Publications by authors named "Jiali Deng"

39 Publications

Tracing Management and Epidemiological Characteristics of COVID-19 Close Contacts in Cities Around Chengdu, China.

Front Public Health 2021 15;9:645798. Epub 2021 Dec 15.

Emergency and Business Management Office, Chengdu Center for Disease Control and Prevention, Chengdu, China.

Close contacts have become a potential threat to the spread of coronavirus disease 2019 (COVID-19). The purpose of this study was to understand the epidemiological characteristics of close contacts of confirmed or suspected cases of COVID-19 in the surrounding cities of Chengdu, China, so as to provide a basis for the management strategy of close contacts. Close contacts were determined through epidemiological investigation of indicated cases, and relevant information was entered in the "Close Contact Information Management System." Retrospective data of close contacts from January 22 to May 1, 2020 were collected and organized. Meanwhile, the contact mode, isolation mode, and medical outcome of close contacts were descriptively analyzed. A total of 986 close contacts were effectively traced, with an average age of (36.69 ± 16.86) years old, who were mainly distributed in cities of eastern Chengdu. The frequency of contact was mainly occasional contact, 80.42% of them were relatives and public transportation personnel. Besides, the time of tracking close contacts and feedback was (10.64 ± 5.52) and (7.19 ± 6.11) days, respectively. A total of seven close contacts were converted to confirmed cases. Close contacts of COVID-19 have a risk of invisible infection. Early control of close contacts may be helpful to control the epidemic of COVID-19.
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http://dx.doi.org/10.3389/fpubh.2021.645798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714902PMC
January 2022

Circadian Variation in the Median Effective Dose of Epidural Ropivacaine for Labor Analgesia.

Front Med (Lausanne) 2021 18;8:669264. Epub 2021 Nov 18.

Department of Anesthesia, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Labor pain perception has been demonstrated to exhibit a circadian rhythm with lower pain scores during the day compared with the night. This study aimed to determine and compare the median effective dose (ED) of ropivacaine in parturients having epidural labor analgesia during the day vs. during the night. The study group consisted of 60 nulliparous healthy parturients who were assigned to one of two groups according to the time they requested labor analgesia: Day Group (7:01 am to 7:00 pm) and Night Group (7:01 pm to 7:00 am). A bolus of.15% ropivacaine was administered epidurally and effective analgesia was defined as the attainment of a visual analog scale (VAS) pain score ≤ 10 mm within 30 min. The dose of ropivacaine for the first parturient in each group was 18 mg. The dose for each subsequent parturient was varied with increments or decrements of 3 mg based on the response of the previous subject. The ED was calculated using up-down sequential analysis. Probit regression was used to estimate the relative mean potency of ropivacaine between groups. The ED (mean [95% CI]) of ropivacaine was lower in the Day Group (17.9 [16.5-19.4] mg) than in the Night Group (20.9 [19.2-22.7] mg) ( = 0.003). The estimate of relative potency for ropivacaine for the Night Group vs. the Day Group was 0.85 (95% CI:0.56-0.98). Under the conditions of this study, the dose requirement for epidural ropivacaine for labor analgesia was ~ 15% greater during the night than during the day. Chinese Clinical Trial Registry (No.: ChiCTR1900025269. http://www.chictr.org.cn/showprojen.aspx?proj=36993).
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http://dx.doi.org/10.3389/fmed.2021.669264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636744PMC
November 2021

Exercise downregulates HIPK2 and HIPK2 inhibition protects against myocardial infarction.

EBioMedicine 2021 Dec 24;74:103713. Epub 2021 Nov 24.

Shanghai Engineering Research Center of Organ Repair, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong 226011, China; Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai, 200444, China. Electronic address:

Background: Exercise can protect myocardial infarction (MI) and downregulate cardiac Homeodomain-Interacting Protein Kinase 2 (HIPK2). However, the role of HIPK2 in MI is unclear.

Methods: HIPK2 mice and miR-222 rats, HIPK2 inhibitor (PKI1H) and adeno-associated virus serotype 9 (AAV9) carrying miR-222 were applied in the study. Animals were subjected to running, swimming, acute MI or post-MI remodeling. HIPK2 inhibition and P53 activator were used in neonatal rat cardiomyocytes (NRCMs) and human embryonic stem cell-derived cardiomyocytes (hESC-CMs) subjected to oxygen glucose deprivation/reperfusion (OGD/R). Serum miR-222 levels were analyzed in healthy people and MI patients that were survival or readmitted to the hospital and/or died.

Findings: Cardiac HIPK2 protein levels were reduced by exercise while increased in MI. In vitro, HIPK2 suppression by lentiviral vectors or inhibitor prevented apoptosis induced by OGD/R in NRCMs and hESC-CMs. HIPK2 inhibitor-treated mice and HIPK2 mice reduced infarct size after acute MI, and preserved cardiac function in MI remodeling. Mechanistically, protective effect against apoptosis by HIPK2 suppression was reversed by P53 activators. Furthermore, increasing levels of miR-222, targeting HIPK2, protected post-MI cardiac dysfunction, whereas cardiac dysfunction post-MI was aggravated in miR-222 rats. Moreover, serum miR-222 levels were significantly reduced in MI patients, as well as in MI patients that were readmitted to the hospital and/or died compared to those not.

Interpretation: Exercise-induced HIPK2 suppression attenuates cardiomyocytes apoptosis and protects MI by decreasing P-P53. Inhibition of HIPK2 represents a potential novel therapeutic intervention for MI.

Funding: This work was supported by the grants from National Key Research and Development Project (2018YFE0113500 to JJ Xiao), National Natural Science Foundation of China (82020108002, 81722008, and 81911540486 to JJ Xiao, 81400647 to MJ Xu, 81800265 to YJ Liang), Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-09-E00042 to JJ Xiao), the grant from Science and Technology Commission of Shanghai Municipality (18410722200 and 17010500100 to JJ Xiao), the "Dawn" Program of Shanghai Education Commission (19SG34 to JJ Xiao), Shanghai Sailing Program (21YF1413200 to QL Zhou). JS is supported by Horizon2020 ERC-2016-COG EVICARE (725229).
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http://dx.doi.org/10.1016/j.ebiom.2021.103713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626841PMC
December 2021

Al-Modified CuO/CuO for High-Temperature Thermochemical Energy Storage: from Reaction Performance to Modification Mechanism.

ACS Appl Mater Interfaces 2021 Dec 22;13(48):57274-57284. Epub 2021 Nov 22.

State Key Laboratory of Clean Energy Utilization, Zhejiang University, 38 Zheda Road, Hangzhou 310027, China.

Next-generation concentrated solar power plants with high-temperature energy storage requirements stimulate the pursuit of advanced thermochemical energy storage materials. Copper oxide emerges as an attractive option with advantages of high energy density and low cost. But its easy sinterability limits its reversibility and cyclic stability performance. In this work, aluminum-doped copper oxides are synthesized and evaluated via thermogravimetric analysis. The reversibility of Cu-Al oxides reaches 99.5% in the first redox cycle and maintains 81.1% of the initial capacity after 120 cycles. The Al element can modify the CuO particle surface in the form of CuAlO, which separates the copper oxide particles from each other during redox cycles to avoid agglomeration and participates in the redox reaction. Through DFT analysis, the introduction of Al is found to increase the formation energy of copper vacancies in copper oxides, which helps avoid the sintering problem and thus improves the oxidation rate. This study provides a generalizable operational mechanism of element doping and can serve as a guideline for the optimization of high-performance materials in thermochemical energy storage.
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http://dx.doi.org/10.1021/acsami.1c17592DOI Listing
December 2021

Non-coding RNA basis of muscle atrophy.

Mol Ther Nucleic Acids 2021 Dec 19;26:1066-1078. Epub 2021 Oct 19.

Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong 226011, China.

Muscle atrophy is a common complication of many chronic diseases including heart failure, cancer cachexia, aging, etc. Unhealthy habits and usage of hormones such as dexamethasone can also lead to muscle atrophy. However, the underlying mechanisms of muscle atrophy are not completely understood. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), play vital roles in muscle atrophy. This review mainly discusses the regulation of ncRNAs in muscle atrophy induced by various factors such as heart failure, cancer cachexia, aging, chronic obstructive pulmonary disease (COPD), peripheral nerve injury (PNI), chronic kidney disease (CKD), unhealthy habits, and usage of hormones; highlights the findings of ncRNAs as common regulators in multiple types of muscle atrophy; and summarizes current therapies and underlying mechanisms for muscle atrophy. This review will deepen the understanding of skeletal muscle biology and provide new strategies and insights into gene therapy for muscle atrophy.
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http://dx.doi.org/10.1016/j.omtn.2021.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569427PMC
December 2021

Intermittent Leucine Deprivation Produces Long-lasting Improvement in Insulin Sensitivity by Increasing Hepatic Gcn2 Expression.

Diabetes 2022 Feb;71(2):206-218

Chinese Academy of Sciences Key Laboratory of Nutrition, Metabolism and Food Safety, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.

Leucine deprivation improves insulin sensitivity; however, whether and how this effect can be extended are unknown. We hypothesized that intermittent leucine deprivation (ILD) might produce a long-term effect on improved insulin sensitivity via the formation of metabolic memory. Consistently, seven ILD cycles of treatment (1-day leucine-deficient diet, 3-day control diet) in mice produced a long-lasting (after a control diet was resumed for 49 days) effect on improved whole-body and hepatic insulin sensitivity in mice, indicating the potential formation of metabolic memory. Furthermore, the effects of ILD depended on hepatic general control nondepressible 2 (GCN2) expression, as verified by gain- and loss-of-function experiments. Moreover, ILD increased Gcn2 expression by reducing its DNA methylation at two CpG promoter sites controlled by demethylase growth arrest and DNA damage inducible b. Finally, ILD also improved insulin sensitivity in insulin-resistant mice. Thus, ILD induces long-lasting improvements in insulin sensitivity by increasing hepatic Gcn2 expression via a reduction in its DNA methylation. These results provide novel insights into understanding of the link between leucine deprivation and insulin sensitivity, as well as potential nutritional intervention strategies for treating insulin resistance and related diseases. We also provide evidence for liver-specific metabolic memory after ILD and novel epigenetic mechanisms for Gcn2 regulation.
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http://dx.doi.org/10.2337/db21-0336DOI Listing
February 2022

Micro/nano topography of selective laser melting titanium inhibits osteoclastogenesis via mediation of macrophage polarization.

Biochem Biophys Res Commun 2021 12 15;581:53-59. Epub 2021 Sep 15.

Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong, China. Electronic address:

Selective laser melting (SLM) titanium (Ti) implants have shown good prospects for personalized clinical application, but further research is necessary to develop stabilized long-term properties. Since surface modification has been proven bioactive for osseointegration, conventional Ti surface treatment technologies, including sandblasting/acid-etching (SLA) and sandblasting/alkali-heating (SAH), were applied to construct micro and micro/nano surfaces. The SAH group with netlike nano-structure topography exhibited appropriate surface roughness and high hydrophilicity, and as expected, the osseointegration capacities in vivo of the three groups were in order of SAH > SLA > SLM. Besides, both in vivo and in vitro studies revealed that the SLA- and SAH-treated SLM Ti implants significantly inhibited osteoclast activity of peri-implants. Considering the close associations between osteoclasts and macrophages, the effects of Ti surface topography on macrophage polarization were detected. The results showed that the SLA- and SAH-treated SLM Ti implants, especially the latter, had the capacity to promote macrophage polarization to the M2 phenotype. Moreover, the cell culture supernatants of M2 macrophages and RAW264.7 cells seeded on SLA- and SAH-treated SLM Ti surfaces had an adverse effect on osteoclastogenesis. Collectively, this study demonstrated that micro/nano topographies of SLM Ti implants were effective for osseointegration promotion, and their inhibition of osteoclastogenesis might be attributed to macrophage polarization. Our findings shed some light on clinical application of SLM Ti implants and also prove a specific association between macrophage polarization and osteoclastogenesis.
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http://dx.doi.org/10.1016/j.bbrc.2021.09.021DOI Listing
December 2021

Efficacy of Hemiarthroplasty vs. Locking Plate Fixation for Proximal Humerus Fractures: A Meta-Analysis.

Front Surg 2021 21;8:651554. Epub 2021 Sep 21.

Department of Orthopedics, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Sichuan, China.

Proximal humerus fractures are common in a clinic and account for ~6% of all adult fractures. Hemiarthroplasty (HA) or locking plate (LP) fixation is currently recommended for the treatment of complex proximal humerus fractures (PHFs); however, there is no uniform standard for optimal surgical treatment or functional recovery. We conducted a meta-analysis to compare the efficacy of LP and HA in the treatment of PHFs. Relative studies associated with HA and LP were searched in December 2020 in the PubMed, Embase, Cochrane Library, and OVID databases. The quality of the studies, functional outcomes (including the Constant-Murley score (CMS), American Shoulder and Elbow Surgeons Score (ASES), Simple Shoulder Test (SST), Short Form Health Survey (SF-12v2), complications, and reoperation rate were extracted and analyzed with the Stata 14.0 software. A total of 958 patients from 12 studies were included in the meta-analysis, which showed that patients treated with LP had a significantly lower reoperation rate, a higher complication rate, and a higher CMS score than those treated with HA. There were no significant differences in ASES, SST, or SF-12v2 scores between treatment groups. Compared with HA, LP exhibited better clinical efficacy in some aspects. However, large sample and randomized, controlled studies are needed for further validation.
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http://dx.doi.org/10.3389/fsurg.2021.651554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490867PMC
September 2021

Gut microbes in gastrointestinal cancers.

Semin Cancer Biol 2021 Apr 1. Epub 2021 Apr 1.

Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai, 200444, China. Electronic address:

Gut microbes (GMs), dominated by bacteria, play important roles in many physiological processes. The structures and functions of GMs are closely related to human health, the occurrence and development of diseases and the rapid recovery of the body. Gastrointestinal cancers are the major diseases affecting human health worldwide. With the development of metagenomic technology and the wide application of new generation sequencing technology, a large number of studies suggest that complex GMs are related to the occurrence and development of gastrointestinal cancers. Fecal microbiota transplantation (FMT) and probiotics can treat and prevent the occurrence of gastrointestinal cancers. This article reviews the latest research progress of microbes in gastrointestinal cancers from the perspectives of the correlation, the influence mechanism and the application, so as to provide new directions for the prevention, early diagnosis and treatment of gastrointestinal cancers.
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http://dx.doi.org/10.1016/j.semcancer.2021.03.037DOI Listing
April 2021

Current Studies and Future Directions of Exercise Therapy for Muscle Atrophy Induced by Heart Failure.

Front Cardiovasc Med 2020 23;7:593429. Epub 2020 Oct 23.

Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai, China.

Muscle atrophy is a common complication of heart failure. At present, there is no specific treatment to reverse the course of muscle atrophy. Exercise training, due to the safety and easy operation, is a recommended therapy for muscle atrophy induced by heart failure. However, the patients with muscle atrophy are weak in mobility and may not be able to train for a long time. Therefore, it is necessary to explore novel targets of exercise protection for muscle atrophy, so as to improve the quality of life and survival rate of patients with muscular atrophy induced by heart failure. This article aims to review latest studies, summarize the evidence and limitations, and provide a glimpse into the future of exercise for the treatment of muscle atrophy induced by heart failure. We wish to highlight some important findings about the essential roles of exercise sensors in muscle atrophy induced by heart failure, which might be helpful for searching potential therapeutic targets for muscle wasting induced by heart failure.
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http://dx.doi.org/10.3389/fcvm.2020.593429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644508PMC
October 2020

Gene therapy for cardiovascular diseases in China: basic research.

Gene Ther 2020 08 27;27(7-8):360-369. Epub 2020 Apr 27.

Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, School of Life Science, Shanghai University, Shanghai, 200444, China.

Cardiovascular disease has become a major disease affecting health in the whole world. Gene therapy, delivering foreign normal genes into target cells to repair damages caused by defects and abnormal genes, shows broad prospects in treating different kinds of cardiovascular diseases. China has achieved great progress of basic gene therapy researches and pathogenesis of cardiovascular diseases in recent years. This review will summarize the latest research about gene therapy of proteins, epigenetics, including noncoding RNAs and genome-editing technology in myocardial infarction, cardiac ischemia-reperfusion injury, atherosclerosis, muscle atrophy, and so on in China. We wish to highlight some important findings about the essential roles of basic gene therapy in this field, which might be helpful for searching potential therapeutic targets for cardiovascular disease.
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http://dx.doi.org/10.1038/s41434-020-0148-6DOI Listing
August 2020

SHU00238 Promotes Colorectal Cancer Cell Apoptosis Through miR-4701-3p and miR-4793-3p.

Front Genet 2019 10;10:1320. Epub 2020 Jan 10.

School of Life Science, Shanghai University, Shanghai, China.

Colorectal cancer is one of the most leading causes of death. Searching for new therapeutic targets for colorectal cancer is urgently needed. SHU00238, an isoxazole derivative, was reported to suppress colorectal tumor growth through microRNAs. But the underlying mechanisms still remain unknown. Here, we explored the mechanism of SHU00238 on colorectal cancer by RT-PCR, CCK-8, flow cytometry, mirTarBase, and GO enrichment analysis. We screened partial microRNAs regulated by SHU00238 in colorectal cancer cells. Furthermore, we identified that miR-4701-3p and miR-4793-3p can reverse the acceleration of SHU00238 on colorectal cancer cell apoptosis in HCT116 Cells. Finally, we found that SMARCA5, MBD3, VPS53, EHD4 are estimated to mediate the regulation of miR-4701-3p and miR-4793-3p on colorectal cancer cell apoptosis, which targets ATP-dependent chromatin remodeling pathway and endocytic recycling pathway. Taken together, our study reveals that SHU00238 promotes colorectal cancer cell apoptosis through miR-4701-3p and miR-4793-3p, which provide a potential drug target and therapeutic strategy for colorectal cancer.
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http://dx.doi.org/10.3389/fgene.2019.01320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965150PMC
January 2020

Autophagy inhibition prevents glucocorticoid-increased adiposity via suppressing BAT whitening.

Autophagy 2020 03 18;16(3):451-465. Epub 2019 Jun 18.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

The mechanisms underlying glucocorticoid (GC)-increased adiposity are poorly understood. Brown adipose tissue (BAT) acquires white adipose tissue (WAT) cell features defined as BAT whitening under certain circumstances. The aim of our current study was to investigate the possibility and mechanisms of GC-induced BAT whitening. Here, we showed that one-week dexamethasone (Dex) treatment induced BAT whitening, characterized by lipid droplet accumulation, in vitro and in vivo. Furthermore, autophagy and ATG7 (autophagy related 7) expression was induced in BAT by Dex, and treatment with the autophagy inhibitor chloroquine or adenovirus-mediated ATG7 knockdown prevented Dex-induced BAT whitening and fat mass gain. Moreover, Dex-increased ATG7 expression and autophagy was mediated by enhanced expression of BTG1 (B cell translocation gene 1, anti-proliferative) that stimulated activity of CREB1 (cAMP response element binding protein 1). The importance of BTG1 in this regulation was further demonstrated by the observed BAT whitening in adipocyte-specific BTG1-overexpressing mice and the attenuated Dex-induced BAT whitening and fat mass gain in mice with BTG1 knockdown in BAT. Taken together, we showed that Dex induces a significant whitening of BAT via BTG1- and ATG7-dependent autophagy, which might contribute to Dex-increased adiposity. These results provide new insights into the mechanisms underlying GC-increased adiposity and possible strategy for preventing GC-induced side effects via the combined use of an autophagy inhibitor. ACADL: acyl-Coenzyme A dehydrogenase, long-chain; ACADM: acyl-Coenzyme A dehydrogenase, medium-chain; ACADS: acyl-Coenzyme A dehydrogenase, short-chain; ADIPOQ: adiponectin; AGT: angiotensinogen; Atg: autophagy-related; BAT: brown adipose tissue; BTG1: B cell translocation gene 1, anti-proliferative; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; CIDEA: cell death-inducing DNA fragmentation factor, alpha subunit-like effector A; CPT1B: carnitine palmitoyltransferase 1b, muscle; CPT2: carnitine palmitoyltransferase 2; CQ: chloroquine; Dex: dexamethasone; eWAT: epididymal white adipose tissue; FABP4: fatty acid binding protein 4, adipocyte; FFAs: free fatty acids; GCs: glucocorticoids; NRIP1: nuclear receptor interacting protein 1; OCR: oxygen consumption rate; PBS: phosphate-buffered saline; PPARA: peroxisome proliferator activated receptor alpha; PPARG: peroxisome proliferator activated receptor gamma; PPARGC1A: peroxisome proliferator activated receptor, gamma, coactivator 1 alpha; PRDM16: PR domain containing 16; PSAT1: phosphoserine aminotransferase 1; RB1: RB transcriptional corepressor 1; RBL1/p107: RB transcriptional corepressor like 1; SQSTM1: sequestosome 1; sWAT: subcutaneous white adipose tissue; TG: triglycerides; UCP1: uncoupling protein 1 (mitochondrial, proton carrier); WT: wild-type.
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http://dx.doi.org/10.1080/15548627.2019.1628537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999619PMC
March 2020

Fabrication of graphene oxide incorporated polymer monolithic fiber as solid phase microextraction device for determination of organophosphate esters in soil samples.

J Chromatogr A 2019 Mar 17;1588:17-24. Epub 2018 Dec 17.

Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, Institute of Environmental Chemistry, College of Chemistry, Central China Normal University, Wuhan, 430079, China. Electronic address:

A novel solid phase microextraction fiber named graphene oxide incorporated poly acrylamide-ethylene glycol dimethacrylate (GO-poly AM-EDGMA) monolithic fiber has been successfully prepared in a fused silica capillary tube (250 μm, i.d.) via thermally initiated polymerization using acrylamide (AM) as the monomer, ethylene glycol dimethacrylate (EGDMA) as the crosslinker, dimethylformamide dispersed by GO as porogens, and then obtained by removing 1 cm wall from one end of the fused silica capillary tube. The fiber has large surface area (536 m g), pore capacity (0.694 cm g) good thermal stability (up to 320 ℃), long service life and good reproducibility (RSD <5% throughout 110 times) which facilitated for high throughput headspace solid phase microextraction (HS-SPME) coupled to gas chromatograph (GC) analysis. The HS-SPME/GC method using the new fiber was evaluated by the determination of five organophosphate esters (OPEs) in soil samples coupled to flame photometric detector (FPD). The proposed HS-SPME-GC/FPD method yielded satisfactory limits of quantification (0.03 ng g∼0.24 ng g); linearity (≥0.99), good intra- and inter-day precision expressed as relative standard deviations for a single fiber were in the range of 5.2-9.0% and 4.8-9.0%, respectively, and fiber-to-fiber reproducibility was in the range of 5.9-9.7%. The method was applied for the analysis of OPEs in environmental soil samples and the relative recoveries were found to be in the range from 80.1 to 105.6%. Based on these features, the new fiber has great potential for widespread use as a high throughput trace analysis tool.
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http://dx.doi.org/10.1016/j.chroma.2018.12.034DOI Listing
March 2019

Hepatic c-Jun regulates glucose metabolism via FGF21 and modulates body temperature through the neural signals.

Mol Metab 2019 02 12;20:138-148. Epub 2018 Dec 12.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, China. Electronic address:

Objective: c-Jun, a prominent member of the activator protein 1 (AP-1) family, is involved in various physiology processes such as cell death and survival. However, a role of hepatic c-Jun in the whole-body metabolism is poorly understood.

Methods: We generated liver-specific c-Jun knock-out (c-jun) mice to investigate the effect of hepatic c-Jun on the whole-body physiology, particularly in blood glucose and body temperature. Primary hepatocytes were also used to explore a direct regulation of c-Jun in gluconeogenesis.

Results: c-jun mice showed higher hepatic gluconeogenic capacity compared with control mice, and similar results were obtained in vitro. In addition, fibroblast growth factor 21 (FGF21) expression was directly inhibited by c-Jun knockdown and adenovirus-mediated hepatic FGF21 over-expression blocked the effect of c-Jun on gluconeogenesis in c-jun mice. Interestingly, c-jun mice also exhibited higher body temperature, with induced thermogenesis and uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT). Furthermore, the body temperature became comparable between c-jun and control mice at thermoneutral temperature (30 °C). Moreover, the activity of sympathetic nervous system (SNS) was increased in c-jun mice and the higher body temperature was inhibited by beta-adrenergic receptor blocker injection. Finally, the activated SNS and increased body temperature in c-jun mice was most likely caused by the signals from the brain and hepatic vagus nerve, as the expression of c-Fos (the molecular marker of neuronal activation) was changed in several brain areas controlling body temperature and body temperature was decreased by selective hepatic vagotomy.

Conclusions: These data demonstrate a novel function of hepatic c-Jun in the regulation of gluconeogenesis and body temperature via FGF21 and neural signals. Our results also provide novel insights into the organ crosstalk in the regulation of the whole-body physiology.
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http://dx.doi.org/10.1016/j.molmet.2018.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358569PMC
February 2019

Overexpression of USP5 contributes to tumorigenesis in non-small cell lung cancer via the stabilization of β-catenin protein.

Am J Cancer Res 2018 1;8(11):2284-2295. Epub 2018 Nov 1.

Department of Anesthesia, Jiaxing Maternity and Child Health Care Hospital, Jiaxing University Jiaxing 314001, Zhejiang, China.

The ubiquitin-specific protease 5 (USP5), a deubiquitinating enzyme, has been identified as a tumor promoter in several types of human cancer. However, the role of USP5 in non-small lung cancer (NSCLC) has not yet been elucidated. In this study, we found that USP5 was upregulated in NSCLC tissues compared with normal tissues. High expression of USP5 was correlated with large primary tumor size, poor differentiation and advanced TNM stage, and led to a significantly shorter overall survival (OS). USP5 overexpression enhanced, whereas USP5 silencing impaired the cell proliferation and colony formation of NSCLC cells . Moreover, knockdown of USP5 in H1299 cells inhibited tumor growth . Mechanistically, we found that USP5 deubiquitinated β-catenin, prevented ubiquitination mediated β-catenin degradation and promoted β-catenin nuclear accumulation, leading to the activation of Wnt/β-catenin signal pathway in NSCLC cells. Taken together, these findings suggest that USP5 functions as an oncogene in NSCLC and its oncogenic activity involves in part through Wnt/β-catenin signal pathway.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291653PMC
November 2018

ATF4 Deficiency Promotes Intestinal Inflammation in Mice by Reducing Uptake of Glutamine and Expression of Antimicrobial Peptides.

Gastroenterology 2019 03 16;156(4):1098-1111. Epub 2018 Nov 16.

Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. Electronic address:

Background & Aims: Activating transcription factor 4 (ATF4) regulates genes involved in the inflammatory response, amino acid metabolism, autophagy, and endoplasmic reticulum stress. We investigated whether its activity is altered in patients with inflammatory bowel diseases (IBDs) and mice with enterocolitis.

Methods: We obtained biopsy samples during endoscopy from inflamed and/or uninflamed regions of the colon from 21 patients with active Crohn's disease (CD), 22 patients with active ulcerative colitis (UC), and 38 control individuals without IBD and of the ileum from 19 patients with active CD and 8 individuals without IBD in China. Mice with disruption of Atf4 specifically in intestinal epithelial cells (Atf4ΔIEC mice) and Atf4-floxed mice (controls) were given dextran sodium sulfate (DSS) to induce colitis. Some mice were given injections of recombinant defensin α1 (DEFA1) and supplementation of l-alanyl-glutamine or glutamine in drinking water. Human and mouse ileal and colon tissues were analyzed by quantitative real-time polymerase chain reaction, immunoblots, and immunohistochemistry. Serum and intestinal epithelial cell (IEC) amino acids were measured by high-performance liquid chromatography-tandem mass spectrometry. Levels of ATF4 were knocked down in IEC-18 cells with small interfering RNAs. Microbiomes were analyzed in ileal feces from mice by using 16S ribosomal DNA sequencing.

Results: Levels of ATF4 were significantly decreased in inflamed intestinal mucosa from patients with active CD or active UC compared with those from uninflamed regions or intestinal mucosa from control individuals. ATF4 was also decreased in colonic epithelia from mice with colitis vs mice without colitis. Atf4ΔIEC mice developed spontaneous enterocolitis and colitis of greater severity than control mice after administration of DSS. Atf4ΔIEC mice had decreased serum levels of glutamine and reduced levels of antimicrobial peptides, such as Defa1, Defa4, Defa5, Camp, and Lyz1, in ileal Paneth cells. Atf4ΔIEC mice had alterations in ileal microbiomes compared with control mice; these changes were reversed by administration of glutamine. Injections of DEFA1 reduced the severity of spontaneous enteritis and DSS-induced colitis in Atf4ΔIEC mice. We found that expression of solute carrier family 1 member 5 (SLC1A5), a glutamine transporter, was directly regulated by ATF4 in cell lines. Overexpression of SLC1A5 in IEC-18 or primary IEC cells increased glutamine uptake and expression of antimicrobial peptides. Knockdown of ATF4 in IEC-18 cells increased expression of inflammatory cytokines, whereas overexpression of SLC1A5 in the knockdown cells reduced cytokine expression. Levels of SLC1A5 were decreased in inflamed intestinal mucosa of patients with CD and UC and correlated with levels of ATF4.

Conclusions: Levels of ATF4 are decreased in inflamed intestinal mucosa from patients with active CD or UC. In mice, ATF4 deficiency reduces glutamine uptake by intestinal epithelial cells and expression of antimicrobial peptides by decreasing transcription of Slc1a5. ATF4 might therefore be a target for the treatment of IBD.
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http://dx.doi.org/10.1053/j.gastro.2018.11.033DOI Listing
March 2019

d-/l-Isothymidine incorporation in the core sequence of aptamer BC15 enhanced its binding affinity to the hnRNP A1 protein.

Org Biomol Chem 2018 10;16(40):7488-7497

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.

The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was reported to participate in the development of a variety of tumors. BC15 is a DNA aptamer targeting hnRNP A1. Firstly, through sequence truncation, we identified 31-mer sequence BC15-31 as the core sequence of BC15 with a strong binding affinity and high selectivity to the hnRNP A1 protein. Isothymidine (isoT) modification was then applied for the structural optimization of BC15-31, systematic modification and biological evaluation were carried out. Incorporation of isoT in the 1,3 sites at the 5'-end of BC15-31 can significantly enhance the protein affinity. Chemical modifications close to the 3'-end can greatly improve the stability of the aptamer. Furthermore, BC15-31 modified with isoT at both the 5'-end and 3'-end displayed an additive effect with enhanced bioactivity and stability at the same time. Our study strategy on BC15 provides a useful guideline for chemical modification and optimization of the aptamer for further clinical application.
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http://dx.doi.org/10.1039/c8ob01454jDOI Listing
October 2018

SGK1/FOXO3 Signaling in Hypothalamic POMC Neurons Mediates Glucocorticoid-Increased Adiposity.

Diabetes 2018 04 10;67(4):569-580. Epub 2018 Jan 10.

Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China

Although the central nervous system has been implicated in glucocorticoid-induced gain of fat mass, the underlying mechanisms are poorly understood. The aim of this study was to investigate the possible involvement of hypothalamic serum- and glucocorticoid-regulated kinase 1 (SGK1) in glucocorticoid-increased adiposity. It is well known that SGK1 expression is induced by acute glucocorticoid treatment, but it is interesting that we found its expression to be decreased in the arcuate nucleus of the hypothalamus, including proopiomelanocortin (POMC) neurons, following chronic dexamethasone (Dex) treatment. To study the role of SGK1 in POMC neurons, we produced mice that developed or experienced adult-onset SGK1 deletion in POMC neurons (PSKO). As observed in Dex-treated mice, PSKO mice exhibited increased adiposity and decreased energy expenditure. Mice overexpressing constitutively active SGK1 in POMC neurons consistently had the opposite phenotype and did not experience Dex-increased adiposity. Finally, Dex decreased hypothalamic α-melanocyte-stimulating hormone (α-MSH) content and its precursor expression via SGK1/FOXO3 signaling, and intracerebroventricular injection of α-MSH or adenovirus-mediated FOXO3 knockdown in the arcuate nucleus largely reversed the metabolic alterations in PSKO mice. These results demonstrate that POMC SGK1/FOXO3 signaling mediates glucocorticoid-increased adiposity, providing new insights into the mechanistic link between glucocorticoids and fat accumulation and important hints for possible treatment targets for obesity.
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http://dx.doi.org/10.2337/db17-1069DOI Listing
April 2018

Ultrasensitive determination of highly polar trimethyl phosphate in environmental water by molecularly imprinted polymeric fiber headspace solid-phase microextraction.

J Sep Sci 2018 Mar 9;41(5):1104-1111. Epub 2018 Jan 9.

Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, Institute of Environmental Chemistry, College of Chemistry, Central China Normal University, Wuhan, China.

A sensitive, accurate, and cost effective method for the quantification of trimethyl phosphate, which is highly polar and volatile, in environmental water is presented. Trimethyl phosphate was headspace solid-phase microextracted on a molecularly imprinted polymeric fiber, and then the fiber was thermally desorbed in the gas chromatograph injector, and the compound was determined. The trimethyl phosphate imprinted polymeric fiber was prepared by copolymerization in a fused silica capillary tube and obtained by removal of the wall of fused silica capillary tube. The monolithic fiber displayed good selectivity toward trimethyl phosphate among its structural analogues. It was thermally stable up to 320°C so that it can withstand the high temperature of the gas chromatograph injector for desorption. The factors influencing the performance of its headspace solid-phase microextraction were studied. Under the optimal conditions, the method for quantification of trimethyl phosphate in environmental water was well developed. It exhibited significant linearity, the lowest limit of quantification to date, and good recoveries. Using this method, trimethyl phosphate was detected in five out of seven environmental water samples at concentration levels from 0.28 to 1.22 μg/L, illustrating the heavy pollution of trimethyl phosphate in environmental water.
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http://dx.doi.org/10.1002/jssc.201701048DOI Listing
March 2018

Insertion of an intrathecal catheter in parturients reduces the risk of post-dural puncture headache: A retrospective study and meta-analysis.

PLoS One 2017 5;12(7):e0180504. Epub 2017 Jul 5.

Department of Cardiothoracic Surgery, First Hospital of Jiaxing, School of Medicine, Jiaxing University, Jiaxing, Zhejiang, China.

This study aimed to determine whether insertion of an intrathecal catheter following accidental dural puncture (ADP) in obstetric patients can reduce the incidence of post-dural puncture headache (PDPH) and the requirement of a therapeutic epidural blood patch (TEBP). This was also compared with relocating the epidural catheter at a different vertebral interspace. A retrospective study was performed, as well as a meta-analysis of the literature to further validate our findings. We reviewed the records of 86 obstetric patients who suffered from ADP during epidural anesthesia or combined spinal-epidural anesthesia from October 2015 to November 2016 at our institution. Although, there was no significant decrease in the incidence of PDPH (P = 0.08), the requirement for a TEBP (P = 0.025) was significantly reduced in the intrathecal catheter group compared with the relocated group. In the meta-analysis, 13 eligible studies including 1044 obstetric patients were finally identified. To estimate the pooled risk ratios (RRs), fixed or random effect models were used depending on the heterogeneity. We initially found that an intrathecal catheter significantly reduced the incidence of PDPH (pooled RR = 0.823; 95% CI = 0.700-0.967; P = 0.018) and the requirement of a TEBP (pooled RR = 0.616; 95% CI = 0.443-0.855; P = 0.004). Our study shows that insertion of an intrathecal catheter following ADP might be an effective and dependable method for reducing the risk of a PDPH and requirement for a TEBP in obstetric patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180504PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498039PMC
October 2017

Chemical modification improves the stability of the DNA aptamer GBI-10 and its affinity towards tenascin-C.

Org Biomol Chem 2017 Feb;15(5):1174-1182

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

Aptamers are useful tools in molecular imaging due to their numerous attractive properties, such as excellent affinity and selectivity to diverse types of target molecules and biocompatibility. We carried out structure-activity relationship studies with the tenascin-C (TN-C) binding aptamer GBI-10, which is a promising candidate in tumor imaging. To increase the tumor targeting ability and nuclease resistance under physiological conditions, systematic modifications of GBI-10 with single and multiple 2'-deoxyinosine (2'-dI) or d-/l-isonucleoside (d-/l-isoNA) were performed. Results indicated that sector 3 of the proposed secondary structure is the most important region for specific binding with TN-C. By correlating the affinity of eighty-four GBI-10 derivatives with their predicted secondary structure by Zuker Mfold, we first validated the preferred secondary structure at 37 °C. We found that d-/l-isoNA modified GBI-10 derivatives exhibited improved affinity to the target as well as plasma stability. Affinity measurement and confocal imaging analysis highlighted one potent compound: 4A/26T/32T, which possessed a significantly increased targeting ability to tumor cells. These results revealed the types of modified nucleotides, and the position and number of substituents in GBI-10 that were critical to the TN-C binding ability. Stabilized TN-C-binding DNA aptamers were prepared and they could be further developed for tumor imaging. Our strategy to introduce 2'-dI and d-/l-isoNA modifications after the selection process is likely to be generally applicable to improve the in vivo stability of aptamers without compromising their binding ability.
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http://dx.doi.org/10.1039/c6ob02577cDOI Listing
February 2017

Deletion of ATF4 in AgRP Neurons Promotes Fat Loss Mainly via Increasing Energy Expenditure.

Diabetes 2017 03 19;66(3):640-650. Epub 2016 Dec 19.

Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, People's Republic of China

Although many functions of activating transcription factor 4 (ATF4) are identified, a role of ATF4 in the hypothalamus in regulating energy homeostasis is unknown. Here, we generated adult-onset agouti-related peptide neuron-specific ATF4 knockout (AgRP-ATF4 KO) mice and found that these mice were lean, with improved insulin and leptin sensitivity and decreased hepatic lipid accumulation. Furthermore, AgRP-ATF4 KO mice showed reduced food intake and increased energy expenditure, mainly because of enhanced thermogenesis in brown adipose tissue. Moreover, AgRP-ATF4 KO mice were resistant to high-fat diet-induced obesity, insulin resistance, and liver steatosis and maintained at a higher body temperature under cold stress. Interestingly, the expression of FOXO1 was directly regulated by ATF4 via binding to the cAMP-responsive element site on its promoter in hypothalamic GT1-7 cells. Finally, expression was reduced in the arcuate nucleus (ARC) of the hypothalamus of AgRP-ATF4 KO mice, and adenovirus-mediated overexpression of FOXO1 in ARC increased the fat mass in AgRP-ATF4 KO mice. Collectively, our data demonstrate a novel function of ATF4 in AgRP neurons of the hypothalamus in energy balance and lipid metabolism and suggest hypothalamic ATF4 as a potential drug target for treating obesity and its related metabolic disorders.
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http://dx.doi.org/10.2337/db16-0954DOI Listing
March 2017

Polydopamine/dialdehyde starch/chitosan composite coating for in-tube solid-phase microextraction and in-situ derivation to analysis of two liver cancer biomarkers in human blood.

Anal Chim Acta 2016 Sep 1;935:113-20. Epub 2016 Jul 1.

Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Institute of Public Health and Molecular Medicine Analysis, Central China Normal University, Wuhan 430079, China.

In order to highly enrich two liver cancer biomarkers (hexanal and 2-butanone) in human blood, in this study, natural nontoxic polydopamine/dialdehyde starch/chitosan (PD/DAS/CHI) coating material was synthesized and immobilized on the inner wall of polytetrafluoro-ethlyene (PTFE) tube. It was used to develop the method based on in-tube solid-phase microextraction (IT-SPME) with in-situ derivatization (ISD) coupled to high performance liquid chromatography for the determination of the above mentioned two liver cancer biomarkers in human blood. The simple, rapid and sensitive IT-SPME-ISD method can be finished within 11 min. Under optimum conditions, the limits of detection (LODs) were 1.4 and 1.6 nmol L(-1) for hexanal and 2-butanone, respectively. The relative recoveries from real human blood samples were in the range from 70% to 91% with the intra- and inter-day precisions less than 7.2%. Furthermore, this method was successfully applied for the analysis of hexanal and 2-butanone in blood samples from healthy people with 0.42 ± 0.05 and 0.34 ± 0.04 μmol L(-1), while liver cancer patients with 1.90 ± 0.07  μmol L(-1) and 0.91 ± 0.07 μmol L(-1), respectively. The t-test's results showed there is a statistically significant difference between the data from healthy persons and liver cancer patients. Hence, the developed method might be applied in the screening of suspected liver cancer patients.
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http://dx.doi.org/10.1016/j.aca.2016.06.031DOI Listing
September 2016

Liver-specific Gene Inactivation of the Transcription Factor ATF4 Alleviates Alcoholic Liver Steatosis in Mice.

J Biol Chem 2016 08 12;291(35):18536-46. Epub 2016 Jul 12.

From the Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China

Although numerous biological functions of the activating transcription factor 4 (ATF4) have been identified, a direct effect of ATF4 on alcoholic liver steatosis has not been described previously. The aim of our current study is to investigate the role of ATF4 in alcoholic liver steatosis and elucidate the underlying mechanisms. Here, we showed that the expression of ATF4 is induced by ethanol in hepatocytes in vitro and in vivo, and liver-specific ATF4 knock-out mice are resistant to ethanol-induced liver steatosis, associated with stimulated hepatic AMP-activated protein kinase (AMPK) activity. Furthermore, adenovirus-mediated AMPK knockdown significantly reversed the suppressive effects of ATF4 deficiency on ethanol-induced liver steatosis in mice. In addition, ethanol-fed ATF4 knock-out mice exhibit AMPK-dependent inhibition of fatty acid synthase and stimulation of carnitine palmitoyltransferase 1 (CPT1) in the liver. Moreover, hepatic Tribbles homolog 3 (TRB3) expression was stimulated by ethanol in an ATF4-dependent manner, and adenovirus-mediated TRB3 knockdown blocked ATF4-dependent ethanol-induced AMPK inhibition and triglyceride accumulation in AML-12 cells. Finally, TRB3 directly interacted with AMPK to suppress its phosphorylation. Taken together, these results identify the ATF4-TRB3-AMPK axis as a novel pathway responsible for ethanol-induced liver steatosis.
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http://dx.doi.org/10.1074/jbc.M116.726836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000098PMC
August 2016

A Novel Function of Hepatic FOG2 in Insulin Sensitivity and Lipid Metabolism Through PPARα.

Diabetes 2016 08 3;65(8):2151-63. Epub 2016 May 3.

Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China

Friend of GATA 2 (FOG2) is a transcriptional cofactor involved mostly in cardiac function. The aim of this study was to investigate the role of hepatic FOG2 in insulin sensitivity and lipid accumulation. FOG2 overexpression by adenovirus-expressing FOG2 (Ad-FOG2) significantly attenuates insulin signaling in hepatocytes in vitro. Opposite effects were observed when FOG2 was knocked down through adenovirus-expressing small hairpin RNA for FOG2 (Ad-shFOG2). Furthermore, FOG2 knockdown by Ad-shFOG2 ameliorated insulin resistance in leptin receptor-mutated (db/db) mice, and FOG2 overexpression by Ad-FOG2 attenuated insulin sensitivity in C57BL/6J wild-type (WT) mice. In addition, Ad-FOG2 reduced, whereas Ad-shFOG2 promoted, hepatic triglyceride (TG) accumulation in WT mice under fed or fasted conditions, which was associated with increased or decreased hepatic peroxisome proliferator-activated receptor α (PPARα) expression, respectively. Moreover, the improved insulin sensitivity and increased hepatic TG accumulation by Ad-shFOG2 were largely reversed by adenovirus-expressing PPARα (Ad-PPARα) in WT mice. Finally, we generated FOG2 liver-specific knockout mice and found that they exhibit enhanced insulin sensitivity and elevated hepatic TG accumulation, which were also reversed by Ad-PPARα. Taken together, the results demonstrate a novel function of hepatic FOG2 in insulin sensitivity and lipid metabolism through PPARα.
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http://dx.doi.org/10.2337/db15-1565DOI Listing
August 2016

BTG1 ameliorates liver steatosis by decreasing stearoyl-CoA desaturase 1 (SCD1) abundance and altering hepatic lipid metabolism.

Sci Signal 2016 05 17;9(428):ra50. Epub 2016 May 17.

Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

Liver steatosis, a condition in which lipid accumulates in liver cells, is a leading cause of many liver diseases. The livers of patients with hepatocellular carcinoma, a cancer characterized by liver steatosis, have decreased abundance of the transcription cofactor BTG1 (B cell translocation gene 1). We showed that the livers of db/db mice, which are a genetic model of obesity, had decreased BTG1 mRNA and protein abundance. BTG1 overexpression ameliorated liver steatosis in db/db mice, whereas knockdown of BTG1 induced liver steatosis in wild-type mice. Consistent with these changes, we found that BTG1 decreased triglyceride accumulation in cultured hepatocytes. BTG1 overexpression inhibited the expression of the gene encoding stearoyl-CoA desaturase 1 (SCD1), an enzyme involved in the synthesis of fatty acids, by suppressing the activity of activating transcription factor 4 (ATF4). Knockdown of SCD1 prevented liver steatosis in wild-type mice induced by knockdown of BTG1. Conversely, the ability of BTG1 overexpression to ameliorate liver steatosis in db/db mice was negated by ATF4 overexpression. Moreover, BTG1 transgenic mice were resistant to liver steatosis induced by a high-carbohydrate diet. BTG1 abundance was decreased by this diet through a pathway that involved mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase 1 (S6K1), and cAMP response element-binding protein (CREB). Together, our study identifies a role of BTG1 in regulating hepatic lipid metabolism and specifically in preventing ATF4 and SCD1 from inducing liver steatosis.
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http://dx.doi.org/10.1126/scisignal.aad8581DOI Listing
May 2016

Roles of Cx43 and AKAP95 in ovarian cancer tissues in G1/S phase.

Int J Clin Exp Pathol 2015 1;8(11):14315-24. Epub 2015 Nov 1.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University Xiamen 361102, Fujian, PR China.

Objective: The purpose of this study was to investigate the expression of A-kinase anchor protein 95 (AKAP95), cell cycle protein E1 (cyclinE1) and D1 (cyclinD1), and gap junction protein connexin 43 (Cx43) in ovarian cancer tissues, the relationship between four proteins and clinicopathologic parameters, and the correlation between these proteins.

Methods: The expression of proteins in 54 cases of ovarian cancer tissues was detected by immunohistochemical method.

Results: The positive expression rates of AKAP95, cyclinD1 and cyclinE1 in ovarian cancer tissues were 72.22%, 66.67% and 79.63%, respectively, which were higher than that of ovarian pericarcinoma tissues expressing as 33.33%, 25% and 8.30% (P<0.05). The positive expression rate of Cx43 in ovarian cancer tissues was 40.74%, which was lower than that of ovarian pericarcinoma tissues expressing as 75%; respectively, and the difference was statistically significant between groups (P<0.05). The expression of cyclinD1 in ovarian cancer tissues was related to the histologic type (P<0.05) while it showed no correlation with the degree of differentiation (P>0.05). Additionally, the expression of AKAP95, Cx43 and cyclinE1 in ovarian cancer tissues showed no correlation with the degree of differentiation or the histologic type (P>0.05). Protein expressions of AKAP95, Cx43 and cyclinE1 were correlated with each other (P<0.05), and the expressions of cyclinD1, cyclinE1 and Cx43 were also correlated with each other (P<0.05). However, AKAP95 and cyclinD1 showed no correlation (P>0.05).

Conclusion: AKAP95, cyclinD1 and cyclinE1 play an important role in promoting the process of ovarian cancer formation. The tumor inhibitory effects of Cx43 protein on the pathogenesis of ovarian cancer were weakened. The expression of cyclinD1 in ovarian cancer tissues is related to the histologic type while it shows no correlation with the degree of differentiation. Additionally, the expression of AKAP95, Cx43 and cyclinE1 in ovarian cancer tissues shows no correlation with the degree of differentiation or the histologic type. AKAP95 expression is correlated with Cx43 and cyclinE1 expression; Cx43 expression is correlated with AKAP95, cyclinD1 and cyclinE1 expression; cyclinE1 expression is correlated with AKAP95, Cx43, cyclinD1 expression; cyclinD1 expression is correlated with Cx43 and cyclinE1 expression, while AKAP95 and cyclinD1 show no correlation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713533PMC
October 2016

MAPK1/3 regulate hepatic lipid metabolism via ATG7-dependent autophagy.

Autophagy 2016 13;12(3):592-3. Epub 2016 Jan 13.

a Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences , Shanghai , China.

Although many biological functions of MAPK1/ERK2-MAPK3/ERK1 (mitogen-activated protein kinase 1/3) have been reported, a direct effect of MAPK1/3 on hepatic lipid metabolism remains largely unknown. We recently showed that activation of MAPK1/3 ameliorates liver steatosis in LEPR (leptin receptor)-deficient (db/db) mice, a classic animal model for liver steatosis. Consistent with these results, knockdown of MAPK1/3 promotes liver steatosis in C57/B6J wild-type (WT) mice. Autophagic flux and ATG7 (autophagy related 7) levels are increased by MAPK1/3 activation or decreased by MAPK1/3 knockdown in livers and primary hepatocytes. Blockade of autophagic flux by chloroquine (CQ) or ATG7 knockdown reverses the ameliorated liver steatosis in MAPK1/3-activated db/db mice. Together, these findings identify a beneficial role for MAPK1/3 in liver steatosis that is mediated by ATG7-dependent autophagy, which provides novel insights into the mechanisms underlying liver steatosis and create a rationale for targeting MAPK1/3 in the treatment of liver steatosis.
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http://dx.doi.org/10.1080/15548627.2015.1135282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836014PMC
December 2016
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