Publications by authors named "Xiangwei Liu"

28 Publications

  • Page 1 of 1

Research on Subpixel Algorithm of Fixed-Point Tool Path Measurement.

Comput Intell Neurosci 2021 3;2021:7270908. Epub 2021 Sep 3.

School of Mechanical and Automation, Shanghai University, Shanghai 201900, China.

Tool safety is an important part of machining and machine tool safety, and machine tool path image detection can effectively obtain the in-machine condition of a tool. To obtain an accurate image edge and improve image processing accuracy, a novel subpixel edge detection method is proposed in this study. The precontour is segmented by binarization, the second derivative in the neighborhood of the demand point is calculated, and the obtained value is sampled according to the specified rules for curve fitting. The point whose curve ordinate is 0 is the subpixel position. The experiment proves that an improved subpixel edge can be obtained. Results show that the proposed method can extract a satisfactory subpixel contour, which is more accurate and reliable than the edge results obtained by several current pixel-level operators, such as the Canny operator, and can be used in edge detection with high-accuracy requirements, such as the contour detection of online tools.
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http://dx.doi.org/10.1155/2021/7270908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433006PMC
September 2021

Fuscoside Attenuates Bone Loss in Bone Defects by Regulating The Rankl/Nlrp3/Opg Pathway in Rats.

Cell J 2021 Sep 29;23(4):451-456. Epub 2021 Aug 29.

Department of Traumatic Orthopedics, Chifeng Municipal Hospital, Chifeng, Inner Mongolia, China. Email:

Objective: This study evaluated the beneficial effect of fuscoside in the repair of bone defects (BDs) and the possible molecular mechanism thereof.

Materials And Methods: In this experimental study, a BD was induced by drilling the rat tibia. The rats were then administered oral fuscoside, at 200 or 300 mg/kg, for 2 weeks. The effect of treatment was assessed based on the bone formation score and on the levels of cytokines and biochemical markers in serum. Tibial expression of the proteins involved in the Rankl/Nlrp3/Opg pathway was determined by quantitative reverse-transcription polymerase chain reaction and western blot assay, and histopathological changes by haematoxylin and eosin and TRAP staining.

Results: In the fuscoside-treated BD rats, the bone formation score improved and inflammatory cytokine levels were reduced. The levels of biochemical markers improved as well, as did the expression of apoptosis proteins. Fuscoside also attenuated the expression of Rankl, Opg, Nlrp3, Runx2, Osterix, and Osteocalcin (Oc) proteins in the tibial tissue of the BD rats and reversed the abnormal histopathological changes.

Conclusion: These results suggest that fuscoside improves BD repair by reducing the differentiation of osteoclasts and by regulating the Rankl/Nlrp3/Opg pathway.
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http://dx.doi.org/10.22074/cellj.2021.7736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405081PMC
September 2021

Long non-coding RNA KCNQ1OT1 promotes cell viability and migration as well as inhibiting degradation of CHON-001 cells by regulating miR-126-5p/TRPS1 axis.

Adv Rheumatol 2021 06 9;61(1):31. Epub 2021 Jun 9.

Orthopaedic Ward 2 (Trauma Surgery), Chifeng Municipal Hospital, No.1, Zhaowuda Road, Chifeng City, 024000, Inner Mongolia, China.

Background: Osteoarthritis (OA) is defined as a degenerative disease. Pivotal roles of long non-coding RNA (lncRNAs) in OA are widely elucidated. Herein, we intend to explore the function and molecular mechanism of lncRNA KCNQ1OT1 in CHON-001 cells.

Methods: Relative expression of KCNQ1OT1, miR-126-5p and TRPS1 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was examined by MTT assay. The migratory ability of chondrocytes was assessed by transwell assay. Western blot was used to determine relative protein expression of collagen II, MMP13 and TRPS1. Dual-luciferase reporter (DLR) assay was applied to test the target of lncRNA KCNQ1OT1 or miR-126-5p.

Results: Relative expression of KCNQ1OT1 and TRPS1 was reduced, whereas miR-126-5p was augmented in cartilage tissues of post-traumatic OA patients compared to those of subjects without post-traumatic OA. Increased KCNQ1OT1 or decreased miR-126-5p enhanced cell viability and migration, and repressed extracellular matrix (ECM) degradation in CHON-001 cells. MiR-126-5p was the downstream target of KCNQ1OT1, and it could directly target TRPS1. There was an inverse correlation between KCNQ1OT1 and miR-126-5p or between miR-126-5p and TRPS1. Meantime, there was a positive correlation between KCNQ1OT1 and TRPS1. The promoting impacts of KCNQ1OT1 on cell viability and migration as well as the suppressive impact of KCNQ1OT1 on ECM degradation were partially abolished by miR-126-5p overexpression or TRPS1 knockdown in CHON-001 cells.

Conclusions: Overexpression of KCNQ1OT1 attenuates the development of OA by sponging miR-126-5p to target TRPS1. Our findings may provide a possible therapeutic strategy for human OA in clinic.
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http://dx.doi.org/10.1186/s42358-021-00187-3DOI Listing
June 2021

5,10,15,20-tetrakis (4-carboxyl phenyl) porphyrin-functionalized urchin-like CuCoO as an excellent artificial nanozyme for determination of dopamine.

Mikrochim Acta 2021 04 23;188(5):171. Epub 2021 Apr 23.

College of Chemical and Biological Engineering, Shandong University of Science and Technology, Qingdao, 266590, People's Republic of China.

Urchin-like peroxidase mimics 5,10,15,20-tetrakis (4-carboxyl phenyl) porphyrin-functionalized CuCoO nanospheres (Por-CuCoO) has been fabricated as an excellent visual biosensor. X-ray diffractometry (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) have been employed to characterize the composition, morphologies, and elemental analysis of the as-synthesized Por-CuCoO. The catalytic activity of Por-CuCoO was evaluated by the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) with the aid of HO, which exhibited a visual blue change with an absorption maximum at 652 nm for only 10 s. The peroxidase-like behaviors of Por-CuCoO conformed to the Michaelis-Menten equation. Electrochemistry, radical scavenger, and fluorescence probe experiments verified that electron transfer, •O radicals, and holes (h) are the important factors during the catalytic oxidation of TMB. Based on the inhibition of dopamine (DA) on TMB oxidation, the Por-CuCoO-based colorimetric biosensor has been successfully constructed for sensitive determination of DA witha detection limit (LOD) of 0.94 μΜ. In addition, colorimetry was validated to detect DA in serum samples with high sensitivity and good selectivity. 5,10,15,20-tetrakis (4-carboxyl phenyl) porphyrin-functionalized urchin-like CuCoO (Por-CuCoO) with excellent peroxidase activity, ascribed to the synergistic effect between •O radicals and holes (h). A fast colorimetric sensor on the basis of Por-CuCoO has been constructed to quantitatively determine dopamine concentration in human serums.
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http://dx.doi.org/10.1007/s00604-021-04819-9DOI Listing
April 2021

Photoelectrochemical thrombin biosensor based on perylene-3,4,9,10-tetracarboxylic acid and Au co-functionalized ZnO nanorods with signal-off quenching effect of [email protected]

Analyst 2021 Feb;146(3):855-863

Shandong Provincial Key Laboratory/Collaborative Innovation Center of Chemical Energy Storage & Novel Cell Technology; College of Chemical and Chemical Engineering, Liaocheng University, Liaocheng 252059, China.

In this work, a thrombin photoelectrochemical aptasensor was reported based on a photoanode of perylene-3,4,9,10-tetracarboxylic acid (PTCA), Au nanoparticle co-functionalized ZnO nanorods (ZnO NRs) and the "signal-off" amplification effect of [email protected] The photocurrent response of the ZnO NRs was improved greatly due to the excellent visible-light photoelectric performance of PTCA and the surface plasmon resonance (SPR) effect of Au nanoparticles. Due to the specific recognition between thrombin and aptamers, the non-conductive complex with a steric hindrance structure blocked the diffusion path of the electron donating ascorbic acid (AA) and then the "signal-off" [email protected] quencher was captured. The quencher blocked the irradiation light toward the ZnO NRs/PTCA/Au electrode and competitively consumed the electron donor AA that could have been involved in the oxidation reaction with photogenerated holes of PTCA, resulting in the further decrease of the photocurrent. Based on the evident photocurrent response of the photoanode and the superior quenching strategies, the detection limit of thrombin is as low as 33 fM with a wide linear detection range from 0.0001 nM to 50 nM. The prepared biosensor also exhibited good specificity, reproducibility and stability, suggesting potential application in thrombin specific detection.
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http://dx.doi.org/10.1039/d0an02167aDOI Listing
February 2021

Association between depressive symptoms and arterial stiffness: a cross-sectional study in the general Chinese population.

BMJ Open 2020 02 28;10(2):e033408. Epub 2020 Feb 28.

Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan, China

Objectives: To determine the independent relationship between depressive symptoms and arterial stiffness in the general Chinese population, and to explore possible interactive factors in the relationship.

Design: A cross-sectional study.

Setting And Participants: Consecutive participants who received routine health physical examination in an affiliated hospital of a comprehensive university in Hunan Province, China, between September 2013 and March 2014 were examined. After exclusion of subjects not meeting the criteria, a total of 1334 subjects aged 22-77 years were recruited for final analysis.

Measures: The Patient Health Questionnaire-9 was employed to assess the degree of depressive symptoms: 0-4 no depressive symptoms, 5-9 mild depressive symptoms and 10-27 moderate to severe depressive symptoms. Brachial-ankle pulse wave velocity (baPWV) was measured to determine arterial stiffness.

Results: There was a slight increase in baPWV across elevated degrees of depressive symptoms (p=0.025). Multivariate linear regression analysis revealed that mild depressive symptoms and moderate to severe depressive symptoms were independently associated with baPWV compared with no depressive symptoms after adjusting for baseline confounders (beta-coefficient: 40.3, 95% CI 6.6 to 74.1; beta-coefficient: 87.7, 95% CI 24.0 to 151.5, respectively). Further stratified analyses indicated that the relationship between degree of depressive symptoms and baPWV was predominant in subjects who had normal or normal-high blood pressure, or combined with hypertension (p for interaction=0.016), or in subjects with diabetes mellitus (p for interaction=0.004), examined in multivariate linear regressions. In addition, after adjustment, a significant association between moderate to severe depressive symptoms and baPWV was also found in female subjects younger than 60 years, although the interactive effect was not significant (p for interaction=0.056).

Conclusions: Depressive symptoms are independently associated with arterial stiffness, especially in subjects whose blood pressures are beyond the optimal range and combined with diabetes mellitus.
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http://dx.doi.org/10.1136/bmjopen-2019-033408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050321PMC
February 2020

Pixelated Carrier Phase-Shifting Shearography Using Spatiotemporal Low-Pass Filtering Algorithm.

Sensors (Basel) 2019 Nov 26;19(23). Epub 2019 Nov 26.

School of Instrument Science and Opto-Electronics Engineering, Hefei University of Technology, Hefei 230009, China.

Shearography has been widely used in non-destructive testing due to its advantages in providing full-field, high precision, real-time measurement. The study presents a pixelated carrier phase-shifting shearography using a pixelated micropolarizer array. Based on the shearography, a series of shearograms are captured and phase maps corresponding to deformation are measured dynamically and continuously. Using the proposed spatiotemporal filtering algorithm in the complex domain, the set of phase maps are simultaneously low-pass filtered in the spatial and temporal domains, resulting in better phase quality than spatial low-pass filtering. By accumulating the temporally adjacent phase, the phase corresponding to large deformation can be evaluated; thus, large deformations can be accurately measured and protected from speckle noise, allowing internal defects to be easily identified. The capability of the proposed shearography is described by theoretical discussions and experiments.
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http://dx.doi.org/10.3390/s19235185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928890PMC
November 2019

Local Application of Semaphorin 3A Combined with Adipose-Derived Stem Cell Sheet and Anorganic Bovine Bone Granules Enhances Bone Regeneration in Type 2 Diabetes Mellitus Rats.

Stem Cells Int 2019 31;2019:2506463. Epub 2019 Jul 31.

State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Implantology, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032 Shaanxi, China.

Bone tissue regeneration is considered to be the optimal solution for bone loss. However, diabetic patients have a greater risk of poor bone healing or bone grafting failure than nondiabetics. The purpose of this study was to investigate the influence of the complexes of an adipose-derived stem cell sheet (ASC sheet) and Bio-Oss® bone granules on bone healing in type 2 diabetes mellitus (T2DM) rats with the addition of semaphorin 3A (Sema3A). The rat ASC sheets showed stronger osteogenic ability than ASCs , as indicated by the extracellular matrix mineralization and the expression of osteogenesis-related genes at mRNA level. An ASC sheet combined with Bio-Oss® bone granules promoted bone formation in T2DM rats as indicated by microcomputed tomography (micro-CT) and histological analysis. In addition, Sema3A promoted the osteogenic differentiation of ASC sheets and local injection of Sema3A promoted T2DM rats' calvarial bone regeneration based on ASC sheet and Bio-Oss® bone granule complex treatment. In conclusion, the local injection of Sema3A and the complexes of ASC sheet and Bio-Oss® bone granules could promote osseous healing and are potentially useful to improve bone healing for T2DM patients.
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http://dx.doi.org/10.1155/2019/2506463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701320PMC
July 2019

Construction and validation of the CRISPR/dCas9-EZH2 system for targeted H3K27Me3 modification.

Biochem Biophys Res Commun 2019 04 20;511(2):246-252. Epub 2019 Feb 20.

Department of Implantation, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China. Electronic address:

Cell phenotypes are closely related to the epigenome, which could be precisely regulated by the targeted manipulation of epigenetic marks. Here, we have successfully produced a targeted histone methylation system, which consists of nuclease-null dCas9 protein, the sgRNA fused with PP7 RNA aptamers and the Enhancer of Zeste Homolog 2 (EZH2) fused to PP7 coat protein (PCP). Guided by the dCas9/sgRNA-PP7, the PCP-EZH2 can specifically target gene loci to catalyze 3 methylation of histone H3 lysine 27, resulting in the inhibition of gene expression. This kind of gene inhibition system is supposed to be highly effective, specific and flexible. As a proof-of-concept study, sgRNA targeting C/ebpα promoter region was designed. In the cells co-infected with the dCas9, sgRNA/C/ebpα-PP7 and PCP-EZH2, the expression of C/ebpα gene was significantly reduced via induction of trimethylation to H3K27 on C/ebpα promoter, with the results epigenetically inherited in the daughter cells. In conclusion, our results successfully established a gene modification system consisting of dCas9/sgRNA-PP7 and PCP-EZH2, providing a robust tool for targeted manipulation of gene epigenetic modification and expression.
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http://dx.doi.org/10.1016/j.bbrc.2019.02.011DOI Listing
April 2019

Systematic Evolution of Ligands by Exosome Enrichment: A Proof-of-Concept Study for Exosome-Based Targeting Peptide Screening.

Adv Biosyst 2019 02 27;3(2):e1800275. Epub 2018 Dec 27.

State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, China.

Selection of a peptide that binds preferentially to targeted cells or tissues is a prerequisite for targeted therapy. Although in vivo phage display is a high-throughput method, it is restricted in identifying target ligands specific for different vascular beds. In this study, the exosomes are repurposed for targeting peptide screening. Briefly, the signal peptide region of Lamp2b (a membrane protein on the exosomes) in the N-terminus is engineered to fuse with 10 aa long random peptides, while the C-terminus of Lamp2b is fused with the MS2 coating protein (MCP). Then, the whole Lamp2b-MCP open reading frame (ORF) is further engineered to harbor a 3'UTR sequence consisting of MS2. The resultant exosomes from engineered Lamp2b-MCP expressing cells display the 10 aa peptides on the outside while containing the genetic information inside. By proof-of-principle experiments, the exosomes with different peptides could preferentially distribute to different tissues besides the spleen and liver. Furthermore, detailed target sequences for different tissues are enriched by rounds of selection. In summary, the established novel targeted peptide screening strategy, namely, "exosome display," has broad applicability, especially for displaying and screening targeted peptides for the cells outside the capillary with condense barriers, like the neurons in the brain.
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http://dx.doi.org/10.1002/adbi.201800275DOI Listing
February 2019

Aldehyde dehydrogenase 2 deficiency promotes atherosclerotic plaque instability through accelerating mitochondrial ROS-mediated vascular smooth muscle cell senescence.

Biochim Biophys Acta Mol Basis Dis 2019 07 11;1865(7):1782-1792. Epub 2018 Oct 11.

Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital, Fudan University Shanghai 200032, China. Electronic address:

Previous evidence has indicated a beneficial role for aldehyde dehydrogenase 2 (ALDH2) in suppressing atherosclerotic plaque progression and instability. However, the underlying mechanism remains somewhat elusive. This study was designed to examine the effect of ALDH2 deficiency on high-cholesterol diet-induced atherosclerotic plaque progression and plaque vulnerability in atherosclerosis-prone ApoE knockout (ApoE) mice with a focus on foam cell formation in macrophages and senescence of vascular smooth muscle cells (VSMCs). Serum lipid profile, plaque progression, and plaque vulnerability were examined in ApoE and ALDH2/ApoE double knockout (ALDH2ApoE) mice after high-cholesterol diet intake for 8 weeks. ALDH2 deficiency increased the serum levels of triglycerides while it decreased levels of total cholesterol and high-density lipoprotein cholesterol. Unexpectedly, ALDH2 deficiency reduced the plaque area by 58.9% and 37.5% in aorta and aortic sinus, respectively. Plaque instability was aggravated by ALDH2 deficiency along with the increased necrotic core size, decreased collagen content, thinner fibrous cap area, decreased VSMC content, and increased macrophage content. In atherosclerotic lesions, ALDH2 protein was located in both macrophages and VSMCs. Further results revealed downregulated ALDH2 expression in aorta of aged ApoE mice compared with young mice. However, in vitro study suggested that ALDH2 expression was upregulated in bone marrow-derived macrophages (BMDMs) with an opposite effect in VSMCs following 80 μg/ml oxidized low-density lipoprotein (oxLDL) treatment. Interestingly, ALDH2 deficiency displayed little effect in oxLDL-induced foam cell formation from BMDMs, while ALDH2 knockdown by siRNA and ALDH2 overexpression by lentivirus infection promoted and retarded oxLDL-induced VSMC senescence, respectively. Mechanistically, ALDH2 mitigated oxLDL-induced overproduction of mitochondrial reactive oxygen species (mROS) and activation of downstream p53/p21/p16 pathway. Clearance of mROS by mitoTEMPO significantly reversed the promotive effect of ALDH2 knockdown on VSMC senescence. Taken together, our data revealed that ALDH2 deficiency suppressed atherosclerotic plaque area while facilitating plaque instability possibly through accelerating mROS-mediated VSMC senescence. This article is part of a Special Issue entitled: Genetic and epigenetic regulation of aging and longevity edited by Jun Ren & Megan Yingmei Zhang.
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http://dx.doi.org/10.1016/j.bbadis.2018.09.033DOI Listing
July 2019

Correlations of DAPT score and PRECISE-DAPT score with the extent of coronary stenosis in acute coronary syndrome.

Medicine (Baltimore) 2018 Sep;97(39):e12531

Department of Cardiology, Xiangya Hospital, Central South University, Changsha, China.

Dual antiplatelet therapy (DAPT) score and PRECISE-DAPT score were recommended for decision making of optimal DAPT in discriminating the risk of thrombosis and bleeding. But the relationships between 2 scoring tools with the extent of coronary stenosis have not been established.We retrospectively enrolled 359 patients of acute coronary syndrome (ACS) who received percutaneous coronary intervention. Both DAPT score and PRECISE-DAPT score were calculated, and patients were divided by their recommended cut-offs. Gensini score and triple-vessel disease (3-VD) were chosen to evaluate the severity of coronary stenosis.Overall, 54.9% and 10.0% of the patients had higher DAPT score (≥2) or PRECISE-DAPT score (≥25). Patients with higher DAPT score had increased stent counts, total length of stents, Gensini score, and proportion of 3-VD, but decreased minimum diameter of stent. But these differences were not found in PRECISE-DAPT subgroups. When divided into quartiles of both scoring systems, the highest Gensini score and proportions of 3-VD were found in the fourth quartile of both DAPT score and PRECISE-DAPT score. Moreover, both DAPT score and PRECISE-DAPT score were independent risk factors of Gensini score after adjustment (P < .001 and P = .047). Furthermore, an increase of 1 point of DAPT score and 5 points of PRECISE-DAPT score resulted by 51% (odds ratios [OR]: 1.51, 95% confidence interval [CI]:1.19-1.91, P = .001) and 34% (OR: 1.34, 95% CI: 1.11-1.62, P = .003) increase in risk of 3-VD after adjustment.Both DAPT score and PRECISE-DAPT score were independently associated with the degree of coronary stenosis in patients with ACS.
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http://dx.doi.org/10.1097/MD.0000000000012531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181461PMC
September 2018

Delivery of antagomiR204-conjugated gold nanoparticles from PLGA sheets and its implication in promoting osseointegration of titanium implant in type 2 diabetes mellitus.

Int J Nanomedicine 2017 26;12:7089-7101. Epub 2017 Sep 26.

State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Implant Dentistry.

Impaired osseointegration of the implant remains the big hurdle for dental implant therapy in diabetic patients. In this study, the authors first identified that miR204 was strikingly highly expressed in the bone mesenchymal stem cells (BMSCs) of diabetic rats. Forced expression of miR204 repressed the osteogenic potential of BMSCs, while inhibition of miR204 significantly increased the osteogenic capacity. Moreover, the miR204 inhibitor was conjugated with gold nanoparticles (AuNP-antagomiR204) and dispersed them in the poly(lactic-co-glycolic acid) (PLGA) solution. The AuNP-antagomiR204 containing PLGA solution was applied for coating the surface of titanium implant. Electron microscope revealed that an ultrathin sheet was formed on the surface of the implant, and the AuNPs were evenly dispersed in the coated PLGA sheet. Cellular experiments revealed that these encapsulated AuNP-antagomiR204 were able to be released from the PLGA sheet and uptaken by adherent BMSCs. In vivo animal study further confirmed that the AuNP-antagomiR204 released from PLGA sheet promoted osseointegration, as revealed by microcomputerized tomography (microCT) reconstruction and histological assay. Taken together, this study established that miR204 misexpression accounted for the deficient osseointegation in diabetes mellitus, while PLGA sheets aided the release of AuNP-antagomiR204, which would be a promising strategy for titanium implant surface functionalization toward better osseointegration.
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http://dx.doi.org/10.2147/IJN.S124584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5627761PMC
January 2018

The influence of direct laser metal sintering implants on the early stages of osseointegration in diabetic mini-pigs.

Int J Nanomedicine 2017 31;12:5433-5442. Epub 2017 Jul 31.

State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Xi'an, Shaanxi, China.

Background: High failure rates of oral implants have been reported in diabetic patients due to the disruption of osseointegration. The aim of this study was to investigate whether direct laser metal sintering (DLMS) could improve osseointegration in diabetic animal models.

Methods: Surface characterizations were carried out on two types of implants. Cell morphology and the osteogenic-related gene expression of MG63 cells were observed under conditions of DLMS and microarc oxidation (MAO). A diabetes model in mini-pigs was established by intravenous injection of streptozotocin (150 mg/kg), and a total of 36 implants were inserted into the mandibular region. Micro-computed tomography (micro-CT) and histologic evaluations were performed 3 and 6 months after implantation.

Results: The Ra (the average of the absolute height of all points) of MAO surface was 2.3±0.3 µm while the DLMS surface showed the Ra of 27.4±1.1 µm. The cells on DLMS implants spread out more podia than those on MAO implants through cell morphology analysis. Osteogenic-related gene expression was also dramatically increased in the DLMS group. Obvious improvement was observed in the micro-CT and Van Gieson staining analyses of DLMS implants compared with MAO at 3 months, although this difference disappeared by 6 months. DLMS implants showed a higher bone-implant contact percentage (33.2%±11.2%) at 3 months compared with MAO group (18.9%±7.3%) while similar results were showed at 6 months between DLMS group (42.8%±10.1%) and MAO group (38.3%±10.8%).

Conclusion: The three-dimensional environment of implant surfaces with highly porous and fully interconnected channel and pore architectures can improve cell spreading and accelerate the progress of osseointegration in diabetic mini-pigs.
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http://dx.doi.org/10.2147/IJN.S138615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546787PMC
February 2018

Mitochondrial aldehyde dehydrogenase-2 deficiency compromises therapeutic effect of ALDH bright cell on peripheral ischemia.

Redox Biol 2017 10 29;13:196-206. Epub 2017 May 29.

Institute of Biomedical Science, Fudan University, Shanghai 200032, China; Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai 200032, China. Electronic address:

The autologous ALDH bright (ALDH) cell therapy for ischemic injury is clinically safe and effective, while the underlying mechanism remains elusive. Here, we demonstrated that the glycolysis dominant metabolism of ALDH cells is permissive to restore blood flow in an ischemic hind limb model compared with bone marrow mononuclear cells (BMNCs). PCR array analysis showed overtly elevated Aldh2 expression of ALDH cells following hypoxic challenge. Notably, ALDH cells therapy induced blood flow recovery in this model was reduced in case of ALDH2 deficiency. Moreover, significantly reduced glycolysis flux and increased reactive oxygen species (ROS) levels were detected in ALDH cell from Aldh2-/- mice. Compromised effect on blood flow recovery was also noticed post transplanting the human ALDH cell from ALDH2 deficient patients (GA or AA genotypes) in this ischemic hindlimb mice model. Taken together, our findings illustrate the indispensable role of ALDH2 in maintaining glycolysis dominant metabolism of ALDH cell and advocate that patient's Aldh2 genotype is a prerequisite for the efficacy of ALDH cell therapy for peripheral ischemia.
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http://dx.doi.org/10.1016/j.redox.2017.05.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458766PMC
October 2017

Sedentary lifestyle related exosomal release of Hotair from gluteal-femoral fat promotes intestinal cell proliferation.

Sci Rep 2017 03 31;7:45648. Epub 2017 Mar 31.

Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, 710032, China.

Pioneering epidemiological work has established strong association of sedentary lifestyle and obesity with the risk of colorectal cancer, while the detailed underlying mechanism remains unknown. Here we show that Hotair (HOX transcript antisense RNA) is a pro-adipogenic long non-coding RNA highly expressed in gluteal-femoral fat over other fat depots. Hotair knockout in adipose tissue results in gluteal-femoral fat defect. Squeeze of the gluteal-femoral fat induces intestinal proliferation in wildtype mice, while not in Hotair knockout mice. Mechanistically, squeeze of the gluteal-femoral fat induces exosomal Hotair secretion mainly by transcriptional upregulation of Hotair via NFκB. And increased exosomal Hotair in turn circulates in the blood and is partially endocytosed by the intestine, finally promoting the stemness and proliferation of intestinal stem/progenitor cells via Wnt activation. Clinically, obese subjects with sedentary lifestyle have much higher exosomal HOTAIR expression in the serum. These findings establish that sedentary lifestyle promotes exosomal Hotair release from the gluteal-femoral fat, which in turn facilitates intestinal stem and/or progenitor proliferation, raising a possible link between sedentary lifestyle with colorectal tumorigenesis.
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http://dx.doi.org/10.1038/srep45648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374500PMC
March 2017

Osteogenic activity of titanium surfaces with hierarchical micro-/nano-structures obtained by hydrofluoric acid treatment.

Int J Nanomedicine 2017 16;12:1317-1328. Epub 2017 Feb 16.

State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Disease & Shaanxi Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an.

An easier method for constructing the hierarchical micro-/nano-structures on the surface of dental implants in the clinic is needed. In this study, three different titanium surfaces with microscale grooves (width 0.5-1, 1-1.5, and 1.5-2 μm) and nanoscale nanoparticles (diameter 20-30, 30-50, and 50-100 nm, respectively) were obtained by treatment with different concentrations of hydrofluoric acid (HF) and at different etching times (1%, 3 min; 0.5%, 12 min; and 1.5%, 12 min, respectively; denoted as groups HF1, HF2, and HF3). The biological response to the three different titanium surfaces was evaluated by in vitro human bone marrow-derived mesenchymal stem cell (hBMMSC) experiments and in vivo animal experiments. The results showed that cell adhesion, proliferation, alkaline phosphatase activity, and mineralization of hBMMSCs were increased in the HF3 group. After the different surface implants were inserted into the distal femurs of 40 rats, the bone-implant contact in groups HF1, HF2, and HF3 was 33.17%±2.2%, 33.82%±3.42%, and 41.04%±3.08%, respectively. Moreover, the maximal pullout force in groups HF1, HF2, and HF3 was 57.92±2.88, 57.83±4.09, and 67.44±6.14 N, respectively. The results showed that group HF3 with large micron grooves (1.5-2.0 μm) and large nanoparticles (50-100 nm) showed the best bio-functionality for the hBMMSC response and osseointegration in animal experiments compared with other groups.
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http://dx.doi.org/10.2147/IJN.S123930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5317262PMC
April 2017

A decomposable silica-based antibacterial coating for percutaneous titanium implant.

Int J Nanomedicine 2017 6;12:371-379. Epub 2017 Jan 6.

State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Oral Implants, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China.

Although percutaneous titanium implants have become one of the best choices as retainers in the facial defects, peri-implantitis still occurs at a significant rate. This unwanted complication occurs due to adhesion of bacteria and subsequent biofilm formation. To solve this problem, we have developed a novel antibiotic nanodelivery system based on self-decomposable silica nanoparticles. In this study, silica-gentamycin (SG) nanoparticles were successfully fabricated using an innovative one-pot solution. The nanoparticles were incorporated within a gelatin matrix and cross-linked on microarc-oxidized titanium. To characterize the SG nanoparticles, their particle size, zeta potential, surface morphology, in vitro drug release, and decomposition process were sequentially evaluated. The antibacterial properties against the gram-positive , including bacterial viability, antibacterial rate, and bacteria morphology, were analyzed using SG-loaded titanium specimens. Any possible influence of released gentamycin on the viability of human fibroblasts, which are the main component of soft tissues, was investigated. SG nanoparticles from the antibacterial titanium coating continuously released gentamycin and inhibited growth. In vitro investigation showed that the obtained nanodelivery system has good biocompatibility. Therefore, this design can be further investigated as a method to prevent infection around percutaneous implants.
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http://dx.doi.org/10.2147/IJN.S123622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5229168PMC
March 2017

Mitochondrial aldehyde dehydrogenase 2 deficiency aggravates energy metabolism disturbance and diastolic dysfunction in diabetic mice.

J Mol Med (Berl) 2016 11 3;94(11):1229-1240. Epub 2016 Aug 3.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Fenglin Road 180, Shanghai, 200032, People's Republic of China.

Diabetes causes energy metabolism disturbance and may lead to cardiac dysfunction. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) protects cardiac function from myocardial damage. Therefore, understanding of its roles in diabetic heart is critical for developing new therapeutics targeting ALDH2 and mitochondrial function for diabetic hearts. This study investigated the impact of ALDH2 deficiency on diastolic function and energy metabolism in diabetic mice. Diabetes was induced in ALDH2 knockout and wild-type mice by streptozotocin. Cardiac function was determined by echocardiography. Glucose uptake, energy status, and metabolic profiles were used to evaluate cardiac energy metabolism. The association between ALDH2 polymorphism and diabetes was also analyzed in patients. Echocardiography revealed preserved systolic function and impaired diastolic function in diabetic ALDH2-deficient mice. Energy reserves (phosphocreatine/adenosine triphosphate ratio) were reduced in the diabetic mutants and were associated with diastolic dysfunction. Western blot analysis showed that diabetes induces accumulated lipid peroxidation products and escalated AMP-activated protein kinase-LKB1 pathway. Further, ALDH2 deficiency exacerbated the diabetes-induced deficient myocardial glucose uptake and other perturbations of metabolic profiles. Finally, ALDH2 mutations were associated with worse diastolic dysfunction in diabetic patients. Together, our results demonstrate that ALDH2 deficiency and resulting energy metabolism disturbance is a part of pathology of diastolic dysfunction of diabetic hearts, and suggest that patients with ALDH2 mutations are vulnerable to diabetic damage.

Key Message: ALDH2 deficiency exacerbates diastolic dysfunction in early diabetic hearts. ALDH2 deficiency triggers decompensation of metabolic reserves and energy metabolism disturbances in early diabetic hearts. ALDH2 deficiency potentiates oxidative stress and AMPK phosphorylation induced by diabetes via post-translational regulation of LKB1. Diabetic patients with ALDH2 mutations are predisposed to worse diastolic dysfunction.
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http://dx.doi.org/10.1007/s00109-016-1449-5DOI Listing
November 2016

Semaphorin 3A Shifts Adipose Mesenchymal Stem Cells towards Osteogenic Phenotype and Promotes Bone Regeneration In Vivo.

Stem Cells Int 2016 19;2016:2545214. Epub 2016 Sep 19.

State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Implant Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an 710032, China.

Adipose mesenchymal stem cells (ASCs) are considered as the promising seed cells for bone regeneration. However, the lower osteogenic differentiation capacity limits its therapeutic efficacy. Identification of the key molecules governing the differences between ASCs and BMSCs would shed light on manipulation of ASCs towards osteogenic phenotype. In this study, we screened semaphorin family members in ASCs and BMSCs and identified Sema3A as an osteogenic semaphorin that was significantly and predominantly expressed in BMSCs. The analyses in vitro showed that the overexpression of Sema3A in ASCs significantly enhanced the expression of bone-related genes and extracellular matrix calcium deposition, while decreasing the expression of adipose-related genes and thus lipid droplet formation, resembling a BMSCs phenotype. Furthermore, Sema3A modified ASCs were then engrafted into poly(lactic-co-glycolic acid) (PLGA) scaffolds to repair the critical-sized calvarial defects in rat model. As expected, Sema3A modified ASCs encapsulation significantly promoted new bone formation with higher bone volume fraction and bone mineral density. Additionally, Sema3A was found to simultaneously increase multiple Wnt related genes and thus activating Wnt pathway. Taken together, our study here identifies Sema3A as a critical gene for osteogenic phenotype and reveals that Sema3A-modified ASCs would serve as a promising candidate for bettering bone defect repair.
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http://dx.doi.org/10.1155/2016/2545214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5046026PMC
September 2016

Aldehyde Dehydrogenase-2 Roles in Ischemic Cardiovascular Disease.

Curr Drug Targets 2017 ;18(15):1817-1823

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China.

Background: Coronary heart disease is the leading cause of mortality and morbidity, incurring a major burden of medical care. Even with increasing application of emergent recanalization (PCI and CABG) therapy, ischemia and ischemic reperfusion injury remain as the dominant pathological process that damages cardiomyocytes. Mitochondrial Aldehyde dehydrogenase-2 (ALDH2) is a multifunctional enzyme catalyzing the oxidation of aldehydes.

Objective: Accumulating data have shown that ALDH2 can help restore mitochondria function by eliminating toxic aldehyde and participating in cellular signaling important for cell adaption and survival. This article reviews the biology and pathobiology roles of ALDH2 in the ischemic cardiovascular disease, focusing on the genetic evidence associated with the oriental patients.

Conclusion: The ALDH2*2 mutant allele (deficiency genotype) is present in nearly half of the East Asian population. Development of a safe way to restore ALDH2 function in this population thus has unique clinical implication.
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http://dx.doi.org/10.2174/1389450117666160912174417DOI Listing
June 2018

Trans-Fatty Acids Aggravate Obesity, Insulin Resistance and Hepatic Steatosis in C57BL/6 Mice, Possibly by Suppressing the IRS1 Dependent Pathway.

Molecules 2016 May 30;21(6). Epub 2016 May 30.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.

Trans-fatty acid consumption has been reported as a risk factor for metabolic disorders and targeted organ damages. Nonetheless, little is known about the roles and mechanisms of trans-fatty acids in obesity, insulin resistance (IR) and hepatic steatosis. Adult C57BL/6 male mice were fed with four different diets for 20 weeks: normal diet (ND), high fat diet (HFD), low trans-fatty acids diet (LTD) and high trans-fatty acid diet (HTD). The diet-induced metabolic disorders were assessed by evaluating body weight, glucose tolerance test, hepatic steatosis and plasma lipid profiles post 20-week diet. Histological (H&E, Oil-Red-O) staining and western blot analysis were employed to assess liver steatosis and potential signaling pathways. After 20-weeks of diet, the body weights of the four groups were 29.61 ± 1.89 g (ND), 39.04 ± 4.27 g (HFD), 34.09 ± 2.62 g (LTD) and 43.78 ± 4.27 g (HTD) (p < 0.05), respectively. HFD intake significantly impaired glucose tolerance, which was impaired further in the mice consuming the HTD diet. The effect was further exacerbated by HTD diet. Moreover, the HTD group exhibited significantly more severe liver steatosis compared with HFD group possibly through regulating adipose triglyceride lipase. The group consuming the HTD also exhibited significantly reduced levels of IRS1, phosphor-PKC and phosphor-AKT. These results support our hypothesis that consumption of a diet high in trans-fatty acids induces higher rates of obesity, IR and hepatic steatosis in male C57BL/6 mice, possibly by suppressing the IRS1dependent pathway.
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http://dx.doi.org/10.3390/molecules21060705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273562PMC
May 2016

Mitochondrial Aldehyde Dehydrogenase 2 Regulates Revascularization in Chronic Ischemia: Potential Impact on the Development of Coronary Collateral Circulation.

Arterioscler Thromb Vasc Biol 2015 Oct 27;35(10):2196-206. Epub 2015 Aug 27.

From the Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital (X.L., H.Z., P.W., L.S., L.X., C.S., F.F., C.W., K.H., Y.Z., J.G., J.R., A.S.), Institute of Biomedical Science (X.S., L.X., X.M., Y.Z., J.G., A.S.), Department of Cardiology, Huashan Hospital (Z.D.), Fudan University, Shanghai, P.R. China; Center for Cardiovascular Research and Alternative Medicine, School of Pharmacy, University of Wyoming College of Health Sciences, Laramie (X.L., J.R.); Dongfang Hospital, Tongji University, Shanghai, P.R. China (H.L.); and Department of Cardiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China (J.Z.).

Objective: Revascularization is an essential process to compensate for cardiac underperfusion and, therefore, preserves cardiac function in the face of chronic ischemic injury. Recent evidence suggested a vital role of aldehyde dehydrogenase 2 (ALDH2) in cardiac protection after ischemia. This study was designed to determine whether ALDH2 regulates chronic ischemia-induced angiogenesis and to explore the underlying mechanism involved. Moreover, the clinical impact of the ALDH2 mutant allele on the development of coronary collateral circulation (CCC) was evaluated.

Approach And Results: Mice limb ischemia was performed. Compared with wild-type, ALDH2 deletion significantly reduced perfusion recovery, small artery and capillary density, and increased muscle atrophy in this ischemic model. In vitro, ALDH2-knockdown reduced proliferation, migration and hypoxia triggered endothelial tube formation of endothelial cells, the effects of which were restored by ALDH2 transfection. Further examination revealed that ALDH2 regulated angiogenesis possibly through hypoxia-inducible factor-1α/vascular endothelial growth factor pathways. To further discern the role of ALDH2 deficiency in the function of bone marrow stem/progenitor cells, cross bone marrow transplantation was performed between wild-type and ALDH2-knockout mice. However, there was no significant improvement for wild-type bone marrow transplantation into knockout mice. ALDH2 genotyping was screened in 139 patients with chronic total occlusion recruited to Zhongshan Hospital (2011.10-2014.4). Patients with poor CCC (Rentrop 0-1; n=51) exhibited a higher frequency of the AA genotype than those with enriched CCC (Rentrop 2-3; n=88; 11.76% versus 1.14%; P=0 0.01). However, the AA group displayed less enriched CCC frequency in Logistic regression model when compared with the GG group (odds ratio=0.08; 95% confidence interval, 0.009-0.701; P=0 0.026). Furthermore, serum vascular endothelial growth factor level tended to be lower in patients with ALDH2 mutation.

Conclusions: This study demonstrated that ALDH2 possesses an intrinsic capacity to regulate angiogenesis via hypoxia-inducible factor-1α and vascular endothelial growth factor. Patients with ALDH2-deficient genotype displayed a higher risk of developing poor CCC. Therapeutic individualization based on ALDH2 allele distribution may thus improve the therapeutic benefit, especially in the East Asian decedents.
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http://dx.doi.org/10.1161/ATVBAHA.115.306012DOI Listing
October 2015

Aberrant hypermethylation of aldehyde dehydrogenase 2 promoter upstream sequence in rats with experimental myocardial infarction.

Biomed Res Int 2015 5;2015:503692. Epub 2015 Jan 5.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China ; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

Background: Aldehyde dehydrogenase 2 (ALDH2) plays a crucial role in myocardial protection against ischemia. Downregulation of ALDH2 was evidenced after myocardial infarction and the underlying mechanism is not fully understood. DNA methylation can regulate gene transcription in epigenetic level. We thus hypothesized that DNA methylation may affect ALDH2 expression in myocardial infarction (MI).

Methods: MI was induced in Sprague-Dawley rats. MI border zone tissues were harvested at 1st week, 2nd week, and 3rd week after MI. Bisulfite sequencing PCR (BSP) was performed to detect the methylation levels of ALDH2 core promoter. Sequenom MassARRAY platform (MassARRAY) was used to examine the methylation levels of ALDH2 promoter upstream sequence. ALDH2 protein and mRNA expression were assayed by Western blot and real-time PCR, respectively.

Results: Compared with Sham group, ALDH2 protein and mRNA expression of MI groups was significantly downregulated. Compared with Sham group, DNA methylation level of CpG sites in ALDH2 promoter upstream sequence was significantly higher in MI groups in a time-dependent manner (CpG1, CpG2, and CpG7, P < 0.01). DNA methylation did not affect ALDH2 core promoter sequence during the progress of MI. No significant difference was detected in DNA methylation level of ALDH2 promoter upstream sequence among MI groups.

Conclusion: Aberrant hypermethylation of CpG sites in ALDH2 promoter upstream sequence is associated with myocardial ischemia injury and may partly result in ALDH2 downregulation after MI.
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http://dx.doi.org/10.1155/2015/503692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4299765PMC
October 2015

Acetaldehyde dehydrogenase 2 (ALDH2) deficiency exacerbates pressure overload-induced cardiac dysfunction by inhibiting Beclin-1 dependent autophagy pathway.

Biochim Biophys Acta 2015 Feb 30;1852(2):310-8. Epub 2014 Jul 30.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China; Institute of Biomedical Science, Fudan University, Shanghai 200032, China.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) was demonstrated to play cardioprotective roles in cardiovascular diseases. Nonetheless, little is known about the roles and mechanisms of ALDH2 in pressure overload-induced cardiac damages. In this study, we revealed that ALDH2 deficiency overtly exacerbated transverse aortic constriction (TAC)-induced cardiac dysfunction. Cardiomyocyte enlargement was observed in both WT and ALDH2-/- mice in HE-stained myocardial tissue samples at 8 weeks post TAC surgery. Mitochondrial morphology and structure were also significantly damaged post TAC surgery and the changes were aggravated in ALDH2-/- TAC hearts. ALDH2 deficiency also depressed myocardial autophagy in hearts at 8 weeks post TAC surgery with a potential mechanism of repressing the expression of Beclin-1 and promoting the interaction between Bcl-2 and Beclin-1. These data indicate that ALDH2 deficiency exacerbates the pressure overload induced cardiac dysfunction partly by inhibiting Beclin-1 dependent autophagy pathway. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.
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http://dx.doi.org/10.1016/j.bbadis.2014.07.014DOI Listing
February 2015

Naoxintong protects against atherosclerosis through lipid-lowering and inhibiting maturation of dendritic cells in LDL receptor knockout mice fed a high-fat diet.

Curr Pharm Des 2013 ;19(33):5891-6

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai 200032,PR China. ;

Naoxintong (NXT), a Chinese Materia Medica standardized product, extracted from 16 various kinds of Chinese traditional herbal medicines including Salvia miltiorrhiza, Angelica sinennsis, Astragali Radix, is clinically effective in treating atherosclerosisrelated diseases. Here, we tested the hypothesis that the anti-atherosclerosis effects of NXT might be mediated by suppressing maturation of dendritic cells (DCs) in a mice model of atherosclerosis. LDLR(-/-) mice fed a high-fat diet were treated with placebo, NXT (0.7 g/kg/d, oral diet) or simvastatin (100mg/kg/d, oral diet) for 8 weeks, respectively. NXT treatment significantly reduced plasma triglyceride (112 ± 18 mg/dl vs. 192 ± 68 mg/dl, P<0.05) and total cholesterol (944 ± 158 mg/dl vs. 1387 ± 208 mg/dl, P<0.05) compared to placebo treatment. Vascular lesions were significantly smaller and macrophage content and amount of DCs in plaques were significantly less in NXT and simvastatin groups than in placebo group (all P<0.05). In addition, expressions of splenic DC membrane molecules (CD40, CD86 and CD80) and the plasma level of IL-12p70 were significantly lower in NXT and simvastatin groups than in placebo group. In conclusion, NXT protects against atherosclerosis through lipid-lowering and inhibiting DCs maturation in this mice model of atherosclerosis.
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http://dx.doi.org/10.2174/1381612811319330008DOI Listing
April 2014

MicroRNA-34a promotes cardiomyocyte apoptosis post myocardial infarction through down-regulating aldehyde dehydrogenase 2.

Curr Pharm Des 2013 ;19(27):4865-73

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, PR China.

MicroRNA-34a (miR-34a) promotes apoptosis via down-regulating many anti-apoptotic proteins. Aldehyde dehydrogenase 2 (ALDH2) is an anti-apoptotic enzyme whose activity decline associates with myocardial injury. We tested hypothesis that miR-34a might play a pro-apoptotic role in myocardial infarction (MI) by down-regulating ALDH2. MiR-34a was highly increased while ALDH2 expression was decreased after experimental MI. Overexpression of miR-34a in neonatal rat cardiomyocyte could significantly enhance apoptosis and down-regulate ALDH2 expression. In 293 cells, luciferase reporter assay results demonstrated that ALDH2 was a direct target of miR-34a. Serum miR-34a levels in acute myocardial infarction (AMI) patients and rats were significantly higher than healthy subjects and sham rats. Our results proved that miR-34a could promote cardiomyocyte apoptosis via negatively regulating ALDH2 and circulating miR-34a was increased in the condition of MI. Thus, miR-34a may constitute a new therapeutic target and diagnostic marker for patients with MI.
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http://dx.doi.org/10.2174/13816128113199990325DOI Listing
February 2014

Gene silencing by adenovirus-delivered siRNA.

FEBS Lett 2003 Mar;539(1-3):111-4

Department of Nuclear Medicine, University of Ulm, Robert-Koch-Strasse 8, D-89070 Ulm, Germany.

RNA interference is the process that double-stranded RNA induces the homology-dependent degradation of cognate mRNA mediated by 21-23 nucleotide short interfering RNA (siRNA). Here, we describe a simple virus vector for efficient delivery of siRNA into mammalian cells utilizing the well-defined H1-RNA promoter and conventional adenovirus. In this pilot study, p53 was targeted by this vector. Our results demonstrate efficient and specific knock-down of p53 in breast cancer MCF-7 and lung carcinoma A549 cells and indicate a prospective application of this siRNA expressing recombinant adenovirus system in functional genomics, cancer gene therapy and virus inhibition.
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http://dx.doi.org/10.1016/s0014-5793(03)00209-6DOI Listing
March 2003
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