2O2, which was evidenced by improvements in cell viability, adhesive ability and migratory ability, decreases in the apoptotic index and reactive oxygen species (ROS) production and several biochemical parameters in HUVECs. Immunofluorescence and Western blotting showed that H2O2 treatment increased the levels of p-JAK2, p-STAT3, Cytochrome c, Bax and Caspase3 and decreased the levels of Bcl2, whereas melatonin treatment partially reversed these effects. We, for the first time, demonstrate that the inhibition of the JAK2/STAT3 signaling pathway results in a protective effect against endothelial OSI. The protective effects of melatonin against OSI, at least partially, depend upon JAK2/STAT3 inhibition.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0057941PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3590213PMC
September 2013

[Effect of Kaixin San on learning and memory in chronic stress depression model rats].

Zhongguo Zhong Yao Za Zhi 2012 Aug;37(16):2439-43

Department of Clinical Pharmacology, Center of Pharmacy, Chinese PLA General Hospital, Beijing 100853, China.

Objective: To study the effect of classic ancient prescription Kaixin San (KXS) on learning and memory abilities in chronic stress depression model rats and its possible mechanisms.

Method: Rats were randomly assigned to six groups: the control group, the model group, the positive drug group (fluoxetine 10 mg x kg(-1)) and KXS groups (1000, 500, 250, 125 mg x kg(-1)). KXS were orally administrated to CMS rats for 21 days. The anti-depression activity of KXS was assessed using the sucrose consumption and the open-field test. The protecting effect for learning and memory abilities was assessed using the Morris water maze (MWM) test. Furthermore, the levels of monoamine neurotransmitters, acetylcholine (Ach) and acetyl cholinesterase (AchE) in the total brain and brain-derived neurotrophic factor (BDNF) protein in the hippocampus were determined.

Result: The behavior test showed that KXS significantly increased the sucrose consumption and total distance in the open-field test and notably reduce the incubation period of location and navigation in the MWM test. It could also help increase the number of times passing through the platform, the swimming distance and time in quadrant of original platform, the levels of serotonin (5-HT) and dopamine (DA) , noradrenergic (NE), Ach, BDNF protein and reduce the level of AchE in the CMS-induced rats.

Conclusion: KXS can ameliorate the CMS-induced depression behavior in rats and improved their learning and memory abilities, which may be related to the increase in monoamine neurotransmitters, Ach and BDNF levels.
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August 2012

Curcumin attenuates endothelial cell oxidative stress injury through Notch signaling inhibition.

Cell Signal 2013 Mar 5;25(3):615-29. Epub 2012 Dec 5.

Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.

Previous studies have demonstrated that Notch signaling pathway plays a regulatory role in cellular oxidative stress injury (OSI). In this study, our aim was to explore the role of the Notch signaling pathway in hydrogen peroxide (H(2)O(2))-induced OSI and the protective effect of curcumin during (H(2)O(2))-induced injury in human umbilical vein endothelial cells (HUVECs). DAPT, a specific inhibitor of the Notch signaling pathway, and Notch1 siRNA were used to study Notch activity. Further, HUVECs were exposed to H(2)O(2) in the absence or presence of curcumin. DAPT and Notch1 siRNA significantly inhibited OSI and the expression of Notch1 and Hes1. Curcumin conferred a protective effect on the HUVECs against H(2)O(2), which was evidenced by improved cell viability, adhesive ability and migratory ability and a decreased apoptotic index, decreased production of reactive oxygen species (ROS) and a reduction in several biochemical parameters. Immunofluorescence and Western blotting analyses demonstrated that H(2)O(2) treatment upregulated the expression of Notch1, Hes1, Caspase3, Bax and cytochrome c downregulated the expression of Bcl2, and treatment with curcumin reversed these effects. We demonstrated for the first time that the inhibition of Notch signaling pathway imparts a protective effect against endothelial OSI. The protective effects of curcumin against OSI are at least in part dependent on Notch1 inhibition.
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http://dx.doi.org/10.1016/j.cellsig.2012.11.025DOI Listing
March 2013
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