Publications by authors named "Hui Sheng"

125 Publications

Spatial learning and memory deficits induced by prenatal glucocorticoid exposure depend on hippocampal CRHR1 and CXCL5 signaling in rats.

J Neuroinflammation 2021 Apr 2;18(1):85. Epub 2021 Apr 2.

Department of Gynecology and Obstetrics and Research Center for Molecular Metabolomics, Xiangya Hospital Central South University, Changsha, 410008, China.

Background: Prenatal synthetic glucocorticoid (sGC) exposure increases the susceptibility to cognitive and affective disorders in postnatal life. We previously demonstrated that prenatal sGC exposure results in an increase in corticotropin-releasing hormone (CRH) receptor type 1 (CRHR1) expression in the hippocampus of rats, and CRHR1 is involved in synapse formation via regulation of C-X-C chemokine ligand 5 (CXCL5) in hippocampus. We sought to investigate that the roles of CRHR1 and CXCL5 in learning and memory impairment caused by prenatal sGC exposure.

Methods: Pregnant rats were administered with saline or dexamethasone (DEX) from gestational day (GD) 14 to GD21. DEX offspring at 2-day old were treated with saline and CRHR1 antagonists (antalarmin and CP154526) for 7 days. Some DEX offspring received intra-hippocampal injection of AAV9 carrying CXCL5 gene. Spatial learning and memory was assessed by Morris water maze test. Immunofluorescence analysis was applied to show synapsin I and PSD95 signals in hippocampus. Synapsin I and PSD95 protein level and CXCL5 concentration were determined by western blotting and ELISA, respectively. Organotypic hippocampal slice cultures were used to investigate the effect of DEX on CXCL5 production in vitro.

Results: Both male and female DEX offspring displayed impairment of spatial learning and memory in adulthood. Synapsin I and PSD95 signals and CXCL5 levels were decreased in DEX offspring. DEX offspring with antalarmin and CP154526 treatment showed improved spatial learning and memory. Antalarmin and CP154526 treatment increased synapsin I and PSD95 signals and CXCL5 concentration in hippocampus. Bilaterally hippocampal injection of AAV9 carrying CXCL5 gene improved the spatial learning and memory and increased CXCL5 concentration and synapsin I and PSD95 levels in hippocampus. DEX dose-dependently suppressed CXCL5 production in cultured hippocammpal slices, which was prevented by antalarmin treatment.

Conclusion: CRHR1 and CXCL5 signaling in the hippocampus are involved in spatial learning and memory deficits caused by prenatal DEX exposure. CRHR1 activation contributes to decreased CXCL5 production in hippocampus induced by prenatal DEX treatment. Our study provides a molecular basis of prenatal GC exposure programming spatial learning and memory.
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http://dx.doi.org/10.1186/s12974-021-02129-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019183PMC
April 2021

The lncRNA XIST/miR-125b-2-3p axis modulates cell proliferation and chemotherapeutic sensitivity via targeting Wee1 in colorectal cancer.

Cancer Med 2021 04 5;10(7):2423-2441. Epub 2021 Mar 5.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: Numerous reports on microRNAs have illustrated their role in tumor growth and metastasis. Recently, a new prognostic factor, miR-125b-2-3p, has been identified for predicting chemotherapeutic sensitivity in advanced colorectal cancer (CRC). However, the specific mechanisms and biological functions of miR-125b-2-3p in advanced CRC under chemotherapy have yet to be elucidated.

Methods: MiR-125b-2-3p expression was detected by real-time PCR (RT-PCR) in CRC tissues. The effects of miR-125b-2-3p on the growth, metastasis, and drug sensitivity of CRC cells were tested in vitro and in vivo. Based on multiple databases, the upstream competitive endogenous RNAs (ceRNAs) and the downstream genes for miR-125b-2-3p were predicted by bioinformatic analysis, followed by the experiments including luciferase reporter assays, western blot assays, and so on.

Results: MiR-125b-2-3p was significantly lowly expressed in the tissues and cell lines of CRC. Higher expression of miR-125b-2-3p was associated with relatively lower proliferation rates and fewer metastases. Moreover, overexpressed miR-125b-2-3p remarkably improved chemotherapeutic sensitivity of CRC in vivo and in vitro. Mechanistically, miR-125b-2-3p was absorbed by long noncoding RNA (lncRNA) XIST regulating WEE1 G2 checkpoint kinase (WEE1) expression. The upregulation of miR-125b-2-3p inhibited the proliferation and epithelial-mesenchymal transition (EMT) of CRC induced by lncRNA XIST.

Conclusions: Lower miR-125b-2-3p expression resulted in lower sensitivity of CRC to chemotherapy and was correlated with poorer survival of CRC patients. LncRNA XIST promoted CRC metastasis acting as a ceRNA for miR-125b-2-3p to mediate WEE1 expression. LncRNA XIST-miR-125b-2-3p-WEE1 axis not only regulated CRC growth and metastasis but also contributed to chemotherapeutic resistance to CRC.
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http://dx.doi.org/10.1002/cam4.3777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982616PMC
April 2021

The Source of Glycolytic Intermediates in Mammalian Tissues.

Cell Metab 2021 Feb 19;33(2):367-378.e5. Epub 2021 Jan 19.

Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA. Electronic address:

Glycolysis plays a central role in organismal metabolism, but its quantitative inputs across mammalian tissues remain unclear. Here we use C-tracing in mice to quantify glycolytic intermediate sources: circulating glucose, intra-tissue glycogen, and circulating gluconeogenic precursors. Circulating glucose is the main source of circulating lactate, the primary end product of tissue glycolysis. Yet circulating glucose highly labels glycolytic intermediates in only a few tissues: blood, spleen, diaphragm, and soleus muscle. Most glycolytic intermediates in the bulk of body tissue, including liver and quadriceps muscle, come instead from glycogen. Gluconeogenesis contributes less but also broadly to glycolytic intermediates, and its flux persists with physiologic feeding (but not hyperinsulinemic clamp). Instead of suppressing gluconeogenesis, feeding activates oxidation of circulating glucose and lactate to maintain glucose homeostasis. Thus, the bulk of the body slowly breaks down internally stored glycogen while select tissues rapidly catabolize circulating glucose to lactate for oxidation throughout the body.
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http://dx.doi.org/10.1016/j.cmet.2020.12.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088818PMC
February 2021

The Survival Advantage of Females at Premenopausal Age Is Race Dependent in Colorectal Cancer.

Biomed Res Int 2020 30;2020:7434783. Epub 2020 Dec 30.

Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

Background: A female prognostic advantage in younger individuals has been demonstrated in various cancers. Several large-scale analyses based on different racial backgrounds have reported inconsistent results in colorectal cancer. The aim of the present study was to evaluate the prognostic value of sex and age in patients with colorectal cancer of different ethnic groups.

Methods: We identified 71,812 eligible patients from the Surveillance, Epidemiology and End Results database. According to age at diagnosis, the patients were categorized into premenopausal age (≤45 yrs), menopausal age (46-54 yrs), and postmenopausal age (≥55 yrs) subgroups for further analysis.

Results: Multivariate analysis identified the female survival advantage to be significant in the premenopausal age subgroup ( = 0.002, HR (95% CI): 0.73 (0.60-0.89)), diminished in the menopausal age subgroup ( = 0.09), and absent in the postmenopausal age subgroup ( = 0.96). Furthermore, the female survival advantage at premenopausal age was significant only in white patients ( = 0.001, HR (95% CI): 0.68 (0.54-0.87)) and not in either American Indian/Alaska Native or Asian or Pacific Islander patients. There was a trend of better survival of females in black patients ( = 0.07).

Conclusions: Sex was a major prognostic factor in colorectal cancer patients, especially premenopausal women, and the difference was also associated with race.
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http://dx.doi.org/10.1155/2020/7434783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787739PMC
December 2020

Calcification of lower extremity arteries is related to the presence of osteoporosis in postmenopausal women with type 2 diabetes mellitus: a cross-sectional observational study.

Osteoporos Int 2021 Jan 7. Epub 2021 Jan 7.

Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

It is unknown whether there is any relationship between extremity arterial macroangiopathy and osteoporosis in type 2 diabetic mellitus (T2DM) patients. We provide evidence to show the association between lower extremity arterial calcification and the presence of osteoporosis in postmenopausal T2DM women, but not in T2DM men of similar age.

Purpose: To investigate the relationship between lower extremity arterial calcification and the presence of osteoporosis in type 2 diabetic mellitus (T2DM) patients.

Methods: We performed a retrospective cross-sectional study in patients with T2DM. They were assigned into two groups (patients with or without vascular calcification) in both sexes. Clinical characteristics, presence of osteoporosis, and bone metabolic markers were compared. Arterial calcification was determined by ultrasonography examination. Osteoporosis was defined based on the measurements from dual-energy X-ray absorptiometry. The relationship between the lower extremity arterial calcification and the presence of osteoporosis was analyzed. Statistical analysis was performed in SPSS 26.0.

Results: A total of 933 T2DM patients (535 men ≥ 50 years old, and 398 postmenopausal women) were identified and analyzed. A significant association between arterial calcification and osteoporosis was only observed in women, with a higher prevalence of osteoporosis observed in women with calcification (40.8%) than in women without calcification (26.9%) (P = 0.004). Compared to women without calcification, women with calcification had lower bone mineral densities in the hip (P < 0.001) and femoral neck (P < 0.001). Ordinal logistic regression analysis showed that women with calcification had a nearly 2-fold increased risk for osteoporosis, even after adjusting for age, duration of T2DM, body mass index, pulse pressure, clearance of creatinine, glycosylated hemoglobin, and fasting C-peptide. Similar differences were not identified between men with and without calcification.

Conclusion: Calcification of lower extremity arteries is related with the presence of osteoporosis in postmenopausal T2DM women.
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http://dx.doi.org/10.1007/s00198-020-05775-5DOI Listing
January 2021

PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer.

J Transl Med 2020 12 11;18(1):475. Epub 2020 Dec 11.

Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dong Feng Road East, Guangzhou, 510060, Guangdong, China.

Background: The outcomes of immune checkpoint inhibitors in cancer patients with liver metastases are poor, which may be related to a different tumor microenvironment in liver metastases from primary tumors. This study was aimed to analyze PD-L1 expression and the immune microenvironment status in liver metastases and compare the differences of PD-L1 expression between primary tumors and liver metastases of colorectal cancer.

Methods: 74 cases of pathologically confirmed colorectal cancer with liver metastasis underwent resection from our hospital were included. Tissue microarrays were used for the interpretation of PD-L1 expression, cluster of differentiation 4 (CD4) and CD8 density by immunohistochemistry. We evaluated the disparity between primary tumor and liver metastasis in PD-L1 expression, CD4 and CD8 density and analyzed the factors associated with obvious PD-L1 disparity.

Results: The expression of PD-L1 was positively related to the density of CD4 and CD8 in liver metastases. The expression of PD-L1 in liver metastases was higher than in primary tumors in certain subgroups, including patients with concurrent liver metastases (n = 63, p = 0.05), patients receiving concurrent resection of primary and metastatic tumors (n = 56, p = 0.04). The two subgroups generally reflected those without inconsistent external influences, such as treatment and temporal factors, between primary tumors and liver metastases. In these subgroups, the intrinsic differences of microenvironment between primary tumors and liver metastases could be identified. Furthermore, tumor differentiation [moderate vs. poor: OR = 0.23, 95% CI: 0.03-0.99, p = 0.05)] were demonstrated to be associated with obvious discordance of PD-L1 expression between primary tumors and liver metastases.

Conclusions: The expression of PD-L1 in liver metastases was higher than in primary tumors in subgroups, reflecting intrinsic microenvironment differences between primary and metastatic tumors. Obvious discordance of PD-L1 expression between primary tumor and liver metastasis was significantly related to the tumor differentiation.
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http://dx.doi.org/10.1186/s12967-020-02636-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730753PMC
December 2020

Heat Shock Protein 90α Provides an Effective and Novel Diagnosis Strategy for Nasopharyngeal Carcinoma.

Adv Ther 2021 01 3;38(1):413-422. Epub 2020 Nov 3.

State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Laboratory Medicine, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Introduction: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated tumor occurring in southeastern Asia. Due to insidious onset, it is difficult to diagnose NPC from clinical symptoms. Thus, there is an urgent need for non-invasive, high-performance biomarkers to aid the clinical diagnosis of NPC. Heat shock protein 90α (HSP90α) is an important member of the heat shock protein family that significantly increases under stress conditions such as oxidation and tumors. This is the first investigation of the role of Hsp90α in the diagnosis and progress of NPC.

Methods: Plasma Hsp90α was detected by ELISA in 196 newly diagnosed NPC patients, 76 corresponding post-treatment NPC patients, 230 VCA-IgA-positive normal subjects and 106 healthy controls.

Results: (1) The level of Hsp90α in plasma of 196 NPC patients was (212.16 ± 144.32) ng/ml, which was significantly higher than that in VCA-IgA-positive normal subjects (68.12 ± 64.94 ng/ml, P < 0.001) and healthy controls (35.87 ± 17.47 ng/ml, P < 0.001); (2) the levels of Hsp90α in patients with NPC in the early stage (I + II), stage III and stage IV were significantly different (159.69 ± 117.12 pg/ml vs. 195.24 ± 126.38 pg/ml vs. 250.85 ± 164.66 pg/ml, P = 0.018 and P = 0.029, respectively). The level of Hsp90α in plasma in patients with metastasis of NPC and those without metastasis was significantly different (P < 0.001); (3) Hsp90α is closely related to EBV DNA levels, but not to the VCA-IgA titer and EA-IgA titer; (4) the levels of Hsp90α in plasma of patients with NPC before and after treatment were significantly different (212.16 ± 144.32 pg/ml vs. 62.36 ± 34.04 pg/ml, P < 0.001); (5) the ROC curves demonstrated that the sensitivity of plasma Hsp90α in distinguishing NPC patients from healthy controls was 74.50% and the specificity was 99.10% (AUC = 0.931, 95% CI 0.903-0.958).

Conclusion: The study found that the plasma HSP90α level is closely related to the clinical stage, metastasis and therapeutic effect of NPC. HSP90α may serve as a new biomarker for diagnosis and treatment of NPC.
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http://dx.doi.org/10.1007/s12325-020-01518-4DOI Listing
January 2021

Systematic analysis of the transcriptome in small-cell carcinoma of the oesophagus reveals its immune microenvironment.

Clin Transl Immunology 2020 5;9(10):e1173. Epub 2020 Oct 5.

State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat-sen University Cancer Center Guangzhou China.

Objectives: Although the genomic landscape of small-cell carcinoma of the oesophagus (SCCE) has been dissected, its transcriptome-level aberration and immune microenvironment status are unknown.

Methods: Using ultra-deep whole transcriptome sequencing, we analysed the expression profile of nine paired SCCE samples and compared the transcriptome with public transcriptomic data set of normal oesophageal mucosa and other cancer types. Based on the transcriptome data, the immune signatures were investigated. The genomic data of 55 SCCE samples were also applied for immune checkpoint blockade therapy (ICBT) biomarker evaluation including microsatellite instability (MSI) status, tumor mutation burden (TMB) and neoantigen burden (TNB). Also, we evaluated the CD8, CD68 and programmed death-ligand 1 (PD-L1) in 62 retrospective SCCE samples with IHC assay.

Results: Differential expression analysis revealed that the cell cycle, p53, and Wnt pathways are significantly deregulated in SCCE. Immune microenvironment analysis showed that high leucocyte infiltration and adaptive immune resistance did occur in certain individuals, while the majority showed a relatively suppressive immune status. Immune checkpoints such as CD276 and LAG-3 were upregulated, and higher M2 macrophage infiltration in tumor tissues. Furthermore, normal tissues adjacent to the tumors of SCCE presented a more activated inflammatory status than tumor-free healthy controls. These observations showed that ICBT might benefit SCCE patients. As the critical biomarker of ICBT, TMB of SCCE was 3.64 with the predictive objective response rate 13.2%, while the PD-L1-positive rate was 43%.

Conclusions: Our study systematically characterized the immune microenvironment in small-cell carcinoma of the esophagus and provided evidence that several patients with SCCE may benefit from immune checkpoint blockade therapy.
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http://dx.doi.org/10.1002/cti2.1173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536114PMC
October 2020

Utilizing tandem mass spectrometry for metabolic flux analysis.

Lab Invest 2021 Apr 29;101(4):423-429. Epub 2020 Sep 29.

Department of Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

Metabolic flux analysis (MFA) aims at revealing the metabolic reaction rates in a complex biochemical network. To do so, MFA uses the input of stable isotope labeling patterns of the intracellular metabolites. Elementary metabolic unit (EMU) is the computational framework to simulate the metabolite labeling patterns in a network, which was originally designed for simulating mass isotopomer distributions (MIDs) at the MS1 level. Recently, the EMU framework is expanded to simulate tandem mass spectrometry data. Tandem mass spectrometry has emerged as a new experimental approach to provide information on the positional isotope labeling of metabolites and therefore greatly improves the precision of MFA. In this review, we will discuss the new EMU framework that can accommodate the tandem mass isotopomer distributions (TMIDs) data. We will also analyze the improvement on the MFA precision by using TMID. Our analysis shows that combining the MIDs of the parent and daughter ions and the TMID for the MFA is more powerful than using TMID alone.
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http://dx.doi.org/10.1038/s41374-020-00488-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987671PMC
April 2021

Circ_0086720 knockdown strengthens the radiosensitivity of non-small cell lung cancer via mediating the miR-375/SPIN1 axis.

Neoplasma 2021 Jan 16;68(1):96-107. Epub 2020 Sep 16.

Department of Radiotherapy, Affiliated Hospital of Hebei University of Engineering, Handan, China.

Radioresistance is an important cause of cancer treatment failure. Circular RNAs (circRNAs) play crucial roles in cancer development, including the radioresistance. This research aimed to determine the function and related mechanism of circ_0086720 in the radioresistance of non-small cell lung cancer (NSCLC). The expression of circ_0086720, miR-375, and Spindlin 1 (SPIN1) was measured using a quantitative real-time polymerase chain reaction (qRT-PCR). Cell survival fraction was analyzed using colony formation assay, and cell apoptosis was monitored by flow cytometry assay. The activities of caspase 3 and caspase 9 were assessed using the corresponding commercial kits. The protein levels of SPIN1 and γH2AX were detected by western blot. Bioinformatics analysis was performed to predict the targets of circ_0086720 and miR-375. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay were conducted to validate the interaction between miR-375 and circ_0086720 or SPIN1. The animal model was constructed to ascertain the role of circ_0086720 in vivo. The expression of circ_0086720 and SPIN1 was increased in the radioresistant NSCLC tissues, while miR-375 expression was decreased. The circ_0086720 knockdown sensitized NSCLC cells to the radiation to further inhibit cell survival and induce cell apoptosis. Circ_0086720 targeted miR-375 and suppressed miR-375 expression, and miR-375 bound to SPIN1 to impair SPIN1 expression. miR-375 deficiency or SPIN1 overexpression could attenuate circ_0086720 knockdown-mediated radiosensitivity. The circ_0086720 knockdown also enhanced radiosensitivity to further block tumor growth in vivo. To conclude, circ_0086720 downregulation enhanced the sensitivity of NSCLC to radiation by regulating the miR-375/SPIN1 axis, contributing to the improvement of the radiotherapies in NSCLC.
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http://dx.doi.org/10.4149/neo_2020_200331N333DOI Listing
January 2021

Coastline extraction and land use change analysis using remote sensing (RS) and geographic information system (GIS) technology - A review of the literature.

Rev Environ Health 2020 Nov 17;35(4):453-460. Epub 2020 Aug 17.

Department of Environmental Sciences, University of Peshawar, Peshawar, Pakistan.

Coastlines mapping techniques or the coastline automated analyses have been sought after. In practice, various sorts of seacoasts, for example, biological, silty, arenaceous, artificial, and bedrock coasts, have their own attributes, which force various degrees of intricacy on coastline mapping. As an extraordinary kind of complex artificial coast, aquaculture coast is shaped by the farming of aquatic organisms on silt tidal flats. With the rapid growth of coastal aquaculture in recent years, aquaculture coasts have increased in some developing countries. It has been estimated that aquaculture coasts constitute about 30% of all coastlines in mainland China. In order to identify, monitor, model, and manage the vast expanse of coastal aquaculture, effective methods of extracting aquaculture coastlines from remotely sensed imagery are desired. Secondly, with the rapid economic development in coastal areas, the development of coastal zone resources is also increasing day by day, which benefits the development of island coastal zone. Using oneself has become an important link in the development of marine economy. Due to the limited coastal resources and low environmental carrying capacity, the overexploitation and utilization of coastal resources will lead to a series of problems, such as coastal erosion, coastal migration and accumulation, island area reduction, etc., Both man-made activities and natural factors will lead to coastline changes, which will lead to corresponding changes in coastal ecological environment, thus affecting the coordinated development of coastal economy and the survival of coastal residents. Therefore, efficient, accurate and timely acquisition of coastline information and research on the spatial-temporal changes of coastline are of great significance to the protection of the living environment of coastal residents, the effective development of island and coastal resources, the coordination of sustainable economic development in coastal areas and the mitigation of marine disasters. This paper presents a review of those papers reporting coastline extraction and land use and land cover (LULC) change analysis using remote sensing (RS) and geographic information system (GIS) technology.
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http://dx.doi.org/10.1515/reveh-2019-0103DOI Listing
November 2020

Quantitative Fluxomics of Circulating Metabolites.

Cell Metab 2020 10 12;32(4):676-688.e4. Epub 2020 Aug 12.

Lewis Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Washington Road, Princeton, NJ 08544, USA. Electronic address:

Mammalian organs are nourished by nutrients carried by the blood circulation. These nutrients originate from diet and internal stores, and can undergo various interconversions before their eventual use as tissue fuel. Here we develop isotope tracing, mass spectrometry, and mathematical analysis methods to determine the direct sources of circulating nutrients, their interconversion rates, and eventual tissue-specific contributions to TCA cycle metabolism. Experiments with fifteen nutrient tracers enabled extensive accounting for both circulatory metabolic cycles and tissue TCA inputs, across fed and fasted mice on either high-carbohydrate or ketogenic diet. We find that a majority of circulating carbon flux is carried by two major cycles: glucose-lactate and triglyceride-glycerol-fatty acid. Futile cycling through these pathways is prominent when dietary content of the associated nutrients is low, rendering internal metabolic activity robust to food choice. The presented in vivo flux quantification methods are broadly applicable to different physiological and disease states.
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http://dx.doi.org/10.1016/j.cmet.2020.07.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544659PMC
October 2020

A Randomized Controlled Trial on Evaluation of Plasma Epstein-Barr Virus Biomarker for Early Diagnosis in Patients With Nasopharyngeal Carcinoma.

Adv Ther 2020 10 11;37(10):4280-4290. Epub 2020 Aug 11.

Department of Laboratory Medicine, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Introduction: Early diagnosis of nasopharyngeal carcinoma (NPC) remains a major problem in Southern China. Epstein-Barr virus (EBV) biomarkers have been widely used in NPC screening. This study aims to evaluate the early diagnostic performances of individual EBV biomarkers in NPC.

Methods: The levels of EBV biomarkers-IgA antibodies against EBV nuclear antigen 1 (EBNA1-IgA), EBV capsid antigen (VCA-IgA), EBV early antigen (EA-IgA), EBV BZLF1 transcription activator protein (Zta-IgA) and IgG antibodies against EBV BRLF1 transcription activator protein (Rta-IgG)-from 106 NPC patients (stage I and II) and 150 normal subjects were measured. VCA-IgA and EA-IgA were detected by immunofluorescence assay (IFA), EBNA1-IgA, Rta-IgG and Zta-IgA were measure by enzyme-linked immunosorbent assay (ELISA), and EBV DNA was detected by qPCR. Statistical analyses of a single index were conducted to evaluate the significance of NPC early diagnosis and TNM classification.

Results: The level of EBNA1-IgA, EBV DNA, VCA-IgA, EA-IgA, Rta-IgG and Zta-IgA in early-stage NPC was significantly higher than in healthy controls (all P < 0.001). EBNA1-IgA yielded the biggest area under the curve (AUC) of 0.962 in distinguishing early-stage NPC patients from the normal subjects, with a sensitivity of 91.5% and a specificity of 98.7%. However, EBV biomarker levels were not associated with tumor size (all P > 0.050), whereas four biomarker levels (EBNA1-IgA, EBV DNA, VCA-IgA, EA-IgA) were related to lymph node metastasis (N0 and N1-2), among which EBNA1-IgA and EBV DNA showed good performance. Finally, high correlation was found between VCA-IgA and EA-IgA (r > 0.800).

Conclusion: A single EBNA1-IgA exhibits excellent discrimination performance in early diagnosis of NPC and could become a promising marker for NPC screening.
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http://dx.doi.org/10.1007/s12325-020-01461-4DOI Listing
October 2020

Systematic Analysis of the Aberrances and Functional Implications of Ferroptosis in Cancer.

iScience 2020 Jul 20;23(7):101302. Epub 2020 Jun 20.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, China. Electronic address:

Ferroptosis is a type of cell death related to cancer; however, the characteristics of ferroptosis in cancers are still uncertain. Based on the data in The Cancer Genome Atlas, we found that most ferroptosis regulator genes (FRGs) were differentially expressed in tumors, somatic copy number alterations (SCNA) and DNA methylation contributed to their aberrant expression. We established the ferroptosis potential index (FPI) to reveal the functional roles of ferroptosis and noticed that the FPI was higher in tumors than in normal tissues in most cancers and was associated with subtypes and clinical features. The FPI was negatively correlated with several metabolic pathways but positively associated with several important metastasis-related pathways and immune-related pathways. High FPI predicted poor prognosis in several tumors, whereas FPI and FRGs impacted drug sensitivity. Our study presents a systematic analysis of ferroptosis and its regulatory genes and highlights the potential of ferroptosis-based cancer therapy.
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http://dx.doi.org/10.1016/j.isci.2020.101302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334617PMC
July 2020

DSA-guided percutaneous sclerotherapy for children with oropharyngeal low-flow venous malformation.

Exp Ther Med 2020 May 6;19(5):3405-3410. Epub 2020 Mar 6.

Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.

The present study investigated the efficacy and safety of digital subtraction angiography-guided 3% polidocanol foam sclerosing agent, as well as the combination of pingyangmycin and dexamethasone, for the treatment of children with oropharyngeal low-flow venous malformation. A total of 27 children with 35 lesions with oropharyngeal low-flow venous malformation were included. The subjects were randomly divided into Groups A (13 patients with 16 lesions, treated with 3% polidocanol foam sclerosing agent) and B (14 patients with 19 lesions, treated with pingyangmycin + dexamethasone), respectively. The clinical efficacies and adverse reactions were analyzed and compared between these two groups. The average number of treatment times for Group A was 2.45±0.6, with an efficacy rate of 87.50%, while the average number of treatment times for Group B was 2.07±0.4, with an efficacy rate of 84.21%. No significant difference was found in the average treatment times or efficacy rates between Groups A and B. In addition, the adverse reaction incidence for Groups A and B were 38.46 and 14.29%, respectively, with statistically significant differences between these two groups. The combination of pingyangmycin and dexamethasone was safe and effective in treating children with oropharyngeal low-flow venous malformation, with fewer adverse reactions and is worthy of clinical promotion.
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http://dx.doi.org/10.3892/etm.2020.8581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132246PMC
May 2020

Novel Prognostic Scores Based on Plasma Prothrombin Time and Fibrinogen Levels in Patients With AFP-Negative Hepatocellular Carcinoma.

Cancer Control 2020 Jan-Dec;27(1):1073274820915520

Department of Laboratory Medicine, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

Noninvasive tools for the prognosis of α-fetoprotein negative hepatocellular carcinoma (HCC) are urgently needed. The present study proposed a prognostic system based on preoperative plasma prothrombin time and fibrinogen (PT/Fbg system). With respect to α-fetoprotein (AFP)-negative HCC, we compared the prognostic value in PT/Fbg system, Glasgow Prognostic Score, and aminotransferase/aspartate aminotransferase ratio. The present study retrospectively analyzed patient characteristics, clinicopathological factors, and the level of pretreatment biomarkers in 628 patients with HCC. Patients with increased PT and Fbg levels were allocated a score of 2, patients with only one of these abnormalities were assigned score 1, and patients with neither of these abnormalities were allocated a score of 0. The following distributions of the PT/Fbg system scores were observed: 187 (29.78%) patients had a score of 0, 305 (30.65%) had a score of 1, and 134 (22.69%) patients had a preoperative score of 2. The prognostic significance of the PT/Fbg system was determined using univariate and multivariate Cox hazard analyses in AFP-negative HCC. Multivariate analysis revealed that patients with a higher PT/Fbg system exhibited worse overall survival (OS) than patients with a lower PT/Fbg system. Our study proposes preoperative evaluation of the plasma PT/Fbg system to predict the OS of patients with AFP-negative HCC.
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http://dx.doi.org/10.1177/1073274820915520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158590PMC
October 2020

2 Is Required for Asexual Development and Plant Infection.

Mol Plant Microbe Interact 2020 May 2;33(5):727-741. Epub 2020 Apr 2.

Shandong Provincial Key Laboratory for Biology of Vegetable Diseases and Insect Pests, College of Plant Protection, Shandong Agricultural University, Tai'an, 271018, China.

In bacteria, FtsZ proteins form a Z ring that is the initial step preceding septal fission. FtsZ proteins enable the division of mitochondria in early eukaryotes and are present in some kingdoms but have been lost in animals, fungi, and plants. Here, we have identified two ortholog genes of FtsZs, designated 1 and 2. Overexpression of 2 in fully complemented the overexpression phenotype of . In contrast, overexpression of 1 in had minimal impact on cell division and separation. Thus, we focused on evaluating the impact of altered expression of 2 in , as it exhibited the strongest phenotype. 2 was expressed at the highest levels in mycelia, sporangia, and germinating cysts, as well as in late infection. 2 mis-expression lines showed aberrant asexual growth and development of . Alterations in the expression of 2 changed the distribution of mitochondria in hyphae and sporangia and, also, affected the number, size, and shape of actin plaques. Silencing of 2 restrained growth and development of invasive structures, especially cysts and sporangia, substantially inhibiting the ability of transformants to cause blight lesions. In overexpressed transformant lines, cyst and sporangial germination rates were only half that of controls, but hyphal growth from direct germination of sporangia was more rapid than controls. These transformant lines were only slightly impaired in virulence relative to controls. This study emphasizes the essential role of the evolutionarily conserved FtsZ2 proteins in affecting cytoskeleton dynamics.
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http://dx.doi.org/10.1094/MPMI-01-20-0002-RDOI Listing
May 2020

Inhibition of fatty acid catabolism augments the efficacy of oxaliplatin-based chemotherapy in gastrointestinal cancers.

Cancer Lett 2020 03 2;473:74-89. Epub 2020 Jan 2.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China; Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, China. Electronic address:

Gastrointestinal cancer causes countless deaths every year due to therapeutic resistance. However, whether metabolic alterations contribute to chemoresistance is not well understood. In this study, we report that fatty acid (FA) catabolism was activated in gastrointestinal cancer cells treated with oxaliplatin, which exhibited higher expression of the rate-limiting enzymes carnitine palmitoyltransferase 1B (CPT1B) and CPT2. The clinical analysis also showed that high expression of these enzymes was associated with poor oxaliplatin-based chemotherapy outcomes in patients. Furthermore, genetic or pharmacological inhibition of CPT2 with perhexiline disturbed NADPH and redox homeostasis and increased reactive oxygen species (ROS) generation and cell apoptosis in gastrointestinal cancer cells following oxaliplatin treatment. Specifically, the combination of oxaliplatin and perhexiline significantly suppressed the progression of gastrointestinal cancer in cell-based xenograft and patient-derived xenograft (PDX) models. Mechanistically, CPT2 was transcriptionally upregulated by nuclear factor of activated T cells 3 (NFATc3), which translocated to the nucleus in response to oxaliplatin treatment. In summary, our study suggests that the inhibition of CPT-mediated FA catabolism combined with conventional chemotherapy is a promising therapeutic strategy for patients with gastrointestinal cancers.
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http://dx.doi.org/10.1016/j.canlet.2019.12.036DOI Listing
March 2020

Circulating tumor DNA methylation profiles enable early diagnosis, prognosis prediction, and screening for colorectal cancer.

Sci Transl Med 2020 01;12(524)

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, P. R. China.

Circulating tumor DNA (ctDNA) has emerged as a useful diagnostic and prognostic biomarker in many cancers. Here, we conducted a study to investigate the potential use of ctDNA methylation markers for the diagnosis and prognostication of colorectal cancer (CRC) and used a prospective cohort to validate their effectiveness in screening patients at high risk of CRC. We first identified CRC-specific methylation signatures by comparing CRC tissues to normal blood leukocytes. Then, we applied a machine learning algorithm to develop a predictive diagnostic and a prognostic model using cell-free DNA (cfDNA) samples from a cohort of 801 patients with CRC and 1021 normal controls. The obtained diagnostic prediction model discriminated patients with CRC from normal controls with high accuracy (area under curve = 0.96). The prognostic prediction model also effectively predicted the prognosis and survival of patients with CRC ( < 0.001). In addition, we generated a ctDNA-based molecular classification of CRC using an unsupervised clustering method and obtained two subgroups of patients with CRC with significantly different overall survival ( = 0.011 in validation cohort). Last, we found that a single ctDNA methylation marker, cg10673833, could yield high sensitivity (89.7%) and specificity (86.8%) for detection of CRC and precancerous lesions in a high-risk population of 1493 participants in a prospective cohort study. Together, our findings showed the value of ctDNA methylation markers in the diagnosis, surveillance, and prognosis of CRC.
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http://dx.doi.org/10.1126/scitranslmed.aax7533DOI Listing
January 2020

Adenocarcinoma with mixed subtypes is a rare but aggressive histologic subtype in colorectal cancer.

BMC Cancer 2019 Nov 8;19(1):1071. Epub 2019 Nov 8.

Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dong Feng Road East, Guangzhou, 510060, Guangdong Province, China.

Background: Although numerous studies have investigated the clinicopathologic and prognostic relevance of mucinous adenocarcinoma (MAC) and signet-ring cell carcinoma (SRCC) compared with classic adenocarcinoma (CA), little is known about the prognosis of adenocarcinoma with mixed subtypes (AM) and the differences among these four subtypes.

Methods: The statistics of colorectal cancer registered in the Surveillance, Epidemiology and End Results (SEER) database were retrieved and analyzed. We also compared the clinicopathologic and prognostic relevance between CA, SRCC, MAC, and AM.

Results: The frequencies of these four subtypes were 69.9% (CA, n = 15,812), 25.1% (MAC, n = 5689), 3.6% (SRCC, n = 814) and 1.4% (AM, n = 321), respectively. All of MAC, SRCC, and AM were significantly related with aggressive features. Only SRCC and AM were identified as independent poor prognostic markers for overall survival by multivariate analysis. The aggressiveness of AM was between MAC and SRCC according to the clinicopathologic associations. The prognosis of AM was significantly worse than MAC but comparable with SRCC.

Conclusions: We confirmed the clinicopathologic relevance with aggressive features of MAC and SRCC, as well as poor prognostic relevance of SRCC by analyzing a large study population data set. Furthermore, we identified AM as a rare but aggressive histologic subtype in colorectal cancer, to which particular attention should be given in clinical practice.
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http://dx.doi.org/10.1186/s12885-019-6245-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842229PMC
November 2019

Corrigendum to "Inhibition of the NF-κB pathway by nafamostat mesilate suppresses colorectal cancer growth and metastasis" [Cancer Lett. 380 (2016) 87-97].

Cancer Lett 2020 Jan 14;469:526. Epub 2019 Oct 14.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address:

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http://dx.doi.org/10.1016/j.canlet.2019.10.001DOI Listing
January 2020

AMPKα1 confers survival advantage of colorectal cancer cells under metabolic stress by promoting redox balance through the regulation of glutathione reductase phosphorylation.

Oncogene 2020 01 17;39(3):637-650. Epub 2019 Sep 17.

Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, China.

Patients with stage II or III colorectal cancer (CRC) exhibit various clinical outcomes after radical treatments. The 5-year survival rate was between 50 and 87%. However, the underlying mechanisms of the variation remain unclear. Here we show that AMPKα1 is overexpressed in CRC patient specimens and the high expression is correlated with poor patient survival. We further reveal a previously unrecognized function of AMPKα1, which maintains high level of reduced glutathione to keep reduction-oxidation reaction (redox) homeostasis under stress conditions, thus promoting CRC cell survival under metabolic stress in vitro and enhancing tumorigenesis in vivo. Mechanistically, AMPKα1 regulate the glutathione reductase (GSR) phosphorylation possibly through residue Thr507 which enhances its activity. Suppression of AMPKα1 by using nano-sized polymeric vector induces a favorable therapeutic effect, especially when in combination with oxaliplatin. Our study uncovers a novel function of AMPKα1 in redox regulation and identifies a promising therapeutic strategy for treatment of CRC.
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http://dx.doi.org/10.1038/s41388-019-1004-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962094PMC
January 2020

Metabolite Exchange between Mammalian Organs Quantified in Pigs.

Cell Metab 2019 09 27;30(3):594-606.e3. Epub 2019 Jun 27.

Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. Electronic address:

Mammalian organs continually exchange metabolites via circulation, but systems-level analysis of this shuttling process is lacking. Here, we compared, in fasted pigs, metabolite concentrations in arterial blood versus draining venous blood from 11 organs. Greater than 90% of metabolites showed arterial-venous differences across at least one organ. Surprisingly, the liver and kidneys released not only glucose but also amino acids, both of which were consumed primarily by the intestine and pancreas. The liver and kidneys exhibited additional unexpected activities: liver preferentially burned unsaturated over more atherogenic saturated fatty acids, whereas the kidneys were unique in burning circulating citrate and net oxidizing lactate to pyruvate, thereby contributing to circulating redox homeostasis. Furthermore, we observed more than 700 other cases of tissue-specific metabolite production or consumption, such as release of nucleotides by the spleen and TCA intermediates by pancreas. These data constitute a high-value resource, providing a quantitative atlas of inter-organ metabolite exchange.
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http://dx.doi.org/10.1016/j.cmet.2019.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726553PMC
September 2019

Treadmill Exercise Ameliorates Depression-Like Behavior in the Rats With Prenatal Dexamethasone Exposure: The Role of Hippocampal Mitochondria.

Front Neurosci 2019 26;13:264. Epub 2019 Mar 26.

Department of Physiology, Second Military Medical University, Shanghai, China.

Prenatal exposure to synthetic glucocorticoids (sGCs) can increase the risk of affective disorders, such as depression, in adulthood. Given that exercise training can ameliorate depression and improve mitochondrial function, we sought to investigate whether exercise can ameliorate depression-like behavior induced by prenatal sGC exposure and mitochondria function contributes to that behavior. At first, we confirmed that prenatal dexamethasone (Dex) administration in late pregnancy resulted in depression-like behavior and elevated level of circulatory corticosterone in adult offspring. We then found that mRNA and protein expression of a number of mitochondrial genes was changed in the hippocampus of Dex offspring. Mitochondria in the hippocampus showed abnormal morphology, oxidative stress and dysfunction in Dex offspring. Intracerebroventricular (ICV) injection of the mitochondrial superoxide scavenger mitoTEMPO significantly alleviated depression-like behavior but did not significantly affect circulatory corticosterone level in Dex offspring. The adult Dex offspring treated with treadmill exercise starting at four-weeks of age showed ameliorated depressive-like behavior, improved mitochondrial morphology and function and reduced circulatory corticosterone level. Our data suggest mitochondria dysfunction contributes to depression-like behavior caused by prenatal sGC exposure. Intervention with exercise training in early life can reverse depression caused by prenatal Dex exposure, which is associated with improvement of mitochondrial function in the hippocampus.
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http://dx.doi.org/10.3389/fnins.2019.00264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443890PMC
March 2019

A novel score based on serum apolipoprotein A-1 and C-reactive protein is a prognostic biomarker in hepatocellular carcinoma patients.

BMC Cancer 2018 Nov 28;18(1):1178. Epub 2018 Nov 28.

Department of Laboratory Medicine, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.

Background: The aim of this study was to propose a prognostic scoring system based on preoperative serum apolipoprotein A-1 and C-reactive protein (ApoA-1 and CRP, AC score) levels and to evaluate the prognostic value of these markers in patients with hepatocellular carcinoma (HCC).

Methods: In all, 539 consecutive cases diagnosed with HCC from 2009 to 2012 at Sun Yat-sen University Cancer Center were analysed. The characteristics and levels of pretreatment lipids (ApoA-1, apolipoprotein B (Apo-B), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TGs)) and CRP were reviewed and determined by univariate and multivariate Cox hazard models. Then, the AC score was proposed, which combines two independent risk factors (ApoA-1 and CRP).

Results: The optimal cut-off points in our study were determined according to established reference ranges. Patients with decreased ApoA-1 levels (< 1.090 g/L) and increased CRP levels (≥3.00 mg/L) exhibited a significantly poor overall survival (OS) and disease-free survival (DFS). The AC score was calculated as follows: patients with decreased ApoA-1 and elevated CRP were given a score of 3, patients with only one of these abnormalities were given a score of 2, and those with no abnormalities were given a score of 1. Patients with a higher AC score showed more progressive disease and a poorer prognosis. This was observed not only in the entire cohort (for OS, P < 0.001; for DFS, P < 0.001) but also in the subgroups stratified by pathological stage (stage I-II and stage III-IV). The discriminatory ability of the AC score in HCC was assessed according to the AUC values. The AUC value of the AC score (AUC: 0.676, 95% CI: 0.629-0.723, P < 0.001) was higher than that of AFP. In addition, the combination of the AFP and AC scores (AUC: 0.700, 95% CI: 0.655-0.745, P < 0.001) was superior to the AFP and AC scores alone.

Conclusions: The AC score is a significant valuable predictor of OS and DFS and could more accurately differentiate the prognosis of HCC patients. As this study is a retrospective analysis, the value of the AC score should be validated in large prospective trials.
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http://dx.doi.org/10.1186/s12885-018-5028-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260712PMC
November 2018

Quantitative Analysis of the Whole-Body Metabolic Fate of Branched-Chain Amino Acids.

Cell Metab 2019 02 15;29(2):417-429.e4. Epub 2018 Nov 15.

Perelman School of Medicine, University of Pennsylvania, 3400 Civic Boulevard, Philadelphia, PA 19104, USA. Electronic address:

Elevations in branched-chain amino acids (BCAAs) associate with numerous systemic diseases, including cancer, diabetes, and heart failure. However, an integrated understanding of whole-body BCAA metabolism remains lacking. Here, we employ in vivo isotopic tracing to systemically quantify BCAA oxidation in healthy and insulin-resistant mice. We find that most tissues rapidly oxidize BCAAs into the tricarboxylic acid (TCA) cycle, with the greatest quantity occurring in muscle, brown fat, liver, kidneys, and heart. Notably, pancreas supplies 20% of its TCA carbons from BCAAs. Genetic and pharmacologic suppression of branched-chain alpha-ketoacid dehydrogenase kinase, a clinically targeted regulatory kinase, induces BCAA oxidation primarily in skeletal muscle of healthy mice. While insulin acutely increases BCAA oxidation in cardiac and skeletal muscle, chronically insulin-resistant mice show blunted BCAA oxidation in adipose tissues and liver, shifting BCAA oxidation toward muscle. Together, this work provides a quantitative framework for understanding systemic BCAA oxidation in health and insulin resistance.
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http://dx.doi.org/10.1016/j.cmet.2018.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365191PMC
February 2019

Enzymatically synthesized poly(amino-co-ester) polyplexes for systemic delivery of pcDNA-miRNA-214 to suppress colorectal cancer liver metastasis.

J Mater Chem B 2018 Oct 24;6(40):6365-6376. Epub 2018 Sep 24.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 510060, China.

Liver metastases from colorectal cancer (CRC) are the major cause of cancer-related deaths in CRC patients. In our previous study, microRNA-214 (miR-214) was identified in CRC patients as a novel regulator of CRC liver metastasis, which could serve as a therapeutic target to inhibit CRC proliferation and metastasis. In this study, we aim to develop a new CRC treatment strategy based on miR-214 gene therapy using biodegradable non-viral gene vectors. We developed multifunctional quaternary polyplexes that consist of cationic poly(ω-pentadecalactone-co-N-methyldiethyleneamine-co-sebacate) (PPMS) for DNA condensation to form a nano-sized polyplex core, hyaluronic acids (HA) grafted with a poly(ethylene glycol) (PEG) (HA-g-mPEG) shell for polyplex stabilization and targeted delivery, and nuclear localization signal (NLS) peptides for enhanced intracellular transport of pDNA to the nucleus. The results showed that the DNA/NLS/PPMS/HA-g-mPEG quaternary polyplexes could enhance DNA condensation, increase cellular uptake efficiency and decrease cytotoxicity. Most importantly, the quaternary polyplexes showed favorable transfection efficiency both in vitro and in vivo. The colony formation and migration ability were significantly inhibited in HCT116 cells transfected with pcDNA-miR-214 quaternary polyplexes. The up-regulation of miR-214 in HCT116 cells by pre-transfection of polyplexes-miR-214 could remarkably inhibit tumor growth and liver metastases in a xenograft mouse model. Furthermore, systemic administration of miR-214 using this multifunctional vector resulted in dramatic inhibition of liver metastasis without obvious toxicity in CRC xenografted mice. Collectively, systemic delivery of pcDNA-miR-214 by this multifunctional vector could be a powerful and highly specific therapeutic approach in the treatment of CRC liver metastasis.
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http://dx.doi.org/10.1039/c8tb01932kDOI Listing
October 2018

Sedimentary record of polycyclic aromatic hydrocarbons in mud deposits along the southeastern coast of Liaodong Peninsula and its relation to the anthropogenic and natural activities in the Northeast China.

Chemosphere 2019 Feb 19;216:31-39. Epub 2018 Oct 19.

Key Laboratory of Coast and Island Development (Nanjing University), Ministry of Education, Nanjing 210093, China; School of Geographic and Oceanographic Sciences, Nanjing University, Nanjing 210093, China.

The concentrations of polycyclic aromatic hydrocarbons (PAHs) in two Pb-dated sediment cores collected from mud deposits along the southeastern coast of the Liaodong Peninsula were investigated to reconstruct the sedimentary records of PAHs and their relationship with anthropogenic and natural activities. The concentrations of 16 PAHs (∑PAHs) were low and remained stable before the year 1820, reflecting an autarkic agricultural civilization. From 1820 to 1900, with the gradual lifting of prohibition, people migrated into Northeast China, resulting in the release of large amounts of ∑PAHs into the environment. At the beginning of the 1900s, the ∑PAH levels in the two cores displayed increasing trends with significant fluctuations, linked to a period of social turbulence with continuous wars in Northeast China. After 1949, vertical ∑PAH trends in the cores predominantly reflected trends in economic development. Based on the different PAH composition trends (2-3-ring and 4-6-ring PAHs), we consider that historical energy usage in Northeast China can be divided into three stages: biomass fuel use dominated before 1920, biomass and fossil fuels co-existed from 1920 to 1980, and fossil fuels dominated after 1980. In addition, this study also demonstrates that the PAH concentrations (2-3-ring PAHs) in these two sediment cores can be used, to a certain extent, to identify anthropogenic fire events.
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http://dx.doi.org/10.1016/j.chemosphere.2018.10.093DOI Listing
February 2019

New fluorescent chemosensors based on mononuclear copper complex for highly selective and sensitive detection of phosphate anion in aqueous solution and living cells.

Spectrochim Acta A Mol Biomol Spectrosc 2019 Jan 6;207:96-104. Epub 2018 Sep 6.

School of Pharmacy, Jiangsu Provincial Key Laboratory of Coastal Wetland Bioresources and Environmental Protection, Yancheng Teachers' University, Yancheng, Jiangsu 224051, People's Republic of China.

Three new probes, named, [Cu(L1)]Cl (C1), [Cu(L2)]Cl (C2) and [Cu(L3)]Cl (C3) were synthesized and well characterized. The probes C1, C2 and C3 were successfully achieved for the efficient detection of PO as turn-on fluorescence chemosensors in DMSO/HO (v:v = 2:8, Tris-HCl pH = 7.20). The limit of detection (LOD) of probes C1, C2 or C3 for PO could be as low as 0.029 μM, 0.048 μM, 0.079 μM, respectively, which were effectively applied for the determination of the PO concentration in environmental water of swimming pool. What's more, the binding constant between probes C1, C2, C3 and PO are estimated to be 3.11 × 10 M (R = 0.9992), 1.84 × 10 M (R = 0.9956), 1.93 × 10 M (R = 0.9976), respectively. The proposed mechanism for the "on-off-on" fluorescence response was confirmed by ESI-MS and fluorescence spectrum. Moreover, the membrane-permeable probe C1 was successfully demonstrated in monitoring of PO in cultured HepG2 cells.
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http://dx.doi.org/10.1016/j.saa.2018.09.008DOI Listing
January 2019