Publications by authors named "Jingyuan Xu"

49 Publications

Chemoproteomic profiling reveals celastrol as a potential modulator of cholesterol signaling.

Chem Commun (Camb) 2022 Jan 18. Epub 2022 Jan 18.

School of Biotechnology and Food Engineering, Changshu Institute of Technology, Suzhou 215500, China.

We report a quantitative chemoproteomic approach that utilizes a clickable photoreactive probe for global profiling of celastrol targets, which may significantly improve the current understanding of celastrol's mode of action.
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http://dx.doi.org/10.1039/d1cc05986fDOI Listing
January 2022

NLRP3 promotes immune escape by regulating immune checkpoints: A pan-cancer analysis.

Int Immunopharmacol 2022 Jan 10;104:108512. Epub 2022 Jan 10.

Department of Hepatobiliary Pancreatic Surgery, the First Hospital of Ningbo City, Ningbo 315010, China. Electronic address:

NLRP3 plays a pathogenic role in tumorigenesis by regulating innate and acquired immunity, apoptosis, differentiation, and intestinal microbes in tumors. Our research aimed to investigate the role of NLRP3 in pan-cancers based on multi-omics data in the TCGA database. Most types of tumors showed increased expression of NLRP3. Among them, the overexpressed NLRP3 in liver hepatocellular carcinoma (LIHC) and ovarian cancer (OV) indicated worse overall survival (OS). Further analysis also confirmed overexpressed NLRP3 in colon cancer (COAD) indicated a high probability of microsatellite instability (MSI) and low tumor mutational burden (TMB), which indicated a better response to immune checkpoint inhibitors (ICIs). Interestingly, overexpression of NLRP3 was closely related to high infiltration of immune cells (T cells, B cells, etc.) and overexpressed immune checkpoints (PD-1, PD-L1, LAG3, etc.). These results demonstrated NLRP3 promoted immune escape in cancers. Finally, we investigated the expression of various immune checkpoints by treating NLRP3 inhibitor MCC950 during the co-culture of peripheral blood mononuclear cells (PBMC) and LIHC cell line Hep3B. MCC950 significantly repressed the expression of PD-L1 and LAG3, and promoted the apoptosis rate of Hep3B. In conclusion, our research demonstrated the role of NLRP3 in pan-cancer, especially in LIHC. Inhibition of NLRP3 promoted the killing effect of T cells to cancer cells by repressing the expression of immune checkpoints.
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http://dx.doi.org/10.1016/j.intimp.2021.108512DOI Listing
January 2022

Acoustic characteristics of looped-tube thermoacoustic refrigerators with external and in-built acoustic drivers: A comparative study.

J Acoust Soc Am 2021 Dec;150(6):4406

Clean Energy Processes Laboratory, Department of Chemical Engineering, Imperial College London, London, SW7 2AZ, United Kingdom.

Thermoacoustic refrigerators (TARs) are in the first place acoustic systems. It is indispensable to conduct an acoustic analysis of the entire system before a thermodynamic analysis of the thermoacoustic core. This study focuses on the acoustic characteristics of looped-tube TARs integrated with single (or dual) external (or in-built) acoustic driver(s). System-level acoustic models are established for the looped-tube TARs, and their acoustic performances are discussed and compared. Results show that looped-tube TARs with a single acoustic driver have a standing-wave acoustic field no matter whether the configuration is symmetric or not. The eigenmodes of the TAR are not influenced by the location of the external acoustic driver but are affected by the location of the in-built acoustic driver. New pairs of resonance and anti-resonance frequencies show up for TARs with an asymmetric configuration. Compared with looped-tube TARs with a single external (or in-built) acoustic driver, looped-tube TARs with dual external (or in-built) acoustic drivers have the same (or different) eigenmodes. A standing-wave acoustic field is present inside the loop only when the two acoustic drivers work in in-phase and anti-phase modes. At other phase differences between the two acoustic drivers, the acoustic field inside the loop becomes hybrid, containing both standing- and traveling-wave components. The theoretical methodology and analytical results in this study are valuable in comprehending the acoustic behavior of electrically-driven looped-tube TARs, providing useful guidelines for the active control of acoustic field and heat transport in the thermoacoustic core.
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http://dx.doi.org/10.1121/10.0009034DOI Listing
December 2021

Management of acne vulgaris: summary of NICE guidance.

BMJ 2021 09 20;374:n1800. Epub 2021 Sep 20.

University of Southampton, Southampton, UK.

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http://dx.doi.org/10.1136/bmj.n1800DOI Listing
September 2021

Sudden coma at the onset of severe refractory thrombotic thrombocytopenic purpura with successful treatment.

Transfus Apher Sci 2021 Dec 30;60(6):103225. Epub 2021 Jul 30.

Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, PR China. Electronic address:

Most patients develop coma several days after the onset of thrombotic thrombocytopenic purpura (TTP) caused by microvascular occlusion. However, aggravated coma as the first symptom of TTP has rarely been reported. Although plasma exchange (PEX) and steroids have reduced mortality, the prognosis of patients with TTP is still poor. We reported a patient with refractory TTP presenting with aggravated coma on admission. After days of successful PEX, rituximab, and glucocorticoid therapy for clinical remission, the patient regained consciousness and returned to his normal life with a good outcome. Our case highlights that TTP should be considered when coma occurs as the first symptom.
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http://dx.doi.org/10.1016/j.transci.2021.103225DOI Listing
December 2021

Hip Landmark Detection With Dependency Mining in Ultrasound Image.

IEEE Trans Med Imaging 2021 12 30;40(12):3762-3774. Epub 2021 Nov 30.

Developmental dysplasia of the hip (DDH) is a common and serious disease in infants. Hip landmark detection plays a critical role in diagnosing the development of neonatal hip in the ultrasound image. However, the local confusion and the regional weakening make this task challenging. To solve these challenges, we explore the stable hip structure and the distinguishable local features to provide dependencies for hip landmark detection. In this paper, we propose a novel architecture named Dependency Mining ResNet (DM-ResNet), which investigates end-to-end dependency mining for more accurate and much faster hip landmark detection. First of all, we convert the landmark detection to the heatmap estimation by ResNet to build a strong baseline architecture for fast and accurate detection. Secondly, a dependency mining module is explored to mine the dependencies and leverage both the local and global information to decline the local confusion and strengthen the weakening region. Thirdly, we propose a simple but effective local voting algorithm (LVA) that seeks trade-off between long-range and short-range dependencies in the hip ultrasound image. Besides, a dataset with 2000 annotated hip ultrasound images is constructed in our work. It is the first public hip ultrasound dataset for open research. Experimental results show that our method achieves excellent precision in hip landmark detection (average point error of 0.719mm and successful detection rate within 1mm of 79.9%).
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http://dx.doi.org/10.1109/TMI.2021.3097355DOI Listing
December 2021

Comprehensive Transcriptome Analysis of Rare Plants under NO stress.

Genes (Basel) 2021 05 17;12(5). Epub 2021 May 17.

College of Landscape Architecture, Nanjing Forestry University, Nanjing 210037, China.

We evaluated a transcriptome using high-throughput Illumina HiSeq sequencing and related it to the morphology, leaf anatomy, and physiological parameters of under NO stress. The molecular mechanism of the NO stress response was evaluated using sequencing data. NO stress adversely affected the morphology, leaf anatomy, and total peroxidase (POD) activity. Through RNA-seq analysis, we used NCBI to compare the transcripts with nine databases and obtained their functional annotations. We annotated up to 2255 million clean Illumina paired-end RNA-seq reads, and 250,200 unigene sequences were assembled based on the resulting transcriptome data. More than 89% of the transcripts were functionally annotated. Under NO stress, 1119 genes were upregulated and 1240 were downregulated. According to the KEGG pathway and GO analyses, photosynthesis, chloroplasts, plastids, and the stimulus response are related to NO stress. Additionally, NO stress changed the expression of POD families, and the , , and genes exhibited high expression. The transcriptome analysis of leaves under NO stress supplies a reference for studying the molecular mechanism of resistance to NO stress. The given transcriptome data represent a valuable resource for studies on plant genes, which will contribute towards genome annotations during future genome projects.
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http://dx.doi.org/10.3390/genes12050754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156095PMC
May 2021

A new risk factor indicator for papillary thyroid cancer based on immune infiltration.

Cell Death Dis 2021 01 6;12(1):51. Epub 2021 Jan 6.

Department of General Surgery, Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 201399, Shanghai, China.

Increasing evidence has indicated a close association between immune infiltration in cancer and clinical outcomes. However, related research in thyroid cancer is still deficient. Our research comprehensively investigated the immune infiltration of thyroid cancer. Data derived from TCGA and GEO databases were analyzed by the CIBERSORT, ESTIMATE, and EPIC algorithms. The CIBERSORT algorithm calculates the proportions of 22 types of immune cells. ESTIMATE algorithm calculates a stromal score to represent all stromal cells in cancer. The EPIC algorithm calculates the proportions of cancer-associated fibroblasts (CAFs) and endothelial cells (ECs), which are the main components of stromal cells. We analyzed the correlation of immune infiltration with clinical characteristics and outcomes of patients. We determined that the infiltration of CD8 T cells improved the survival of thyroid cancer patients. Overexpression of immune checkpoints was closely related to the development of thyroid cancer. In general, stromal cells were associated with the progression of thyroid cancer. Interestingly, CAFs and ECs had opposite roles in this process. In addition, the BRAF mutation was related to the upregulation of immune checkpoints and CAFs and the downregulation of CD8 T cells and ECs. Finally, we constructed an immune risk score model to predict the prognosis and development of thyroid cancer. Our research demonstrated a comprehensive panorama of immune infiltration in thyroid cancer, which may provide potential value for immunotherapy.
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http://dx.doi.org/10.1038/s41419-020-03294-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791058PMC
January 2021

A Ventilator-associated Pneumonia Prediction Model in Patients With Acute Respiratory Distress Syndrome.

Clin Infect Dis 2020 12;71(Suppl 4):S400-S408

Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.

Background: Mechanical ventilation is crucial for acute respiratory distress syndrome (ARDS) patients and diagnosis of ventilator-associated pneumonia (VAP) in ARDS patients is challenging. Hence, an effective model to predict VAP in ARDS is urgently needed.

Methods: We performed a secondary analysis of patient-level data from the Early versus Delayed Enteral Nutrition (EDEN) of ARDSNet randomized controlled trials. Multivariate binary logistic regression analysis established a predictive model, incorporating characteristics selected by systematic review and univariate analyses. The model's discrimination, calibration, and clinical usefulness were assessed using the C-index, calibration plot, and decision curve analysis (DCA).

Results: Of the 1000 unique patients enrolled in the EDEN trials, 70 (7%) had ARDS complicated with VAP. Mechanical ventilation duration and intensive care unit (ICU) stay were significantly longer in the VAP group than non-VAP group (P < .001 for both) but the 60-day mortality was comparable. Use of neuromuscular blocking agents, severe ARDS, admission for unscheduled surgery, and trauma as primary ARDS causes were independent risk factors for VAP. The area under the curve of the model was .744, and model fit was acceptable (Hosmer-Lemeshow P = .185). The calibration curve indicated that the model had proper discrimination and good calibration. DCA showed that the VAP prediction nomogram was clinically useful when an intervention was decided at a VAP probability threshold between 1% and 61%.

Conclusions: The prediction nomogram for VAP development in ARDS patients can be applied after ICU admission, using available variables. Potential clinical benefits of using this model deserve further assessment.
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http://dx.doi.org/10.1093/cid/ciaa1518DOI Listing
December 2020

Clinical Characteristics and Outcomes of Patients With Severe COVID-19 Induced Acute Kidney Injury.

J Intensive Care Med 2021 Mar 3;36(3):319-326. Epub 2020 Dec 3.

Department of Critical Care Medicine, Faculty of Medicine and Dentistry, 3158University of Alberta, Edmonton, Alberta, Canada.

Background: The incidence and outcome of Coronavirus disease 2019 (COVID-19)-induced kidney injury have been variably described. We aimed to describe the clinical characteristics, correlates and outcomes of critically ill patients with severe COVID-19 complicated by acute kidney injury (AKI).

Methods: We performed a multicenter retrospective cohort study of 671 critically ill adults with laboratory-confirmed COVID-19 from 19 hospitals in China between January 1 to February 29, 2020. Data were captured on demographics, comorbidities, symptoms, acute physiology, laboratory parameters, interventions, and outcomes. The primary exposure was ICU admission for confirmed COVID-19 related critically illness. The primary outcome was 28-day mortality. Secondary outcomes included factors associated with AKI, organ dysfunction, treatment intensity, and health services use.

Measurements And Main Results: Of 671 severe COVID-19 patients (median [IQR] 65 [56-73] years; male sex 65% (n = 434); hypertension 43% (n = 287) and APACHE II score 10 [7-14]), 39% developed AKI. Patients with AKI were older, had greater markers of inflammation and coagulation activation, and had greater acuity and organ dysfunction as presentation. Despite similar treatment with antivirals, patients with AKI had lower viral conversion negative rates than those without AKI. The 28-day mortality was much higher in AKI patients than patients without AKI (72% vs. 42%), and there was an increase in 28-day mortality according to the severity of AKI. Non-survivors were less likely to receive antiviral therapy [132 (70%) vs. 65 (88%)] compared with survivors and have lower viral negative conversion rate [17 (9%) vs. 47 (64%)].

Conclusions: Acute kidney injury was quite common in severe COVID-19 pneumonia, which associated with higher mortality.
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http://dx.doi.org/10.1177/0885066620970858DOI Listing
March 2021

Colon cancer combined with obesity indicates improved survival- research on relevant mechanism.

Aging (Albany NY) 2020 11 10;12(23):23778-23794. Epub 2020 Nov 10.

Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China.

Obesity contributes to the incidence of various tumors, including colon cancer. However, the impact of obesity on patients' survival and related mechanisms remains unclear. Multi-omics data of 227 cases of colon cancer patients combined with clinical characteristics data were acquired from The Cancer Genome Atlas (TCGA) database. We confirmed obesity as an independent prognostic factor for improved overall survival of colon cancer patients. We demonstrated that hypoxia pathways were repressed in obese patients by regulating miR-210. Immune checkpoints PD-1 and LAG3 were also downregulated in obese patients, which indicated enhanced immune surveillance. The frequency of PIK3CA and KRAS mutations was decreased in obese patients. The sites and types of TP53 mutation were alternated in obesity patients. In conclusion, our research demonstrated the potential mechanisms of prolonged survival in colon cancer patients combined with obesity, which may provide potential value for improving the prognosis of colon cancer.
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http://dx.doi.org/10.18632/aging.103972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762486PMC
November 2020

Tolerance of fifteen hydroponic ornamental plant species to formaldehyde stress.

Environ Pollut 2020 Oct 11;265(Pt B):115003. Epub 2020 Jun 11.

Southern Modern Forestry Cooperation and Innovation Center, Nanjing Forestry University, Nanjing, Jiangsu Province, 210037, PR China; College of Landscape Architecture, Nanjing Forestry University, Nanjing, Jiangsu Province, 210037, PR China; College of Art and Design, Nanjing Forestry University, Nanjing, Jiangsu Province, 210037, PR China. Electronic address:

An indoor formaldehyde enriched environment was created by an automatic fumigation system with timing and concentration control. Selected hydroponic plant species were exposed in formaldehyde concentrations of 10 mg m, 50 mg m and 100 mg m respectively for 6 days with 10-h-treatment each day. Changes in morphological characteristics including leaf damage rate, leaf damage time and survival rate were monitored to evaluate morphological resistance to formaldehyde. Assessed physiological parameters were leaf chlorophyll content (Chl), leaf malondialdehyde content (MDA), activity of leaf formaldehyde dehydrogenase (FADH), leaf water soluble sugar content (WSS), and leaf proline content (Pro). Under formaldehyde suppression, reduction of Chl and increase of MDA and Pro were observed. Varying by species, FADH and WSS peaked at certain formaldehyde concentrations. A Principal Component Analysis (PCA) method was adopted to evaluate key factors in hydroponic plants' tolerance to formaldehyde. Among the 15 species selected, the best 5 performing species are Spathiphyllum floribundum, Alocasia cucullata, Davallia bullata, Syngonium podophyllum 'Pixie', and Schefflera octophylla. The study helps people to select the best ornamental plants for indoor air pollution control. The response of hydroponic plant species to formaldehyde was studied for eco-friendly indoor air pollution control.
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http://dx.doi.org/10.1016/j.envpol.2020.115003DOI Listing
October 2020

Chemoproteomic Profiling of Cobalamin-Independent Methionine Synthases in Plants with a Covalent Probe.

J Agric Food Chem 2020 Jul 16;68(30):8050-8056. Epub 2020 Jul 16.

School of Biotechnology and Food Engineering, Changshu Institute of Technology, Changshu, Jiangsu 215500, China.

Cobalamin-independent methionine synthases (MS) are zinc-binding methyltransferases that catalyze methionine biosynthesis in higher plants, which are enzymes critically involved in seed germination and plant growth. Here, we report a highly selective sulfonyl fluoride-based probe for chemoproteomic profiling of MS enzymes in living systems of the model plant , as implemented in in-gel-, mass spectrometry-, and imaging-based platforms. This probe holds promise for facilitating and accelerating fundamental research and industrial application of MS enzymes, particularly in the contexts of MS1/2-targeting herbicide screening and design.
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http://dx.doi.org/10.1021/acs.jafc.0c03301DOI Listing
July 2020

Molecular Imaging and Quantitative Profiling of Fatty Acid Synthase with a Chemical Probe.

Anal Chem 2020 03 25;92(6):4419-4426. Epub 2020 Feb 25.

School of Biotechnology and Food Engineering, Changshu Institute of Technology, Changshu, Jiangsu 215500, China.

Cancer cells rely on fatty acid synthase (FASN), a key enzyme for de novo biosynthesis of long chain fatty acids, to sustain their proliferative potential and drive invasion. Unfortunately, conventional FASN assays are technically inadequate for discerning otherwise elusive FASN activity in complex biological milieux, which has hindered progress in the functional study of FASN and development of its inhibitors. Here, we describe a chemical probe with unprecedented selectivity and sensitivity for the labeling of active FASN in living cells, thus demonstrating a new analytical modality for visualizing endogenous FASN activity and exploring opportunities for drug discovery.
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http://dx.doi.org/10.1021/acs.analchem.9b05327DOI Listing
March 2020

An intramolecular catalytic hairpin assembly on a DNA tetrahedron for mRNA imaging in living cells: improving reaction kinetics and signal stability.

Chem Sci 2019 Dec 18;11(7):1985-1990. Epub 2019 Dec 18.

Hunan Provincial Key Laboratory of Materials Protection for Electric Power and Transportation, Hunan Provincial Engineering Research Center for Food Processing of Aquatic Biotic Resources, School of Chemistry and Food Engineering, Changsha University of Science and Technology Changsha 410114 P. R. China

Enzyme-free amplification techniques based on dynamic DNA self-assembly (DDSA) have recently been developed for the detection of mRNA in living cells. However, signal generation in traditional DDSA amplifiers is mainly dependent on the random diffusion of dissociative probes in a bulk solution, which is generally accompanied by poor kinetics and interference from complex biological systems. In this work, a new amplifier based on the design of an intramolecular catalytic hairpin assembly (intra-CHA) is proposed for the FRET imaging of mRNA in living cells. Compared with that in the free catalytic hairpin assembly (free-CHA), probes H1 and H2 in intra-CHA were simultaneously fixed on a DNA tetrahedron. The distance between them was closer, the local concentration of H1 and H2 in intra-CHA was theoretically approximately 808-times higher than that in free-CHA, and the initial reaction rate was enhanced 15.6 fold. Due to the spatial confinement effect, the reaction kinetics for target-catalyzed signal generation were significantly improved. By virtue of the three-dimensional nanostructure, H1 and H2 in the intra-CHA amplifier entered cells without any transfection or nanocarrier, and the probes and their products were free from biological interference, providing much higher signal stability for the reliable imaging of mRNA in living cells.
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http://dx.doi.org/10.1039/c9sc04916aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148388PMC
December 2019

Target genes associated with lipid and glucose metabolism in non-alcoholic fatty liver disease.

Lipids Health Dis 2019 Dec 5;18(1):211. Epub 2019 Dec 5.

Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, NO.157 West 5th Road, Xi'an, 710004, China.

Background: Insulin resistance (IR) and lipid peroxidation are accepted as 'two-hit' hypothesis of Non-alcoholic fatty liver disease (NAFLD). However, there are few published research on identifying genes which connect lipid and glucose metabolism by gene microarray.

Objective: To identify target genes related to lipid and glucose metabolism that might be responsible for the pathogenesis of NAFLD.

Methods: A rat model of NAFLD was established by feeding male rats with high-fat diet and gene expression profiles of liver tissues were determined using Agilent DNA microarray. We then investigated differentially expressed genes (DEGs) and intersection of them by using Gene Ontology (GO) and Pathway Analyses. Target genes were verified by Real-time polymerase chain reaction (RT-PCR).

Results: Compared with control, 932 genes, including 783 up-regulated and 149 down-regulated, exhibited differences in expression. The up-regulated genes were involved in biosynthesis, cell development, cell differentiation and down-regulated genes contributed to biological metabolic process, adipokine metabolic pathway and insulin signaling pathway. We identified genes involved in insulin signaling pathway, Notch signaling pathway and lipid synthetic process to be closely related to liver fat accumulation and insulin resistance. Among them, IGFBP7, Notch1 and HMGCR were up-regulated (2.85-fold, 3.22-fold, and 2.06-fold, respectively, all P < 0.05) and ACACB was down-regulated (2.08-fold, P < 0.01). These four genes supposed to connect lipid and glucose metabolism after GO and Pathway analyses.

Conclusions: These findings provide innovative information on the whole genome expression profile due to high-fat diet feeding, and bring new insight into the regulating effects of genes on the lipid and glucose metabolism of NAFLD.
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http://dx.doi.org/10.1186/s12944-019-1154-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894500PMC
December 2019

MSC-secreted TGF-β regulates lipopolysaccharide-stimulated macrophage M2-like polarization via the Akt/FoxO1 pathway.

Stem Cell Res Ther 2019 11 26;10(1):345. Epub 2019 Nov 26.

Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, No.87, Dingjiaqiao, Gulou District, Nanjing, 210009, China.

Background: An uncontrolled inflammatory response is a critical pathophysiological feature of sepsis. Mesenchymal stem cells (MSCs) induce macrophage phenotype polarization and reduce inflammation in sepsis. MSC-secreted transforming growth factor beta (TGF-β) participated in the immune modulatory function of MSCs. However, the underlying mechanism of MSC-secreted TGF-β was not fully elucidated in regulation macrophage M2-like polarization.

Methods: The paracrine effects of MSCs on macrophage polarization were studied using a co-culture protocol with LPS-stimulated RAW264.7 cells/mouse peritoneal macrophages and MSCs. The effect of TGF-β in the co-culture system was blocked by the TGF-β receptor inhibitor. To determine the role of MSC-secreted TGF-β, we used recombinant TGF-β to culture with LPS-stimulated RAW264.7 cells. In addition, we employed antibody microarray analysis to determine the mechanisms of MSC secreted TGF-β on LPS-stimulated RAW264.7 cell/mouse peritoneal macrophage M2-like polarization. Furthermore, we used an Akt inhibitor and a FoxO1 inhibitor to inhibit the Akt/FoxO1 pathway. The nuclear translocation of FoxO1 was detected by Western blot.

Results: MSCs induced LPS-stimulated RAW264.7 cell/mouse peritoneal macrophage polarization towards the M2-like phenotype and significantly reduced pro-inflammatory cytokine levels via paracrine, which was inhibited by TGF-β receptor inhibitor. Furthermore, we found that MSC-secreted TGF-β enhanced the macrophage phagocytic ability. The antibody microarray analysis and Western blot verified that TGF-β treatment activated the Akt/FoxO1 pathway in LPS-stimulated macrophages, TGF-β-induced FoxO1 nuclear translocation and obviously expressed in the cytoplasm, the effects of TGF-β regulatory effects on LPS-stimulated macrophage were inhibited by pre-treatment with Akt inhibitor and FoxO1 inhibitor.

Conclusions: TGF-β secreted by MSCs could skew LPS-stimulated macrophage polarization towards the M2-like phenotype, reduce inflammatory reactions, and improve the phagocytic ability via the Akt/FoxO1 pathway, providing potential therapeutic strategies for sepsis.
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http://dx.doi.org/10.1186/s13287-019-1447-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878630PMC
November 2019

Asymptomatic Indurated Plaque in a 16-year-Old Girl: Answer.

Am J Dermatopathol 2019 Dec;41(12):948-949

Department of Pathology, Western General Hospital and the University of Edinburgh, Edinburgh, United Kingdom.

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http://dx.doi.org/10.1097/DAD.0000000000001221DOI Listing
December 2019

DNA-Templated Fluorescent Nanoclusters for Metal Ions Detection.

Molecules 2019 Nov 19;24(22). Epub 2019 Nov 19.

Hunan Provincial Engineering Research Center for Food Processing of Aquatic Biotic Resources, School of Chemistry and Food Engineering, Changsha University of Science and Technology, Changsha 410114, China.

DNA-templated fluorescent nanoclusters (NCs) have attracted increasing research interest on account of their prominent features, such as DNA sequence-dependent fluorescence, easy functionalization, wide availability, water solubility, and excellent biocompatibility. Coupling DNA templates with complementary DNA, aptamers, G-quadruplex, and so on has generated a large number of sensors. Additionally, the preparation and applications of DNA-templated fluorescent NCs in these sensing have been widely studied. This review firstly focuses on the properties of DNA-templated fluorescent NCs, and the synthesis of DNA-templated fluorescent NCs with different metals is then discussed. In the third part, we mainly introduce the applications of DNA-templated fluorescent NCs for sensing metal ions. At last, we further discuss the future perspectives of DNA-templated fluorescent NCs in the synthesis and sensing metal ions in the environmental and biological fields.
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http://dx.doi.org/10.3390/molecules24224189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891495PMC
November 2019

Insulin-like growth factor binding protein 7 accelerates hepatic steatosis and insulin resistance in non-alcoholic fatty liver disease.

Clin Exp Pharmacol Physiol 2019 12 29;46(12):1101-1110. Epub 2019 Aug 29.

Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

An association between increased insulin-like growth factor binding protein-7 (IGFBP7) expression and insulin resistance in metabolic diseases has been reported. However, the role and molecular mechanism of IGFBP-7 in non-alcoholic fatty liver disease (NAFLD) remains largely unknown. Therefore, the potential function of IGFBP7 in the pathological progression of NAFLD was explored in this investigation. For in vivo experiments, an animal model of NAFLD was established in C57BL/6 mice by feeding a high-fat diet (HFD), and IGFBP7 was knocked down by injecting adeno-associated adenovirus (AAV)-mediated short-hairpin (sh)-IGFBP7 into the liver. We found that AAV-sh-IGFBP7 treatment significantly alleviated hepatocyte injury and inhibited hepatic lipid accumulation by reducing lipogenesis-associated gene expression. Furthermore, downregulation of IGFBP7 markedly ameliorated IR and restored impaired insulin signalling by elevating the phosphorylation levels of IRS-1, Akt and GSK3β in HFD-treated mice. Similar results were also confirmed by an in vitro study in a palmitic acid (PA)-stimulated HepG2 cell model. In conclusion, our study demonstrates that IGFBP7 contributes to hepatic steatosis and insulin resistance in NAFLD development, which might serve as a novel therapeutic agent for the treatment of NAFLD.
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http://dx.doi.org/10.1111/1440-1681.13159DOI Listing
December 2019

Norepinephrine vs Vasopressin: Which Vasopressor Should Be Discontinued First in Septic Shock? A Meta-Analysis.

Shock 2020 01;53(1):50-57

Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.

Background: Patients with septic shock in whom norepinephrine (NE) infusion alone is insufficient to raise blood pressure require the concomitant administration of vasopressin (VP). However, current guidelines do not advise clinicians as to which vasoactive agent to discontinue first once the patient's septic shock begins to resolve. Moreover, there is controversial data guiding clinicians on how to discontinue vasopressors for septic shock patients who are receiving a combination therapy of NE and VP.

Methods: The PubMed, EMBASE, and Cochrane Central Register databases were searched from the database inception until October 18, 2018. Studies were limited to adult patients with septic shock who received concomitant NE and VP treatment, that included different orders of vasopressor discontinuation. The primary outcome was the incidence of hypotension. Overall mortality, ICU mortality, and length of stay (LOS) in the ICU were secondary outcomes. Sensitivity and subgroup analyses as well as trial sequential analysis were performed.

Results: One prospective randomized controlled trial and seven retrospective cohort studies were included in present meta-analysis. Compared with discontinuing VP first, the incidence of hypotension was significantly lower when NE was discontinued first (odds ratio, OR 0.3, 95% confidence interval, CI 0.10 to 0.86, P = 0.02; I = 91%). No significant difference was detected in either overall mortality (OR 1.28, 95% CI 0.77 to 2.10, P = 0.34) or ICU mortality (OR 0.99, 95% CI 0.74 to 1.34, P = 0.96) between these two groups. Furthermore, ICU LOS was also evaluated in five studies, and no statistical significance was observed between the two groups with different orders in weaning vasopressors (mean difference 1.35, 95% CI -2.05 to 4.74, P = 0.44). The subgroup analyses suggested a significant association between hypotension and the practice of discontinuing VP first specifically in patients with a low usage rate of corticosteroids (odds ratio, OR 0.18, 95% confidence interval, CI 0.04 to 0.78, P = 0.02). The trial sequential analysis indicated a lack of sufficient evidence to draw conclusions from the current results (required information size  = 11 821).

Conclusions: In adults with septic shock treated with concomitant VP and NE therapy, discontinuing VP first may lead to a higher incidence of hypotension but is not associated with mortality or ICU LOS. Further prospective studies with larger sample sizes are warranted.
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http://dx.doi.org/10.1097/SHK.0000000000001345DOI Listing
January 2020

An experimental study to quantify road greenbelts and their association with PM concentration along city main roads in Nanjing, China.

Sci Total Environ 2019 Jun 20;667:710-717. Epub 2019 Feb 20.

College of Art & Design, Nanjing Forestry University, China.

Air pollution is an important environmental and health concern all over the world and PM is one of the most important constituents of air pollution. In urban area with high population density, vehicles contribute a big portion of PM. The effect of vegetations along road, i.e., road greenbelts, on PM concentration is still a hot research topic. This study used three-dimensional green volume (3DGV, the three-dimensional volume of the crown and stems of all vegetations including trees, shrubs and grass) to evaluate the vegetation quantity of road greenbelts along four main roads in Nanjing, China. High spatial resolution images were collected with unmanned aerial vehicle (UAV) for othomosaic and feature extraction analysis. A Geographic Information System (GIS) database was developed to cover the location, crown diameter, crown height, and 3DGV information of vegetations in the road greenbelts. The environmental benefits of the road greenbelts were evaluated based on 3DGV information. The relationship between 3DGV of road greenbelts and PM concentration was analyzed and it was found that large 3DGV does not mean lower PM concentration. A road greenbelt with even vertical distribution of biomass and diversified vegetation species works better to reduce PM concentration. The implication of this research is that road greenbelt development should systematically consider surface water control, noise reduction, recreation, aesthetic, and air pollution control, thus to maximize its ecoservices to human being.
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http://dx.doi.org/10.1016/j.scitotenv.2019.02.306DOI Listing
June 2019

Overexpressing p130/E2F4 in mesenchymal stem cells facilitates the repair of injured alveolar epithelial cells in LPS-induced ARDS mice.

Stem Cell Res Ther 2019 03 6;10(1):74. Epub 2019 Mar 6.

Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, No.87 Dingjiaqiao Road, Gulou District, Nanjing, 210009, People's Republic of China.

Background: Low differentiation rates of mesenchymal stem cells (MSCs) limit their therapeutic effects on patients in clinical studies. Our previous study demonstrated that overexpressing p130 or E2F4 affected the multipotential differentiation of MSCs, and the underlying mechanism was attributed to the regulation of the G1 phase. Improving the efficiency of MSC differentiation into epithelial cells is considered to be a new method. Therefore, this study was conducted to evaluate the effects of overexpressing p130 or E2F4 in MSCs on improving re-epithelization in lipopolysaccharide (LPS)-induced ARDS animals.

Methods: Mouse MSCs (mMSCs) stably transfected with p130 and E2F4 were transplanted intratracheally into LPS-induced ARDS mice. After 7 and 14 days, the mice were sacrificed, and the histopathology of the lungs was assessed by haematoxylin-eosin staining and lung injury scoring. Homing and differentiation of mMSCs were analysed by labelling and tracking mMSCs with NIR815 dye and immunofluorescent staining. Surfactant proteins A and C and occludin in the lungs were assessed by western blot. Permeability was evaluated by analysing the protein concentration of BALF using ELISA. Alveolar fluid clearance was assessed by absorbance measurements of BALF. Lung fibrosis was assessed by Masson's trichrome staining and Ashcroft scoring.

Results: The engraftment of mMSCs overexpressing p130 or E2F4 led to attenuated histopathological impairment of the lung tissue, and the lung injury scores of the LPS+mBM-MSC-p130 and LPS+mBM-MSC-E2F4 groups were also decreased (p < 0.05). Overexpression of p130 or E2F4 also increased the retention of mMSCs in the lung (p < 0.05), increased differentiation into type II alveolar epithelial cells (p < 0.05), and improved alveolar epithelial permeability (p < 0.05). Additionally, mMSCs overexpressing p130 or E2F4 inhibited lung fibrosis according to the deposition of collagen and the fibrosis score in the lungs (p < 0.05).

Conclusion: Overexpressing p130 or E2F4 in mMSCs could further improve the injured structure and function of epithelial cells in the lungs of ARDS mice as a result of improved differentiation of mMSCs into epithelial cells.
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http://dx.doi.org/10.1186/s13287-019-1169-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404316PMC
March 2019

Early and dynamic alterations of Th2/Th1 in previously immunocompetent patients with community-acquired severe sepsis: a prospective observational study.

J Transl Med 2019 02 27;17(1):57. Epub 2019 Feb 27.

Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.

Background: T helper (Th) cells regulate sepsis processes, including primary pathogen clear and secondary pathogen defence. The objectives of this study were to determine the early and dynamic alterations of Th1 and Th2 populations to community-acquired severe sepsis upon onset among previously immunocompetent patients and whether it was related to clinical outcomes.

Methods: This prospective observational cohort study was conducted at a general intensive care unit (ICU) of a tertiary teaching hospital in China. Immunocompetent patients with community-acquired severe sepsis within 24 h upon onset were included as septic group. Healthy volunteers and critically ill patients without severe sepsis were recruited as controls. Whole blood was collected on D0, 3rd day (D3) and 7th day (D7) for septic group and once upon enrollment for controls. Th1 and Th2 populations were measured by flow cytometry and assessed for associations with 28-day mortality using cox proportional hazard models. Associations of dynamic alterations of Th cell subpopulations with clinical outcomes were investigated.

Results: This study demonstrated that community-acquired severe sepsis patients (n = 71) had increased Th2/Th1 and Th2 populations, compared to healthy controls (n = 7) and critically ill patients without severe sepsis (n = 7) at admission. Among the septic cohort, values of Th2/Th1 were significantly higher in non-survivors than survivors on D0 (p = 0.04), D3 (p < 0.001) and D7 (p < 0.001). Patients with persistently increasing Th2/Th1 demonstrated the highest mortality (47.1%) and incidence of ICU-acquired infections (64.7%).

Conclusions: Th2/Th1 was markedly up-regulated with Th2 dominance upon community-acquired severe sepsis onset among previously immunocompetent patients and its persistently dynamic increase was associated with ICU-acquired infections and 28-day death. Trial registration Institutional Ethics Committee of Zhongda Hospital, 2014ZDSYLL086, registered in June 2014-prospectively registered; ClinicalTrials.gov, NCT02883218, registered on 25 Aug 2016-retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT02883218?cond=NCT02883218&rank=1.
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http://dx.doi.org/10.1186/s12967-019-1811-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391803PMC
February 2019

Effects of chloride content of intravenous crystalloid solutions in critically ill adult patients: a meta-analysis with trial sequential analysis of randomized trials.

Ann Intensive Care 2019 Feb 13;9(1):30. Epub 2019 Feb 13.

Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.

Background: Intravenous crystalloid solutions are administered commonly for critically ill patients. We performed this meta-analysis of randomized trials with trial sequential analysis (TSA) to evaluate effects of chloride content of intravenous crystalloid solutions on clinical outcomes among critically ill adult patients.

Methods: Electronic databases were searched up to June 1, 2018, for randomized trials of use of balanced crystalloids versus 0.9% saline solutions in critically ill adult patients. The outcome variables included mortality, renal outcomes, serum content alterations and organ function. Subgroup analysis was conducted according to patient settings, types or volume of crystalloid fluid, or among sepsis versus non-sepsis, TBI versus non-TBI or subpopulations by the categories of baseline kidney function. Random errors were evaluated by trial sequential analysis.

Results: Eight studies with 19,301 patients were analyzed. A trend of in-hospital survival benefit with no statistical difference could be observed with balanced crystalloids compared with 0.9% saline (RR 0.92, 95% CI 0.85-1.0, p = 0.06). The use of balanced crystalloid solutions was associated with longer RRT-free days (SMD 0.09, 95% CI 0.06-0.12, p < 0.001), less risk of increase in serum concentrations of chloride (SMD - 1.23, 95% CI - 1.59 to - 0.87, p < 0.001) and sodium (SMD - 1.28, 95% CI - 1.65 to - 0.92, p < 0.001), less risk of decline in serum base deficit (SMD - 0.58, 95% CI - 0.98 to - 0.18, p = 0.004), longer ventilator-free days (SMD 0.08, 95% CI 0.05-0.11, p < 0.001) and vasopressor-free days (SMD 0.04, 95% CI 0.00-0.07, p = 0.02). Subgroup analysis showed that balanced crystalloid solutions were associated with a reduced in-hospital mortality rate among septic patients (RR 0.86, 95% CI 0.75-0.98; p = 0.02) and non-traumatic brain injury patients (RR 0.90, 95% CI 0.82-0.99, p = 0.02), while the TSA results indicated a larger sample size is still in need.

Conclusions: Limited evidence supported statistical survival benefit with balanced crystalloid solutions, while it benefited in reducing organ support duration and fluctuations in serum electrolyte and base excess and was associated with decreased in-hospital mortality in subpopulation with sepsis and non-TBI. Large-scale rigorous randomized trials with better designs are needed to provide robust evidence for clinical management. Trial registration The protocol for this meta-analysis was registered on PROSPERO: International prospective register of systematic reviews (CRD42018102661), https://www.crd.york.ac.uk/prospero/#recordDetails.
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http://dx.doi.org/10.1186/s13613-019-0506-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374495PMC
February 2019

In Situ Amplification-Based Imaging of RNA in Living Cells.

Angew Chem Int Ed Engl 2019 08 14;58(34):11574-11585. Epub 2019 May 14.

School of Chemistry and Food Engineering, Changsha University of Science and Technology, Changsha, 410114, China.

Owing to its important physiological functions, especially as molecular biomarkers of diseases, RNA is an important focus of biomedicine and biochemical sensing. Signal amplification detection has been put forward because of the need for accurate identification of RNA at low expression levels, which is significant for the early diagnosis and therapy of malignant diseases. However, conventional amplification methods for RNA analysis depend on the use of enzymes, fixation of cells, and thermal cycling, which confine their performance to cell lysates or dead cells, thus the imaging of RNA in living cells remained until recently little explored. In recent years, the advance of isothermal amplification of nucleic acids has opened paths for meeting this need in living cells. This minireview tracks the development of in situ amplification assays for RNAs in living cells, and highlights the potential challenges facing this field, aiming to improve the development of in vivo isothermal amplification as well as usher in new frontiers in this fertile research area.
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http://dx.doi.org/10.1002/anie.201812449DOI Listing
August 2019

The Effect of High-Flow Nasal Oxygen Therapy on Postoperative Pulmonary Complications and Hospital Length of Stay in Postoperative Patients: A Systematic Review and Meta-Analysis.

J Intensive Care Med 2020 Oct 26;35(10):1129-1140. Epub 2018 Dec 26.

Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.

Objective: To evaluate the effect of high-flow nasal cannula oxygen (HFNO) therapy on hospital length of stay (LOS) and postoperative pulmonary complications (PPCs) in adult postoperative patients.

Data Sources: PubMed, Embase, the Cochrane Library, Web of Science of Studies, China National Knowledge Index, and Wan Fang databases were searched until July 2018.

Study Selection: Randomized controlled trials (RCTs) comparing HFNO with conventional oxygen therapy or noninvasive mechanical ventilation in adult postoperative patients were included. The primary outcomes were hospital LOS and PPCs; short-term mortality (defined as intensive care unit, hospital, or 28-day mortality) and intubation rate were the secondary outcomes.

Data Extraction: Demographic variables, high-flow oxygen therapy application, effects, and side effects were retrieved. Data were analyzed by the methods recommended by the Cochrane Collaboration. The strength of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation. Random errors were evaluated with trial sequential analysis.

Data Synthesis: Fourteen studies (2568 patients) met the inclusion criteria and were included. Compared to the control group, the pooled effect showed that HFNO was significantly associated with a shorter hospital stay (mean difference: -0.81; 95% confidence interval [CI]: -1.34 to -0.29, = .002), but not mortality (risk ratio [RR]: 1.0, 95% CI: 0.63 to 1.59, = 1.0). Weak evidence of a reduction in reintubation rate (RR: 0.76, 95% CI: 0.57-1.01, = .06) and PPC rate (RR: 0.89, 95% CI: 0.75-1.06, = .18) with HFNO versus control group was recorded.

Conclusions: The available RCTs suggest that, among the adult postoperative patients, HFNO therapy compared to the control group significantly reduces hospital LOS.
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http://dx.doi.org/10.1177/0885066618817718DOI Listing
October 2020

Baicalin regulates SirT1/STAT3 pathway and restrains excessive hepatic glucose production.

Pharmacol Res 2018 10 23;136:62-73. Epub 2018 Aug 23.

Department of Resources Science of Traditional Chinese Medicines, China Pharmaceutical University, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Sirtuin 1 (SirT1) and signal transducer and activator of transcription 3 (STAT3) oppositely regulate hepatic gluconeogenic genes and the association remains to be elucidated. Baicalin is a natural flavonoid with beneficial effects on glucose and lipid metabolism. This study aims to investigate the effect of baicalin on hepatic gluconeogenesis with focus on the regulation of fatty acid mobilization and SirT1/STAT3 pathway. In HFD feeding or fasting state, hepatic gluconeogenesis and fatty acid oxidation induced SirT1 expression due to the increased nicotinamide adenine dinucleotide (NAD) contents. Baicalin reduces endogenous glucose production via suppression of hepatic gluconeogenesis and decreased SirT1 induction via reducing NAD accumulation in an energy-sensing way. Fasting increased SirT1 protein in STAT3 immunoprecipitation products and less in the liver of baicalin-treated mice, indicating that baicalin blocked the binding of SirT1 to STAT3 and thus preserved STAT3 acetylation. SirT1 knockdown enhanced the protective effect of baicalin on pyruvate-induced STAT3 phosphorylation and acetylation, these results further indicated that the regulation of STAT3 activity by baicalin was dependent on SirT1. Moreover, HFD feeding increased gene expression for PGC-1α in the liver, but the transcriptional regulation was inhibited by baicalin treatment. SirT1 overexpression and STAT3 inhibition enhanced pyruvate-mediated PGC-1α gene expression, suggesting that deacetylation of STAT3 by SirT1 is required for PGC-1α activity on hepatic gluconeogenesis. Taken together, these results showed that baicalin restrained HGP via inhibiting SirT1 activity coupled with STAT3 acetylation and subsequent PGC-1α suppression, suggesting that hepatic SirT1 and STAT3 pathway may provide therapeutic advantages for the control of hyperglycemia.
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http://dx.doi.org/10.1016/j.phrs.2018.08.018DOI Listing
October 2018

Asymptomatic Indurated Plaque in a 16-Year-Old Girl: Challenge.

Am J Dermatopathol 2019 Dec;41(12):e156-e157

Department of Pathology, Western General Hospital and the University of Edinburgh, Edinburgh, United Kingdom.

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http://dx.doi.org/10.1097/DAD.0000000000001220DOI Listing
December 2019

Stable overexpression of p130/E2F4 affects the multipotential abilities of bone-marrow-derived mesenchymal stem cells.

J Cell Physiol 2018 12 10;233(12):9739-9749. Epub 2018 Jul 10.

Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.

Bone-marrow-derived mesenchymal stem cells (MSCs) have great potential in transplantation medicine due to their multiple advantages. However, the controlled differentiation of MSCs is one of the key aspects of effective clinical transplantation. Growing evidence suggests that the cell cycle plays an important role in regulating differentiation, while p130 and E2F4 are key to cell cycle checkpoints. The aim of the study is to evaluate the effects and mechanism of p130/E2F4 on the multidifferentiation of MSCs. Our data showed that the transduction efficiencies of p130 or E2F4 mediated by lentiviral vectors were 80.3%-84.4%. p130 and E2F4 mRNA expression was significantly higher in MSC-p130 and MSC-E2F4 cells than in MSC normal control (NC) cells. Similar results were also observed for p130 and E2F4 protein expression. After osteogenic or adipogenic differentiation, the G1 phase was significantly delayed in the MSC-p130 and MSC-E2F4 groups compared with that in the MSC-NC group. However, the G1 phase in the MSC-p130 and MSC-E2F4 groups did the opposite after chondrogenic differentiation. Moreover, overexpressing p130 or E2F4 significantly improved osteogenic differentiation while inhibiting adipogenic and chondrogenic differentiation of mouse MSCs (mMSCs). Moreover, overexpressing p130 or E2F4 significantly improved migration but not proliferation of mMSCs. Our data suggest that cell cycle regulation may be involved in p130/E2F4-mediated changes in the multipotential abilities of bone-marrow-derived mMSCs.
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http://dx.doi.org/10.1002/jcp.26926DOI Listing
December 2018
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