Publications by authors named "Meng Duan"

61 Publications

High Site Selectivity in Electrophilic Aromatic Substitutions: Mechanism of C-H Thianthrenation.

J Am Chem Soc 2021 Sep 21. Epub 2021 Sep 21.

Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm Platz 1, D-45470 Mülheim an der Ruhr, Germany.

The introduction of thianthrene as a linchpin has proven to be a versatile strategy for the C-H functionalization of aromatic compounds, featuring a broad scope and fast diversification. The synthesis of aryl thianthrenium salts has displayed an unusually high regioselectivity, notably superior to those observed in halogenation or borylation reactions for various substrates. We report an experimental and computational study on the mechanism of aromatic C-H thianthrenation reactions, with an emphasis on the elucidation of the reactive species and the nature of the exquisite site selectivity. Mechanisms involving a direct attack of arene to the isolated -trifluoracetylthianthrene -oxide () or to the thianthrene dication () via electron transfer under acidic conditions are identified. A reversible interconversion of the different Wheland-type intermediates before a subsequent, irreversible deprotonation is proposed to be responsible for the exceptional selectivity of the reaction.
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http://dx.doi.org/10.1021/jacs.1c06281DOI Listing
September 2021

Fas signaling in adipocytes promotes low-grade inflammation and lung metastasis of colorectal cancer through interaction with Bmx.

Cancer Lett 2021 Sep 16;522:93-104. Epub 2021 Sep 16.

Chronic Disease Research Institute, The Children's Hospital, and National Clinical Research Center for Child Health, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Department of Nutrition and Food Hygiene, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address:

Obesity is a global public health issue. Obesity-related chronic low-grade inflammation (meta-inflammation) can lead to aberrant adipokine release and promote cardiometabolic diseases and obesity-related tumors. However, the mechanisms involved in the initiation of inflammatory responses in obesity and obesity-related tumors as well as metastasis are not fully understood. In this study, we found that the increased tumor necrosis factor-alpha (TNF-α) in adipocytes promoted the lung metastasis of MC38 colon cancer cells via Fas signaling. The release of TNF-α and interleukin (IL)-6 by Fas signaling in adipocytes was caused by the activation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways mediated by the interaction of Fas with Bmx, a non-receptor tyrosine kinase. Moreover, the Fas/Bmx complex is involved in the inflammation of adipocytes via Fas at the Tyr189 site and SH2 domain of Bmx. This is the first study to report the interaction between Fas and Bmx in adipocyte inflammation, which may provide clues for the development of potential new treatment strategies for obesity-related diseases.
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http://dx.doi.org/10.1016/j.canlet.2021.09.024DOI Listing
September 2021

Organocatalytic enantioselective dearomatization of thiophenes by 1,10-conjugate addition of indole imine methides.

Nat Commun 2021 08 12;12(1):4881. Epub 2021 Aug 12.

Department of Chemistry, the Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.

Catalytic asymmetric dearomatization (CADA) is a powerful tool for the rapid construction of diverse chiral cyclic molecules from cheap and easily available arenes. This work reports an organocatalytic enantioselective dearomatization of substituted thiophenes in the context of a rare remote asymmetric 1,10-conjugate addition. By suitable stabilization of the thiophenyl carbocation with an indole motif in the form of indole imine methide, excellent remote chemo-, regio-, and stereocontrol in the nucleophilic addition can be achieved with chiral phosphoric acid catalysis under mild conditions. This protocol can be successfully extended to the asymmetric dearomatization of other heteroarenes including selenophenes and furans. Control experiments and DFT calculations demonstrate a possible pathway in which hydrogen bonding plays an important role in selectivity control.
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http://dx.doi.org/10.1038/s41467-021-25165-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361129PMC
August 2021

Is there a relationship between psoriasis and hepatitis C? A meta-analysis and bioinformatics investigation.

Virol J 2021 07 2;18(1):135. Epub 2021 Jul 2.

School of Life Science, Beijing University of Chinese Medicine, Beijing, China.

Background: The relationship between psoriasis and hepatitis C was previously controversial, so our purpose is to investigate this connection.

Methods: We conducted a systematic review of the case-control, cross-sectional and cohort studies examining the association between psoriasis and hepatitis C in PubMed, EMBASE and Cochrane library databases and investigated the overlapping genes between psoriasis targets and hepatitis C targets using bioinformatics analysis. Based on overlapping genes and hub nodes, we also constructed the protein-protein interaction (PPI) network and module respectively, followed by the pathway enrichment analysis.

Results: We included 11 publications that reported a total of 11 studies (8 cross-sectional and 3 case-control). The case-control and cross-sectional studies included 25,047 psoriasis patients and 4,091,631 controls in total. Psoriasis was associated with a significant increase of prevalent hepatitis C (OR 1.72; 95% confidence interval [CI] (1.17-2.52)). A total of 389 significant genes were common to both hepatitis C and psoriasis, which mainly involved IL6, TNF, IL10, ALB, STAT3 and CXCL8. The module and pathway enrichment analyses showed that the common genes had the potential to influence varieties of biological pathways, including the inflammatory response, cytokine activity, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, which play an important role in the pathogenesis of hepatitis C and psoriasis.

Conclusion: Patients with psoriasis display increased prevalence of hepatitis C and the basic related mechanisms between hepatitis C and psoriasis had been preliminarily clarified.
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http://dx.doi.org/10.1186/s12985-021-01606-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252322PMC
July 2021

Deciphering Reactivity and Selectivity Patterns in Aliphatic C-H Bond Oxygenation of Cyclopentane and Cyclohexane Derivatives.

J Org Chem 2021 Aug 11;86(15):9925-9937. Epub 2021 Jun 11.

Dipartimento di Scienze e Tecnologie Chimiche, Università "Tor Vergata", Via della Ricerca Scientifica, 1, I-00133 Rome, Italy.

A kinetic, product, and computational study on the reactions of the cumyloxyl radical with monosubstituted cyclopentanes and cyclohexanes has been carried out. HAT rates, site-selectivities for C-H bond oxidation, and DFT computations provide quantitative information and theoretical models to explain the observed patterns. Cyclopentanes functionalize predominantly at C-1, and tertiary C-H bond activation barriers decrease on going from methyl- and -butylcyclopentane to phenylcyclopentane, in line with the computed C-H BDEs. With cyclohexanes, the relative importance of HAT from C-1 decreases on going from methyl- and phenylcyclohexane to ethyl-, isopropyl-, and -butylcyclohexane. Deactivation is also observed at C-2 with site-selectivity that progressively shifts to C-3 and C-4 with increasing substituent steric bulk. The site-selectivities observed in the corresponding oxidations promoted by ethyl(trifluoromethyl)dioxirane support this mechanistic picture. Comparison of these results with those obtained previously for C-H bond azidation and functionalizations promoted by the PINO radical of phenyl and -butylcyclohexane, together with new calculations, provides a mechanistic framework for understanding C-H bond functionalization of cycloalkanes. The nature of the HAT reagent, C-H bond strengths, and torsional effects are important determinants of site-selectivity, with the latter effects that play a major role in the reactions of oxygen-centered HAT reagents with monosubstituted cyclohexanes.
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http://dx.doi.org/10.1021/acs.joc.1c00902DOI Listing
August 2021

Early postnatal irradiation-induced age-dependent changes in adult mouse brain: MRI based characterization.

BMC Neurosci 2021 04 21;22(1):28. Epub 2021 Apr 21.

Radiation Physiology Laboratory, Nuclear Research and Safety Initiative, National University of Singapore, CREATE Tower, 1 CREATE Way #04-01, Singapore, 138602, Singapore.

Background: Brain radiation exposure, in particular, radiotherapy, can induce cognitive impairment in patients, with significant effects persisting for the rest of their life. However, the main mechanisms leading to this adverse event remain largely unknown. A study of radiation-induced injury to multiple brain regions, focused on the hippocampus, may shed light on neuroanatomic bases of neurocognitive impairments in patients. Hence, we irradiated BALB/c mice (male and female) at postnatal day 3 (P3), day 10 (P10), and day 21 (P21) and investigated the long-term radiation effect on brain MRI changes and hippocampal neurogenesis.

Results: We found characteristic brain volume reductions in the hippocampus, olfactory bulbs, the cerebellar hemisphere, cerebellar white matter (WM) and cerebellar vermis WM, cingulate, occipital and frontal cortices, cerebellar flocculonodular WM, parietal region, endopiriform claustrum, and entorhinal cortex after irradiation with 5 Gy at P3. Irradiation at P10 induced significant volume reduction in the cerebellum, parietal region, cingulate region, and olfactory bulbs, whereas the reduction of the volume in the entorhinal, parietal, insular, and frontal cortices was demonstrated after irradiation at P21. Immunohistochemical study with cell division marker Ki67 and immature marker doublecortin (DCX) indicated the reduced cell division and genesis of new neurons in the subgranular zone of the dentate gyrus in the hippocampus after irradiation at all three postnatal days, but the reduction of total granule cells in the stratum granulosun was found after irradiation at P3 and P10.

Conclusions: The early life radiation exposure during different developmental stages induces varied brain pathophysiological changes which may be related to the development of neurological and neuropsychological disorders later in life.
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http://dx.doi.org/10.1186/s12868-021-00635-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061041PMC
April 2021

Effect of a genetically engineered interferon-alpha versus traditional interferon-alpha in the treatment of moderate-to-severe COVID-19: a randomised clinical trial.

Ann Med 2021 12;53(1):391-401

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.

Background: There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. To compare the effectiveness of a novel genetically engineered recombinant super-compound interferon (rSIFN-co) with traditional interferon-alpha added to baseline antiviral agents (lopinavir-ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19.

Method: In this multicenter randomized (1:1) trial, patients hospitalized with moderate-to-severe COVID-19 received either rSIFN-co nebulization or interferon-alpha nebulization added to baseline antiviral agents for no more than 28 days. The primary endpoint was the time to clinical improvement. Secondary endpoints included the overall rate of clinical improvement assessed on day 28, the time to radiological improvement and virus nucleic acid negative conversion.

Results: A total of 94 patients were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon-alpha group). The time to clinical improvement was 11.5 days versus 14.0 days (95% CI 1.10 to 2.81,  = .019); the overall rate of clinical improvement on day 28 was 93.5% versus 77.1% (difference, 16.4%; 95% CI 3% to 30%); the time to radiological improvement was 8.0 days versus 10.0 days ( = .002), the time to virus nucleic acid negative conversion was 7.0 days versus 10.0 days ( = .018) in the rSIFN-co and interferon alpha arms, respectively. Adverse events were balanced with no deaths among groups.

Conclusions And Relevance: rSIFN-co was associated with a shorter time of clinical improvement than traditional interferon-alpha in the treatment of moderate-to-severe COVID-19 when combined with baseline antiviral agents. rSIFN-co therapy alone or combined with other antiviral therapy is worth to be further studied.Key messagesThere are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. Interferon alphas, by inducing both innate and adaptive immune responses, have shown clinical efficacy in treating severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus.In this multicenter, head-to-head, randomized, clinical trial which included 94 participants with moderate-to-severe COVID-19, the rSIFN-co plus antiviral agents (lopinavir-ritonavir or umifenovir) was associated with a shorter time of clinical improvement than interferon-alpha plus antiviral agents.
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http://dx.doi.org/10.1080/07853890.2021.1890329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906612PMC
December 2021

The online-to-offline (O2O) food delivery industry and its recent development in China.

Eur J Clin Nutr 2021 02 2;75(2):232-237. Epub 2021 Feb 2.

Chronic Disease Research Institute, The Children's Hospital, and National Clinical Research Center for Child Health, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

This paper offers a unique perspective about the development of the online-to-offline (O2O) food delivery industry from 2017 to 2019 in China. This study demonstrates the latest transformation and improvements of the O2O market that address some common problems in the early stages of the development of this raising industry in China. New strategies and regulations from the O2O platforms, food providers, and national and local governments are discussed. In our view, the mission of the O2O industry in general has shifted from pursuing enormous quantity to ensuring high quality. China's O2O food delivery industry warrants further attention and studies as it grows and develops into the future. We suggest future studies to work on its economic, behavioral, and health impacts on population level as it encompasses both great risks and rewards.
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http://dx.doi.org/10.1038/s41430-020-00842-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851805PMC
February 2021

Combination Therapy Using Kartogenin-Based Chondrogenesis and Complex Polymer Scaffold for Cartilage Defect Regeneration.

ACS Biomater Sci Eng 2020 11 13;6(11):6276-6284. Epub 2020 Oct 13.

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.

Articular cartilage has a highly organized structure, responsible for supporting tremendous mechanical loads. How to repair defected articular cartilage has become a great challenge as the avascular nature of cartilage limits its regenerative ability. Aiming to facilitate chondrogenic differentiation and cartilage regeneration, we recently explored a novel combination therapy using soluble poly-l-lysine/Kartogenin (L-K) nanoparticles and a poly(lactic--glycolic acid) PLGA/methacrylated hyaluronic acid (PLHA) complex scaffold. The potential use for joint cartilage reconstruction was investigated through L-K nanoparticles stimulating adipose-derived stem cells (ADSCs) on PLHA scaffolding, which ultimately differentiated into cartilage . In this study, on one hand, an effective method was established for obtaining uniform L-K nanoparticles by self-assembly. They were further proved to be biocompatible to ADSCs cytotoxicity assays and to accelerate ADSCs secreting type 2 collagen in a dose-dependent manner by immunofluorescence. On the other hand, the porous PLHA scaffold was manufactured by the combination of coprecipitation and ultraviolet (UV) cross-linking. Nanoindentation technology-verified PLHA had an appropriate stiffness close to actual cartilage tissue. Additional microscopic observation confirmed that the PLHA platform supported proliferation and chondrogenesis for ADSCs . In the presence of ADSCs, a 12-week osteochondral defect regeneration by the combination therapy showed that smooth and intact cartilage tissue successfully regenerated. Furthermore, the results of combination therapy were superior to those of phosphate-buffered saline (PBS) only, KGN, or KGN/PLHA treatment. The results of magnetic resonance imaging (MRI) and histological assessment indicated that the renascent tissue gradually regenerated while the PLHA scaffold degraded. In conclusion, we have developed a novel multidimensional combination therapy of cartilage defect repair that facilitated cartilage regeneration. This strategy has a great clinical translational potential for articular cartilage repair in the near future.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00724DOI Listing
November 2020

Characterization of dietary patterns and assessment of their relationships with metabolomic profiles: A community-based study.

Clin Nutr 2021 05 10;40(5):3531-3541. Epub 2020 Dec 10.

Chronic Disease Research Institute, The Children's Hospital, National Clinical Research Center for Child Health, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Department of Nutrition and Food Hygiene, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China. Electronic address:

Background & Aims: Determining dietary patterns in China is challenging due to lack of external validation and objective measurements. We aimed to characterize dietary patterns in a community-based population and to validate these patterns using external validation cohort and metabolomic profiles.

Design: We studied 5145 participants, aged 18-80 years, from two districts of Hangzhou, China. We used one district as the discovery cohort (N = 2521) and the other as the external validation cohort (N = 2624). We identified dietary patterns using a k-means clustering. Associations between dietary patterns and metabolic conditions were analyzed using adjusted logistic models. We assessed relationships between metabolomic profile and dietary patterns in 214 participants with metabolomics data.

Results: We identified three dietary patterns: the traditional (rice-based), the mixed (rich in dairy products, eggs, nuts, etc.), and the high-alcohol diets. Relative to the traditional diet, the mixed (OR = 1.7, CI 1.3-2.4) and the high-alcohol diets (OR = 1.9, CI 1.3-2.7) were associated with type 2 diabetes and hypertension, respectively. Similar results were confirmed in the external validation cohort. In addition, we also identified 18 and 22 metabolites that could distinguish the mixed (error rate = 12%; AUC = 96%) and traditional diets (error rate = 19%; AUC = 88%) from the high-alcohol diet.

Conclusions: Despite the complexity of Chinese diet, identifying dietary patterns helps distinguish groups of individuals with high risk of metabolic diseases, which can also be validated by external population and metabolomic profiles.
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http://dx.doi.org/10.1016/j.clnu.2020.12.006DOI Listing
May 2021

Omics research in vascular calcification.

Clin Chim Acta 2020 Dec 21;511:319-328. Epub 2020 Oct 21.

The Second Affiliated Hospital of Guilin Medical University, Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin 541100, China. Electronic address:

Vascular calcification (VC), the pathological process of hydroxyapatite mineral deposition in the vascular system, is closely associated with aging, atherosclerotic plaque formation, cardiovascular disease (CVD) and diabetes mellitus (DM). Studies have shown that VC is related to cellular phenotypic changes, extracellular vesicles, disordered calcium and phosphate homeostasis, and an imbalance between inducers and inhibitors of VC. Unfortunately, there is currently no effective preventive or targeted treatment for pathologic condition. The rapid evolution of omics technology (genomics, epigenomics, transcriptomics, proteomics and metabolomics) has provided a novel approach for elucidation of pathophysiologic mechanisms in general and those associated with VC specifically. Here, we review articles published over the last twenty years and focus on the current state, challenges, limitations and future of omics in VC research and clinical practice. Highlighting potential targets based on omics technology will improve our understanding of this pathologic condition and assist in the development of potential treatment options for VC related disease.
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http://dx.doi.org/10.1016/j.cca.2020.10.022DOI Listing
December 2020

Omics research in vascular calcification.

Clin Chim Acta 2020 Dec 21;511:198-207. Epub 2020 Oct 21.

The Second Affiliated Hospital of Guilin Medical University, Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin 541100, China. Electronic address:

Vascular calcification (VC), the pathological process of hydroxyapatite mineral deposition in the vascular system, is closely associated with aging, atherosclerotic plaque formation, cardiovascular disease (CVD) and diabetes mellitus (DM). Studies have shown that VC is related to cellular phenotypic changes, extracellular vesicles, disordered calcium phosphate homeostasis and an imbalance between inducers and inhibitors of VC. Unfortunately, there is currently no effective preventive or targeted treatment for this disorder. Recently, the evolution of omics technology (genomics, epigenomics, transcriptomics, proteomics and metabolomics) has paved the way for elucidation of complex biochemical processes and, as such, may provide new insight on VC. Accordingly, we conducted a review of articles published over the last twenty years and herein focus on current and future potential of omics technology in clarifying mechanisms of this disease process. Identification of new biomarkers will provide additional tools in characterizing this pathology and will further assist in the development of potential therapeutic targets.
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http://dx.doi.org/10.1016/j.cca.2020.10.021DOI Listing
December 2020

Development of α,α-Disubstituted Crotylboronate Reagents and Stereoselective Crotylation via Brønsted or Lewis Acid Catalysis.

J Am Chem Soc 2020 10 14;142(43):18355-18368. Epub 2020 Oct 14.

Department of Chemistry and Biochemistry, Auburn University, Auburn, Alabama 36849, United States.

The development of α,α-disubstituted crotylboronate reagents is reported. Chiral Brønsted acid-catalyzed asymmetric aldehyde addition with the developed -crotylboron reagent gave ()--1,2-oxaborinan-3-enes with excellent enantioselectivities and -selectivities. With BF·OEt catalysis, the stereoselectivity is reversed, and ()-δ-boryl--homoallylic alcohols are obtained with excellent -selectivities from the same -crotylboron reagent. The -crotylboron reagent also participates in BF·OEt-catalyzed crotylation to furnish ()-δ-boryl--homoallylic alcohols with good -selectivities. DFT computations establish the origins of observed enantio- and stereoselectivities of chiral Brønsted acid-catalyzed asymmetric allylation. Stereochemical models for BF·OEt-catalyzed reactions are proposed to rationalize the -selective allyl additions. These reactions generate highly valuable homoallylic alcohol products with a stereodefined trisubstituted alkene unit. The synthetic utility is further demonstrated by the total syntheses of salinipyrones A and B.
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http://dx.doi.org/10.1021/jacs.0c04107DOI Listing
October 2020

Use of bioactive extracellular matrix fragments as a urethral bulking agent to treat stress urinary incontinence.

Acta Biomater 2020 11 6;117:156-166. Epub 2020 Oct 6.

Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Eastern Institute of Urologic Reconstruction, Shanghai Jiao Tong University, Shanghai 200233, China. Electronic address:

Injection of urethral bulking agents is a low-risk, minimally invasive surgical procedure to treat stress urinary incontinence (SUI). In this study, we developed a promising injectable bulking agent comprising extracellular matrix fragments of adipose-derived stem cell sheets (ADSC ECM) and investigated its effectiveness in urethral bulking therapy. The structural integrity and proteins of ADSC sheet ECM were well retained in decellularized ADSC ECM fragments. To locate transplanted ADSC ECM fragments, they were labeled with ultrasmall super-paramagnetic iron oxide nanoparticles, which enabled in vivo monitoring after implantation in a SUI rat model for up to 4 weeks. When ADSC ECM fragments were injected into the rat urethra, they became fully integrated with the surrounding tissue within 1 week. Four weeks after transplantation, host cells had regenerated within the ADSC ECM fragment injection area. Moreover, new smooth muscle tissue had formed around the ADSC ECM fragments, as confirmed by positive staining of myosin. These results indicate that injection of ECM fragments may be a promising minimally invasive approach for treating SUI.
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http://dx.doi.org/10.1016/j.actbio.2020.09.049DOI Listing
November 2020

The crosstalk between platelets and body fat: A reverse translational study.

Clin Nutr 2021 04 19;40(4):2025-2034. Epub 2020 Sep 19.

Chronic Disease Research Institute, The Children's Hospital, National Clinical Research Center for Child Health, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Department of Nutrition and Food Hygiene, School of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address:

Background & Aims: Our previous study found that platelet counts were positively associated with body fat percentage in human. In the present study, we conducted a reverse translational study to explore the role of platelets in modulating pre-adipocyte proliferation in mice.

Methods: Mouse pre-adipocyte cell line (3T3-L1) and human pre-adipocytes harvested from female subcutaneous fat were used. Pre-adipocytes were co-cultured with platelets or platelet releasate, which were isolated from mice or humans. The cell viability and proliferative ability of the pre-adipocytes were examined by MTT and flow cytometry assays. Western blotting analysis was used to determine the phosphorylation levels of proteins in the mTOR pathway.

Results: The number of platelets in the adipose tissues from obese mice was significantly higher than that from lean mice. Platelets and collagen-activated platelet releasate stimulated the proliferation of human pre-adipocytes and 3T3-L1 cells in vitro. Besides, platelets from obese mice were more potent in stimulating pre-adipocyte proliferation than those from lean control mice. Mechanistically, platelets enhanced pre-adipocyte proliferation through the acceleration of cell cycle progression from G0/G1 to S phase cell cycle progression. At the molecular level, platelets promoted pre-adipocyte proliferation through mTOR pathway-mediated upregulation of cyclin D1 expression.

Conclusion: In conclusion, platelets and platelet releasate play an important role in the proliferation of pre-adipocytes. Our study may provide new clues and the molecular mechanism of the causal pathways between platelets and body fat to explain the finding we observed in population study.
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http://dx.doi.org/10.1016/j.clnu.2020.09.023DOI Listing
April 2021

Transforming the lower eyelid longitudinal incision direction to conceal the closure line: Longitudinal incision horizontal closure.

J Am Acad Dermatol 2020 Apr 29. Epub 2020 Apr 29.

Department of Dermatologic Surgery, The Third People's Hospital of Hangzhou, Zhejiang, China.

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http://dx.doi.org/10.1016/j.jaad.2020.04.130DOI Listing
April 2020

LncRNA EMX2OS Induces Proliferation, Invasion and Sphere Formation of Ovarian Cancer Cells via Regulating the miR-654-3p/AKT3/PD-L1 Axis.

Cancer Manag Res 2020 24;12:2141-2154. Epub 2020 Mar 24.

Department of Gynecology, Jining No. 1 People's Hospital, Jining, Shandong 272000, People's Republic of China.

Purpose: Long noncoding RNA (lncRNA) deregulation is frequent in human ovarian cancers (OCs), but the role of specific miRNAs involved in this disease remains elusive. LncRNA EMX2OS was previously reported to act as an oncogene in human cancers. However, their accurate expression, function and underlying mechanisms in OC are largely unclear.

Materials And Methods: The levels of EMX2OS in OC tissues and cell lines were determined by quantitative real-time PCR, and the function of EMX2OS was then analyzed both in vitro and in vivo. Luciferase assays and immunoprecipitation assays were performed to analyze the association between EMX2OS and miR-654 expression in OC cells.

Results: EMX2OS is overexpressed in human ovarian cancer tissues. Knockdown of EMX2OS reduced, while overexpression of EMX2OS enhanced the proliferation, invasion and sphere formation of OC cells. In addition, EMX2OS enhanced tumor growth in an in vivo xenograft model of human OC. We discovered that EMX2OS directly binds to miR-654 and suppresses its expression, thus leading to the upregulation of AKT3, which served as a direct target of miR-654. Moreover, miR-654 inhibited cell proliferation, invasion and sphere formation, and restoration of AKT3 reversed the effects of EMX2OS silencing or miR-654 overexpression. Furthermore, PD-L1 was identified as the key oncogenic component acting downstream of AKT3 in OC cells. Ectopic expression of PD-L1 reversed the anti-cancer functions by EMX2OS knockdown, AKT3 silencing or miR-654 upregulation in OC cells.

Conclusion: These results demonstrated that the EMX2OS/miR-654/AKT3/PD-L1 axis confers aggressiveness in ovarian cancer and may represent a therapeutic target for OC metastasis.
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http://dx.doi.org/10.2147/CMAR.S229013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102881PMC
March 2020

Chiral Phosphoric Acid Dual-Function Catalysis: Asymmetric Allylation with α-Vinyl Allylboron Reagents.

Angew Chem Int Ed Engl 2020 06 22;59(26):10540-10548. Epub 2020 Apr 22.

Department of Chemistry and Biochemistry, Auburn University, Auburn, AL, 36849, USA.

We report a dual function asymmetric catalysis by a chiral phosphoric acid catalyst that controls both enantioselective addition of an achiral α-vinyl allylboronate to aldehydes and pseudo-axial orientation of the α-vinyl group in the transition state. The reaction produces dienyl homoallylic alcohols with high Z-selectivities and enantioselectivities. Computational studies revealed that minimization of steric interactions between the alkyl groups of the diol on boron and the chiral phosphoric acid catalyst influence the orientation of α-vinyl substituent of the allylboronate reagent to occupy a pseudo-axial position in the transition state.
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http://dx.doi.org/10.1002/anie.202000039DOI Listing
June 2020

[email protected] mesenchymal stem cells as an "oxygen-laden guided-missile" for the enhanced photodynamic therapy on lung cancer.

Nanoscale 2020 Feb;12(5):3090-3102

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China.

The critical issue in nanoscale medicine delivery systems is the targeted efficiency to guarantee the maximum accumulation of nanodrugs in tumors to exert better therapeutic action. In this study, we adopted an active and potent strategy based on mesenchymal stem cells (MSCs) certified with excellent tumor-tropism ability to load and ship [email protected] nanoparticles into a tumor site. Notably, under the premise of the negligible cellular toxicity of [email protected] on MSCs, its considerable uptake by MSCs enabled this nanoplatform ([email protected]) to distribute increasingly inside the tumor. Briefly, a Ce6 photosensitizer was bound to MnO2 nanospheres by physical adsorption, improving its own stability in blood circulation. Furthermore, the delivered [email protected] could modulate the tumor microenvironment (TME) by high sensitivity to excess hydrogen protons (H+) and H2O2. Thus, O2 generated by these reactions served as an abundant source for 1O2 conversion under a 633 nm laser exposure, which overcame the crucial bottleneck of the unfavorable hypoxia condition in TME for photodynamic therapy (PDT). In addition, MnO2 decomposed into Mn2+, which was represented by high T1 relaxivity in magnetic resonance imaging (MRI). The Mn2+ was finally removed rapidly from the body by liver metabolism and kidney filtration. These results endowed the original nanoplatform with striking potential for MSC-guided, Ce6-converted, MRI-monitored PDT for further innovation of a clinical cancer diagnosis-treatment agent.
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http://dx.doi.org/10.1039/c9nr07947eDOI Listing
February 2020

The Neuroprotective Effect of Amitriptyline on Radiation-Induced Impairment of Hippocampal Neurogenesis.

Dose Response 2019 Oct-Dec;17(4):1559325819895912. Epub 2019 Dec 20.

Radiation Physiology Laboratory, Singapore Nuclear Research and Safety Initiative, National University of Singapore, Singapore.

The radioprotective effect of amitriptyline, an inhibitor of acid sphingomyelinase (ASMase), on radiation-induced impairment of hippocampal neurogenesis, loss of interneuron, and animal weight changes was investigated in BALB/c mice by immunostaining of biomarkers for cell division (Ki67), immature neurons (doublecortin or DCX), and interneurons (parvalbumin or PV) in the dentate gyrus (DG) of hippocampus. The results indicated that preirradiation (with 10 mg/kg, 2 times per day, for 7 consecutive days) or postirradiation (with 10 mg/kg, 2 times per day, for 14 consecutive days) treatment (pretreatment or posttreatment) with intraperitoneal injection of amitriptyline prevented the loss of newly generated neurons, proliferating cells, and interneurons in the subgranular zone of the DG. At the molecular level, pretreatment or posttreatment inhibited the expression of sphingomyelin phosphodiesterase 1 () gene which codes for ASMase. The pretreatment for 7 days also prevented radiation-induced weight loss from 2 to 3 weeks, but not within 1 week after irradiation. On the other hand, the posttreatment with amitriptyline for 14 days could improve animal weight gain from 4 to 6 weeks after irradiation. The present study suggests that amitriptyline may be a promising candidate radio-neuroprotective drug to improve radiation-induced impairment of hippocampal neurogenesis and relevant neurological and neuropsychological disorders.
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http://dx.doi.org/10.1177/1559325819895912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926988PMC
December 2019

PD1 CD8 T cells correlate with exhausted signature and poor clinical outcome in hepatocellular carcinoma.

J Immunother Cancer 2019 11 29;7(1):331. Epub 2019 Nov 29.

The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences/University of Chinese Academy of Sciences, Shanghai, 200031, China.

Background: CD8 T cells differentiate into exhausted status within tumors, including hepatocellular carcinoma (HCC), which constitutes a solid barrier to effective anti-tumor immunity. A detailed characterization of exhausted T cells and their prognostic value in HCC is lacking.

Methods: We collected fresh tumor tissues with adjacent non-tumor liver tissues and blood specimens of 56 HCC patients, as well as archived samples from two independent cohorts of HCC patients (n = 358 and n = 254), who underwent surgical resection. Flow cytometry and multiplex immunostaining were used to characterize CD8 T cells. Patient prognosis was evaluated by Kaplan-Meier analysis and Cox regression analysis.

Results: CD8 T cells were classified into three distinct subpopulations: PD1, PD1 and PD1. PD1 CD8 T cells were significantly enriched in tumor compared to adjacent non-tumor liver tissues. PD1 CD8 T cells highly expressed exhaustion-related inhibitory receptors (TIM3, CTLA-4, etc.) and transcription factors (Eomes, BATF, etc.). In addition, PD1 CD8 T cells expressed low levels of cytotoxic molecules and displayed a compromised capacity to produce pro-inflammatory cytokines while the expression of anti-inflammatory IL-10 was up-regulated following mitotic stimulation. Furthermore, PD1 CD8 T cells shared features with tissue resident memory T cells and were also characterized in an aberrantly activated status with an apoptosis-prone potential. In two independent cohorts of HCC patients (n = 358 and n = 254), we demonstrated that PD1 or TIM3PD1 CD8 T cells were significantly correlated with poor prognosis, and the latter was positioned in close proximity to PD-L1 tumor associated macrophages.

Conclusion: The current study unveils the unique features of PD1 CD8 exhausted T cells in HCC, and also suggests that exhausted T cells could act as a biomarker to select the most care-demanding patients for tailored therapies.
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http://dx.doi.org/10.1186/s40425-019-0814-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884778PMC
November 2019

A modular approach for cytosolic protein delivery: metal ion-induced self-assembly of gold nanoclusters as a general platform.

Nanoscale 2019 Nov;11(46):22237-22242

Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.

We developed a versatile and modular method for cytosolic protein delivery through metal ion-induced co-assembly of gold nanoclusters and proteins into supramolecular assemblies. The versatility and high efficiency of this strategy to assemble and deliver various proteins into living cells were demonstrated. Importantly, the activity of proteins was maintained during the delivery. This modular approach provides an exciting and promising new nano-platform for cytosolic protein delivery.
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http://dx.doi.org/10.1039/c9nr07334eDOI Listing
November 2019

Matrix metalloproteinase-2-targeted superparamagnetic [email protected] nanoprobes for dual-mode imaging and photodynamic therapy.

Nanoscale 2019 Oct;11(39):18426-18435

Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Micro Fabrication of the Ministry of Education, Department of Instrument Science and Technology, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China.

This work explored the application of matrix metalloproteinase 2-targeted superparamagnetic nanoprobes for magnetic resonance imaging (MRI), near infrared (NIR) fluorescence imaging and photodynamic therapy of tumors. PEG, PAMAM (G5) and matrix metalloproteinase 2 (MMP2) were attached to the surface of carboxylated Fe3O4 nanoparticles (NPs) using a chemical coupling method and then finally loaded with the photosensitizer chlorin e6 (Ce6). In vitro and in vivo experiments demonstrated that the [email protected] nanoprobes exhibited excellent stability, precise tumor targeting and biocompatibility. Furthermore, the fluorescence properties of [email protected] nanoprobes were analogous to Ce6 and could be employed for fluorescence imaging. Meanwhile, the [email protected] nanoprobes have also been shown to be effective as contrast agents for T2-weighted MRI. The target molecule MMP2 enhanced the tumor targeting ability of [email protected] nanoprobes. Additionally, the [email protected] nanoprobes significantly inhibited tumor growth compared with PBS and free Ce6. This work will inspire greater enthusiasm for the construction of multifunctional magnetic nanoplatforms for biomedical applications.
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http://dx.doi.org/10.1039/c9nr06774dDOI Listing
October 2019

Asymmetric Desymmetrization of Oxetanes for the Synthesis of Chiral Tetrahydrothiophenes and Tetrahydroselenophenes.

Angew Chem Int Ed Engl 2019 12 23;58(50):18055-18060. Epub 2019 Oct 23.

Department of Chemistry and Shenzhen Research Institute, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.

Chiral tetrahydrothiophenes and tetrahydroselenophenes are highly useful structural units. Described here is a new catalytic asymmetric approach for their synthesis. With a suitable chiral Brønsted acid catalyst, an oxetane desymmetrization by a well-positioned internal sulfur or selenium nucleophile proceeded efficiently to generate all-carbon quaternary stereocenters with excellent enantioselectivities. Taming the sulfur and selenium nucleophile in the form of a thioester and selenoester, respectively, is crucial to the success of this work. This approach also allows the facile synthesis of chiral tetrahydrothiopyrans. Mechanistic studies, including DFT calculations, suggested an intramolecular acyl-transfer pathway. Utilities of the chiral products are also demonstrated.
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http://dx.doi.org/10.1002/anie.201910917DOI Listing
December 2019

Distribution of HPV 16 E6 gene variants in screening women and its associations with cervical lesions progression.

Virus Res 2019 11 4;273:197740. Epub 2019 Sep 4.

Tianjin Central Hospital of Gynecology Obstetrics, No. 156 Nankai San Ma Road, Nankai District, Tianjin, China. Electronic address:

The aim of this study is to investigate distribution of human papillomavirus (HPV) 16 variants in screening healthy women and the potential association between HPV 16 variants and progression of cervical lesions. For this study a total of 2000 healthy women in Tianjin urban area and 212 patients who were HPV 16 positive and underwent colposcopy were analyzed for HPV 16 variants by pyrosequencing. The results show that the HPV 16 was the most prevalent genotype in Tianjin healthy women and five HPV 16 variant types were detected. The HPV 16 variants were determined by sequencing parital E6 region and the detected variants were European prototype E-T350 (E-p), E-G350, E-C109 G, Asian (As) and Asian-American (AA), among which the E-p variant was the most prevalent (82.76%) followed by As variant. Interestingly, in patients with suspected cervical lesions the most prevalent variant was As variant (54.9%) by increasing significance with severity of cervical diseases (OR 4.337; 95% CI 1.248-15.067; P = 0.021), and followed by HPV 16 E-p variant while E-G350 variant only appeared in HSIL and cervical cancer. Our results show that HPV 16 E-p variant was more prevalent than As in Tianjin healthy screening women while As variant was the most frequently type in HSIL and cervical cancer. It is suggested that the mutation of HPV 16 Asian variants, comparing with HPV 16 E-p variants, might contribute to the transformation from HPV 16 persistent infection to cervical cancer.
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http://dx.doi.org/10.1016/j.virusres.2019.197740DOI Listing
November 2019

Enhancing Upconversion Luminescence Efficiency via Chiral β-NaYF:Er/Yb Microcrystals Based on Mesoscale Regulation.

ACS Omega 2018 Dec 28;3(12):18730-18738. Epub 2018 Dec 28.

Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Micro Fabrication of the Ministry of Education, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.

Chirality, universal characteristics of nature, introduces asymmetry in synthetic materials. Revealing the microscopic asymmetry of macroscopically symmetric materials is the key to control the growth of chiral materials and give full play to their application potential. Materials for photon upconversion (UC) are of great interest for many applications owing to their anti-Stoke luminescence process, especially for chiral UC materials. For the preparation of UC materials, a tiny change in reaction parameters will lead to variations in morphology, phase components, and fluorescence intensity, as well as its chirality. Because of the strict reaction conditions for the formation of chiral UC materials, there are no reports of the successful synthesis of chiral UC materials. Therefore, a facile method for the controllable synthesis of chiral UC materials is highly desired. Herein, chiral-assembled hexagonal prisms of β-NaYF:Er/Yb microcrystals were synthesized to realize the smart manipulation of their morphology as well as a great improvement of the fluorescence efficiency. We proposed a three-stage doped β-NaYF crystal growth mechanism on mesoscale regulation, where the fluorescence enhancement principle of chirality was revealed. The enhancement of fluorescence efficiency of chiral UC materials endows their promising application in luminescent displays.
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http://dx.doi.org/10.1021/acsomega.8b02919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644319PMC
December 2018

Fas signaling-mediated T9 cell differentiation favors bowel inflammation and antitumor functions.

Nat Commun 2019 07 2;10(1):2924. Epub 2019 Jul 2.

Institute of Immunology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, 310058, Hangzhou, China.

Fas induces apoptosis in activated T cell to maintain immune homeostasis, but the effects of non-apoptotic Fas signaling on T cells remain unclear. Here we show that Fas promotes T9 cell differentiation by activating NF-κB via Ca-dependent PKC-β activation. In addition, PKC-β also phosphorylates p38 to inactivate NFAT1 and reduce NFAT1-NF-κB synergy to promote the Fasinduced T9 transcription program. Fas ligation exacerbates inflammatory bowel disease by increasing T9 cell differentiation, and promotes antitumor activity in p38 inhibitor-treated T9 cells. Furthermore, low-dose p38 inhibitor suppresses tumor growth without inducing systemic adverse effects. In patients with tumor, relatively high T9 cell numbers are associated with good prognosis. Our study thus implicates Fas in CD4 T cells as a target for inflammatory bowel disease therapy. Furthermore, simultaneous Fas ligation and low-dose p38 inhibition may be an effective approach for T9 cell induction and cancer therapy.
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http://dx.doi.org/10.1038/s41467-019-10889-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606754PMC
July 2019

Landscape of infiltrating B cells and their clinical significance in human hepatocellular carcinoma.

Oncoimmunology 2019;8(4):e1571388. Epub 2019 Feb 7.

Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.

As a major cellular component in tumor microenvironment, the distribution, frequency, and prognostic significance of infiltrating B cell subsets in hepatocellular carcinoma (HCC) remain controversial. Using tyramide signal amplification (TSA) based fluorescent multiplexed immunohistochemistry , we evaluated the distribution and frequency of B cell subsets in two independent HCC cohorts (n = 619). The results were further confirmed by flow cytometry. Correlations of B cell subsets with clinicopathologic features and patient prognosis were analyzed. Five B cell subsets were defined by multiplexed immunohistochemistry and each subset was clearly separated by t-SNE dimension reduction analysis. Notably, the densities of all B cell subsets were significantly decreased in the tumor. The frequency of plasma cells within B cells was most abundant in the tumor. In training cohort (n = 258), high densities of tumor-infiltrating CD20 B cells, naive B cells, IgM memory B cells, CD27 isotype-switched memory B cells, and plasma cells were associated with superior survival. Multivariate analysis further identified CD20 B cells, naive B cells, and CD27 isotype-switched memory B cells as independent prognosticators for survival. Unsupervised cluster analysis confirmed increased B cell subsets harbored superior survival. In addition, high density of B cells was correlated with smaller tumor size and well differentiation. The results were validated in the independent cohort of 361 HCC patients. Intratumor infiltration of B cells is significantly impaired during HCC progression. High densities of tumor-infiltrating B cells imply a better clinical outcome. Therapies designed to target B cells may be a novel strategy in HCC.
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http://dx.doi.org/10.1080/2162402X.2019.1571388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422393PMC
February 2019

Activated and Exhausted MAIT Cells Foster Disease Progression and Indicate Poor Outcome in Hepatocellular Carcinoma.

Clin Cancer Res 2019 Jun 5;25(11):3304-3316. Epub 2019 Feb 5.

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.

Purpose: Innate immunity is an indispensable arm of tumor immune surveillance, and the liver is an organ with a predominance of innate immunity, where mucosal-associated invariant T (MAIT) cells are enriched. However, little is known about the phenotype, functions, and immunomodulatory role of MAIT cells in hepatocellular carcinoma (HCC). The distribution, phenotype, and function of MAIT cells in patients with HCC were evaluated by both flow cytometry (FCM) and bioassays. Transcriptomic analysis of MAIT cells was also performed. Prognostic significance of tumor-infiltrating MAIT cells was validated in four independent cohorts of patients with HCC.

Results: Despite their fewer densities in HCC tumor than normal liver, MAIT cells were significantly enriched in the HCC microenvironment compared with other mucosa-associated organs. Tumor-derived MAIT cells displayed a typical CCR7CD45RACD45ROCD95 effector memory phenotype with lower costimulatory and effector capabilities. Tumor-educated MAIT cells significantly upregulated inhibitory molecules like PD-1, CTLA-4, TIM-3, secreted significantly less IFNγ and IL17, and produced minimal granzyme B and perforin while shifting to produce tumor-promoting cytokines like IL8. Transcriptome sequencing confirmed that tumor-derived MAIT cells were reprogrammed toward a tumor-promoting direction by downregulating genes enriched in pathways of cytokine secretion and cytolysis effector function like and and by upregulating genes like , and (). High infiltration of MAIT cells in HCC significantly correlated with an unfavorable clinical outcome, revealed by FCM, qRT-PCR, and multiplex IHC analyses, respectively.

Conclusions: HCC-infiltrating MAIT cells were functionally impaired and even reprogrammed to shift away from antitumor immunity and toward a tumor-promoting direction..
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http://dx.doi.org/10.1158/1078-0432.CCR-18-3040DOI Listing
June 2019

O-GlcNAc transferase activates stem-like cell potential in hepatocarcinoma through O-GlcNAcylation of eukaryotic initiation factor 4E.

J Cell Mol Med 2019 04 24;23(4):2384-2398. Epub 2019 Jan 24.

Key Laboratory of Glycoconjuates Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan, Shanghai, People's Republic of China.

O-GlcNAcylation catalysed by O-GlcNAc transferase (OGT) is a reversible post-translational modification. O-GlcNAcylation participates in transcription, epigenetic regulation, and intracellular signalling. Dysregulation of O-GlcNAcylation in response to high glucose or OGT expression has been implicated in metabolic diseases and cancer. However, the underlying mechanisms by which OGT regulates hepatoma development remain largely unknown. Here, we employed the lentiviral shRNA-based system to knockdown OGT to analyse the contribution of OGT in hepatoma cell proliferation and stem-like cell potential. The sphere-forming assay and western blot analysis of stem-related gene expression were used to evaluate stem-like cell potential of hepatoma cell. We found that the level of total O-GlcNAcylation or OGT protein was increased in hepatocellular carcinoma. OGT activated stem-like cell potential in hepatoma through eukaryotic initiation factor 4E (eIF4E) which bound to stem-related gene Sox2 5'-untranslated region. O-GlcNAcylation of eIF4E at threonine 168 and threonine 177 protected it from degradation through proteasome pathway. Expression of eIF4E in hepatoma was determined by immunostaining in 232 HCC patients, and Kaplan-Meier survival analysis was used to determine the correlation of eIF4E expression with prognosis. High glucose promoted stem-like cell potential of hepatoma cell through OGT-eIF4E axis. Collectively, our findings indicate that OGT promotes the stem-like cell potential of hepatoma cell through O-GlcNAcylation of eIF4E. These results provide a mechanism of HCC development and a cue between the pathogenesis of HCC and high glucose condition.
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http://dx.doi.org/10.1111/jcmm.14043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433694PMC
April 2019
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