Publications by authors named "Jieyu Wu"

20 Publications

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Inflammatory cell-derived CXCL3 promotes pancreatic cancer metastasis through a novel myofibroblast-hijacked cancer escape mechanism.

Gut 2021 Feb 10. Epub 2021 Feb 10.

Department of Microbiology, Tumor and Cell Biology, Biomedicum, Karolinska Institutet, Stockholm, Sweden

Objective: Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy and lacks effective treatment. We aimed to understand molecular mechanisms of the intertwined interactions between tumour stromal components in metastasis and to provide a new paradigm for PDAC therapy.

Design: Two unselected cohorts of 154 and 20 patients with PDAC were subjected to correlation between interleukin (IL)-33 and CXCL3 levels and survivals. Unbiased expression profiling, and genetic and pharmacological gain-of-function and loss-of-function approaches were employed to identify molecular signalling in tumour-associated macrophages (TAMs) and myofibroblastic cancer-associated fibroblasts (myoCAFs). The role of the IL-33-ST2-CXCL3-CXCR2 axis in PDAC metastasis was evaluated in three clinically relevant mouse PDAC models.

Results: IL-33 was specifically elevated in human PDACs and positively correlated with tumour inflammation in human patients with PDAC. CXCL3 was highly upregulated in IL-33-stimulated macrophages that were the primary source of CXCL3. CXCL3 was correlated with poor survival in human patients with PDAC. Mechanistically, activation of the IL-33-ST2-MYC pathway attributed to high CXCL3 production. The highest level of CXCL3 was found in PDAC relative to other cancer types and its receptor CXCR2 was almost exclusively expressed in CAFs. Activation of CXCR2 by CXCL3 induced a CAF-to-myoCAF transition and α-smooth muscle actin (α-SMA) was uniquely upregulated by the CXCL3-CXCR2 signalling. Type III collagen was identified as the CXCL3-CXCR2-targeted adhesive molecule responsible for myoCAF-driven PDAC metastasis.

Conclusions: Our work provides novel mechanistic insights into understanding PDAC metastasis by the TAM-CAF interaction and targeting each of these signalling components would provide an attractive and new paradigm for treating pancreatic cancer.
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http://dx.doi.org/10.1136/gutjnl-2020-322744DOI Listing
February 2021

Assessment of Internet Hospitals in China During the COVID-19 Pandemic: National Cross-Sectional Data Analysis Study.

J Med Internet Res 2021 01 20;23(1):e21825. Epub 2021 Jan 20.

Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China.

Background: Internet hospitals in China are being rapidly developed as an innovative approach to providing health services. The ongoing COVID-19 pandemic has triggered the development of internet hospitals that promote outpatient service delivery to the public via internet technologies. To date, no studies have assessed China's internet hospitals during the COVID-19 pandemic.

Objective: This study aimed to elucidate the characteristics of China's internet hospitals and assess the health service capacity of these hospitals.

Methods: Data on 711 internet hospitals were collected from official websites, the WeChat (Tencent Inc) platform, smartphone apps, and the Baidu search engine until July 16, 2020.

Results: As of July 16, 2020, 711 internet hospitals were developed in mainland China. More than half of these internet hospitals (421/711, 59.2%) were established during 2019 (206/711, 29%) and 2020 (215/711, 30.2%). Furthermore, about one-third (215/711, 30.2%) of internet hospitals were established at the beginning of 2020 as an emergency response to the COVID-19 epidemic. The 711 internet hospitals consisted of the following 3 types of hospitals: government-oriented (42/711, 5.91%), hospital-oriented (143/711, 20.11%), and enterprise-oriented internet hospitals (526/711, 73.98%). The vast majority of internet hospitals were traditional hospitals (526/711, 74%). Nearly 46.1% (221/711) of internet hospitals requested doctors to provide health services at a specific web clinic. Most patients (224/639, 35.1%) accessed outpatient services via WeChat. Internet hospitals' consulting methods included SMS text messaging consultations involving the use of graphics (552/570, 96.8%), video consultations (248/570, 43.5%), and telephone consultations (238/570, 41.8%). The median number of available web-based doctors was 43, and the median consultation fees of fever clinics and other outpatient clinics were ¥0 (US $0) per consultation and ¥6 (US $0.93) per consultation, respectively. Internet hospitals have provided various services during the COVID-19 pandemic, including medical prescription, drug delivery, and medical insurance services.

Conclusions: The dramatic increase of internet hospitals in China has played an important role in the prevention and control of COVID-19. Internet hospitals provide different and convenient medical services for people in need.
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http://dx.doi.org/10.2196/21825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819672PMC
January 2021

S100A11 Promotes Liver Steatosis via FOXO1-Mediated Autophagy and Lipogenesis.

Cell Mol Gastroenterol Hepatol 2021 17;11(3):697-724. Epub 2020 Oct 17.

Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, Yunnan, China; Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China; Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. Electronic address:

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is becoming a severe liver disorder worldwide. Autophagy plays a critical role in liver steatosis. However, the role of autophagy in NAFLD remains exclusive and under debate. In this study, we investigated the role of S100 calcium binding protein A11 (S100A11) in the pathogenesis of hepatic steatosis.

Methods: We performed liver proteomics in a well-established tree shrew model of NAFLD. The expression of S100A11 in different models of NAFLD was detected by Western blot and/or quantitative polymerase chain reaction. Liver S100A11 overexpression mice were generated by injecting a recombinant adenovirus gene transfer vector through the tail vein and then induced by a high-fat and high-cholesterol diet. Cell lines with S100a11 stable overexpression were established with a recombinant lentiviral vector. The lipid content was measured with either Bodipy staining, Oil Red O staining, gas chromatography, or a triglyceride kit. The autophagy and lipogenesis were detected in vitro and in vivo by Western blot and quantitative polymerase chain reaction. The functions of Sirtuin 1, histone deacetylase 6 (HDAC6), and FOXO1 were inhibited by specific inhibitors. The interactions between related proteins were analyzed by a co-immunoprecipitation assay and immunofluorescence analysis.

Results: The expression of S100A11 was up-regulated significantly in a time-dependent manner in the tree shrew model of NAFLD. S100A11 expression was induced consistently in oleic acid-treated liver cells as well as the livers of mice fed a high-fat diet and NAFLD patients. Both in vitro and in vivo overexpression of S100A11 could induce hepatic lipid accumulation. Mechanistically, overexpression of S100A11 activated an autophagy and lipogenesis process through up-regulation and acetylation of the transcriptional factor FOXO1, consequently promoting lipogenesis and lipid accumulation in vitro and in vivo. Inhibition of HDAC6, a deacetylase of FOXO1, showed similar phenotypes to S100A11 overexpression in Hepa 1-6 cells. S100A11 interacted with HDAC6 to inhibit its activity, leading to the release and activation of FOXO1. Under S100A11 overexpression, the inhibition of FOXO1 and autophagy could alleviate the activated autophagy as well as up-regulated lipogenic genes. Both FOXO1 and autophagy inhibition and Dgat2 deletion could reduce liver cell lipid accumulation significantly.

Conclusions: A high-fat diet promotes liver S100A11 expression, which may interact with HDAC6 to block its binding to FOXO1, releasing or increasing the acetylation of FOXO1, thus activating autophagy and lipogenesis, and accelerating lipid accumulation and liver steatosis. These findings indicate a completely novel S100A11-HDAC6-FOXO1 axis in the regulation of autophagy and liver steatosis, providing potential possibilities for the treatment of NAFLD.
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http://dx.doi.org/10.1016/j.jcmgh.2020.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841444PMC
October 2020

Visualization of human T lymphocyte-mediated eradication of cancer cells in vivo.

Proc Natl Acad Sci U S A 2020 09 28;117(37):22910-22919. Epub 2020 Aug 28.

Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, 171 65 Stockholm, Sweden;

Lymphocyte-based immunotherapy has emerged as a breakthrough in cancer therapy for both hematologic and solid malignancies. In a subpopulation of cancer patients, this powerful therapeutic modality converts malignancy to clinically manageable disease. However, the T cell- and chimeric antigen receptor T (CAR-T) cell-mediated antimetastatic activity, especially their impacts on microscopic metastatic lesions, has not yet been investigated. Here we report a living zebrafish model that allows us to visualize the metastatic cancer cell killing effect by tumor- infiltrating lymphocytes (TILs) and CAR-T cells in vivo at the single-cell level. In a freshly isolated primary human melanoma, specific TILs effectively eliminated metastatic cancer cells in the living body. This potent metastasis-eradicating effect was validated using a human lymphoma model with CAR-T cells. Furthermore, cancer-associated fibroblasts protected metastatic cancer cells from T cell-mediated killing. Our data provide an in vivo platform to validate antimetastatic effects by human T cell-mediated immunotherapy. This unique technology may serve as a precision medicine platform for assessing anticancer effects of cellular immunotherapy in vivo before administration to human cancer patients.
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http://dx.doi.org/10.1073/pnas.2009092117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502706PMC
September 2020

Mobile health technology combats COVID-19 in China.

J Infect 2021 01 27;82(1):159-198. Epub 2020 Jul 27.

School of Public Health, Fujian Medical University, No. 1 Xuefu North Road, Fuzhou 350122, China. Electronic address:

China empowers mobile health technologies to fight against COVID-19 pandemic. The success of mobile health here may be a useful reference for other parts of the world. We explore China's application of mobile health technologies to replenishing traditional public-health and social approaches for mitigating and suppressing COVID-19, and found that Internet hospitals alleviate the unavailability, inaccessibility, and inequity of health services during the outbreak; the fact-check and information-release platforms reduce the spread of misinformation; and the infection risk scoring systems facilitate restoring the order of production and life.
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http://dx.doi.org/10.1016/j.jinf.2020.07.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384407PMC
January 2021

Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors.

Nat Commun 2020 07 24;11(1):3704. Epub 2020 Jul 24.

Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 171 77, Stockholm, Sweden.

FGF-2 displays multifarious functions in regulation of angiogenesis and vascular remodeling. However, effective drugs for treating FGF-2 tumors are unavailable. Here we show that FGF-2 modulates tumor vessels by recruiting NG2 pricytes onto tumor microvessels through a PDGFRβ-dependent mechanism. FGF-2 tumors are intrinsically resistant to clinically available drugs targeting VEGF and PDGF. Surprisingly, dual targeting the VEGF and PDGF signaling produces a superior antitumor effect in FGF-2 breast cancer and fibrosarcoma models. Mechanistically, inhibition of PDGFRβ ablates FGF-2-recruited perivascular coverage, exposing anti-VEGF agents to inhibit vascular sprouting. These findings show that the off-target FGF-2 is a resistant biomarker for anti-VEGF and anti-PDGF monotherapy, but a highly beneficial marker for combination therapy. Our data shed light on mechanistic interactions between various angiogenic and remodeling factors in tumor neovascularization. Optimization of antiangiogenic drugs with different principles could produce therapeutic benefits for treating their resistant off-target cancers.
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http://dx.doi.org/10.1038/s41467-020-17525-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382445PMC
July 2020

Eradication of tumor growth by delivering novel photothermal selenium-coated tellurium nanoheterojunctions.

Sci Adv 2020 04 8;6(15):eaay6825. Epub 2020 Apr 8.

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 171 77, Sweden.

Two-dimensional nanomaterial-based photothermal therapy (PTT) is currently under intensive investigation as a promising approach toward curative cancer treatment. However, high toxicity, moderate efficacy, and low uniformity in shape remain critical unresolved issues that hamper their clinical application. Thus, there is an urgent need for developing versatile nanomaterials to meet clinical expectations. To achieve this goal, we developed a stable, highly uniform in size, and nontoxic nanomaterials made of tellurium-selenium (TeSe)-based lateral heterojunction. Systemic delivery of TeSe nanoparticles in mice showed highly specific accumulation in tumors relative to other healthy tissues. Upon exposure to light, TeSe nanoparticles nearly completely eradicated lung cancer and hepatocellular carcinoma in preclinical models. Consistent with tumor suppression, PTT altered the tumor microenvironment and induced immense cancer cell apoptosis. Together, our findings demonstrate an exciting and promising PTT-based approach for cancer eradication.
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http://dx.doi.org/10.1126/sciadv.aay6825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141822PMC
April 2020

Effect of catechin liposomes on the nitrosamines and quality of traditional Chinese bacon.

Food Funct 2019 Feb;10(2):625-634

Zhejiang Provincial Key Laboratory of Biometrology and Inspection and Quarantine, China Jiliang University, Hangzhou 310018, China.

The instability of catechins (CT) is currently a challenge for their application in the food industry. This study explored whether or not the protective effects of liposome encapsulation on CT could enhance the role of CT as antioxidants in reducing nitrosamines (NAs) in traditional Chinese bacon (TCB). The samples were further characterized by the analysis of volatile compounds, color parameters, and texture profile during storage to assess the effects of catechin liposomes (CTL) on TCB. Results showed that the increase in NAs in fried TCB was strongly dependent on the storage time. CTL could reduce the production of NAs in fried TCB (40.45%) more strongly than CT (15.13%) after 49 days of storage. Higher phenol contents were found in CTL (1515.25 × 106 area unit (AU)) than those in control (1451.73 × 106 AU) and CT (1391.10 × 106 AU) TCB at the end of storage. The addition of antioxidants increased (p < 0.05) a* values in the following order: CTL > CT > control with mean values of 6.54, 5.09, and 3.92, respectively, after 49-day storage. Conversely, the addition of CTL decreased (p < 0.05) the hardness of TCB. Encapsulating CT in the liposomes can effectively reduce the NAs in TCB and positively affect its quality. This technique may guide the potential application of liposomes in the meat industry.
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http://dx.doi.org/10.1039/c8fo01677aDOI Listing
February 2019

Systematic bias between blinded independent central review and local assessment: literature review and analyses of 76 phase III randomised controlled trials in 45 688 patients with advanced solid tumour.

BMJ Open 2018 09 10;8(9):e017240. Epub 2018 Sep 10.

Department of Thoracic Surgery and Oncology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Objective: Unbiased assessment of tumour response is crucial in randomised controlled trials (RCTs). Blinded independent central review is usually used as a supplemental or monitor to local assessment but is costly. The aim of this study is to investigate whether systematic bias existed in RCTs by comparing the treatment effects of efficacy endpoints between central and local assessments.

Design: Literature review, pooling analysis and correlation analysis.

Data Sources: PubMed, from 1 January 2010 to 30 June 2017.

Eligibility Criteria For Selecting Studies: Eligible articles are phase III RCTs comparing anticancer agents for advanced solid tumours. Additionally, the articles should report objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) or time to progression (TTP); the treatment effect of these endpoints, OR or HR, should be based on central and local assessments.

Results: Of 76 included trials involving 45 688 patients, 17 (22%) trials reported their endpoints with statistically inconsistent inferences (p value lower/higher than the probability of type I error) between central and local assessments; among them, 9 (53%) trials had statistically significant inference based on central assessment. Pooling analysis presented no systematic bias when comparing treatment effects of both assessments (ORR: OR=1.02 (95% CI 0.97 to 1.07), p=0.42, I=0%; DCR: OR=0.97 (95% CI 0.92 to 1.03), p=0.32, I=0%); PFS: HR=1.01 (95% CI 0.99 to 1.02), p=0.32, I=0%; TTP: HR=1.04 (95% CI 0.95 to 1.14), p=0.37, I=0%), regardless of funding source, mask, region, tumour type, study design, number of enrolled patients, response assessment criteria, primary endpoint and trials with statistically consistent/inconsistent inferences. Correlation analysis also presented no sign of systematic bias between central and local assessments (ORR, DCR, PFS: r>0.90, p<0.01; TTP: r=0.90, p=0.29).

Conclusions: No systematic bias could be found between local and central assessments in phase III RCTs on solid tumours. However, statistically inconsistent inferences could be made in many trials between both assessments.
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http://dx.doi.org/10.1136/bmjopen-2017-017240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144327PMC
September 2018

The prognostic value of metformin for advanced non-small cell lung cancer: a systematic review and meta-analysis.

Transl Lung Cancer Res 2018 Jun;7(3):389-396

Department of Thoracic Surgery and Oncology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.

Background: The prognostic value of Metformin for concurrent non-small cell lung cancer (NSCLC) has been controversial in previous individual studies and meta-analyses. In order to further investigate the value of this medication, we conducted a systematic review and meta-analysis for patients with advanced or inoperable NSCLC.

Methods: We searched articles from PubMed, Scopus and Web of Science databases; the time interval was from the inception date of the databases to 1 September 2017. Inclusion criteria for eligible studies were: advanced or inoperable NSCLC; Metformin as an experimental group, and non-Metformin usage as a control group; progression-free survival (PFS) or overall survival (OS) as the outcome, with available hazard ratio (HR). Data synthesis was conducted based on the random-effect model.

Results: From a total of 97 articles in databases, we included seven eligible studies. Among them, only one study compared Metformin usage and non-Metformin usage for NSCLC patients who didn't have diabetes mellitus (DM): no significant difference was found in either OS or PFS. The remaining six studies compared Metformin usage and non-Metformin usage for patients with concurrent NSCLC and DM: according to meta-analysis, significantly prolonged OS was found in Metformin usage rather than non-Metformin usage [pooled HR =0.87 (0.77-0.99), P=0.04]; no significant difference was indicated in PFS [pooled HR =0.85 (0.67-1.07), P=0.16]. In subgroup analysis, among patients with late-stage NSCLC and DM, significant difference was found, regardless of OS [pooled HR =0.81 (0.70-0.94), P<0.01] or PFS [pooled HR =0.71 (0.58-0.88), P<0.01]. However, among patients with local advanced NSCLC and DM, there was no significant difference [OS: pooled HR =1.05 (0.79-1.40), P=0.74; PFS: pooled HR =0.94 (0.68-1.32), P=0.74].

Conclusions: The prognostic value of Metformin for concurrent late-stage NSCLC and DM was demonstrated. It deserves further confirmation and explanation.
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http://dx.doi.org/10.21037/tlcr.2018.03.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037960PMC
June 2018

Cancer Lipid Metabolism Confers Antiangiogenic Drug Resistance.

Cell Metab 2018 Jul 31;28(1):104-117.e5. Epub 2018 May 31.

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 171 77, Sweden. Electronic address:

Intrinsic and evasive antiangiogenic drug (AAD) resistance is frequently developed in cancer patients, and molecular mechanisms underlying AAD resistance remain largely unknown. Here we describe AAD-triggered, lipid-dependent metabolic reprogramming as an alternative mechanism of AAD resistance. Unexpectedly, tumor angiogenesis in adipose and non-adipose environments is equally sensitive to AAD treatment. AAD-treated tumors in adipose environment show accelerated growth rates in the presence of a minimal number of microvessels. Mechanistically, AAD-induced tumor hypoxia initiates the fatty acid oxidation metabolic reprogramming and increases uptake of free fatty acid (FFA) that stimulates cancer cell proliferation. Inhibition of carnitine palmitoyl transferase 1A (CPT1) significantly compromises the FFA-induced cell proliferation. Genetic and pharmacological loss of CPT1 function sensitizes AAD therapeutic efficacy and enhances its anti-tumor effects. Together, we propose an effective cancer therapy concept by combining drugs that target angiogenesis and lipid metabolism.
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http://dx.doi.org/10.1016/j.cmet.2018.05.005DOI Listing
July 2018

Antioxidant and Antimicrobial Effects of Catechin Liposomes on Chinese Dried Pork.

J Food Prot 2018 05;81(5):827-834

5 Food Science Institute, Zhejiang Academy of Agricultural Sciences, 298 Desheng Road, Hangzhou 310021, People's Republic of China.

In this study, catechin (CT), catechin liposome (CTL), and α-tocopherol (TP) were added to Chinese dried pork to achieve a healthy lipid composition. Their effectiveness in prevention of lipid oxidation was determined by measuring the values of thiobarbituric acid-reactive substances and peroxides. The total viable count in samples was used to identify the antimicrobial activities of CT, CTL, and TP, and the pH values of the samples were determined. Chinese dried pork with antioxidants added at 600 mg/kg was subjected to sensory evaluation. Thiobarbituric acid-reactive substance values, peroxide values, and total viable counts indicated that CTL significantly enhanced the antioxidant and antibacterial effects of CT on Chinese dried pork, especially after storage at room temperature for 25 days. Compared with the two other antioxidants, CTL could better maintain the pH stability of Chinese dried pork at room temperature. Sensory evaluation revealed that the scores of CTL were better than those of CT and TP in terms of preserving the color, flavor, tenderness, and overall acceptability of Chinese dried pork. Use of CTL in Chinese dried pork had good antioxidant and antibacterial effects and maintained color, flavor, and tenderness at a relatively stable level, suggesting that CTL could be used as an antioxidant in Chinese dried pork to enhance oxidative stability and prolong shelf life.
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http://dx.doi.org/10.4315/0362-028X.JFP-17-452DOI Listing
May 2018

How to design carbohydrate diet regimens for heart disease patients.

Eur J Prev Cardiol 2018 06 23;25(9):979-980. Epub 2018 Mar 23.

1 School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

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http://dx.doi.org/10.1177/2047487318766602DOI Listing
June 2018

PHA-4/FoxA senses nucleolar stress to regulate lipid accumulation in Caenorhabditis elegans.

Nat Commun 2018 03 22;9(1):1195. Epub 2018 Mar 22.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Center for Excellence in Animal Evolution and Genetics, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.

The primary function of the nucleolus is ribosome biogenesis, which is an extremely energetically expensive process. Failures in ribosome biogenesis cause nucleolar stress with an altered energy status. However, little is known about the underlying mechanism linking nucleolar stress to energy metabolism. Here we show that nucleolar stress is triggered by inactivation of RSKS-1 (ribosomal protein S6 kinase), RRP-8 (ribosomal RNA processing 8), and PRO-2/3 (proximal proliferation), all of which are involved in ribosomal RNA processing or inhibition of rDNA transcription by actinomycin D (AD), leading to excessive lipid accumulation in Caenorhabditis elegans. The transcription factor PHA-4/FoxA acts as a sensor of nucleolar stress to bind to and transactivate the expression of the lipogenic genes pod-2 (acetyl-CoA carboxylase), fasn-1 (fatty acid synthase), and dgat-2 (diacylglycerol O-acyltransferase 2), consequently promoting lipid accumulation. Importantly, inactivation of pha-4 or dgat-2 is sufficient to abolish nucleolar stress-induced lipid accumulation and prolonged starvation survival. The results revealed a distinct PHA-4-mediated lipogenesis pathway that senses nucleolar stress and shifts excessive energy for storage as fat.
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http://dx.doi.org/10.1038/s41467-018-03531-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864837PMC
March 2018

White light, autofluorescence and narrow-band imaging bronchoscopy for diagnosing airway pre-cancerous and early cancer lesions: a systematic review and meta-analysis.

J Thorac Dis 2016 Nov;8(11):3205-3216

Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China;; China State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou 510120, China;; National Clinical Research Centre of Respiratory Disease, Guangzhou 510120, China.

Background: We aimed to summarize the diagnostic accuracy of white light bronchoscopy (WLB) and advanced techniques for airway pre-cancerous lesions and early cancer, such as autofluorescence bronchoscopy (AFB), AFB combined with WLB (AFB + WLB) and narrow-band imaging (NBI) bronchoscopy.

Methods: We searched for eligible studies in seven electronic databases from their date of inception to Mar 20, 2015. In eligible studies, detected lesions should be confirmed by histopathology. We extracted and calculated the 2×2 data based on the pathological criteria of lung tumor, including high-grade lesions from moderate dysplasia (MOD) to invasive carcinoma (INV). Random-effect model was used to pool sensitivity, specificity, diagnostic odds ratio (DOR) and the area under the receiver-operating characteristic curve (AUC).

Results: In 53 eligible studies (39 WLB, 39 AFB, 17 AFB + WLB, 6 NBI), diagnostic performance for high-grade lesions was analyzed based on twelve studies (10 WLB, 7 AFB, 7 AFB + WLB, 1 NBI), involving with totally 2,880 patients and 8,830 biopsy specimens. The sensitivity, specificity, DOR and AUC of WLB were 51% (95% CI, 34-68%), 86% (95% CI, 73-84%), 6 (95% CI, 3-13) and 77% (95% CI, 73-81%). Those of AFB and AFB + WLB were 93% (95% CI, 77-98%) and 86% (95% CI, 75-97%), 52% (95% CI, 37-67%) and 71% (95% CI, 56-87%), 15 (95% CI, 4-57) and 16 (95% CI, 6-41), and 76% (95% CI, 72-79%) and 82% (95% CI, 78-85%), respectively. NBI presented 100% sensitivity and 43% specificity.

Conclusions: With higher sensitivity, advanced bronchoscopy could be valuable to avoid missed diagnosis. Combining strategy of AFB and WLB may contribute preferable diagnosis rather than their alone use for high-grade lesions. Studies of NBI warrants further investigation for precancerous lesions.
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http://dx.doi.org/10.21037/jtd.2016.11.61DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5179382PMC
November 2016

Comparison of detection methods and follow-up study on the tyrosine kinase inhibitors therapy in non-small cell lung cancer patients with ROS1 fusion rearrangement.

BMC Cancer 2016 08 4;16:599. Epub 2016 Aug 4.

Department of Pathology, the First Affiliated Hospital of Guangzhou Medical University, No. 151, Yanjiangxi Road, Guangzhou, 510120, China.

Background: The screening of ROS proto-oncogene 1, receptor tyrosine kinase(ROS1) fusion rearrangement might be potentially beneficial for an effective therapy against non-small cell lung cancer (NSCLC). However, the three main ROS1 rearrangement detection methods have limitations, and no routine protocol for the detection of ROS1 rearrangement in NSCLC is available. In this study, our aims were to compare immunohistochemistry (IHC), fluorescent in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (qRT-PCR) in their ability to detect ROS1 rearrangement in NSCLC, and discuss the clinical characteristics and histopathology of the patients with ROS1 rearrangement. Moreover, the effects of tyrosine kinase inhibitors (TKIs) therapy on the patients with ROS1 rearrangement and advanced stage disease (III b-IV) were investigated.

Methods: Patients with a previously diagnosed NSCLC were recruited in this study from November 2013 to October 2015. IHC was performed using the D4D6 monoclonal antibody (mAb) in an automatic IHC instrument, while FISH and qRT-PCR were carried out to confirm the IHC results. FISH and qRT-PCR positive cases underwent direct sequencing. After detection, patients with advanced ROS1 rearranged NSCLC had received TKI therapy.

Results: Two hundred and thirty-eight patients were included in this study. ROS1 rearrangement was detected in 10 patients. The concordant rate of FISH and qRT-PCR results was 100 %, while in the FISH and IHC results high congruence was present when IHC showed a diffusely (≥60 % tumor cells) 2-3+ cytoplasmic reactivity pattern. Patients harboring ROS1 rearrangement were mostly young (8/10), females (7/10) and non-smokers (7/10) with adenocarcinoma (10/10) and acinar pattern. Most of their tumor were in intermediate grade (6/8). Among these 10 patients, three of them in stage IV with ROS1 rearrangement gained benefits from ROS1 TKI therapy.

Conclusions: IHC, FISH and qRT-PCR can reliably detect ROS1 rearrangement in NSCLC, while IHC can be used as a preliminary screening tool. These results supported the efficacy of ROS1 TKI therapy in treating advanced NSCLC patients with ROS1 rearrangement.
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http://dx.doi.org/10.1186/s12885-016-2582-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973062PMC
August 2016

Iron Overload Coordinately Promotes Ferritin Expression and Fat Accumulation in Caenorhabditis elegans.

Genetics 2016 05 26;203(1):241-53. Epub 2016 Mar 26.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China

The trace element iron is crucial for living organisms, since it plays essential roles in numerous cellular functions. Systemic iron overload and the elevated level of ferritin, a ubiquitous intracellular protein that stores and releases iron to maintain the iron homeostasis in cells, has long been epidemiologically associated with obesity and obesity-related diseases. However, the underlying mechanisms of this association remain unclear. Here, using Caenorhabditis elegans, we show that iron overload induces the expression of sgk-1, encoding the serum and glucocorticoid-inducible kinase, to promote the level of ferritin and fat accumulation. Mutation of cyp-23A1, encoding a homolog of human cytochrome P450 CYP7B1 that is related to neonatal hemochromatosis, further enhances the elevated expression of ftn-1, sgk-1, and fat accumulation. sgk-1 positively regulates the expression of acs-20 and vit-2, genes encoding homologs of the mammalian FATP1/4 fatty acid transport proteins and yolk lipoproteins, respectively, to facilitate lipid uptake and translocation for storage under iron overload. This study reveals a completely novel pathway in which sgk-1 plays a central role to synergistically regulate iron and lipid homeostasis, offering not only experimental evidence supporting a previously unverified link between iron and obesity, but also novel insights into the pathogenesis of iron and obesity-related human metabolic diseases.
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http://dx.doi.org/10.1534/genetics.116.186742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858777PMC
May 2016

Isolation of novel sequences targeting highly variable viral protein hemagglutinin.

MethodsX 2015 16;2:64-71. Epub 2015 Feb 16.

MOE Key Laboratory of Aquatic Product Safety, State Key Laboratory of Biocontrol, Biotechnology Research Center, The School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.

Rapid evolution is a hallmark of the viral kingdom and a major concern for developing universal vaccines. The isolation of substantial numbers of viral sequence variants at highly variable viral protein domains remains a major challenge. We previously developed a combinatorial method for the isolation of novel sequences to cope with rapid viral variations at the G-H loop of Foot and Mouth Disease virus VP1 protein [1]. Here we present a modification of that method in its application in the randomization of the hemagglutinin gene from a H5N2 virus, namely: •removal of potentially stressful region which harbored a stretch of basic amino acids to increase the success rates of gene cloning, and to streamline the process of future engineering of novel viral variants.•clustered randomization in a full-length gene, as the positive rate for partial gene fragment libraries was extremely low before enrichment in the previous FMDV studies.•the use of fusion partner was avoided, which was used previously for protein expression, stabilization of clones and reduction of stresses on host cells.•the use of Poisson distribution is proposed to approximate sequencing output to achieve cost effectiveness.
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http://dx.doi.org/10.1016/j.mex.2015.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487337PMC
July 2015

Pu-erh tea down-regulates sterol regulatory element-binding protein and stearyol-CoA desaturase to reduce fat storage in Caenorhaditis elegans.

PLoS One 2015 6;10(2):e0113815. Epub 2015 Feb 6.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.

Consumption of Pu-erh has been reported to result in numerous health benefits, but the mechanisms underlying purported weight-loss and lowering of lipid are poorly understood. Here, we used the nematode Caenorhaditis elegans to explore the water extract of Pu-erh tea (PTE) functions to reduce fat storage. We found that PTE down-regulates the expression of the master fat regulator SBP-1, a homologue of sterol regulatory element binding protein (SREBP) and its target stearoyl-CoA desaturase (SCD), a key enzyme in fat biosynthesis, leading to an increased ratio of stearic acid (C18:0) to oleic acid (C18:1n-9), and subsequently decreased fat storage. We also found that both the pharyngeal pumping rate and food uptake of C. elegans decreased with exposure to PTE. Collectively, these results provide an experimental basis for explaining the ability of Pu-erh tea in promoting inhibition of food uptake and the biosynthesis of fat via SBP-1 and SCD, thereby reducing fat storage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0113815PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319740PMC
January 2016

Stress-response protein expression and DAF-16 translocation were induced in tributyltin-exposed Caenorhabditis elegans.

Bull Environ Contam Toxicol 2012 Oct 9;89(4):704-11. Epub 2012 Aug 9.

Department of Life Sciences, Huainan Normal University, Huainan 232001, Anhui, China.

Exposure to tributyltin (TBT) with graded sublethal doses (0, 1, 10, 50 and 200 nM) resulted in the release of reactive oxygen species (ROS) and DNA damage in the nematode Caenorhabditis elegans. After the worms carrying transgenic reporters were exposed to TBT, the expressions of superoxide dismutase (SOD-3), glutathione S-transferase (GST-4) and heat shock proteins (HSP-4, HSP-16.2 and HSP-70) were semi-quantified after exposure. The results indicated that TBT caused dose-dependent induction of SOD-3, GST-4, HSP-4 and HSP-70. Furthermore, TBT exposure also induced DAF-16 translocation from cytoplasm to nucleus. The results implicated that C. elegans might be a potential animal model for TBT level monitoring and toxicity assessment.
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http://dx.doi.org/10.1007/s00128-012-0760-2DOI Listing
October 2012