Publications by authors named "Zhiyong Du"

38 Publications

Increased levels of VCAM-1 is associated with higher occurrence of coronary artery disease in adults with moderate to severe obstructive sleep apnea.

Sleep Med 2021 Jul 9;85:131-137. Epub 2021 Jul 9.

Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, 100029, China; Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, China. Electronic address:

Background: Obstructive sleep apnea (OSA) leads to important vascular abnormalities, including the endothelial dysfunction and the production of endothelial cell adhesion molecules. The adhesion molecules play an important role in the process of endothelial dysfunction in the pathogenesis of atherosclerosis. We assess the relationship between the levels of adhesion molecules and the presence of coronary artery disease (CAD) in Chinese adults with moderate to severe OSA.

Methods: The cross-sectional study included a total of 189 Chinese adults: 90 patients with moderate to severe OSA (apnea-hypopnea index≥15 events/h) alone, 40 patients with moderate to severe OSA and CAD, and 59 controls without OSA or with mild OSA and without CAD. We used high-throughput Multiplex Immunobead Assay technology to simultaneously test plasma levels of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). The associations between the levels of circulating adhesion molecules and CAD in moderate to severe OSA patients were evaluated by multivariate logistic regression analysis.

Results: The circulating VCAM-1 levels were significantly elevated in patients suffering from moderate to severe OSA combined CAD compared with patients having moderate to severe OSA alone [853.28 (564.26) vs. 416.61 (301.69) ng/mL, P < 0.001]. Furthermore, circulating VCAM-1 levels were independently associated with CAD (odds ration = 2.113, 95%CI 1.400-2.766, P < 0.001) and showed higher discriminatory accuracy in assessing the presence of CAD (AUC: 0.899, 95%CI 0.849-0.950, P < 0.001) in moderate to severe OSA patients. However, no significant association was found between circulating ICAM-1 levels and CAD in moderate to severe OSA patients.

Conclusions: The circulating VCAM-1 levels were significantly correlated with the presence of CAD in Chinese adults with moderate to severe OSA. The circulating VCAM-1 may function as a novel biomarker for monitoring the development and progression of CAD in patients with moderate to severe OSA.
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http://dx.doi.org/10.1016/j.sleep.2021.07.002DOI Listing
July 2021

Pharmacokinetics/pharmacometabolomics-pharmacodynamics reveals the synergistic mechanism of a multicomponent herbal formula, Baoyuan decoction against cardiac hypertrophy.

Biomed Pharmacother 2021 Jul 7;139:111665. Epub 2021 May 7.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People's Republic of China. Electronic address:

Multicomponent herbal formulas (MCHFs) have earned a wide reputation for their definite efficacy in preventing or treating chronic complex diseases. However, holistic elucidation of the causal relationship between the bioavailable ingredients of MCHFs and their multitarget interactions is very challenging. To solve this problem, pharmacokinetics/pharmacometabolomics-pharmacodynamics (PK/PM-PD) combined with a multivariate biological correlation-network strategy was developed and applied to a classic MCHF, Baoyuan decoction (BYD), to clarify its active components and synergistic mechanism against cardiac hypertrophy (CH). First, multiple plasma metabolic biomarkers for β-adrenergic agonist-induced CH rats were identified by using untargeted metabolomic profiling, and then, these CH-associated endogenous metabolites and the absorbed BYD-compounds in plasma at different treatment stages after oral administration of BYD were analyzed by using targeted PK and PM. Second, the dynamic relationship of BYD-related compounds and CH-associated endogenous metabolites and signaling pathways was built by using multivariate and bioinformatic correlation analysis. Finally, metabolic-related PD indicators were predicted and further verified by biological tests. The results demonstrated that the bioavailable BYD-compounds, such as saponins and flavonoids, presented differentiated and distinctive metabolic features and showed positive or negative correlations with various CH-altered metabolites and PD-indicators related to gut microbiota metabolism, amino acid metabolism, lipid metabolism, energy homeostasis, and oxidative stress at different treatment stages. This study provides a novel strategy for investigating the dynamic interaction between BYD and the biosystem, providing unique insight for disclosing the active components and synergistic mechanisms of BYD against CH, which also supplies a reference for other MCHF related research.
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http://dx.doi.org/10.1016/j.biopha.2021.111665DOI Listing
July 2021

Prediction of Protein Solubility Based on Sequence Feature Fusion and DDcCNN.

Interdiscip Sci 2021 Jul 8. Epub 2021 Jul 8.

School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Background: Prediction of protein solubility is an indispensable prerequisite for pharmaceutical research and production. The general and specific objective of this work is to design a new model for predicting protein solubility by using protein sequence feature fusion and deep dual-channel convolutional neural networks (DDcCNN) to improve the performance of existing prediction models.

Methods: The redundancy of raw protein is reduced by CD-HIT. The four subsequences are built from protein sequence: one global and three locals. The global subsequence is the entire protein sequence, and these local subsequences are obtained by moving a sliding window with some rules. Using G-gap to extract the features of the above four subsequences, a mixed matrix is constructed as the input of one channel which is composed of three-layer convolutional operating. Additional features are extracted by SCRATCH tool as input of another channel, which is consist of a single convolution in order to find hidden relationships and improve the accuracy of predictor. The outputs of two parallel channels are concatenated as the input of the hidden layer. And the prediction of protein solubility is obtained in the output layer. The best protein solubility prediction model is obtained by doing some comparative experiments of different frameworks.

Results: The performance indicators of DDcCNN model (our designed) are as follows: accuracy of 77.82%, Matthew's correlation coefficient of 0.57, sensitivity of 76.13% and specificity of 79.32%. The results of some comparative experiments show that the overall performance of DDcCNN model is better than existing models (GCNN, LCNN and PCNN). The related models and data are publicly deposited at http://www.ddccnn.wang .

Conclusion: The satisfactory performance of DDcCNN model reveals that these features and flexible computational methodologies can reinforce the existing prediction models for better prediction of protein solubility could be applied in several applications, such as to preselect initial targets that are soluble or to alter solubility of target proteins, thus can help to reduce the production cost.
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http://dx.doi.org/10.1007/s12539-021-00456-1DOI Listing
July 2021

Baoyuan decoction (BYD) attenuates cardiac hypertrophy through ANKRD1-ERK/GATA4 pathway in heart failure after acute myocardial infarction.

Phytomedicine 2021 Jun 1;89:153617. Epub 2021 Jun 1.

Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address:

Background: The pathological cardiac functions of ankyrin repeat domain 1 (ANKRD1) in left ventricle can directly aggravate cardiac hypertrophy (CH) and fibrosis through the activation of extracellular signal-regulated kinase (ERK)/ transcription factor GATA binding protein 4 (GATA4) pathway, and subsequently contribute to heart failure (HF). Baoyuan Decoction (BYD), which is a famous classic Chinese medicinal formulation, has shown impressive cardioprotective effects clinically and experimentally. However, the knowledge is still limited in its underlying mechanisms against HF.

Purpose: To explore whether BYD plays a protective role against HF by attenuating CH via the ANKRD1-ERK/GATA4 pathway.

Methods: In vivo, HF rat models were prepared using left anterior descending coronary artery (LADCA) ligation. Rats in the BYD group were administered a dosage of 2.57 g/kg of BYD for 28 days, while in the positive control group rats were given 4.67 mg/kg of Fosinopril. In vitro, a hypertrophic model was constructed by stimulating H9C2 cells with 1 uM Ang II. An ANKRD1-overexpressing cell model was established through transient transfection of ANKRD1 plasmid into H9C2 cells. Subsequently, BYD intervention was performed on the cell models to further elucidate its effects and underlying mechanism.

Results: In vivo results showed that BYD significantly improved cardiac function and inhibited pathological hypertrophy and fibrosis in a rat model of HF post-acute myocardial infarction (AMI). Noticeably, label-free proteomic analysis demonstrated that BYD could reverse the CH-related biological turbulences, mainly through ANKRD1-ERK/GATA4 pathway. Further in vitro results validated that the hypertrophy was attenuated by BYD through suppression of AT1R, ANKRD1, Calpain1, p-ERK1/2 and p-GATA4. The results of in vitro model indicated that BYD could reverse the outcome of transfected over-expression of ANKRD1, including down-regulated expressions of ANKRD1, p-ERK1/2 and p-GATA4.

Conclusion: BYD ameliorates CH and improves HF through the ANKRD1-ERK/GATA4 pathway, providing a novel therapeutic option for the treatment of HF.
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http://dx.doi.org/10.1016/j.phymed.2021.153617DOI Listing
June 2021

Ubiquitin specific peptidase 1 promotes hepatic fibrosis through positive regulation of CXCL1 by deubiquitinating SNAIL.

Dig Liver Dis 2021 Apr 26. Epub 2021 Apr 26.

Department of Endocrinology, Jingmen First People's Hospital, Jingmen 448000, PR China. Electronic address:

Background: Hepatic fibrosis is attributed to an imbalance of extracellular matrix production and lysis. Human hepatic stellate cells (HSCs) have been uncovered to converge through complex interactions with hepatocytes and immune cells, causing scarring in liver damage.

Aims: We aimed to investigate the expression status of ubiquitin specific peptidase 1 (USP1) and its potential mechanisms on HSCs and hepatic fibrosis.

Methods: Hepatic fibrosis animal and cell models were generated using mice with carbon tetrachloride (CCl4) treatment and HSCs LX-2 with TGF-β1 treatment. Relationships among USP1, SNAIL, and CXCL1 were identified via dual-luciferase reporter gene assay, co-immunoprecipitation, and chromatin immunoprecipitation. With gain- and loss-of-experiments, CCK-8 and flow cytometry assays were employed for cell proliferation and apoptosis.

Results: USP1 upregulated SNAIL expression through deubiquitination to increase CXCL1 expression. USP1 downregulation decreased expressions of fibrosis-related genes, suppressed proliferation, and promoted apoptosis in TGF-β1-induced LX-2 cells, which were reversed by SNAIL overexpression. The pro-fibrosis role caused by SNAIL upregulation was abolished by CXCL1 reduction. Promotive function of USP1/SNAIL/CXCL1 axis in hepatic fibrosis was further confirmed in vivo.

Conclusion: These data supported siRNA-mediated silencing of USP1 improved hepatic fibrosis through inhibition of SNAIL and CXCL1, which yields a new therapeutic target for hepatic fibrosis treatment.
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http://dx.doi.org/10.1016/j.dld.2021.02.025DOI Listing
April 2021

The synergistic effects of applying pulsed radiofrequency lesioning of the suprascapular nerve plus physical therapy on pain and function in patients with adhesive capsulitis: A protocol of a prospective, randomized, controlled trial.

Medicine (Baltimore) 2021 Apr;100(14):e25431

Department of Joint Surgery, Zhuzhou Central Hospital, Zhuzhou, Hunan, China.

Background: To our knowledge, there have been no published clinical trials to assess the synergistic effects of applying pulsed radiofrequency (PRF) stimulation of the suprascapular nerve (SSN) plus physical therapy on pain and function in patients with adhesive capsulitis. Therefore, we will conduct this present randomized, double-blind study to evaluate the synergistic effects of applying PRF stimulation of the SSN plus physical therapy on pain and function in patients with adhesive capsulitis.

Methods: The study protocol is a randomized, controlled, double-blind design. Recruitment will be started in March 2021 and completed in October 2022. The treating surgeon will assess 90 patients for eligibility. The study protocol was approved through Institutional Review Board in the People's Hospital of Beilun district of Ningbo. Each patient will be randomized into 3 treatment groups, receiving PRF stimulation of the SSN or physical therapy or both of them. After baseline examination, all patients will be given a full explanation of the treatment protocol and will be required to sign a written informed consent for study participation and for publication of the results. All the data collectors, surgeons, statistical analysts, as well as result assessors are not aware of grouping assignment. The outcomes include Constant score, visual analog scale score, range of motion, and strength.

Results: This protocol will provide a reliable theoretical basis for the following research.

Conclusion: It is assumed that there will be a remarkable difference in postoperative outcomes between the intervention and control groups.

Trial Registration Number: 10.17605/OSF.IO/PZ9ES.
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http://dx.doi.org/10.1097/MD.0000000000025431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036050PMC
April 2021

Is a tourniquet necessary in arthroscopic anterior cruciate ligament reconstruction?: A randomized controlled study protocol.

Medicine (Baltimore) 2021 Feb;100(5):e23724

Department of Joint Surgery, the Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, Hunan, China.

Background: In the past few decades, the number of surgery of anterior cruciate ligament reconstruction (ACLR) implemented in the outpatient centers has dramatically enhanced. There is still a lack of effective randomized controlled trials in the literature to demonstrate the effectiveness of tourniquets. As a kind of prospective clinical trial, this research protocol is conducted to compare the results of ACLR with and without the use of a tourniquet.

Methods: All the patients aged 18 or over who underwent the selective primary anterior cruciate ligament reconstruction in our hospital from November 2020 to January 2022 are eligible to take part in our experiment. Exclusion criteria are history of peripheral neuropathy, pregnancy, lumbar radiculopathy, or surgery to the injured or contralateral knee. After the written informed consent is given, the patients participating in the study are randomly assigned to the tourniquet group (group 1) and the tourniquet free group (group 2) on the day of operation, through utilizing the computer-generated random table with 10 members in each group. And the assignments were kept in an opaque and sealed envelope. Any comments on visual difficulties in the process of operative time, arthroscopy, complications, and total bleeding from suction and drainage, as well as the reduction of postoperative hemoglobin are assessed as the parameters. The software of SPSS v. 24 is applied for all the statistical analyses.

Results: This protocol will provide a reliable theoretical basis for the following research.

Trial Registration: This study protocol was registered in Research Registry (researchregistry6240).
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http://dx.doi.org/10.1097/MD.0000000000023724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870236PMC
February 2021

A novel five-lncRNA signature panel improves high-risk survival prediction in patients with cholangiocarcinoma.

Aging (Albany NY) 2021 01 20;13(2):2959-2981. Epub 2021 Jan 20.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Cholangiocarcinoma (CCA) is a fatal disease with dismal survival rates. Long non-coding RNA (lncRNA) expression profiling as potential prognostic biomarkers play critical roles in tumor initiation, development, and poor prognosis. Identifying specific lncRNA to predict the prognosis of CCA patients in the early stages is very important for improving a patient's survival. In the current study, we aimed to establish a novel risk-stratification lncRNA signature panel in CCA. The initial lncRNA discovery was identified in The Cancer Genome Atlas database (TCGA cohort). The Cox regression analysis was used to establish the lncRNA prognostic model and the receiver operating characteristic (ROC) curve analysis was performed to assess the specificity and sensitivity of the model. This was followed by independent validation of the lncRNA signature in the CCA patients from the First Affiliated Hospital of Wenzhou Medical University (WMU cohort). Furthermore, by using the Gene Ontology function and Kyoto Encyclopedia Gene and Genome pathway enrichment analysis, we explored the potential function of prognosis lncRNA. Finally, five lncRNA (HULC; AL359715.5; AC006504.8; AC090114.2; AP00943.4) were screened to establish the predictive model that significantly associated with poor overall survival(HR:4.879;95%CI,1.587-14.996;=0.006). This five-lncRNA signature model showed excellent accuracy in the TCGA cohort (AUC=0.938), and also robustly predicted survival in the validation WMU cohort(AUC=0.816). Functional enrichment analysis suggested prognostic lncRNA was primarily associated with CCA-related biological processes. Our data established a novel lncRNA signature model for CCA risk-stratification and robust identification of CCA patients with poor molecular genotypes. Moreover, it revealed new molecular mechanisms of CCA.
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http://dx.doi.org/10.18632/aging.202446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880389PMC
January 2021

Extracellular vesicles-derived miR-150-5p secreted by adipose-derived mesenchymal stem cells inhibits CXCL1 expression to attenuate hepatic fibrosis.

J Cell Mol Med 2021 Jan 20;25(2):701-715. Epub 2020 Dec 20.

Department of Endocrinology, Jingmen First People's Hospital, Jingmen, China.

Hepatic fibrosis (HF) is involved in aggravated wound-healing response as chronic liver injury. Extracellular vesicles (EVs) carrying microRNA (miR) have been reported as therapeutic targets for liver diseases. In this study, we set out to explore whether adipose-derived mesenchymal stem cells (ADMSCs)-derived EVs containing miR-150-5p affect the progression of HF. Carbon tetrachloride (CCl ) was firstly used to induce HF mouse models in C57BL/6J mice, and activation of hepatic stellate cells (HSCs) was achieved using transforming growth factor β (TGF-β). EVs were then isolated from ADMSCs and co-cultured with HSCs. The relationship between miR-150-5p and CXCL1 was identified using dual luciferase gene reporter assay. Following loss- and gain-function experimentation, HSC proliferation was examined by MTT assay, and levels of fibrosis-, HSC activation- and apoptosis-related genes were determined in vitro. Additionally, pathological scores, collagen volume fraction (CVF) as well as levels of inflammation- and hepatic injury-associated genes were determined in in vivo. Down-regulated miR-150-5p and elevated CXCL1 expression levels were detected in HF tissues. ADMSCs-derived EVs transferred miR-150-5p to HSCs. CXCL1 was further verified as the downstream target gene of miR-150-5p. Moreover, ADMSCs-EVs containing miR-150-5p markedly inhibited HSC proliferation and activation in vitro. Meanwhile, in vivo experiments also concurred with the aforementioned results as demonstrated by inhibited CVF, reduced inflammatory factor levels and hepatic injury-associated indicators. Both experiments results were could be reversed by CXCL1 over-expression. Collectively, our findings indicate that ADMSCs-derived EVs containing miR-150-5p attenuate HF by inhibiting the CXCL1 expression.
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http://dx.doi.org/10.1111/jcmm.16119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812282PMC
January 2021

The cardiac protection of Baoyuan decoction via gut-heart axis metabolic pathway.

Phytomedicine 2020 Dec 2;79:153322. Epub 2020 Sep 2.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address:

Background: Gut-heart axis has emerged as a novel concept to provide new insights into the complex mechanisms of heart failure (HF) and offer new therapeutic targets. Cardiac hypertrophy (CH) is one of the etiological agents contributing to the development of HF. Baoyuan Decoction (BYD), a traditional Chinese medicine (TCM) formula, exhibits unambiguous effects on treating CH and preventing HF. Previously, we have reported that BYD-targeted endogenous metabolites are potentially linked to gut microbiota metabolism, but the contribution of gut microbiota and metabolic interaction to the cardioprotective efficacy of BYD remains to be elucidated.

Purpose: To investigate whether the gut microbiota plays a key role in anti-CH effects of BYD.

Study Design: A comprehensive strategy via incorporating pharmacodynamics, microbiomics, metabolomics, and microflora suppression model was adopted to investigate the links between the microbiota-host metabolic interaction and BYD efficacy in CH rats.

Method: Firstly, the efficacy evaluation of BYD in treating chronic isoproterenol (ISO)-induced CH rats was performed by using multiple pharmacodynamic approaches. Then, the fecal metabolomics and 16S rRNA sequencing techniques were used to obtain the microbial and metabolic features of BYD against CH. After that, the potential gut-heart axis-based mechanism of BYD against CH was predicted by bioinformatic network analysis and validated by multiple molecular biology approaches. Finally, the antibiotics (AB)-induced gut microbiota suppression was employed to investigate whether the anti-CH effects of BYD is associated with the gut microflora.

Results: The fecal microbial communities and metabolic compositions were significantly altered in ISO-induced CH rats, while BYD effectively ameliorated the CH-associated gut microbiota dysbiosis, especially of Firmicutes and Bacteroidetes, and time-dependently alleviated the disturbance of fecal metabolome and reversed the changes of key CH and gut microbiota-related metabolites, such as short/medium chain fatty acids, primary/secondary bile acids, and amino acids. The mechanism study showed that the anti-CH effect of BYD was related to inhibition of the derivatives of arginine and tryptophan and their downstream pro-hypertrophic, pro-inflammatory, and pro-oxidant signaling pathways. The following microflora suppression test showed that BYD-mediated myocardial protection was decreased either in pharmacodynamics or in metabolic modulation.

Conclusion: This study demonstrates that the protection of BYD against CH is partially gut microbiota dependent, and the regulatory effects of gut metabolism-related tryptophan and arginine derivatives is an important cardioprotection mechanism of BYD.
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http://dx.doi.org/10.1016/j.phymed.2020.153322DOI Listing
December 2020

The synergistic mechanism of total saponins and flavonoids in Notoginseng-Safflower pair against myocardial ischemia uncovered by an integrated metabolomics strategy.

Biomed Pharmacother 2020 Oct 30;130:110574. Epub 2020 Jul 30.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China. Electronic address:

The Notoginseng-Safflower pair composed of Panax notoginseng (Burk.) F. H. Chen and Carthamus tinctorius L. has remarkable clinical efficacy for preventing and treating cardiovascular diseases in China. Notoginseng total saponins (NS) and Safflower total flavonoids (SF) are the major effective ingredients in Notoginseng and Safflower, respectively. Though our previous study showed that the combination of NS and SF (NS-SF) exhibits significant cardioprotective effects for myocardial ischemia (MI), there might be difference in their action mechanisms. However, the anti-MI characteristics of individual NS and SF remains unclear. Herein, an integrated metabolomics strategy coupled with multiple biological methods were employed to investigate the cardioprotective effects of NS and SF alone or in combination against isoproterenol (ISO)-induced MI and to further explore the synergistic relationship between NS and SF. Our results demonstrated that pretreatments with NS, SF, and NS-SF all showed cardioprotective effects against MI injury and NS-SF exhibited to be the best. Interestingly, the results demonstrated that NS and SF exhibited differentiated metabolic targets and mediators in the glycerophospholipid metabolism. Furthermore, administration of NS alone exhibited greater effects on reversing the elevated the proinflammatory metabolites and mediators in MI rats compared to SF alone. However, individual SF showed greater amelioration of MI-disturbed antioxidant and prooxidative metabolites and better inhibition of the oxidative stress than NS alone. Collectively, our study demonstrated that the capability of NS-SF to regulate both metabolic targets of NS and SF might be the basis of NS-SF to produce a cooperative effect greater than their individual effects that enhance the anti-MI efficacy and provided valuable information for the clinical application of Notoginseng-Safflower pair.
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http://dx.doi.org/10.1016/j.biopha.2020.110574DOI Listing
October 2020

High-throughput sequencing of circRNAs reveals novel insights into mechanisms of nigericin in pancreatic cancer.

BMC Genomics 2019 Sep 18;20(1):716. Epub 2019 Sep 18.

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.

Background: Our previous study had proved that nigericin could reduce colorectal cancer cell proliferation in dose- and time-dependent manners by targeting Wnt/β-catenin signaling. To better elucidate its potential anti-cancer mechanism, two pancreatic cancer (PC) cell lines were exposed to increasing concentrations of nigericin for different time periods, and the high-throughput sequencing was performed to explore the circRNA expression profiles after nigericin exposure on pancreatic cancer (PC) cells.

Results: In this study, a total of 183 common differentially expressed circRNAs were identified, and the reliability and validity of the sequencing data were verified by the PCR analysis. According to the parental genes of circRNAs, the GO analysis was performed to predict the most enriched terms in the biological process, cellular components and molecular functions. The KEGG analysis and pathway-pathway network exhibited the potential signal pathways and their regulatory relationships. Meanwhile, a potential competing endogenous RNA (ceRNA) mechanism through a circRNA-miRNA-mRNA network was applied to annotate potential functions of these common differentially expressed circRNAs, and these predicted miRNAs or mRNAs might be involved in nigericin damage.

Conclusions: By the bioinformatics method, our data will facilitate the understanding of nigericin in PC cells, and provide new insight into the molecular mechanism of nigericin toward cancer cells. This is the first report that discusses the potential functions of nigericin in cancers through the bioinformatics method. Our data will facilitate the understanding of nigericin-mediated anti-cancer mechanisms in PC.
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http://dx.doi.org/10.1186/s12864-019-6032-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749718PMC
September 2019

Effects of patient-controlled analgesia with hydromorphone or sufentanil on postoperative pulmonary complications in patients undergoing thoracic surgery: a quasi-experimental study.

BMC Anesthesiol 2018 12 19;18(1):192. Epub 2018 Dec 19.

Department of Anesthesiology, Anesthesiology of Xinqiao Hospital of Third Military Medical University, Shapingba District, Chongqing, 400037, China.

Objective: To compare the analgesic effects of patient-controlled intravenous analgesia (PCA) with hydromorphone and sufentanil after thoracic surgery on postoperative pulmonary complications (PPCs).

Methods: A total of 142 patients who were scheduled for thoracic surgery were randomly allocated to receive PCA with hydromorphone (group A: experimental group): hydromorphone 0.2 mg/kg + dezocine 0.5 mg/kg + ramosetron 0.6 mg diluted with normal saline to 200 mL; or with sufentanil (group B: control group): sufentanil 3.0μg/kg + dezocine 0.5 mg/kg + ramosetron 0.6 mg diluted with normal saline to 200 mL. The parameters of intravenous analgesia pump were set as background dose 4 ml/h, PCA dose 1 mL, locking time 15 min. Pain NRS (numerical rating scale), Ramsay sedation score, nausea or vomiting score were evaluated at 0 h, 6 h, 12 h, 24 h, 48 h after operation. The cases of PPCs (atelectasis, pulmonary infection, respiratory failure), CRP (C-reaction protein) and inflammatory cells (white cell count and percentage of neutrophils) and blood gas analysis at 12 h after operation, length of ICU and postoperative stay were recorded for each patient.

Results: Data of 136 patients were analyzed. Compared with group B (4[IQR:2,2]), the pain NRS in group A (2[IQR:4,4]) was significantly lower at 6 h after operation (P = 0.000). The CRP in group A (69.79 ± 32.13 mg/L) were lower than group B (76.76 ± 43.42 mg/L) after operation, but the difference was not significant (P = 0.427). No difference of nausea or vomiting was found between group A (7.3%) and group B (5.8%) postoperatively (P = 0.999). The PPCs were happened in 11 patients in group A (16.2%) and 22 patients in group B (32.4%) and the difference between two groups was significant (P = 0.027). Seven patients in group A (10.3%) and eighteen patients in group B (26.5%) had clinical evidence of pneumonia and the difference between two groups was significant (P = 0.014). The length of ICU and postoperative stay in group A were 2.73 h and 1.82 days less than group B respectively but the differences were not significant (P = 0.234, P = 0.186 respectively).

Conclusion: Compared with sufentanil, hydromorphone may provide better postoperative analgesic effect with less pulmonary complications for patients undergoing thoracic surgery, and it may accelerate patients' rehabilitation.

Trial Registration: Randomized Controlled Trials ChiCTR1800014282c . Registered 3 January 2018.
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http://dx.doi.org/10.1186/s12871-018-0657-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300916PMC
December 2018

Neonatal exposure to propofol affects interneuron development in the piriform cortex and causes neurobehavioral deficits in adult mice.

Psychopharmacology (Berl) 2019 Feb 10;236(2):657-670. Epub 2018 Nov 10.

Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, 400038, People's Republic of China.

Rationale: Animal studies have shown that early postnatal propofol administration is involved in neurobehavioral alterations in adults. However, the underlying mechanism is not clear.

Methods: We used c-Fos immunohistochemistry to identify activated neurons in brain regions of neonatal mice under propofol exposure and performed behavioral tests to observe the long-term consequences.

Results: Exposure to propofol (30g or 60 mg/kg) on P7 produced significant c-Fos expression in the deep layers of the piriform cortex on P8. Double immunofluorescence of c-Fos with interneuron markers in the piriform cortex revealed that c-Fos was specifically induced in calbindin (CB)-positive interneurons. Repeated propofol exposure from P7 to P9 induced behavioral deficits in adult mice, such as olfactory function deficit in a buried food test, decreased sociability in a three-chambered choice task, and impaired recognitive ability of learning and memory in novel object recognition tests. However, locomotor activity in the open-field test was not generally affected. Propofol treatment also significantly decreased the number of CB-positive interneurons in the piriform cortex of mice on P21 and adulthood.

Conclusions: These results suggest that CB-positive interneurons in the piriform cortex are vulnerable to propofol exposure during the neonatal period, and these neurons are involved in the damage effects of propofol on behavior changes. These data provide a new target of propofol neurotoxicity and may elucidate the mechanism of neurobehavioral deficits in adulthood.
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http://dx.doi.org/10.1007/s00213-018-5092-4DOI Listing
February 2019

H NMR-based dynamic metabolomics delineates the therapeutic effects of Baoyuan decoction on isoproterenol-induced cardiac hypertrophy.

J Pharm Biomed Anal 2019 Jan 29;163:64-77. Epub 2018 Sep 29.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People's Republic of China. Electronic address:

Cardiac hypertrophy (CH) is a major risk factor for many serious heart diseases. Sustained CH is catastrophic, resulting in cardiac dysfunction that eventually leads to heart failure (HF). Baoyuan decoction (BYD) is a famous traditional Chinese medicine (TCM) formula for supplementing and reinforcing Qi, clinically used for the treatment of cardiovascular diseases (CVDs). However, the therapeutic effects of BYD on CH remain unidentified. We herein investigated the effect of BYD on isoproterenol (ISO)-induced CH in rats and the underlying mechanisms by comprehensive pharmacodynamics and H NMR-based dynamic metabolomics analysis of the plasma and urine samples. Results showed that BYD treatment markedly attenuated ISO-induced CH as evidenced by decreasing the left ventricular wall thickness, pathological cardiomyocyte hypertrophy, myocardial collagen fiber deposition and apoptosis, and plasma natriuretic peptide levels. Multivariate trajectory analysis revealed that the BYD treatment could restore the CH-disturbed plasma and urinary metabolite profiles towards the normal metabolic status featuring with a time-dependent tendency. Moreover, the key metabolic alterations in CH rats at different BYD-treated time stages involved energy metabolism, oxidative stress responses, amino acid metabolism, and gut microbiota metabolism. Of particularly, the significant roles of BYD for treating CH lie in the improvement of cardiac energy generation and antioxidant capacity. Our investigation provides a holistic view of BYD for therapeutic intervention of CH through monitoring of the dynamic metabolic changes and the results indicate that BYD may be applied as a potential agent for treating CH.
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http://dx.doi.org/10.1016/j.jpba.2018.09.049DOI Listing
January 2019

Integration of Metabolomics With Pharmacodynamics to Elucidate the Anti-myocardial Ischemia Effects of Combination of Notoginseng Total Saponins and Safflower Total Flavonoids.

Front Pharmacol 2018 25;9:667. Epub 2018 Jun 25.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.

Notoginseng (Sanqi), the roots and rhizomes of and safflower, the flowers of , are widely used traditional Chinese medicines (TCMs) for the treatment of cardiovascular diseases. Positive evidences have fueled growing acceptance for cardioprotective effects of the combination of the notoginseng total saponins and safflower total flavonoids (CNS) against myocardial ischemia (MI). However, the underlying cardioprotective mechanisms of CNS are still obscured. Metabolomics is a comprehensive tool for investigating biological mechanisms of disease, monitoring therapeutic outcomes, and advancing drug discovery and development. Herein, we investigated the cardioprotective effects of CNS on the isoproterenol (ISO)-induced MI rats by using plasma and urine metabolomics based on ultra-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS) and multiple pharmacodynamics approaches. The results showed that pretreatment with CNS could attenuate the cardiac injury resulting from ISO, as evidenced by decreasing the myocardial infarct size, converting the echocardiographic, histopathological, and plasma biochemical abnormalities, and reversing the perturbations of plasma and urine metabolic profiles, particularly for the 55.0 mg/kg dosage group. In addition, 44 metabolites were identified as the potential MI biomarkers, mainly including a range of free fatty acids (FFAs), sphingolipids, and glycerophospholipids. CNS pretreatment group may robustly ameliorate these potential MI-related biomarkers. The accumulation of LysoPCs and FFAs, caused by PLA, may activate NF-κB pathway and increase proinflammatory cytokines. However, our results showed that CNS at 55.0 mg/kg dosage could maximally attenuate the NF-κB signaling pathway, depress the expressions of TNF-α, IL-6, IL-1β, and PLA. The results suggested that the anti-inflammatory property of CNS may contribute to its cardioprotection against MI. Our results demonstrate that the integrating of metabolomics with pharmacodynamics provides a reasonable approach for understanding the therapeutic effects of TCMs and CNS provide a potential candidate for prevention and treatment of MI.
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http://dx.doi.org/10.3389/fphar.2018.00667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026671PMC
June 2018

Integration of Metabonomics and Transcriptomics Reveals the Therapeutic Effects and Mechanisms of Decoction for Myocardial Ischemia.

Front Pharmacol 2018 23;9:514. Epub 2018 May 23.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.

Myocardial ischemia (MI) is an escalating public health care burden worldwide. decoction (BYD) is a traditional Chinese medicine formula with cardioprotective activity; however, its pharmacological characteristics and mechanisms are obscured. Herein, a multi-omics strategy via incorporating the metabonomics, transcriptomics, and pharmacodynamics was adopted to investigate the effects and molecular mechanisms of BYD for treating MI in a rat model of left anterior descending coronary artery (LADCA) ligation. The results indicated that BYD has a significantly cardioprotective role against MI by decreasing the infarct size, converting the echocardiographic abnormalities and myocardial enzyme markers, and reversing the serum metabolic disorders and myocardial transcriptional perturbations resulting from MI. Integrated bioinformatics analysis and literature reports constructed the interaction network based on the changes of the key MI targeted-metabolites and transcripts after BYD treatment and disclosed that the cardioprotection of BYD is mainly involved in the regulation of energy homeostasis, oxidative stress, apoptosis, inflammation, cardiac contractile dysfunction, and extracellular matrix remodeling. The results of histopathological examination, quantitative RT-PCR assay, cardiac energy synthesis, and serum antioxidant assessment complemented the multi-omics findings, and indicated the multi-pathway modulation mechanisms of BYD. Our investigation demonstrated that the multi-omics approach could achieve a complementary and verified view for the comprehensive evaluation of therapeutic effects and complex mechanisms of TCMF like BYD.
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http://dx.doi.org/10.3389/fphar.2018.00514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974172PMC
May 2018

Preoperative hemoglobin-platelet ratio can significantly predict progression and mortality outcomes in patients with T1G3 bladder cancer undergoing transurethral resection of bladder tumor.

Oncotarget 2018 Apr 3;9(26):18627-18636. Epub 2018 Jan 3.

Department of Urology, The Second Hospital of Tianjin Medical University, Hexi District, Tianjin 300211, China.

Objective: To investigate the prognostic role of hematological biomarkers, especially hemoglobin-platelet ratio (HPR) in the oncological outcomes in stage 1 and grade 3 (T1G3) bladder cancer.

Materials And Methods: We identified 457 T1G3 bladder cancer patients who underwent transurethral resection of the bladder (TURB) between 2009 and 2014. Based on hematological parameters (hemoglobin-platelet ratio (HPR), hemoglobin, and platelet counts), recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) and cancer-specific survival (CSS) were analyzed by using Kaplan-Meier analysis. Multivariate Cox regression model was adopted to identify the predictors of oncological outcomes.

Results: Kaplan-Meier survival analysis showed that low HPR (< 0.615), low hemoglobin (< 125g/l) and elevated platelet counts (> 240 × 10/μl) were correlated with poor OS. Low HPR, but not low hemoglobin and high platelet counts, is associated with worse PFS. Low HPR and low hemoglobin, but not elevated platelet counts, are associated with worse CSS. However, no significant difference was observed in RFS according to any of these hematological markers. On multivariate analysis, low HPR (HR = 1.27, 95% CI = 0.81-1.75, = 0.030), low hemoglobin (HR = 1.20, 95% CI = 0.79-1.84, = 0.028) and elevated platelet counts (HR = 1.07, 95% CI = 0.72-1.32, = 0.038) were significantly associated with OS. Low hemoglobin (HR = 1.08, 95% CI = 0.68-1.82, = 0.041) was significantly linked with CSS. Particularly, low HPR was identified as an independent predictor of PFS (HR = 1.16, 95% CI = 0.97-1.49, = 0.033) and CSS (HR = 1.14, 95% CI = 0.87-1.78, = 0.029).

Conclusions: Preoperative HPR can be taken into account as a factor predictive of oncological outcomes for T1G3 bladder cancer, particularly disease progression and mortality outcomes.
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http://dx.doi.org/10.18632/oncotarget.23896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915098PMC
April 2018

The expression of vasohibin-1 and its prognostic significance in bladder cancer.

Exp Ther Med 2017 Oct 18;14(4):3477-3484. Epub 2017 Aug 18.

Department of Urology, Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.

Angiogenesis is important in the development of solid tumors. Vasohibin-1 (VASH-1) is an endothelium-derived protein that acts as an inhibitor of angiogenesis in many different types of cancer. However, the expression of VASH-1 and its clinical value in bladder cancer remain unknown. The current study analyzed the expression of VASH-1, as well as the expression of the angiogenesis-related factors vascular endothelial growth factor-A, hypoxia inducible factor-1α and cluster of differentiation 34 in bladder cancer tissues from 50 patients using immunohistochemistry. The associations between the expression of these factors and the clinicopathological characteristics of the patients were assessed. The current study demonstrated that VASH-1 is primarily expressed in the cytoplasm of bladder cancer cells and in a fraction of vascular endothelial cells. Furthermore, the expression of VASH-1 was positively associated with the tumor stage (P<0.01), pathological grade (P<0.01) and distant metastasis (P<0.05) but not with patient age or sex (P>0.05). Spearman rank correlation tests indicated that levels of those four factors were positively correlated with each other. Kaplan-Meier analysis indicated that high expression of these four factors was significantly associated with lower 5-year overall survival and progression-free survival rates. Collectively, the results of the current study suggest that VASH-1 is clinically significant in bladder cancer and its high expression may predict the progression and prognosis of patients with bladder cancer. The present study also implies that VASH-1 may be a novel target for vascular targeting therapy.
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http://dx.doi.org/10.3892/etm.2017.4969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639433PMC
October 2017

Expression of circular RNA circASXL1 correlates with TNM classification and predicts overall survival in bladder cancer.

Int J Clin Exp Pathol 2017 1;10(8):8495-8502. Epub 2017 Aug 1.

Department of Urology, The Second Hospital of Tianjin Medical University Tianjin, China.

Circular RNAs (circRNAs) as a family of non-coding RNAs are increasingly recognized regarding their biogenesis, regulatory roles in gene expression and clinic significance in developmental diseases and cancers. In this study, we aim to identify circRNAs that may be associated with clinicopathological characteristics of patients with bladder cancer. The circRNAs databases CircBase and circ2 Traits were used to seek circRNAs reported to bladder cancer. The expression levels of the circRNA of interest in paired samples of tumor tissue and adjacent normal mucosa from 61 patients with bladder cancer were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and statistically analyzed. Database search shows that circASXL1 (circBase ID: hsa_circ_0001136) transcribed from the ASXL1 gene locus is among the circRNAs with altered expressions in bladder cancer. Results showed that the expression level of circASXL1 was significantly higher in bladder cancer tissues compared to that in adjacent noncancerous tissues (P<0.001). To be noticed, chi-square tests support that the expression of circASXL1 significantly correlates with tumor grade (=0.025), tumor stage (=0.019), lymph node invasion (=0.011) and distant metastasis (=0.032). The area under ROC curve (AUC) is 0.770 for circASXL1 in predicting tumor invasion (T2-T4 tumors). Kaplan-Meier survival analysis indicates that tumors of high circASXL1 expression are associated with shorter overall survival compared to tumors of low circASXL1 expression. Further, multivariate analysis reveals that circASXL1 is an independent prognostic factor for overall survival for patients with bladder cancer. Expression of circASXL1 in bladder tumor correlates with TNM classification and may independently predict overall survival for patients with bladder cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965445PMC
August 2017

Liver X Receptor β Is Involved in Formalin-Induced Spontaneous Pain.

Mol Neurobiol 2017 03 5;54(2):1467-1481. Epub 2016 Feb 5.

Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, 400038, China.

Increasing evidence indicates that the liver X receptor(LXR) β modulates inflammatory pain. However, the molecular mechanisms through which LXRβ modulates pain are unclear. Here, we found that LXRβ-null mice responded more strongly to acute noxious stimuli than wild-type (WT) littermates (in the hot plate and Hargreaves tests) and had augmented tonic inflammatory pain (in the formalin test). This increased reactivity to inflammatory pain was accompanied by enhanced formalin-evoked Fos and pERK staining of second-order nociceptive neurons. Immunohistochemistry showed that the expression of CGRP, SP, and IB4 was increased in the lamina I-II of the lumbar dorsal horns in formalin-injected LXRβ knockout (KO) mice compared with the WT controls. In addition, LXRβ deletion in the mice enhanced the formalin-induced inflammation with more activated microglia and astrocytes in the spinal cord. Furthermore, the levels of pro-inflammatory cytokines (IL-1β ,TNF-α) as well as NFκB in the formalin-injected paw were elevated by the loss of LXRβ. Taken together, these data indicate that LXRβ is involved in acute as well as inflammatory pain, and thus, it may be considered as a new target for the development of analgesics.
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http://dx.doi.org/10.1007/s12035-016-9737-1DOI Listing
March 2017

Ex Vivo Assay of Electrical Stimulation to Rat Sciatic Nerves: Cell Behaviors and Growth Factor Expression.

J Cell Physiol 2016 Jun 20;231(6):1301-12. Epub 2015 Nov 20.

Département de chirurgie, Faculté de médecine, Centre de recherche du CHU de Québec, Université Laval, Québec (QC), Canada.

Neurite outgrowth and axon regeneration are known to benefit from electrical stimulation. However, how neuritis and their surroundings react to electrical field is difficult to replicate by monolayer cell culture. In this work freshly harvested rat sciatic nerves were cultured and exposed to two types of electrical field, after which time the nerve tissues were immunohistologically stained and the expression of neurotrophic factors and cytokines were evaluated. ELISA assay was used to confirm the production of specific proteins. All cell populations survived the 48 h culture with little necrosis. Electrical stimulation was found to accelerate Wallerian degeneration and help Schwann cells to switch into migratory phenotype. Inductive electrical stimulation was shown to upregulate the secretion of multiple neurotrophic factors. Cellular distribution in nerve tissue was altered upon the application of an electrical field. This work thus presents an ex vivo model to study denervated axon in well controlled electrical field, bridging monolayer cell culture and animal experiment. It also demonstrated the critical role of electrical field distribution in regulating cellular activities.
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http://dx.doi.org/10.1002/jcp.25230DOI Listing
June 2016

Prospects of boswellic acids as potential pharmaceutics.

Planta Med 2015 Mar 25;81(4):259-71. Epub 2015 Feb 25.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.

Boswellic acids have long been considered the main bioactive components of frankincense, and many studies in vitro and in animals as well as several clinical studies have confirmed their various bioactivities. In particular, a large number of mechanistic studies have confirmed their anti-inflammatory and antitumor activities. However, not every boswellic acid exhibits a satisfactory pharmacological performance, which depends on the chemical structure and functional groups of the acid. To enhance the pharmacological values of boswellic acids, derivatization has been specifically applied with the aim of discovering more active derivatives of BAs. In addition, the preliminary pharmacokinetic studies of these compounds using various standard methods show their poor bioavailability in humans and rodents, which has led to questions of their pharmacological relevance and potentially limits their use in clinical practice and pharmaceutical development. To improve these effects, some approaches have shown some improvements in effectiveness, and the new formula compatibility approach is considered a very reasonable method for improving the bioavailability of boswellic acids.
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http://dx.doi.org/10.1055/s-0034-1396313DOI Listing
March 2015

Propofol Administration During Early Postnatal Life Suppresses Hippocampal Neurogenesis.

Mol Neurobiol 2016 Mar 11;53(2):1031-1044. Epub 2015 Jan 11.

Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, 400038, People's Republic of China.

Propofol is currently one of the most widely used intravenous anesthetics and has been indicated to induce cognitive dysfunction in adults. Here, we investigated the effects of propofol exposure during early postnatal life on hippocampal neurogenesis. Propofol (30 or 60 mg/kg) was administered to mice on either postnatal day (P) 7 or P7-P9; cell proliferation and neurogenesis in the dentate gyrus (DG) were evaluated on P8 or P17. It showed that exposure to propofol on P7 decreased hippocampal cell proliferation as indicated by BrdU and Sox2 immunostaining at P8 in propofol treatment at the dosage of 60 mg/kg but not at the dosage of 30 mg/kg. Western blots revealed propofol treatment decreased Akt or extracellular signal-related kinase (ERK) 1/2 phosphorylation in the hippocampus at P8. Propofol treatment on P7 to P9 reduced the numbers of newly formed neurons in the DG at P17, which was accompanied by delay of granule neuron maturation and decreased the density of dendritic spines, particularly the mushroom-shaped mature spines. Furthermore, the in vitro findings indicated propofol suppressed cell proliferation and cell mitosis and activated apoptosis of C17.2 neural stem cell line in a dose-dependent manner. These findings suggest that propofol impairs cell proliferation and inhibits neurogenesis in the immature mouse brain and thus is possibly involved in the cognitive dysfunction induced by propofol anesthesia.
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http://dx.doi.org/10.1007/s12035-014-9052-7DOI Listing
March 2016

Mesenchymal stem cells promote liver regeneration and prolong survival in small-for-size liver grafts: involvement of C-Jun N-terminal kinase, cyclin D1, and NF-κB.

PLoS One 2014 5;9(12):e112532. Epub 2014 Dec 5.

Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: The therapeutic potential of mesenchymal stem cells (MSCs) has been highlighted recently for treatment of acute or chronic liver injury, by possibly differentiating into hepatocyte-like cells, reducing inflammation, and enhancing tissue repair. Despite recent progress, exact mechanisms of action are not clearly elucidated. In this study, we attempted to explore whether and how MSCs protected hepatocytes and stimulated allograft regeneration in small-for-size liver transplantation (SFSLT).

Methods: SFSLT model was established with a 30% partial liver transplantation (30PLT) in rats. The differentiation potential and characteristics of bone marrow derived MSCs were explored in vitro. MSCs were infused transvenously immediately after graft implantation in therapy group. Expressions of apoptosis-, inflammatory-, anti-inflammatory-, and growth factor-related genes were measured by RT-PCR, activities of transcription factors AP-1 and NF-κB were analyzed by EMSA, and proliferative responses of the hepatic graft were evaluated by immunohistochemistry and western blot.

Results: MSCs were successfully induced into hepatocyte-like cells, osteoblasts and adipocytes in vitro. MSCs therapy could not only alleviate ischemia reperfusion injury and acute inflammation to promote liver regeneration, but also profoundly improve one week survival rate. It markedly up-regulated the mRNA expressions of HGF, Bcl-2, Bcl-XL, IL-6, IL-10, IP-10, and CXCR2, however, down-regulated TNF-α. Increased activities of AP-1 and NF-κB, as well as elevated expressions of p-c-Jun, cyclin D1, and proliferating cell nuclear antigen (PCNA), were also found in MSCs therapy group.

Conclusion: These data suggest that MSCs therapy promotes hepatocyte proliferation and prolongs survival in SFSLT by reducing ischemia reperfusion injury and acute inflammation, and sustaining early increased expressions of c-Jun N-terminal Kinase, Cyclin D1, and NF-κB.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0112532PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257551PMC
July 2015

[Observation of the use of percutaneous tracheostomy tube for closed drainage of pneumothorax in intensive care unit].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2014 Dec;26(12):901-4

Department of Critical Care Medicine, Harrison International Peace Hospital, Hebei Medical University, Hengshui 053000, Hebei, China, Corresponding author: Liu Shuhong, Email:

Objective: To explore the effect of the transcutaneous tracheostomy tube in patients with pneumothorax and its clinical value.

Methods: A prospective randomized controlled trial was conducted. Thirty-two patients with pneumothorax admitted to Department of Critical Care Medicine of Harrison International Peace Hospital of Hebei Medical University from June 2010 to June 2014 were enrolled. The patients were divided into control group and observation group, with 16 cases in each group. Beside the treatment for primary disease, the patients in control group received thoracic close drainage with traditional silica gel tube as performed by thoracic surgeons, and those in observation group received thoracic close drainage with transcutaneous tracheostomy tube by intensive care doctors. The curative effect and complications of the two groups were observed.

Results: Compared with control group, the time from diagnosis to operation (minutes:8.00 ± 1.36 vs. 23.06 ± 3.83, t=14.790, P=0.000) and the operation time were significantly shortened (days:5.37 ± 1.02 vs. 7.31 ± 1.70, t=7.286, P=0.000), the frequency of drainage tube replacement (times: 0.18 ± 0.40 vs. 3.87 ± 1.14, t=12.128, P=0.000) and the times of repeated chest radiography (times:1.12 ± 0.34 vs. 2.93 ± 0.77, t=8.589, P=0.000) in observation group were significantly reduced, the length of hospital day was significantly shortened (days:8.30 ± 1.37 vs. 24.56 ± 5.62, t=17.289, P=0.000), the rates of dislocation of drainage tube (0 vs. 3 cases), obstruction of the tube (0 vs. 5 cases), and subcutaneous emphysema (3 vs. 16 cases) were reduced obviously, but there was no difference in incidence of incision infection (1 vs. 3 cases) and infection of thoracic cavity (0 vs. 2 cases).

Conclusions: The usage of transcutaneous tracheostomy tube in patients with pneumothorax is safe and simple. Doctors in ICU can independently do this procedure, and its effect is positive.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2014.12.011DOI Listing
December 2014

Comprehensive identification of active triterpenoid metabolites in frankincense using a coupling strategy.

J Chromatogr B Analyt Technol Biomed Life Sci 2014 Jul 4;963:90-8. Epub 2014 Jun 4.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China; Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China. Electronic address:

Frankincense resins are extensively used as natural remedies in regions ranging from North Africa to China. Triterpenoid metabolites from frankincense exhibit notable anti-inflammatory and anti-tumor properties. In the present paper, without the use of an isolation process, the fragmentation rules and NMR spectral characteristics of triterpenoid metabolites in frankincense are summarized through a coupling method using high performance liquid chromatography-diode array detection/electrospray ionization tandem mass spectrometry (HPLC-DAD/ESI-MS(n)) combined with HPLC-nuclear magnetic resonance (NMR) experiments. Based on this groundwork, a coupling strategy for the comprehensive metabolic profiling of active triterpenoid metabolites from enriched fractions of frankincense was developed. The proposed strategy may serve as a method for the holistic screening of bioactive metabolites in complex TCM samples.
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http://dx.doi.org/10.1016/j.jchromb.2014.05.054DOI Listing
July 2014

1H-NMR-based metabolic analysis of human serum reveals novel markers of myocardial energy expenditure in heart failure patients.

PLoS One 2014 5;9(2):e88102. Epub 2014 Feb 5.

Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China ; Key Laboratory For Organ Failure Research, Ministry of Education of the People's Republic of China, Guangzhou, China.

Objective: Elevated myocardial energy expenditure (MEE) is related with reduced left ventricular ejection fraction, and has also been documented as an independent predictor of cardiovascular mortality. However, the serum small-molecule metabolite profiles and pathophysiological mechanisms of elevated MEE in heart failure (HF) are still lacking. Herein, we used 1H-NMR-based metabolomics analysis to screen for potential biomarkers of MEE in HF.

Methods: A total of 61 subjects were enrolled, including 46 patients with heart failure and 15 age-matched controls. Venous serum samples were collected from subjects after an 8-hour fast. An INOVA 600 MHz nuclear magnetic resonance spectrometer with Carr-Purcell-Melboom-Gill (CPMG) pulse sequence was employed for the metabolomics analysis and MEE was calculated using colored Doppler echocardiography. Metabolomics data were processed using orthogonal signal correction and regression analysis was performed using the partial least squares method.

Results: The mean MEE levels of HF patients and controls were 139.61±58.18 cal/min and 61.09±23.54 cal/min, respectively. Serum metabolomics varied with MEE changed, and 3-hydroxybutyrate, acetone and succinate were significantly elevated with the increasing MEE. Importantly, these three metabolites were independent of administration of angiotensin converting enzyme inhibitor, β-receptor blockers, diuretics and statins (P>0.05).

Conclusions: These results suggested that in patients with heart failure, MEE elevation was associated with significant changes in serum metabolomics profiles, especially the concentration of 3-hydroxybutyrate, acetone and succinate. These compounds could be used as potential serum biomarkers to study myocardial energy mechanism in HF patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0088102PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914925PMC
September 2014

Mesenchymal stem cell-conditioned medium reduces liver injury and enhances regeneration in reduced-size rat liver transplantation.

J Surg Res 2013 Aug 6;183(2):907-15. Epub 2013 Mar 6.

Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University Medical School, Shanghai, China.

Background: Mesenchymal stem cell (MSC) therapy can prevent parenchymal cell loss and promotes tissue repair through the action of trophic, secreted molecules. In this study, we investigated whether MSC-conditioned medium (MSC-CM) could protect hepatocytes and sinusoidal endothelial cells (SECs) and stimulate their regeneration in 50% reduced-size liver transplantation (RSLT).

Materials And Methods: Rats were randomly divided into three groups: sham-operated group, MSC-CM group (rats with 50% RSLT receiving MSC-CM infusion), and medium group (rats with 50% RSLT receiving medium therapy). Graft function, proinflammatory cytokines, incidence of apoptosis, proliferation of hepatocytes and SECs, and the expression of vascular endothelial growth factor and matrix metallopeptidase 9 were assessed in this study.

Results: Systemic infusion of MSC-CM prevented the release of liver injury biomarkers and provided a significant survival benefit. Furthermore, MSC-CM therapy resulted in reduction of apoptosis of hepatocytes and SECs. The number of proliferating hepatocytes and SECs increased 1.2- and 1.6-fold, respectively, accompanied by a decrease in the expression levels of several proinflammatory cytokines and a noticeable decrease in infiltration of neutrophils and activation of Kupffer cells. Also, increased expression of vascular endothelial growth factor and matrix metallopeptidase 9 in the grafts was observed after MSC-CM therapy.

Conclusions: These data suggest that MSC-CM therapy in RSLT provides trophic support to the injured liver by inhibiting SEC and hepatocellular death and stimulating their regeneration.
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http://dx.doi.org/10.1016/j.jss.2013.02.009DOI Listing
August 2013

Mesenchymal stem cells overexpressing C-X-C chemokine receptor type 4 improve early liver regeneration of small-for-size liver grafts.

Liver Transpl 2013 Feb;19(2):215-25

Department of General Surgery, Xinhua Hospital, Shanghai, People's Republic of China.

Mesenchymal stem cell (MSC) therapy can prevent hepatic parenchymal cell loss and promote tissue repair. However, poor MSC engraftment is one of the primary barriers to the effectiveness of cell therapy because culture-expanded MSCs progressively down-regulate C-X-C chemokine receptor type 4 (CXCR4) expression and lose their ability to migrate toward a concentration gradient of stromal cell-derived factor 1a (SDF1a). In this study, we investigated whether a CXCR4-MSC infusion could protect hepatocytes and stimulate regeneration in 50% reduced size liver transplantation (RSLT). Rats that underwent 50% RSLT were randomly divided into 3 groups: a phosphate-buffered solution group (PBS), a green fluorescent protein (GFP)-MSC group, and a CXCR4-MSC group. Rats received 1 mL of PBS with or without a resuspension of GFP-MSCs or CXCR4-MSCs. The factors secreted by MSCs, the graft function, the apoptosis and proliferation of hepatocytes, the efficacy of MSC engraftment, and the expression of SDF1α, albumin (Alb), and cytokeratin 18 (CK18) in engrafted GFP-positive MSCs were assessed. A systemic infusion of GFP-MSCs led to a reduction of the release of liver injury biomarkers and apoptosis of hepatocytes; CXCR4 overexpression did not further reduce the liver injury. However, CXCR4 overexpression enhanced MSC engraftment in liver grafts, improved the effect on the proliferation of hepatocytes, and thus provided a significant 1-week survival benefit. SDF1α expression in grafts was elevated after transplanted CXCR4-MSCs were recruited to the remnant liver. However, engrafted MSCs did not express the markers of hepatocytes, including Alb and CK18, in vivo 168 hours after transplantation. CXCR4 overexpression enhanced the mobilization and engraftment of MSCs into small-for-size liver grafts, in which these cells promoted the early regeneration of the remnant liver not by direct differentiation but perhaps by a paracrine mechanism.
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http://dx.doi.org/10.1002/lt.23577DOI Listing
February 2013
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