Publications by authors named "Yuchen Shi"

20 Publications

  • Page 1 of 1

An Updated Mendelian Randomization Analysis of the Association Between Serum Calcium Levels and the Risk of Alzheimer's Disease.

Front Genet 2021 8;12:731391. Epub 2021 Sep 8.

First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China.

It has been a long time that the relationship between serum calcium levels and Alzheimer's disease (AD) remains unclear. Until recently, observational studies have evaluated the association between serum calcium levels and the risk of AD, however, reported inconsistent findings. Meanwhile, a Mendelian randomization (MR) study had been conducted to test the causal association between serum calcium levels and AD risk, however, only selected 6 serum calcium SNPs as the instrumental variables. Hence, these findings should be further verified using additional more genetic variants and large-scale genome-wide association study (GWAS) dataset to increase the statistical power. Here, we conduct an updated MR analysis of the causal association between serum calcium levels and the risk of AD using a two-stage design. In discovery stage, we conducted a MR analysis using 14 SNPs from serum calcium GWAS dataset ( = 61,079), and AD GWAS dataset ( = 63,926, 21,982 cases, 41,944 cognitively normal controls). All four MR methods including IVW, weighted median, MR-Egger, and MR-PRESSO showed a reduced trend of AD risk with the increased serum calcium levels. In the replication stage, we performed a MR analysis using 166 SNPs from serum calcium GWAS dataset ( = 305,349), and AD GWAS dataset ( = 63,926, 21,982 cases, 41,944 cognitively normal controls). Only the weighted median indicated that genetically increased serum calcium level was associated with the reduced risk of AD. Hence, additional studies are required to investigate these findings.
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http://dx.doi.org/10.3389/fgene.2021.731391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457382PMC
September 2021

Strategies for multivariate analyses of imaging genetics study in Alzheimer's disease.

Neurosci Lett 2021 09 29;762:136147. Epub 2021 Jul 29.

School of Computer Science and Technology, Hangzhou Dianzi University, Hangzhou, Zhejiang 310018, China; Key Laboratory of Intelligent Image Analysis for Sensory and Cognitive Health, Ministry of Industry and Information Technology of China, Hangzhou, Zhejiang 310018, China.

Alzheimer's disease (AD) is an incurable neurodegenerative disease primarily affecting the elderly population. Early diagnosis of AD is critical for the management of this disease. Imaging genetics examines the influence of genetic variants (i.e., single nucleotide polymorphisms (SNPs)) on brain structure and function and many novel approaches of imaging genetics are proposed for studying AD. We review and synthesize the Alzheimer's Disease Neuroimaging Initiative (ADNI) genetic associations with quantitative disease endophenotypes including structural and functional neuroimaging, diffusion tensor imaging (DTI), positron emission tomography (PET), and fluid biomarker assays. In this review, we survey recent publications using neuroimaging and genetic data of AD, with a focus on methods capturing multivariate effects accommodating the large number variables from both imaging data and genetic data. We review methods focused on bridging the imaging and genetic data by establishing genotype-phenotype association, including sparse canonical correlation analysis, parallel independent component analysis, sparse reduced rank regression, sparse partial least squares, genome-wide association study, and so on. The broad availability and wide scope of ADNI genetic and phenotypic data has advanced our understanding of the genetic basis of AD and has nominated novel targets for future pharmaceutical therapy and biomarker development.
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http://dx.doi.org/10.1016/j.neulet.2021.136147DOI Listing
September 2021

Improved parallel magnetic resonance imaging reconstruction with multiple variable density sampling.

Sci Rep 2021 04 26;11(1):9005. Epub 2021 Apr 26.

Beijing Hospital, Beijing, 100730, China.

Generalized auto-calibrating partially parallel acquisitions (GRAPPA) and other parallel Magnetic Resonance Imaging (pMRI) methods restore the unacquired data in k-space by linearly calculating the undersampled data around the missing points. In order to obtain the weight of the linear calculation, a small number of auto-calibration signal (ACS) lines need to be sampled at the center of the k-space. Therefore, the sampling pattern used in this type of method is to full sample data in the middle area and undersample in the outer k-space with nominal reduction factors. In this paper, we propose a novel reconstruction method with a multiple variable density sampling (MVDS) that is different from traditional sampling patterns. Our method can significantly improve the image quality using multiple reduction factors with fewer ACS lines. Specifically, the traditional sampling pattern only uses a single reduction factor to uniformly undersample data in the region outside the ACS, but we use multiple reduction factors. When sampling the k-space data, we keep the ACS lines unchanged, use a smaller reduction factor for undersampling data near the ACS lines and a larger reduction factor for the outermost part of k-space. The error is lower after reconstruction of this region by undersampled data with a smaller reduction factor. The experimental results show that with the same amount of data sampled, using NL-GRAPPA to reconstruct the k-space data sampled by our method can result in lower noise and fewer artifacts than traditional methods. In particular, our method is extremely effective when the number of ACS lines is small.
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http://dx.doi.org/10.1038/s41598-021-88567-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076203PMC
April 2021

Modulating macrophage activities to promote endogenous bone regeneration: Biological mechanisms and engineering approaches.

Bioact Mater 2021 Jan 22;6(1):244-261. Epub 2020 Aug 22.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Macau SAR, China.

A coordinated interaction between osteogenesis and osteoimmune microenvironment is essential for successful bone healing. In particular, macrophages play a central regulatory role in all stages of bone repair. Depending on the signals they sense, these highly plastic cells can mediate the host immune response against the exterior signals of molecular stimuli and implanted scaffolds, to exert regenerative potency to a varying extent. In this article, we first encapsulate the immunomodulatory functions of macrophages during bone regeneration into three aspects, as sweeper, mediator and instructor. We introduce the phagocytic role of macrophages in different bone healing periods ('sweeper') and overview a variety of paracrine cytokines released by macrophages either mediating cell mobilisation, vascularisation and matrix remodelling ('mediator'), or directly driving the osteogenic differentiation of bone progenitors and bone repair ('instructor'). Then, we systematically classify and discuss the emerging engineering strategies to recruit, activate and modulate the phenotype transition of macrophages, to exploit the power of endogenous macrophages to enhance the performance of engineered bone tissue.
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http://dx.doi.org/10.1016/j.bioactmat.2020.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451865PMC
January 2021

Absent in melanoma 2 enhances anti-tumour effects of CAIX promotor controlled conditionally replicative adenovirus in renal cancer.

J Cell Mol Med 2020 09 29;24(18):10744-10755. Epub 2020 Jul 29.

Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, China.

Conditionally replicative adenoviruses (CRAds) were promising approach for solid tumour treatment, but its oncolytic efficiency and toxicity are still not satisfactory for further clinical application. Here, we developed the CAIX promotor (CAIX )-controlled CRAd armed with a tumour suppressor absent in melanoma 2 (AIM2) to enhance its oncolytic potency. The CAIX -AIM2 adenoviruses (Ad-CAIX -AIM2) could efficiently express E1A and AIM2 in renal cancer cells. Compared with Ad-CAIX , Ad-CAIX -AIM2 significantly inhibited cell proliferation and enhanced cell apoptosis and cell killing, thus resulting in the oncolytic efficiency in 786-O cells or OSRC-2 cells. To explore the therapeutic effect, various Ads were intratumourally injected into OSRC-2-xenograft mice. The tumour growth was remarkably inhibited in Ad-CAIX -AIM2-treated group as demonstrated by reduced tumour volume and weight with a low toxicity. The inflammasome inhibitor YVAD-CMK resulted in the reduction of anti-tumour activity by Ad-CAIX -AIM2 in vitro or in vivo, suggesting that inflammasome activation response was required for the enhanced therapeutic efficiency. Furthermore, lung metastasis of renal cancer mice was also suppressed by Ad-CAIX -AIM2 treatment accompanied by the decreased tumour fossil in lung tissues. These results indicated that the tumour-specific Ad-CAIX -AIM2 could be applied for human renal cancer therapy. The therapeutic strategy of AIM2-based CRAds could be a potential and promising approach for the therapy of primary solid or metastasis tumours.
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http://dx.doi.org/10.1111/jcmm.15697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521288PMC
September 2020

β-amyloid-induced gonadotropin-releasing hormone decline involving Forkhead transcription factor FOXO3a and nuclear factor-κB.

Neuroreport 2020 08;31(12):923-927

Department of Neurology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong.

Previously, it has been demonstrated that aging is controlled by the hypothalamus, and that hypothalamus-driven programmatic aging is associated with nuclear factor-κB (NF-κB)-mediated gonadotropin-releasing hormone (GnRH) decrease. Abundant accumulation of β-amyloid (Aβ) has been observed in brains of cognitively normal elderly. However, it is unclear whether Aβ neurotoxicity is involved in aging-associated hypothalamic GnRH decline. GT1-7 cells, which are a cell line of hypothalamic GnRH neurons, were used in the current study to investigate whether and how Aβ decreased GnRH release. The results of the current study demonstrated that Aβ impaired the release of GnRH through activation of NF-κB. Mechanistic studies revealed that Aβ activated NF-κB via Forkhead box protein O3a, thereby inhibiting gnrh1 gene. The results of the present study provided novel insights into the mechanisms underlying aging-dependent hypothalamic GnRH decline.
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http://dx.doi.org/10.1097/WNR.0000000000001488DOI Listing
August 2020

Atomic-Scale Tuning of Graphene/Cubic SiC Schottky Junction for Stable Low-Bias Photoelectrochemical Solar-to-Fuel Conversion.

ACS Nano 2020 Apr 7;14(4):4905-4915. Epub 2020 Apr 7.

Department of Physics, Chemistry and Biology (IFM), Linköping University, 58183 Linköping, Sweden.

Engineering tunable graphene-semiconductor interfaces while simultaneously preserving the superior properties of graphene is critical to graphene-based devices for electronic, optoelectronic, biomedical, and photoelectrochemical applications. Here, we demonstrate this challenge can be surmounted by constructing an interesting atomic Schottky junction epitaxial growth of high-quality and uniform graphene on cubic SiC (3C-SiC). By tailoring the graphene layers, the junction structure described herein exhibits an atomic-scale tunable Schottky junction with an inherent built-in electric field, making it a perfect prototype to systematically comprehend interfacial electronic properties and transport mechanisms. As a proof-of-concept study, the atomic-scale-tuned Schottky junction is demonstrated to promote both the separation and transport of charge carriers in a typical photoelectrochemical system for solar-to-fuel conversion under low bias. Simultaneously, the as-grown monolayer graphene with an extremely high conductivity protects the surface of 3C-SiC from photocorrosion and energetically delivers charge carriers to the loaded cocatalyst, achieving a synergetic enhancement of the catalytic stability and efficiency.
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http://dx.doi.org/10.1021/acsnano.0c00986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304924PMC
April 2020

LncSpA: LncRNA Spatial Atlas of Expression across Normal and Cancer Tissues.

Cancer Res 2020 05 19;80(10):2067-2071. Epub 2020 Mar 19.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

Long noncoding RNAs (lncRNA) play important roles in maintaining morphology and function of tissues, and their regulatory effectiveness is closely associated with spatial expression. To provide a comprehensive spatial atlas of expression for lncRNA, we propose LncSpA (http://bio-bigdata.hrbmu.edu.cn/LncSpA) to explore tissue-elevated (TE) lncRNA across human normal and adult and pediatric cancer tissues. In total, 71,131 and 12,007 TE lncRNAs and 634 clinical-related TE lncRNAs were identified across 38 normal and 33 adult cancer tissues. Moreover, 4,688 TE and 413 clinical-related lncRNAs were identified in pediatric cancer. By quick searching or query options, users can obtain eight major types of detailed information for lncRNA via various visualization techniques, including qualitative and quantitative spatial expression in different resources, coexpressed mRNAs, predicted function, known disease association, and the potential to serve as diagnostic or prognostic markers. LncSpA will be a valuable resource to understand lncRNA functions across tissues and cancers, leading to enhanced therapeutic strategies in precision oncology. SIGNIFICANCE: LncSpA is a new interactive resource that provides the spatial expression pattern of lncRNA across thousands of normal and cancer samples representing major tissue types.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-2687DOI Listing
May 2020

Transcriptomic Analyses for Identification and Prioritization of Genes Associated With Alzheimer's Disease in Humans.

Front Bioeng Biotechnol 2020 21;8:31. Epub 2020 Feb 21.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

Long non-coding RNAs (lncRNAs), as important ncRNA regulators, play crucial roles in the regulation of various biological processes, and their aberrant expression is related to the occurrence and development of diseases, which is gradually validated by more and more studies. Alzheimer's disease (AD) is a chronic neurodegenerative disease that often develops slowly and gradually deteriorates over time. However, which functions the lncRNAs perform in AD are almost unknown. In this study, we performed transcriptome analysis in AD, containing 12,892 known lncRNAs and 19,053 protein-coding genes (PCGs). Further, 14 down-regulated and 39 up-regulated lncRNAs were identified, compared with normal brain samples, which indicated that these lncRNAs might play critical roles in the pathogenesis of AD. In addition, 19 down-regulated and 28 up-regulated PCGs were also detected. Using the differentially expressed lncRNAs and PCGs through the WGCNA method, an lncRNA-mRNA co-expressed network was constructed. The results showed that lncRNAs RP3-522J7, MIR3180-2, and MIR3180-3 were frequently co-expressed with known AD risk PCGs. Interestingly, PCGs in the network are significantly enriched in brain- or AD-related biological functions, including the brain renin-angiotensin system, cell adhesion, neuroprotective role of THOP1 in AD, and so on. Furthermore, it was shown that 18 lncRNAs and 7 PCGs were highly expressed in normal brain tissue relative to other normal tissue types, suggesting their potential as diagnostic markers of AD, especially RP3-522J7, MIR3180-2, MIR3180-3, and CTA-929C8. In total, our study identified a compendium of AD-related dysregulated lncRNAs and characterized the corresponding biological functions of these lncRNAs in AD, which will be helpful to understand the molecular basis and pathogenesis of AD.
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http://dx.doi.org/10.3389/fbioe.2020.00031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047416PMC
February 2020

Fibroblast Growth Factor 21 Attenuates Vascular Calcification by Alleviating Endoplasmic Reticulum Stress Mediated Apoptosis in Rats.

Int J Biol Sci 2019 6;15(1):138-147. Epub 2019 Jan 6.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.

Fibroblast growth factor 21 (FGF21), a hormone with multiple metabolic properties, has proven to be pleiotropic biological effects and may play pivotal role in numerous cardiovascular and metabolic diseases in the future. Vascular calcification (VC) is a concomitant pathological process of various cardiovascular and metabolic diseases. However, the effects of FGF21 on VC remain unclear. Therefore, in this research, we aimed to explore the roles and mechanisms of FGF21 in VC induced by vitamin D plus nicotine (VDN) treatment rats. After 28 days VDN treatment, the calcium overload was confirmed by blood pressure, ultrasound imaging, calcium content, ALP activity and aortic pathological characteristics. In terms of FGF21, exogenous FGF21 can ameliorate the elevation of blood pressure, aortic calcification and related injury in VC rats. To investigate the mechanisms of FGF21 on VC, the endoplasmic reticulum stress (ERS) mediated apoptosis pathways were tested. As a method to detect apoptosis, the increased positive TUNEL staining cells were alleviated by FGF21 treatment. Furthermore, exogenous FGF21 can suppress the increased ERS chaperone, GRP78, in the calcified aortas. In the three pathways of ERS mediated apoptosis, we found CHOP pathway and caspase-12 pathway were involved in the treatment of FGF21, but not p-JNK/JNK pathway. Our study proved for the first time that FGF21 can inhibit the progress of VC by alleviating ERS mediated apoptosis in rats. FGF21 might be a new target for preventing and treating VC.
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http://dx.doi.org/10.7150/ijbs.28873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329919PMC
January 2020

Flat-Band Electronic Structure and Interlayer Spacing Influence in Rhombohedral Four-Layer Graphene.

Nano Lett 2018 09 24;18(9):5862-5866. Epub 2018 Aug 24.

Department of Physics, Chemistry and Biology (IFM) , Linköping University , SE-58183 , Linköping , Sweden.

The stacking order of multilayer graphene significantly influences its electronic properties. The rhombohedral stacking sequence is predicted to introduce a flat band, which has high density of states and the enhanced Coulomb interaction between charge carriers, thus possibly resulting in superconductivity, fractional quantum Hall effect, and many other exotic phases of matter. In this work, we comprehensively study the effect of the stacking sequence and interlayer spacing on the electronic structure of four-layer graphene, which was grown on a high crystalline quality 3C-SiC(111) crystal. The number of graphene layers and coverage were determined by low energy electron microscopy. First-principles density functional theory calculations show distinctively different band structures for ABAB (Bernal), ABCA (rhombohedral), and ABCB (turbostratic) stacking sequences. By comparing with angle-resolved photoelectron spectroscopy data, we can verify the existence of a rhombohedral stacking sequence and a nearly dispersionless electronic band (flat band) near the Fermi level. Moreover, we find that the momentum width, bandgap, and curvature of the flat-band region can be tuned by the interlayer spacing, which plays an important role in superconductivity and many other exotic phases of matter.
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http://dx.doi.org/10.1021/acs.nanolett.8b02530DOI Listing
September 2018

An ortho-aldehyde modified probe to image thiols in living cells with enhanced selectivity.

Talanta 2018 Mar 21;179:326-330. Epub 2017 Nov 21.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Macau SAR, China. Electronic address:

Developing fluorescent probes to image thiols in the living system may provide powerful tools to study the functions of thiol-containing biological molecules. In this study, we report the design and evaluation of a novel turn-on fluorescent probe NQNO for selective detection of thiols in living cells. By introducing an ortho-aldehyde group to NNO, a conventional compound representing a class of thiol-imaging strategy, we obtained NQNO with enhanced selectivity for thiols over the major interferent hydrogen sulfide (HS). NQNO could be applied in phosphate-buffered saline (PBS), where the efficacy of NNO was usually weakened. Notably, NQNO demonstrated solid performance in imaging endogenous thiols in living cells without exerting cytotoxicity. In summary, NQNO has the potential to serve as a safe, sensitive and effective fluorescent probe for thiol imaging in biological systems.
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http://dx.doi.org/10.1016/j.talanta.2017.11.035DOI Listing
March 2018

Fibroblast growth factor 21 ameliorates vascular calcification by inhibiting osteogenic transition in vitamin D3 plus nicotine-treated rats.

Biochem Biophys Res Commun 2018 01 20;495(4):2448-2455. Epub 2017 Dec 20.

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China. Electronic address:

FGF21, a special member of FGF superfamily, has been proven to have pleiotropic metabolic effects and many potential therapeutic action in various metabolic disorders. Vascular calcification (VC), a perplexing clinical issue, is a major risk factor for many cardiovascular diseases, especially for patients with some metabolic diseases. However, the role of FGF21 on VC in vivo remains unclear. Thus, in this study, we observed the effect and mechanism of FGF21 on VC induced by vitamin D3 plus nicotine (VDN) treated rats. After four weeks' treatment, the calcium overload is mainly manifested in the increased blood pressure, aortic calcium content and ALP activity. Also, the HE and Alizarin-red S staining showed the structural damage of calcified vessel walls. In addition, the level of endogenous FGF21/β-Klotho/FGFR1 axis was up-regulated in the aortas of VC rats. Furthermore, exogenous FGF21 treatment significantly ameliorated the aortic injury and calcification in VC rats, and the level of β-Klotho and FGFR1 were furtherly increase. Moreover, FGF21 inhibited the osteogenic transition of VSMCs by down-regulating the expression of bone-associated proteins such as osteopontin (OPN), osteocalcin (OCN) and bone morphogenetic protein-2 (BMP-2), together with restored the expression of SM22α and SM α-actin, which are two of lineage markers in VSMCs. We provide the first evidence that FGF21 can inhibit the development of VC by inhibiting the osteogenic transition of VSMCs in rats. FGF21 might be an efficient endogenous vasoprotective factor for calcification.
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http://dx.doi.org/10.1016/j.bbrc.2017.10.115DOI Listing
January 2018

Enhanced fluorescence detection of proteins using ZnO nanowires integrated inside microfluidic chips.

Biosens Bioelectron 2018 Jan 3;99:368-374. Epub 2017 Aug 3.

Engineering Research Center for Nanophotonics and Advanced Instrument, School of Physics and Materials Science, East China Normal University, Shanghai 200062, China. Electronic address:

Nanostructure-enhanced detection is promising for a number of applications such as early cancer diagnosis, environmental monitoring and mine safety, among which nanostructures integrated microfluidic chips offers unique advantage of ultra-low quantitative analyses. Here, dense ZnO nanowires of varied diameter and length were obtained by changing the content of polyethyleneimine (PEI) and growth time via simple hydrothermal growth in microfluidic channels for protein detection. We showed that this approach was superiorly efficient compared to the conventional hydrothermal method due to the flow-induced replenishment of nutrient and the effect of shear stress. When immobilizing FITC conjugated anti-bovine immunoglobulin G (IgG) on ZnO nanowires, the fluorescence emission was significantly amplified compared to glass substrate and ZnO seed layer. Under the different growth conditions, the most remarkable fluorescence enhancement was observed on the ZnO nanowire substrate grown for 3h with 5mM PEI in solution. It is ascribed not only to the increase of the binding surface area of proteins but also the intrinsic fluorescence enhancement of ZnO nanowires as waveguides. We further used the optimized ZnO nanowires to demonstrate multiple detection of cancer biomarkers, achieving a superior limit of detection (LOD) as low as 1pg/mL in human α-fetoprotein (AFP) assay and 100 fg/mL in carcinoembryonic antigen (CEA) assay with large dynamic range of 6-7 orders, which suggests that ZnO nanowire integrated microfluidic chips are promising for high-throughput fluorescence-based diagnostic assays.
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http://dx.doi.org/10.1016/j.bios.2017.08.003DOI Listing
January 2018

Modulating the phenotype of host macrophages to enhance osteogenesis in MSC-laden hydrogels: Design of a glucomannan coating material.

Biomaterials 2017 Sep 24;139:39-55. Epub 2017 May 24.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Macau SAR, China. Electronic address:

The biomaterials-host interaction is a dynamic process in which macrophages play a vital role of regulation. Depending on the biochemical signals they sense, these highly plastic cells can mediate the immune response against the implanted scaffolds and/or exert regenerative potency to varying extent. Designing appropriate 'exterior signals' for scaffolds may exploit the power of endogenous macrophages to aid the regeneration of engineered tissues. To realise this goal, this study devised an injectable, instantaneously-solidifying coating material (acBSP) based on a unique, macrophage-affinitive glucomannan polysaccharide. Coating of three-dimensional hydrogel constructs with acBSP was rapid, neat and complete, requiring neither chemical reactions nor harsh conditions. Comprehensive in vitro analyses indicated that acBSP efficiently facilitated the adhesion and activation of macrophages and notably induced the macrophages to express pro-osteogenic/-angiogenic genes. Further in vivo assessment of acBSP-coated, mesenchymal stem cells-laden hydrogels in a murine dorsal subcutaneous pocket model demonstrated efficient macrophage activation, desirable scaffold-tissue integration and improved osteogenic differentiation in the delivered cells. In summary, by activating macrophages into a pro-osteogenic phenotype, the acBSP coating has demonstrated its competency as an innovative, open and efficacious platform to harness the power of host immunity for enhancing the regenerative performance of engineered tissue constructs.
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http://dx.doi.org/10.1016/j.biomaterials.2017.05.042DOI Listing
September 2017

[Effects and mechanism of fibroblast growth factor 21 on rat vascular smooth muscle cells calcification].

Zhonghua Xin Xue Guan Bing Za Zhi 2015 Oct;43(10):879-86

Beijing Institute of Heart, Lung and Blood Vessel Diseases, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China; Email:

Objective: To observe the effect and mechanism of fibroblast growth factor 21 (FGF21) on rat vascular smooth muscle cells (VSMCs) calcification in vitro.

Methods: VSMCs was treated with calcification medium containing calcium chloride and β-glycerophosphate to induce rat VSMCs calcification in vitro. VSMCs were divided into 5 groups: the control group (cultured in normal medium), the calcification group (incubated in calcified medium), the FGF21 group (cultured in calcified medium and FGF21), the PD166866 group (cultured in calcified medium and FGF21 and PD166866, inhibitor of fibroblast growth factor receptor-1 (FGFR1)), the GW9662 group (cultured in calcified medium and FGF21 and GW9662, inhibitor of peroxisome proliferators activated receptor-γ (PPAR-γ)). The calcification of VSMCs was detected by calcium content, alkaline phosphatase activity and alizarin red staining. The protein and mRNA expression of FGFR1, β-Klotho, osteocalcin and smooth muscle 22α (SM22α) were determined by western blot analysis and realtime-PCR, respectively.

Results: (1) The mRNA (P < 0.01) and protein expressions of β-Klotho and FGFR1 were significantly downregulated in calcification group compared with control group (P < 0.05 or 0.01). (2) The protein levels and mRNA expression of calcium content, alkaline phosphatase activity and osteocalcin were significantly downregulated, while the protein levels and mRNA of SM22α were significantly increased in FGF21 group compared with calcification group (all P < 0.05). Moreover, alizarin red staining verified positive red nodules on calcified VSMCs was significantly reduced in FGF21 group than in calcification group. (3) Calcium content, alkaline phosphatase activity and alizarin red staining were similar between PD166866 group and calcification group (all P > 0.05). (4) Calcium content, alkaline phosphatase activity and alizarin red staining were similar between GW9662 group and calcification group (all P > 0.05).

Conclusion: The inhibition of VSMCs calcification by FGF21 is mediated by further downregulating FGFR1 and β-Klotho while activating PPAR-γ pathways.
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October 2015

Identifying colon cancer risk modules with better classification performance based on human signaling network.

Genomics 2014 Oct 13;104(4):242-8. Epub 2013 Nov 13.

Institute of Opto-electronics, Harbin Institute of Technology, Harbin, Heilongjiang Province Postal Code: 150080, China. Electronic address:

Identifying differences between normal and tumor samples from a modular perspective may help to improve our understanding of the mechanisms responsible for colon cancer. Many cancer studies have shown that signaling transduction and biological pathways are disturbed in disease states, and expression profiles can distinguish variations in diseases. In this study, we integrated a weighted human signaling network and gene expression profiles to select risk modules associated with tumor conditions. Risk modules as classification features by our method had a better classification performance than other methods, and one risk module for colon cancer had a good classification performance for distinguishing between normal/tumor samples and between tumor stages. All genes in the module were annotated to the biological process of positive regulation of cell proliferation, and were highly associated with colon cancer. These results suggested that these genes might be the potential risk genes for colon cancer.
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http://dx.doi.org/10.1016/j.ygeno.2013.11.002DOI Listing
October 2014

Cancer-related marketing centrality motifs acting as pivot units in the human signaling network and mediating cross-talk between biological pathways.

Mol Biosyst 2013 Dec 20;9(12):3026-35. Epub 2013 Sep 20.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Hei Longjiang Province, China.

Network motifs in central positions are considered to not only have more in-coming and out-going connections but are also localized in an area where more paths reach the networks. These central motifs have been extensively investigated to determine their consistent functions or associations with specific function categories. However, their functional potentials in the maintenance of cross-talk between different functional communities are unclear. In this paper, we constructed an integrated human signaling network from the Pathway Interaction Database. We identified 39 essential cancer-related motifs in central roles, which we called cancer-related marketing centrality motifs, using combined centrality indices on the system level. Our results demonstrated that these cancer-related marketing centrality motifs were pivotal units in the signaling network, and could mediate cross-talk between 61 biological pathways (25 could be mediated by one motif on average), most of which were cancer-related pathways. Further analysis showed that molecules of most marketing centrality motifs were in the same or adjacent subcellular localizations, such as the motif containing PI3K, PDK1 and AKT1 in the plasma membrane, to mediate signal transduction between 32 cancer-related pathways. Finally, we analyzed the pivotal roles of cancer genes in these marketing centrality motifs in the pathogenesis of cancers, and found that non-cancer genes were potential cancer-related genes.
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http://dx.doi.org/10.1039/c3mb70289hDOI Listing
December 2013

Focal segmental glomerulosclerosis is associated with a PDSS2 haplotype and, independently, with a decreased content of coenzyme Q10.

Am J Physiol Renal Physiol 2013 Oct 7;305(8):F1228-38. Epub 2013 Aug 7.

Dept. of Genetics, Univ. of Pennsylvania School of Medicine, 415 Curie Blvd., Philadelphia, PA 19104.

Focal segmental glomerulosclerosis (FSGS) and collapsing glomerulopathy are common causes of nephrotic syndrome. Variants in >20 genes, including genes critical for mitochondrial function, have been associated with these podocyte diseases. One such gene, PDSS2, is required for synthesis of the decaprenyl tail of coenzyme Q10 (Q10) in humans. The mouse gene Pdss2 is mutated in the kd/kd mouse model of collapsing glomerulopathy. We examined the hypothesis that human PDSS2 polymorphisms are associated with podocyte diseases. We genotyped 377 patients with primary FSGS or collapsing glomerulopathy, together with 900 controls, for 9 single-nucleotide polymorphisms in the PDSS2 gene in a case-control study. Subjects included 247 African American (AA) and 130 European American (EA) patients and 641 AA and 259 EA controls. Among EAs, a pair of proxy SNPs was significantly associated with podocyte disease, and patients homozygous for one PDSS2 haplotype had a strongly increased risk for podocyte disease. By contrast, the distribution of PDSS2 genotypes and haplotypes was similar in AA patients and controls. Thus a PDSS2 haplotype, which has a frequency of 13% in the EA control population and a homozygote frequency of 1.2%, is associated with a significantly increased risk for FSGS and collapsing glomerulopathy in EAs. Lymphoblastoid cell lines from FSGS patients had significantly less Q10 than cell lines from controls; contrary to expectation, this finding was independent of PDSS2 haplotype. These results suggest that FSGS patients have Q10 deficiency and that this deficiency is manifested in patient-derived lymphoblastoid cell lines.
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http://dx.doi.org/10.1152/ajprenal.00143.2013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798722PMC
October 2013

Coenzyme Q10 supplementation rescues renal disease in Pdss2kd/kd mice with mutations in prenyl diphosphate synthase subunit 2.

Am J Physiol Renal Physiol 2008 Nov 10;295(5):F1535-44. Epub 2008 Sep 10.

Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095-1569, USA.

Homozygous mice carrying kd (kidney disease) mutations in the gene encoding prenyl diphosphate synthase subunit 2 (Pdss2kd/kd) develop interstitial nephritis and eventually die from end-stage renal disease. The PDSS2 polypeptide in concert with PDSS1 synthesizes the polyisoprenyl tail of coenzyme Q (Q or ubiquinone), a lipid quinone required for mitochondrial respiratory electron transport. We have shown that a deficiency in Q content is evident in Pdss2kd/kd mouse kidney lipid extracts by 40 days of age and thus precedes the onset of proteinuria and kidney disease by several weeks. The presence of the kd (V117M) mutation in PDSS2 does not prevent its association with PDSS1. However, heterologous expression of the kd mutant form of PDSS2 together with PDSS1 in Escherichia coli recapitulates the Q deficiency observed in the Pdss2kd/kd mouse. Dietary supplementation with Q10 provides a dramatic rescue of both proteinuria and interstitial nephritis in the Pdss2kd/kd mutant mice. The results presented suggest that Q may be acting as a potent lipid-soluble antioxidant, rather than by boosting kidney mitochondrial respiration. Such Q10 supplementation may have profound and beneficial effects in treatment of certain forms of focal segmental glomerulosclerosis that mirror the renal disease of the Pdss2kd/kd mouse.
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http://dx.doi.org/10.1152/ajprenal.90445.2008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2584909PMC
November 2008
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