Bo Liu

Sichuan University, Hua-yang, Sichuan, China

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Publications (77)280.62 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A diastereoselective Pd-catalyzed intramolecular cyclopropanation of alkenes with unstabilized allylic tosylhydrazones was developed. This methodology provides an efficient entry toward synthesis of the bicyclo[3.1.0] hexane system with an exo-double bond, and sets the basis for future elaboration of more complex polycyclic motifs.
    Chemical Communications 03/2015; DOI:10.1039/c5cc00235d · 6.38 Impact Factor
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    ABSTRACT: The aim of this study was to discover a small molecule activator BL-AD008 targeting AMPK/ZIPK and inducing apoptosis in cervical cancer. In this study, we systematically constructed the global protein-protein interaction (PPI) network and predicted apoptosis-related protein connections by the Naïve Bayesian model. Then, we identified some classical apoptotic PPIs and other previously unrecognized PPIs between apoptotic kinases, such as AMPK and ZIPK. Subsequently, we screened a series of candidate compounds targeting AMPK/ZIPK, synthesized some compounds and eventually discovered a novel dual-target activator (BL-AD008). Moreover, we found BL-AD008 bear remarkable anti-proliferative activities toward cervical cancer cells and could induce apoptosis by death-receptor and mitochondrial pathways. Additionally, we found that BL-AD008-induced apoptosis was affected by the combination of AMPK and ZIPK. Then, we found that BL-AD008 bear its anti-tumor activities and induced apoptosis by targeting AMPK/ZIPK in vivo. In conclusion, these results demonstrate the ability of systems biology network to identify some key apoptotic kinase targets AMPK and ZIPK; thus providing a dual-target small molecule activator (BL-AD008) as a potential new apoptosis-modulating drug in future cervical cancer therapy.
    Oncotarget 03/2015; · 6.63 Impact Factor
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    ABSTRACT: Wound dressing is critical important for cutaneous wound healing. However, the application of current products is limited due to poor mechanical property, unsuitable water vapor transmission rate (WVTR), poor anti-infective property or poor biocompatibility, etc. In the present study, a microporous silicone rubber membrane bilayer (SRM-B) composed of two layers with different pore sizes was prepared. The physical properties, the influences of pore structure on the bacterial penetration, the cell adhesion and proliferation were studied. Lastly, the effects of the SRM-B on the healing of a mouse full-thickness wound were examined. The data showed that the small pore upper layer of SRM-B could effectively prevent the bacterial invasion, as well as properly keep the water vapor transmission rate; the large pore lower layer of SRM-B could promote the cell adhesion and proliferation. The in vivo results showed that SRM-B could significantly enhance wound re-epithelialization and contraction, which accelerated the wound healing. Our data suggested that the SRM-B, with different particular pore sizes, could serve as a kind of promising wound dressing.
    Biomaterials 02/2015; 40. DOI:10.1016/j.biomaterials.2014.10.077 · 8.31 Impact Factor
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    ABSTRACT: Extracellular signal-regulated kinase1/2 (ERK1/2) plays a crucial role in the resistance of apoptosis in carcinogenesis; however, its targeted small-molecule inhibitors still remain to be discovered. Thus, in this study, we computationally and experimentally screened a series of small-molecule inhibitors targeting ERK toward different types of human breast cancer cells. Subsequently, we synthesized some candidate ERK inhibitors, identified a novel ERK inhibitor (BL-EI001) with anti-proliferative activities, and analyzed the BL-EI001/ERK complex. Moreover, we found that BL-EI001 induced breast cancer cell apoptosis via mitochondrial pathway but independent on Ras/Raf/MEK pathway. In addition, we carried out proteomics analyses for exploring some possible BL-EI001-induced apoptotic pathways, and further found that BL-EI001-induced apoptosis affected ERK phosphorylation in breast cancer. Further, we found that BL-EI001 bear anti-tumor activities without remarkable toxicities, and also induced mitochondrial apoptosis by targeting ERK in vivo. Taken together, these results demonstrate that in silico design and experimental discovery of a synthesized small-molecule ERK inhibitor (BL-EI001)as a potential novel apoptosis-inducing drug in the treatment of breast cancer.
    Oncotarget 01/2015; · 6.63 Impact Factor
  • Source
    Jing Feng, Bo Liu
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    ABSTRACT: This review describes a set of approaches to generate functionalized carbocycles via [3+3] annu-lation and their usefulness for synthesizing frameworks of natural products. This approach relies heavily on the 1,3-dianion/1,3-dielectrophile strategy for annulations of ketones, enamines, 1,3-bis(silyl enol ethers) and other 1,3-dianionic synthons
    Tetrahedron Letters 01/2015; 6. DOI:10.1016/j.tetlet.2015.01.035 · 2.39 Impact Factor
  • Tetrahedron 01/2015; DOI:10.1016/j.tet.2015.01.002 · 2.82 Impact Factor
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    ABSTRACT: Colorectal cancer (CRC) is a major cause of cancer-related death worldwide. The poor prognosis of CRC is mainly due to uncontrolled tumor growth and distant metastases. In this study, we found that the level of FGF8 was elevated in the great majority of CRC cases and high FGF8 expression was significantly correlated with lymph nodes metastasis and worse overall survival. Functional studies showed that FGF8 can induce a more aggressive phenotype displaying epithelial-to-mesenchymal transition (EMT) and enhanced invasion and growth in CRC cells. Consistent with this, FGF8 can also promote tumor growth and metastasis in mouse models. Bioinformatics and pathological analysis suggested that YAP1 is a potential downstream target of FGF8 in CRC cells. Molecular validation demonstrated that FGF8 fully induced nuclear localization of YAP1 and enhanced transcriptional outcomes such as the expression of CTGF and CYR61, while decreasing YAP1 expression impeded FGF-8-induced cell growth, EMT, migration and invasion, revealing that YAP1 is required for FGF8-mediated CRC growth and metastasis. Taken together, these results demonstrate that FGF8 contributes to the proliferative and metastatic capacity of CRC cells and may represent a novel candidate for intervention in tumor growth and metastasis formation.
    Oncotarget 11/2014; · 6.63 Impact Factor
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    ABSTRACT: Polygonatum odoratum lectin (POL), a mannose-binding GNA-related lectin, has been reported to display remarkable anti-proliferative and apoptosis-inducing activities toward a variety of cancer cells; however, the precise molecular mechanisms by which POL induces cancer cell death are still elusive. In the current study, we found that POL could induce both apoptosis and autophagy in human MCF-7 breast cancer cells. Subsequently, we found that POL induced MCF-7 cell apoptosis via the mitochondrial pathway. Additionally, we also found that POL induces MCF-7 cell apoptosis via EGFR-mediated Ras-Raf-MEK-ERK pathway, suggesting that POL may be a potential EGFR inhibitor. Finally, we used proteomics analyses for exploring more possible POL-induced pathways with EGFR, Ras, Raf, MEK and ERK, some of which were consistent with our in silico network prediction. Taken together, these results demonstrate that POL induces MCF-7 cell apoptosis and autophagy via targeting EGFR-mediated Ras-Raf-MEK-ERK signaling pathway, which would provide a new clue for exploiting POL as a potential anti-neoplastic drug for future cancer therapy. Copyright © 2014 Elsevier GmbH. All rights reserved.
    Phytomedicine 10/2014; 21(12):1658–1665. DOI:10.1016/j.phymed.2014.08.002 · 2.88 Impact Factor
  • ChemInform 09/2014; 45(35). DOI:10.1002/chin.201435215
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    ABSTRACT: High intensity focused ultrasound (HIFU)-triggered shape memory has distinct features due to the unique heating mechanism based on polymer chain shearing and friction activated by ultrasonic energy. In this study we chose crosslinked poly(methyl methacrylate-co-butyl acrylate) P(MMA-BA) as a model polymer and studied in detail the HIFU induced thermal effect and shape recovery characteristics. It was found that HIFU heating for polymers is quick and spatially localized, and can be controlled by the ultrasound power, which allows for a spatiotemporally controllable shape memory process. The effects of various parameters including sample thickness, copolymer composition and crosslinker content on the HIFU-induced thermal effect and shape recovery were investigated. Under HIFU irradiation, there exists an optimum sample thickness for a maximum thermal effect and thus better shape recovery, which is different from conventional heating. Moreover, both the copolymer composition and the crosslinker content have a profound effect on the HIFU-induced temperature rise and thus the shape recovery. These effects can be related to changes in the viscoelastic parameter loss tangent (tanδ) of the copolymer around the glass transition temperature Tg that is the transition temperature for the shape recovery process.
    RSC Advances 07/2014; 4(62). DOI:10.1039/C4RA04586F · 3.71 Impact Factor
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    ABSTRACT: In this article, we describe our efforts on the total synthesis of bolivianine (1) and isobolivianine (2), involving the synthesis of onoseriolide (3). The first generation synthesis of bolivianine was completed in 21 steps by following a chiral resolution strategy. Based on the potential biogenetic relationship between bolivianine (1), onoseriolide (3), and β-(E)-ocimene (8), the second generation synthesis of bolivianine was biomimetically achieved from commercially available (+)-verbenone in 14 steps. The improved total synthesis features an unprecedented palladium-catalyzed intramolecular cyclopropanation through an allylic metal carbene, for the construction of the ABC tricyclic system, and a Diels-Alder/intramolecular hetero-Diels-Alder (DA/IMHDA) cascade for installation of the EFG tricyclic skeleton with the correct stereochemistry. Transformation from bolivianine to isobolivianine was facilitated in the presence of acid. The biosynthetic mechanism and the excellent regio- and endo selectivities in the cascade are well supported by theoretical chemistry based on the DFT calculations.
    Chemistry - A European Journal 02/2014; 20(9). DOI:10.1002/chem.201304378 · 5.93 Impact Factor
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    ABSTRACT: Hepatitis B virus (HBV) is a small and enveloped DNA virus, of which chronic infection is the main risk factor of liver cirrhosis and hepatocellular carcinoma. Hepatitis B virus X protein (HBx) is a multifunctional protein encoded by HBV genome, which have significant effects on HBV replication and pathogenesis. Through directly interacting with cellular proteins, HBx is capable to promote HBV replication, regulate transcription of host genes, disrupt protein degradation, modulate signaling pathway, manipulate cell death and deregulate cell cycle. In this review, we briefly discuss the diversified effects of HBx-interactome and their potential clinical significances.
    Expert Review of Proteomics 11/2013; DOI:10.1586/14789450.2014.861745 · 3.90 Impact Factor
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    ABSTRACT: In this study, high-intensity focused ultrasound (HIFU)-induced thermal effects for solid polymer materials are investigated systematically. Infrared camera imaging is used to monitor temperature changes. The effects of polymer structure, HIFU power, and sample thickness on the thermal effect are studied. The results show that the HIFU-induced heating effect is very quickly, and can be controlled spatially and temporally. More importantly, it is obviously different for different polymers. The main reason is attributed to the various inner friction behaviors of macromolecular chains. This fundamental study is helpful to understand the interaction mechanism between HIFU and polymer, when HIFU is used as a trigger for drug release, shape memory, etc.
    Macromolecular Chemistry and Physics 11/2013; 214(22). DOI:10.1002/macp.201300320 · 2.45 Impact Factor
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    ABSTRACT: The authors present a highly selective C2-heteroarylation of pyridines and related azines.
    ChemInform 10/2013; 44(41). DOI:10.1002/chin.201341168
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    ABSTRACT: Reactive oxygen species (ROS), chemically reactive molecules containing oxygen, can form as a natural byproduct of the normal metabolism of oxygen and also have their crucial roles in cell homeostasis. Of note, the major intracellular sources including mitochondria, endoplasmic reticulum (ER), peroxisomes and the NADPH oxidase (NOX) complex have been identified in cell membranes to produce ROS. Interestingly, autophagy, an evolutionarily conserved lysosomal degradation process in which a cell degrades long-lived proteins and damaged organelles, has recently been well-characterized to be regulated by different types of ROS. Accumulating evidence has demonstrated that ROS-modulated autophagy has numerous links to a number of pathological processes, including cancer, ageing, neurodegenerative diseases, type-II diabetes, cardiovascular diseases, muscular disorders, hepatic encephalopathy and immunity diseases. In this review, we focus on summarizing the molecular mechanisms of ROS-regulated autophagy and their relevance to diverse diseases, which would shed new light on more ROS modulators as potential therapeutic drugs for fighting diseases.
    Free Radical Biology and Medicine 07/2013; 65. DOI:10.1016/j.freeradbiomed.2013.07.013 · 5.27 Impact Factor
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    ABSTRACT: Hepatitis B virus (HBV) is a well-known hepadnavirus with a double-stranded circular DNA genome. Although HBV was first described approximately 50 years ago, the precise mechanisms of HBV infection and effective therapeutic strategies remain unclear. Here, we focus on summarizing the complicated mechanisms of HBV replication and infection, as well as genomic factors and epigenetic regulation. Additionally, we discuss in vivo models of HBV, as well as diagnosis, prevention and therapeutic drugs for HBV. Together, the data in this 50-year review may provide new clues to elucidate molecular mechanisms of HBV pathogenesis and shed new light on the future HBV therapies.
    The international journal of biochemistry & cell biology 06/2013; DOI:10.1016/j.biocel.2013.06.017 · 4.89 Impact Factor
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    ABSTRACT: We report the first total synthesis of bolivanine in a 14-step pathway involving the synthesis of onoseriolide. Our synthesis features a palladium-catalyzed intramolecular cyclopropanation involving an allylic metalcarbene, and a Diels-Alder/intramolecular hetero-Diels-Alder (DA/IMHDA) cascade, making the single-step assembly of a tricycle system with proper stereochemistry. The synthetic efforts validate our modified biogenetic hypothesis and have allowed us to confirm the absolute configuration of bolivianine.
    Journal of the American Chemical Society 05/2013; 135(25). DOI:10.1021/ja4040335 · 11.44 Impact Factor
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    ABSTRACT: A variety of 1,3-oxathiolanes can be easily converted to the corresponding ketones in good yields with LTMP in THF. This deprotection methodology shows satisfactory chemoselectivity when other protecting groups, such as dimethylketal, 1,3-dioxolane, 1,3-dithiane, and other acid-sensitive groups, are present within the same substrates.
    Tetrahedron Letters 05/2013; 54(18):2217–2220. DOI:10.1016/j.tetlet.2013.02.053 · 2.39 Impact Factor
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    ABSTRACT: A series of novel chiral Lewis base catalysts were synthesized from l-serine and applied in the hydrosilylation of β-enamino esters, in which the optimal one promoted the reactions to afford a wide variety of β-amino esters in good yields with good enantioselectivities. It is noteworthy that several cyclic substrates were hydrosilylated under the optimal conditions to give the cyclic β-amino esters with high yields, good diastereoselectivities as well as good ee values.
    Organic & Biomolecular Chemistry 04/2013; DOI:10.1039/c3ob40430g · 3.49 Impact Factor
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    ABSTRACT: HBx is well-known to be a multifunctional protein encoded by HBV and its biological functions are mainly dependent on pleiotropic protein-protein interactions (PPIs); however, the global mapping of HBx-interactome has not been established so far. Thus, in this study, we have identified 127 HBx-interacting proteins by a profound GST pull-down assay coupled with mass spectrometry, and constructed a HBx-interactome network and core apoA-I pathways with a series of bioinformatics approaches. One of the identified HBx-binding partners is apolipoprotein A-I (apoA-I), which has a specific role in lipid and cholesterol metabolism. The HBx-apoA-I protein interaction was confirmed by both GST pull-down and co-immunoprecipitation. The ectopic overexpression of apoA-I can lead to a significant inhibition on HBV secretion concomitant with the reduction of cellular cholesterol level. In addition, HBV can modulate the function of apoA-I through HBx which might interact with the 44-189 residues of apoA-I and result in dysfunction of apoA-I such as decreased self-association ability, increased carbonyl level and impaired lipid-binding ability. Our results demonstrate an integrated physical association of HBx and host proteins, especially a novel interactor apoA-I that may influence the HBV secretion, which would shed new light on exploring the complicated mechanisms of HBV manipulation on host cellular functions. BIOLOGICAL SIGNIFICANCE: HBx is well-known to be a multifunctional protein encoded by HBV and its biological functions are mainly dependent on pleiotropic protein-protein interactions. Although a series of HBx-interacting proteins have been identified, a global characterization of HBx interactome has not been reported. In this study, we have identified a total of 127 HBx-interacting proteins by a profound GST pull-down assay coupled with mass spectrometry, and constructed a HBx-interactome network with a series of bioinformatics approaches. Our results demonstrate an integrated physical association of HBx and host proteins which may help us explore the complicated mechanisms of HBV manipulation on host cellular functions. In addition, we validated one of the identified HBx-binding partners, apolipoprotein A-I (apoA-I), which played a significant inhibitory effect on HBV secretion, indicating a crucial role of the HBx-apoA-I axis in HBV life cycle.
    Journal of proteomics 04/2013; DOI:10.1016/j.jprot.2013.03.028 · 5.07 Impact Factor

Publication Stats

1k Citations
280.62 Total Impact Points

Institutions

  • 2008–2015
    • Sichuan University
      • • College of Chemistry
      • • College of Life Sciences
      Hua-yang, Sichuan, China
  • 2013
    • State Key Laboratory of Medical Genetics of China
      Ch’ang-sha-shih, Hunan, China
    • Sun Yat-Sen University of Medical Sciences
      Shengcheng, Guangdong, China