Publications by authors named "Xiaoliang Yang"

56 Publications

CD151 enrichment in exosomes of luminal androgen receptor breast cancer cell line contributes to cell invasion.

Biochimie 2021 Jun 23;189:65-75. Epub 2021 Jun 23.

Laboratory of Theoretical and Computational Nanoscience, CAS Key Laboratory of Nanophotonic Materials and Devices, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Ambient Particles Health Effects and Prevention Techniques, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100190, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China; Sino-Danish Center for Education and Research, University of Chinese Academy of Sciences, Beijing, 100190, PR China. Electronic address:

Breast cancer is the most common and highly heterogeneous disease in women worldwide. Given the challenges in the treatment of advanced metastatic breast cancer, it is necessary to understand the molecular mechanisms related to disease progression. Exosomes play various roles in the progression of tumors, including promoting the invasion and advancing the distant metastasis. To study the molecular mechanisms related to the progression of luminal androgen receptor (LAR) breast cancer, we first isolated exosomes of MDA-MB-453 cells, a representative cell line of LAR. Through quantitative proteomic analysis, we identified 180 proteins specifically enriched in exosomes after comparing with those in cells, microvesicles, and the 150K supernatant. Among these, CD151, a protein involved in the regulation of cell motility was the most enriched one. CD151-knockdown exosomes reduced the invasion ability of the recipient breast cancer cell and lowered the phosphorylation level of tyrosine-protein kinase Lck, indicating that the invasion of LAR breast cancer may be due to CD151-enriched exosomes. Our work reports for the first time that CD151 was highly abundant in the exosomes of MDA-MB-453 cells and expands the understanding of the development process of LAR subtype, suggesting CD151 may be a potential candidate for the treatment of LAR breast cancer.
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http://dx.doi.org/10.1016/j.biochi.2021.06.007DOI Listing
June 2021

Identification and Expression Analyses of the Special 14-3-3 Gene Family in Papaya and its Involvement in Fruit Development, Ripening, and Abiotic Stress Responses.

Biochem Genet 2021 May 19. Epub 2021 May 19.

Key Laboratory of Biology and Genetic Resources of Tropical Crops, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou, 571101, Hainan, China.

Plant 14-3-3 proteins play key roles in regulating growth, development, and stress responses. However, little is known about this gene family in papaya (Carica papaya L.). We characterized eight 14-3-3 genes from the papaya genome and designed them as CpGRF1-8. Based on phylogenetic, conserved motif, and gene structure analyses, papaya CpGRFs were divided into ε and non-ε groups. Expression analysis showed differential and class-specific transcription patterns in different organs. Quantitative real-time polymerase chain reaction analysis showed that most CpGRFs had large changes in expression during fruit development and ripening. This indicated that the CpGRFs were involved in regulating fruit development and ripening. Significant expression changes occurred after cold, salt, and drought treatments in papaya seedlings, indicating that CpGRFs were also involved in signaling responses to abiotic stress. These results provide a transcription profile of 14-3-3 genes in organs, during fruit development and ripening and in response to stress. Some highly expressed, fruit-specific, and stress-responsive candidate CpGRFs will be identified for further genetic improvement of papayas.
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http://dx.doi.org/10.1007/s10528-021-10077-4DOI Listing
May 2021

Advances in the pathophysiology of atopic dermatitis revealed by novel therapeutics and clinical trials.

Pharmacol Ther 2021 Aug 2;224:107830. Epub 2021 Mar 2.

Department of Dermatology, Kyoto University Graduate School of Medicine, Japan.

Atopic dermatitis (AD) is an inflammatory skin disease arising from a complex interplay of genetic, immune, and environmental factors. The development and successful marketing of the anti-IL-4/IL-13 monoclonal antibody, dupilumab, and the topical nonsteroidal phosphodiesterase 4 (PDE4) inhibitor, crisaborole, as well as the Janus kinase (JAK) inhibitor, delgocitinib, have brought hope for developing new therapeutic agents. The efficacy of these treatments contributes to our understanding of the pathophysiology of AD. Dupilumab modulates the Th2-related immune response, demonstrating that IL-4 and IL-13 contribute to epidermal hyperplasia, skin homeostasis, and innate immune responses on the skin surface in AD. The effectiveness of crisaborole reveals that PDE4 contributes to Th2 and Th17/Th22 inflammation and lesional skin barrier dysfunction, while delgocitinib shows that JAK-associated signaling is essential for the inflammatory reaction in AD. This review provides a brief overview of recent research on therapeutic monoclonal antibodies and small biologic molecules for AD and what these treatments reveal about AD pathophysiology.
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http://dx.doi.org/10.1016/j.pharmthera.2021.107830DOI Listing
August 2021

Hypoglossal Nerve Lesions: The Role of a 3D IR-Prepped Fast SPGR High-Resolution 3T MRI Sequence.

J Neuroimaging 2021 01 30;31(1):180-185. Epub 2020 Jul 30.

Department of Radiology, Wuxi Huishan People's Hospital, Wuxi, Jiangsu, China.

Background And Purpose: To assess a 3D high-resolution IR-prepped fast SPGR high-resolution MRI sequence for evaluating hypoglossal nerve lesions.

Methods: The clinical data of 8 patients with hypoglossal nerve lesions admitted from December 2011 to February 2016 were retrospectively analyzed. MRI included contrast-enhanced conventional sequences and a 3D IR-prepped fast SPGR high-resolution T1-weighted (BRAVO) MRI sequence at 3T.

Results: Eight patients had hypoglossal lesions detected by MRI. Conventional enhanced scanning could not clearly display the hypoglossal nerve and canal, while the enhanced 3D high-resolution sequence could. In addition, multiple planar reconstruction clearly displayed the hypoglossal nerve, hypoglossal canal, and lesions in multiple planes.

Conclusions: Compared with conventional MRI, we show superior results from an advanced sequence to improve image quality in characterizing hypoglossal nerve lesions.
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http://dx.doi.org/10.1111/jon.12762DOI Listing
January 2021

DFT-Calculated IR Spectrum Amide I, II, and III Band Contributions of -Methylacetamide Fine Components.

ACS Omega 2020 Apr 8;5(15):8572-8578. Epub 2020 Apr 8.

School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China.

The infrared spectrum (IR) characteristic peaks of amide I, amide II, and amide III bands are marked as amide or peptide characteristic peaks. Through the nuclear magnetic resonance study, -methylacetamide has been determined to have six fine components, which include protonation, hydration, and hydroxy structures. Then the independent IR spectrum of every component in -methylacetamide is calculated by using the density functional theory quantum chemistry method, and the contribution of each component to amide I, II, and III bands is analyzed. The results of this research can help to explain the formation of the amide infrared spectrum, which has positive significance in organic chemistry, analytical chemistry, and chemical biology.
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http://dx.doi.org/10.1021/acsomega.9b04421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178369PMC
April 2020

Overexpression of NtSnRK2.2 enhances salt tolerance in Nicotiana tabacum by regulating carbohydrate metabolism and lateral root development.

Funct Plant Biol 2020 05;47(6):537-543

China Tobacco Hubei Industrial Limited Liability Company, Wuhan, Hubei, Wuhan 430040, China; and Corresponding author. Email:

SnRK2 is a plant-specific protein kinase family implicated in environmental stress tolerance. Individual SnRK2 genes have acquired distinct regulatory properties in response to various environmental stresses. In this study, NtSnRK2.2, a SnRK2 subclass II member in Nicotiana tabacum L., was cloned and characterised. Sequence alignment analysis showed that SnRK2.2 exhibits widespread sequence differences across Nicotiana species. The tissue expression pattern of NtSnRK2.2 showed a root-predominant expression. To investigate its biological function, NtSnRK2.2 was overexpressed in tobacco, which subsequently resulted in increased soluble sugars and more lateral roots under a normal condition. A salt-stress tolerance assay showed that NtSnRK2.2-overexpressing plants exhibited enhanced salt tolerance, which was further confirmed based on its better root architecture and increase in soluble sugars, thereby implying that NtSnRK2.2 is a multifunctional regulatory factor in plants. Together, our results indicated the possible role played by NtSnRK2.2 in maintaining metabolic homeostasis via the regulation of carbohydrate metabolism in response to environmental stress.
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http://dx.doi.org/10.1071/FP19299DOI Listing
May 2020

A new design of divided solenoid with high homogeneity based on linear programming.

Rev Sci Instrum 2020 Jan;91(1):014708

Key Laboratory of Radiation Physics and Technology of Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610064, China.

A novel divided solenoid with high homogeneity is designed through linear programming (LP) for actual guiding magnet application in high power microwave devices. During the LP process, current density, magnetic field homogeneity, and total volume of coils are set as variable, constraint condition, and objective function, respectively. The divided solenoid is designed after calculating current density in the available zone where the coil current exists. After comparing the electrical parameters and magnetic field distribution of the conventional and the new solenoid, it is concluded that the inhomogeneity of the new design is reduced from 10% to 0.7%, the central magnetic field is equal, and other factors are in the same range. The divided solenoid magnet designed by LP is able to achieve high uniformity by improving the winding process and mechanical structure, which also has strong generalization.
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http://dx.doi.org/10.1063/1.5120419DOI Listing
January 2020

LncRNA LOXL1-AS1 promotes endometrial cancer progression by sponging miR-28-5p to upregulate RAP1B expression.

Biomed Pharmacother 2020 May 29;125:109839. Epub 2020 Jan 29.

Department of Reproductive Medicine, Luoyang Center Hospital Affiliated to Zhengzhou University, China. Electronic address:

Background: Increasing lncRNAs are found to be involved in the biological process of multiple cancer types. Herein, we aimed to reveal the role of LOXL1-AS1 in endometrial cancer (EC) progression.

Methods: Tumor and corresponding normal tissues were obtained from EC patients. Si-LOXL1-AS1 and miR-28-5p inhibitor were transfected to downregulate the expressions of LOXL1-AS1 and miR-28-5p, while miR-28-5p mimics were used to upregulate the miR-28-5p expression. CCK-8 and colony assays were applied to estimate the cell proliferation. Flow cytometry was performed to measure the cell apoptosis. Wound healing and transwell assays were conducted to assess the cell migration and invasion abilities. Informatics analysis was used to explore the relationship among LOXL1-AS1, miR-28-5p and RAP1B.

Results: LOXL1-AS1 was found markedly up-regulated in EC tissues and cell lines. LOXL1-AS1 knockdown displayed evident suppression in cell proliferation, migration and invasion, as well as promotion in cell apoptosis. Moreover, the LOXL1-AS1 induced regulatory effects on EC cells were partially reversed by miR-28-5p inhibitor. Mechanistically, LOXL1-AS1 competitively bond to miR-28-5p, resulting in upregulation of RAP1B. Additionally, in vivo study confirmed the findings discovered in vitro.

Conclusions: In summary, LOXL1-AS1 exerted oncogenic roles in EC progression by sponging miR-28-5p and thereby upregulating RAP1B. This finding might provide potential targets for EC therapy.
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http://dx.doi.org/10.1016/j.biopha.2020.109839DOI Listing
May 2020

Classification of Obviously Asymmetric Palpebral Fissures and Correction Based on Double Eyelid Surgery of the Primary Type.

J Craniofac Surg 2020 Mar/Apr;31(2):404-407

Burn and Plastic Surgery Department, Linyi People's Hospital, Linyi.

Bilateral palpebral fissures (PF) are rarely symmetrical. Palpebral plastic surgery is common in the Chinese population. This study aimed to assess the classification of obviously asymmetric palpebral fissures (OAPF). In addition, double eyelid surgery-based correction for the primary subtype was examined. Various clinical signs and etiologies were examined, and OAPF were classified into 3 subtypes: primary, secondary, and aging. For the secondary and aging subtypes, curative surgeries target the relevant underlying conditions. Patients with the primary subtype underwent corrective surgery based on double eyelid operation. After 8 to 12 months of follow-up, the corrective effects of different surgeries were evaluated in patients (n = 48) with primary OAPF. Satisfying look was obtained in all 48 cases, with smooth double eyelid lines and shapes, and no overt asymmetry between the 2 eyes. Thirteen patients developed hypophasis after levator plication, which was resolved within 1 month. Preoperative and postoperative PF were significantly different (1.48 ± 0.24 versus 0.19 ± 0.09 mm; P < 0.05). Overall, patients with OAPF can be classified into the primary, secondary, and aging subtypes. The 48 cases with the primary subtype showed a satisfying look after double eyelid surgery-based correction.
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http://dx.doi.org/10.1097/SCS.0000000000006088DOI Listing
July 2020

Lever-elevating vs. liquid-isolating maneuvers during microwave ablation of high-risk benign thyroid nodules: a prospective single-center study.

Int J Hyperthermia 2019 ;36(1):1239-1245

Department of General Surgery, Central Hospital of Panzhihua City, Panzhihua, China.

To compare the effects of the liquid-isolating maneuver and the lever-elevating maneuver in protecting cervical structures during microwave ablation for treating high-risk benign thyroid nodules. This prospectively study was approved by the Medical Ethics Committee of Panzhihua Central Hospital. A total of 174 patients were enrolled and randomly assigned to a liquid-isolating maneuver group (LIM,  = 87) or a lever-elevating maneuver group (LEM,  = 87). Operation time, postoperative voice change, time to recovery of baseline voice, peri-thyroid hematoma, neck tension, and intraoperative vasovagal reaction were assessed. Operation time was greater in the LIM group than in the LEM group (44.75 ± 13.14 32.87 ± 10.84 min;  = .017).Voice changes were observed in 6 patients in the LIM group and 2 in the LEM group (6.9% 2.3%,  = .278). The time to recovery of baseline voice was significantly greater in the LIM group compared with the LEM group (36.15 ± 10.24 24.48 ± 11.53 days,  = .014). The incidences of peri-thyroid hematoma and neck tension were higher in the LIM than in the LEM group (11.5% 3.4%, 10.3% 2.3%,  = .044 and  = .029). One patient (1.1%) in the LEM group and none of the patients in the LIM group experienced a vasovagal response ( = 1.000). The lever-elevating method is feasible and effective for the microwave ablation of benign thyroid nodules, with better protection of neck structures than observed with the liquid-isolating method.
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http://dx.doi.org/10.1080/02656736.2019.1690711DOI Listing
April 2020

Bone Morphogenetic Protein 15 Knockdown Inhibits Porcine Ovarian Follicular Development and Ovulation.

Front Cell Dev Biol 2019 19;7:286. Epub 2019 Nov 19.

State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.

Bone morphogenetic protein 15 () is strongly associated with animal reproduction and woman reproductive disease. As a multifunctional oocyte-specific secret factor, BMP15 controls female fertility and follicular development in both species-specific and dosage-sensitive manners. Previous studies found that BMP15 played a critical role in follicular development and ovulation rate in mono-ovulatory mammalian species, especially in sheep and human, but study on knockout mouse model implied that BMP15 possibly has minimal impact on female fertility of poly-ovulatory species. However, this needs to be validated in other poly-ovulatory species. To investigate the regulatory role of BMP15 on porcine female fertility, we generated a BMP15-knockdown pig model through somatic nuclear transfer technology. The BMP15-knockdown gilts showed markedly reduced fertility accompanied by phenotype of dysplastic ovaries containing significantly declined number of follicles, increased number of abnormal follicles, and abnormally enlarged antral follicles resulting in disordered ovulation, which is remarkably different from the unchanged fertility observed in BMP15 knockout mice. Molecular and transcriptome analysis revealed that the knockdown of significantly affected both granulosa cells (GCs) and oocytes development, including suppression of cell proliferation, differentiation, and follicle stimulating hormone receptor () expression, leading to premature luteinization and reduced estradiol (E2) production in GCs, and simultaneously decreased quality and meiotic maturation of oocyte. Our results provide evidence of the essential role of BMP15 in porcine ovarian and follicular development, and new insight into the complicated regulatory function of BMP15 in female fertility of poly-ovulatory species.
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http://dx.doi.org/10.3389/fcell.2019.00286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877722PMC
November 2019

Baicalein restrains proliferation, migration, and invasion of human malignant melanoma cells by down-regulating colon cancer associated transcript-1.

Braz J Med Biol Res 2019 25;52(12):e8934. Epub 2019 Nov 25.

Department of Burn and Plastic Surgery, Qingdao Central Hospital, The Affiliated Central Hospital of Qingdao University, Qingdao, Shandong, China.

Baicalein (BAI) is an acknowledged flavonoids compound, which is regarded as a useful therapeutic pharmaceutical for numerous cancers. However, its involvement in melanoma is largely unknown. This study aimed to examine the anti-melanoma function of BAI and unraveled the regulatory mechanism involved. A375 and SK-MEL-28 were treated with BAI for 24 h. Then, CCK-8 assay, flow cytometry, and transwell assay were carried out to investigate cell growth, migration, and invasion. RT-qPCR was applied to detect the expression of colon cancer associated transcript-1 (CCAT1) in melanoma tissues and cells. The functions of CCAT1 in melanoma cells were also evaluated. Western blot was utilized to appraise Wnt/β-catenin or MEK/ERK pathways. BAI restrained cell proliferation and stimulated cell apoptotic capability of melanoma by suppressing cleaved-caspase-3 and cleaved-PARP. Cell migratory and invasive abilities were restrained by BAI via inhibiting MMP-2 and vimentin. CCAT1 was over-expressed in melanoma tissues and down-regulated by BAI in melanoma cells. Overexpressed CCAT1 reversed the BAI-induced anti-growth, anti-migratory, and anti-invasive effects. Furthermore, BAI inhibited Wnt/β-catenin and MEK/ERK pathways-axis via regulating CCAT1. Our study indicated that BAI blocked Wnt/β-catenin and MEK/ERK pathways via regulating CCAT1, thereby inhibiting melanoma cell proliferation, migration, and invasion.
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http://dx.doi.org/10.1590/1414-431X20198934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886380PMC
January 2020

Effects of Xuesaitong on the Pharmacokinetics of Losartan: An UPLC-MS/MS Study.

Evid Based Complement Alternat Med 2019 14;2019:8373476. Epub 2019 Aug 14.

Department of Pharmacy, Shanghai Baoshan Luodian Hospital, Shanghai, China.

The aim of this study was to examine whether Xuesaitong, a multiherbal formulation for coronary heart disease, alters the pharmacokinetics of losartan. Adult male Sprague Dawley rats randomly received losartan (10 mg/kg) or losartan plus Xuesaitong (10 mg/kg) through an oral gavage ( = 6). Multiple blood samples were obtained for up to 36 h to determine the concentrations of losartan and its active metabolite, EXP3174, through ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetics were estimated using a noncompartmental model. The half-life ( ) of losartan was decreased by Xuesaitong (4.26 ± 1.51 vs. 6.35 ± 2.10 h; < 0.05). The apparent volume of distribution ( ) of losartan was also decreased by the combination of losartan and Xuesaitong (4.41 ± 1.61 vs. 7.20 ± 2.41 mL; < 0.05). The time to maximum concentration ( ) of losartan was increased by Xuesaitong (1.06 ± 1.04 vs. 0.13 ± 0.05 h; < 0.05). Xuesaitong also decreased the of EXP3174 (8.22 ± 1.41 vs. 6.29 ± 1.38 h; < 0.05). These results suggest that there is a complex interaction between losartan and Xuesaitong. In addition to enhanced elimination of losartan and EXP3174, Xuesaitong may also decrease the absorption rate and of losartan.
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http://dx.doi.org/10.1155/2019/8373476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710810PMC
August 2019

Baicalein retards proliferation and collagen deposition by activating p38MAPK-JNK via microRNA-29.

J Cell Biochem 2019 09 12;120(9):15625-15634. Epub 2019 May 12.

Department of Burn and Plastic Surgery, Qingdao Central Hospital (The Affiliated Central Hospital of Qingdao University), Qingdao, China.

Immoderate proliferation and deposition of collagen generally result in hypertrophic scars and even keloids. microRNA-29 (miR-29) has been proved as a crucial regulator in these pathological processes. Although mounting evidence have proved baicalein (BAI) impairs scar formation, it is still incompletely understood whether miR-29 participated in the underlying mechanism. In the present study, NIH-3T3 cells were stimulated with BAI, and then cell viability was analyzed by cell counting kit-8 (CCK-8) and Western blot. We further analyzed total soluble collagen, collagen 1, and alpha-smooth muscle actin (α-SMA) in NIH-3T3 cells, which were exposed to transforming growth factor beta 1 (TGF-β1)/BAI, using a Sircol assay kit, quantitative reverse transcription-PCR (qRT-PCR) and Western blot, respectively. Besides, the miR-29 inhibitor was transduced and its transfection efficiency was verified by qRT-PCR. Finally, the phosphorylated p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) were examined by Western blot. BAI effectively retarded NIH-3T3 proliferation in a dose-dependent manner. Besides, TGF-β1-induced deposition of total soluble collagen and synthesis of collagen 1 and α-SMA were repressed by BAI at mRNA and protein levels. However, miR-29 inhibitor reversed the effects of BAI. Remarkably, BAI promoted phosphorylated expression of p38MAPK and JNK while miR-29 inhibitor reversed its effects on the phosphorylated expression of p38MAPK and JNK. BAI effectively weakened the cell viability and repressed TGF-β1-induced total soluble collagen as well as collagen 1 and α-SMA by upregulating miR-29. Mechanically, BAI activates the p38MAPK/JNK pathway by promoting miR-29.
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http://dx.doi.org/10.1002/jcb.28829DOI Listing
September 2019

Down-regulation of 14-3-3zeta reduces proliferation and increases apoptosis in human glioblastoma.

Cancer Gene Ther 2020 06 9;27(6):399-411. Epub 2019 May 9.

Department of Pharmacology and Winship Cancer Institute, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA.

Many efforts have been taken to develop molecule target for cancer therapy. 14-3-3zeta protein has emerged as a critical regulator of diverse cellular pathways in multiple cancers. Furthermore, 14-3-3zeta expression was elevated and a predictor of poor prognosis in glioblastoma. However, there is no information to evaluate the potential effects of 14-3-3zeta RNAi in glioblastoma. The relationship between 14-3-3zeta expression and cell proliferation and apoptosis was tested in primary glioblastoma samples. Through an RNAi approach using human glioblastoma cells as a model system, we demonstrated the role of 14-3-3zeta in glioblastoma proliferation, apoptosis, invasion and tumor growth. The expression of 14-3-3zeta in glioblastoma stem cells was also investigated by immunostaining. The apoptosis was significantly higher in 14-3-3zeta-negative group than in positive group. 14-3-3zeta immunoreactivity score was negatively correlated with the apoptosis, and positively with proliferation in human specimens. 14-3-3zeta RNAi reduced cell proliferation, induced apoptosis, decreased the invasive capability and colony-formation, and impaired the growth of glioblastoma xenografts in nude mice. Moreover, 14-3-3zeta was positively expressed in glioblastoma stem cells. Our data highlight the importance of 14-3-3zeta in glioblastoma and identify 14-3-3zeta as a potential molecular target for glioblastoma treatment.
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http://dx.doi.org/10.1038/s41417-019-0097-7DOI Listing
June 2020

Peptosome Coadministration Improves Nanoparticle Delivery to Tumors through NRP1-Mediated Co-Endocytosis.

Biomolecules 2019 05 5;9(5). Epub 2019 May 5.

CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China.

Improving the efficacy of nanoparticles (NPs) delivery to tumors is critical for cancer diagnosis and therapy. In our previous work, amphiphilic peptide APPA self-assembled nanocarriers were designed and constructed for cargo delivery to tumors with high efficiency. In this study, we explore the use of APPA self-assembled peptosomes as a nanoparticle adjuvant to enhance the delivery of nanoparticles and antibodies to integrin αvβ3 and neuropilin-1 (NRP1) positive tumors. The enhanced tumor delivery of coadministered NPs was confirmed by better magnetosome (Mag)-based T-weighted magnetic resonance imaging (MRI), liposome-based fluorescence imaging, as well as the improved anti-tumor efficacy of monoclonal antibodies (trastuzumab in this case) and doxorubicin (DOX)-containing liposomes. Interestingly, the improvement is most significant for the delivering of compounds that have active or passive tumor targeting ability, such as antibodies or NPs that have enhanced permeability and retention (EPR) effect. However, for non-targeting small molecules, the effect is not significant. In vitro and in vivo studies suggest that both peptosomes and the coadministered compounds might be internalized into cells through a NRP1 mediated co-endocytosis (CoE) pathway. The improved delivery of coadministered NPs and antibodies to tumors suggests that the coadministration with APPA self-assembled peptosomes could be a valuable approach for advancing αvβ3 and NRP1 positive tumors diagnosis and therapy.
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http://dx.doi.org/10.3390/biom9050172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572427PMC
May 2019

Flagellin attenuates experimental sepsis in a macrophage-dependent manner.

Crit Care 2019 Apr 3;23(1):106. Epub 2019 Apr 3.

Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.

Background: Sepsis is the leading cause of death among critically ill patients, and no specific therapeutic agent is currently approved for the treatment of sepsis.

Methods: We assessed the effects of flagellin administration on survival, bacterial burden, and tissue injury after sepsis. In addition, we examined the effects on phagocytosis and bacterial killing in monocytes/macrophages.

Results: Therapeutic administration of flagellin increased bacterial clearance, decreased organ inflammation and injury, and reduced immune cell apoptosis after experimental sepsis, in a Toll-like receptor 5 (TLR5)-dependent manner. Macrophages, but not neutrophils, mediated the beneficial effects of flagellin on experimental sepsis, and flagellin induced macrophage polarization into M1 in septic mice. Flagellin treatment could directly enhance phagocytosis and bacterial killing of macrophages, but not neutrophils. Subsequent studies demonstrated that flagellin could promote phagosome formation and increase reactive oxygen species (ROS) levels in macrophages. Finally, we found that the expression of TLR5 was significantly elevated on the surface of circulating monocytes, but not neutrophils, from patients with sepsis. Higher expression levels of TLR5 on monocytes were associated with increased mortality, documented bacteremia, and higher Sequential Organ Failure Assessment scores of the septic patients. Moreover, flagellin treatment rescued the impaired phagocytosis and bacterial killing ability of monocytes/macrophages from patients who died of sepsis.

Conclusions: These novel findings not only established the potential value of application of flagellin as an immunoadjuvant in treating sepsis, but also provided new insights into targeted therapeutic strategy on the basis of monocyte TLR5 expression in septic patients.
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http://dx.doi.org/10.1186/s13054-019-2408-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446324PMC
April 2019

Bilateral Blindness After Incomplete Coiling of Small Anterior Cerebral Artery Aneurysm: Case Report and Review of Literature.

World Neurosurg 2019 Jun 18;126:296-300. Epub 2019 Mar 18.

Department of Neurosurgery, Third Hospital of People Liberation Army, Baoji, People's Republic of China.

Background: Complications after coiling of large, giant, and thrombosed aneurysms because of increased mass effect on surrounding structures have been widely reported. A case of bilateral blindness after incomplete coil embolization of a small anterior cerebral artery aneurysm is rare. We review the potential mechanisms, clinical progression, and proper treatment needs.

Case Description: A 50-year-old man was urgently admitted with subarachnoid hemorrhage. Digital subtraction angiography (DSA) showed a ruptured aneurysm of the A1 segment, anterior cerebral artery. An endovascular coil occlusion was performed without an additional device. The visual acuity of patient slowly decreased from the 13th day after endovascular intervention. His visual acuity improved after steroid therapy but then deteriorated again. DSA showed an enlarged aneurysm, and an urgent craniotomy was performed for optic nerve decompression. The patient finally became bilaterally blind, although hyperbaric oxygen, neurotrophy drugs, and other supporting treatment was given.

Conclusions: Incomplete aneurysm coiling may result in bilateral blindness, even at a small anterior cerebral artery. Early DSA, steroid therapy, and secondary craniotomy for nerve decompression should be considered promptly for improving clinical outcome before nerve atrophy, although sometimes single steroid therapy is effective.
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http://dx.doi.org/10.1016/j.wneu.2019.03.076DOI Listing
June 2019

Proteomic profiling of RAW264.7 macrophage cells exposed to graphene oxide: insights into acute cellular responses.

Nanotoxicology 2019 02 17;13(1):35-49. Epub 2019 Jan 17.

a CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety , CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology , Beijing , China.

Although the toxicity and molecular mechanisms of graphene oxide (GO) have been reported for several cell types, no proteomic study of GO has yet been conducted on macrophage cells. In this study, we used proteomics based on stable isotope labeling with amino acids in cell culture (SILAC) to quantify the proteomic changes in macrophage RAW 264.7 cells following GO treatment. We found 73 proteins that were significantly dysregulated after GO treatment. The down-regulated proteins included many ribosomal subunit proteins, indicating that GO affected cell growth. The most elevated proteins were lipoprotein lipase (LPL) and lysozyme 1 (LYZ1) which have not been reported before, and both can be used as candidate markers for GO exposure. Further enrichment analysis of the up-regulated proteins indicated these proteins are associated with the integrin complex and membrane rafts, as well as with two signal pathways: the phagosome and steroid biosynthesis pathways. We confirmed a GO concentration-dependent increase in membrane rafts and the production of phagosomes. GO exposure also induced necrotic cell death and an inflammation response in RAW 264.7 cells. We also observed an increase in the oxidative stress response (ROS) and autophagy, and the results suggest that ROS induced autophagy by the ROS-NRF2-P62 pathway.
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http://dx.doi.org/10.1080/17435390.2018.1530389DOI Listing
February 2019

Propranolol suppresses HUVEC viability, migration, VEGF expression, and promotes apoptosis by downregulation of miR-4295.

J Cell Biochem 2019 04 28;120(4):6614-6623. Epub 2018 Oct 28.

Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.

Infantile hemangioma (IH) is a common benign tumor. Human umbilical vein endothelial cells (HUVECs) have the potential of stem cells, which has been widely used in vascular endothelial cell experiments. Oral propranolol was first reported to treat hemangioma in 2008. However, the role of propranolol in IH remains unclear. Therefore, in this study, we investigated the effects of propranolol on HUVECs in vitro, to explore the underlying mechanism of propranolol in IH. HUVECs were treated with 0.15, 1.5, and 15 μM of propranolol, and transfected with microRNA-4295 (miR-4295) mimic. Cell viability, migration, and apoptosis were examined using Cell Counting Kit-8, transwell assay, and flow cytometry analysis, respectively. In addition, the expressions and concentrations of miR-4295, vascular endothelial growth factor (VEGF), VEGF-A, FLT1, FLT2, and FOXF1 were assessed using real-time polymerase chain reaction, Western blot assay, and enzyme-linked immunosorbent assay. We found that 15 μM of propranolol decreased HUVEC viability the most. Then, cell migration and the concentrations of VEGF and VEGF-A were reduced, and apoptosis was increased when treated with propranolol. Meanwhile, the expressions of VEGF, VEGF-A, FLT1, FLT2, and FOXF1 were downregulated by propranolol exposure. Further study showed that miR-4295 expression was upregulated in IH tissues, and propranolol treatment downregulated miR-4295 expression in HUVECs. MiR-4295 overexpression alleviated the reductions of viability, migration, and factors expression, as well as the increase of apoptosis. Propranolol suppressed HUVEC viability, migration, the expression of VEGF, VEGF-A, FLT1/2, FOXF1, and promoted apoptosis via downregulation of miR-4295. This study lays a foundation for further study of the effect of propranolol on IH.
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http://dx.doi.org/10.1002/jcb.27957DOI Listing
April 2019

An Efficient and Robust Framework for SAR Target Recognition by Hierarchically Fusing Global and Local Features.

IEEE Trans Image Process 2018 Dec 3;27(12):5983-5995. Epub 2018 Aug 3.

Automatic target recognition (ATR) of synthetic aperture radar (SAR) images is performed on either global or local features. The global features can be extracted and classified with high efficiency. However, they lack the reasoning capability thus can hardly work well under the extended operation conditions (EOCs). The local features are often more difficult to extract and classify but they provide reasoning capability for EOC target recognition. To combine the efficiency and robustness in an ATR system, a hierarchical fusion of the global and local features is proposed for SAR ATR in this paper. As the global features, the random projection features can be efficiently extracted and effectively classified by sparse representation-based classification (SRC). The physically relevant local descriptors, i.e., attributed scattering centers (ASCs), are employed for local reasoning to handle various EOCs like noise corruption, resolution variance, and partial occlusion. A one-to-one correspondence between the test and template ASC sets is built by the Hungarian algorithm. Then, the local reasoning is performed by evaluating individual matched pairs as well as the false alarms and missing alarms. For the test image to be recognized, it is first classified by the global classifier, i.e., SRC. Once a reliable decision is made, the whole recognition process terminates. When the decision is not reliable enough, it is passed to the local classifier, where a further classification by ASC matching is carried out. Therefore, by the hierarchical fusion strategy, the efficiency of global features and the robustness of local descriptors to various EOCs can be maintained jointly in the ATR system. Extensive experiments on the moving and stationary target acquisition and recognition data set demonstrate that the proposed method achieves superior effectiveness and robustness under both SOC and typical EOCs, i.e., noise corruption, resolution variance, and partial occlusion, compared with some other SAR ATR methods.
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http://dx.doi.org/10.1109/TIP.2018.2863046DOI Listing
December 2018

Evidence that microplastics aggravate the toxicity of organophosphorus flame retardants in mice (Mus musculus).

J Hazard Mater 2018 09 8;357:348-354. Epub 2018 Jun 8.

Program in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.

This study was performed to reveal the health risks of co-exposure to organophosphorus flame retardants (OPFRs) and microplastics (MPs). We exposed mice to polyethylene (PE) and polystyrene (PS) MPs and OPFRs [tris (2-chloroethy) phosphate (TCEP) and tris (1,3-dichloro-2-propyl) phosphate (TDCPP)] for 90 days. Biochemical markers and metabolomics were used to determine whether MPs could enhance the toxicity of OPFRs. Superoxide dismutase (SOD) and catalase (CAT) increased (p < 0.05) by 21% and 26% respectively in 10 μg/L TDCPP + PE group compared to TDCPP group. Lactate dehydrogenase (LDH) in TDCPP + MPs groups were higher (18%-30%) than that in TDCPP groups (p < 0.05). Acetylcholinesterase (AChE) in TCEP + PE groups were lower (10%-19%) than those in TCEP groups (p < 0.05). These results suggested that OPFR co-exposure with MPs induced more toxicity than OPFR exposure alone. Finally, in comparison to controls we observed that 29, 41, 41, 26, 40 and 37 metabolites changed significantly (p < 0.05; fold-change > 1.2) in TCEP, TCEP + PS, TCEP + PE, TDCPP, TDCPP + PS and TDCPP + PE groups, respectively. Most of these metabolites are related to pathways of amino acid and energy metabolism. Our results indicate that MPs aggravate the toxicity of OPFRs and highlight the health risks of MP co-exposure with other pollutants.
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http://dx.doi.org/10.1016/j.jhazmat.2018.06.017DOI Listing
September 2018

A novel percutaneous achievement and maintenance of reduction and screw fixation for acute displaced scaphoid fractures: minimum two-year follow-up.

Int Orthop 2018 08 10;42(8):1911-1916. Epub 2018 Jan 10.

Hand Surgery, The Third Hospital Of Hebei Medical University, No.139, Ziqiang Road, Qiaoxi District, Shijiazhuang, Hebei, 050051, People's Republic of China.

Purpose: The purpose of this study was to introduce a novel method of percutaneous achievement and maintenance of reduction for acute displaced scaphoid fractures and evaluate the feasibility of this method in treating acute displaced scaphoid fractures as well as explore its indications.

Methods: From February 2012 to March 2014, 15 patients with acute displaced scaphoid fractures were treated with our technique. Two Kirschner wires were used to achieve and maintain the reduction of the scaphoid fractures throughout the entire process of the traditional percutaneous screw fixation process. The following parameters including function scores according to modified Mayo wrist scoring system, range of motion (ROM) of the wrist, grip strength, pinch strength, healing time, time to return to work, and final outcomes were recorded.

Result: All patients were followed up with a mean period of 2.5 years (range, 2-3.5 years). All fractures healed with a mean of 9.3 weeks (range, 7-11.5 weeks). All patients returned to pre-injury level of activity within six weeks. The functional scores averaged 90.3 (range, 80-100). ROM of the wrist was equal to that of the contralateral side at three months postoperatively. Grip strength and pinch strength compared with contralateral were 98% and 92%, respectively. All were satisfied with the final outcomes.

Conclusions: Our technique is successfully performed in acute displaced scaphoid fractures resulting in shortened immobilization and prompt functional recovery. It broadens the indications of the percutaneous method, which means the advantages of the percutaneous method are maximally reserved whilst the drawbacks of open reduction were avoided.
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http://dx.doi.org/10.1007/s00264-018-3758-5DOI Listing
August 2018

Elevated production of IL-36α in chronic hepatitis B virus-infected patients correlates with viral load.

Microb Pathog 2017 Dec 21;113:412-415. Epub 2017 Nov 21.

Department of Blood Transfusion, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Chronic hepatitis B (CHB) infection is a typical inflammatory disease characterized by a dysregulated expression of cytokines, which contributes to the pathogenesis of chronic Hepatitis B virus (HBV) infection. IL-36 cytokines (IL-36α, IL-36β, IL-36γ and IL-36Ra) are important players in infection and immunity. However, their roles in the pathogenesis of chronic HBV infection remain unknown. Here the circulating concentrations of IL-36 cytokines from 50 CHB patients and 30 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). Sera concentrations of IL-36α were found to be significantly elevated in CHB patients, while the concentrations of IL-36β, IL-36γ and IL-36Ra were not significantly different in comparison to healthy donors. Furthermore, increased IL-36α concentrations correlated positively with HBV-DNA levels in CHB patients. Our study suggests that IL-36α production was up-regulated during CHB infection, which could be directly related to HBV-DNA loads in CHB patients. The immunoregulatory role of IL-36α in the pathogenesis of chronic HBV infection should be further studied.
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http://dx.doi.org/10.1016/j.micpath.2017.11.023DOI Listing
December 2017

Peptide probes derived from pertuzumab by molecular dynamics modeling for HER2 positive tumor imaging.

PLoS Comput Biol 2017 Apr 13;13(4):e1005441. Epub 2017 Apr 13.

CAS Key Laboratory for Biological Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing, China.

A high level of HER2 expression in breast cancer correlates with a higher tumor growth rate, high metastatic potential, and a poor long-term patient survival rate. Pertuzumab, a human monoclonal antibody, can reduce the effect of HER2 overexpression by preventing HER2 dimerization. In this study, a combination protocol of molecular dynamics modeling and MM/GBSA binding free energy calculations was applied to design peptides that interact with HER2 based on the HER2/pertuzumab crystal structure. Based on a β hairpin in pertuzumab from Glu46 to Lys65-which plays a key role in interacting with HER2-mutations were carried out in silico to improve the binding free energy of the hairpin that interacts with the Phe256-Lys314 of the HER2 protein. Combined the use of one-bead-one-compound library screening, among all the mutations, a peptide (58F63Y) with the lowest binding free energy was confirmed experimentally to have the highest affinity, and it may be used as a new probe in diagnosing and treating HER2-positive breast cancer.
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http://dx.doi.org/10.1371/journal.pcbi.1005441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390981PMC
April 2017

Tumor detection using magnetosome nanoparticles functionalized with a newly screened EGFR/HER2 targeting peptide.

Biomaterials 2017 01 16;115:53-64. Epub 2016 Nov 16.

CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China; CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China. Electronic address:

A novel peptide (P75) targeting EGFR and HER2 is successfully screened from a one-bead-one-compound (OBOC) library containing approximately 2 × 10 peptides built with the aid of computational simulation. In vitro and in vivo analyses show that P75 binds to human epithelial growth factor receptor (EGFR) with nanomolar affinity and to epithelial growth factor receptor-2 (HER2) with a lower affinity but comparable to other reported peptides. The peptide is used to modify the surface of magnetosome nanoparticles (NPs) for targeted magnetic resonance imaging (MRI). In vitro and in vivo fluorescence imaging results suggest peptide P75 modified magnetosomes (Mag-P75) specifically bind to MDA-MB-468 and SKBR3 cells as well as xenograft tumors with surprisingly low accumulation in other organs including liver and kidney. In vivo T-weighted MR imaging studies of the xenograft tumors from SKBR3 and MDA-MB-468 cells show obviously negative contrast enhancement. The high affinity and specificity of P75 to EGFR and HER2 positive tumors, together with the success of peptide functionalized magnetosome NPs for targeted MRI demonstrate the potential of this peptide being used in the EGFR and HER2 positive tumors diagnosis and therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2016.11.022DOI Listing
January 2017

14-3-3zeta Positive Cells Show More Tumorigenic Characters in Human Glioblastoma.

Turk Neurosurg 2016 ;26(6):813-817

Wuhan General Hospital of Guangzhou Military Command, Department of Neurosurgery, Wuhan, China.

Aim: Expression of 14-3-3zeta is upregulated in many cancer types and plays an important role in tumorigenesis. Our previous studies have shown that 14-3-3zeta has a positive expression and is associated with a poor prognosis in patients with glioblastoma. In this study, we investigated whether 14-3-3zeta positive cells show more tumorigenic character and stronger chemotherapy resistance.

Material And Methods: Six human glioblastoma cells lines were derived from the 6 patients with tumor, and the cells were sorted by 14-3-3zeta expression. The cell viability, invasion, tumorigenic ability and chemotherapy resistance were compared between the 14-3-3 positive and negative expression groups.

Results: 14-3-3zeta positive cells displayed oncogenic properties, more tumorigenic character, high invasiveness, tumorsphere formation ability and resistance to temozolomide chemotherapy treatment.

Conclusion: Cells with 14-3-3zeta positive expression show more tumorigenic character and should be administered other treatments in the future.
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http://dx.doi.org/10.5137/1019-5149.JTN.13720-14.1DOI Listing
March 2017

Genome-Wide Identification, Phylogeny, and Expression Analyses of the 14-3-3 Family Reveal Their Involvement in the Development, Ripening, and Abiotic Stress Response in Banana.

Front Plant Sci 2016 22;7:1442. Epub 2016 Sep 22.

Key Laboratory of Biology and Genetic Resources of Tropical Crops, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural SciencesHaikou, China; Key Laboratory of Genetic Improvement of Bananas, Hainan province, Haikou Experimental Station, Chinese Academy of Tropical Agricultural SciencesHaikou, China.

Plant 14-3-3 proteins act as critical components of various cellular signaling processes and play an important role in regulating multiple physiological processes. However, less information is known about the 14-3-3 gene family in banana. In this study, 25 14-3-3 genes were identified from the banana genome. Based on the evolutionary analysis, banana 14-3-3 proteins were clustered into ε and non-ε groups. Conserved motif analysis showed that all identified banana 14-3-3 genes had the typical 14-3-3 motif. The gene structure of banana 14-3-3 genes showed distinct class-specific divergence between the ε group and the non-ε group. Most banana 14-3-3 genes showed strong transcript accumulation changes during fruit development and postharvest ripening in two banana varieties, indicating that they might be involved in regulating fruit development and ripening. Moreover, some 14-3-3 genes also showed great changes after osmotic, cold, and salt treatments in two banana varieties, suggested their potential role in regulating banana response to abiotic stress. Taken together, this systemic analysis reveals the involvement of banana 14-3-3 genes in fruit development, postharvest ripening, and response to abiotic stress and provides useful information for understanding the functions of 14-3-3 genes in banana.
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http://dx.doi.org/10.3389/fpls.2016.01442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031707PMC
September 2016

Serum progranulin levels are elevated in patients with chronic hepatitis B virus infection, reflecting viral load.

Cytokine 2016 09 6;85:26-9. Epub 2016 Jun 6.

Department of Blood Transfusion, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Progranulin (PGRN) is implicated in infection, immunity and host defense, but its role in the pathogenesis of HBV infection remains unknown. Here we investigated whether there is dysregulated production and the clinical significance of circulating PGRN in patients with chronic HBV infection. Serum concentrations of PGRN were analyzed by enzyme-linked immunosorbent assay. Serum PGRN levels were significantly higher in patients with chronic HBV infection than healthy subjects. PGRN levels were significantly associated with HBV-DNA levels, but did not correlate with the concentrations of alanine aminotransferase and aspartate aminotransferase. This study demonstrates increased circulating PGRN production and association between PGRN levels and viral loads in patients with chronic HBV infection, suggesting a functional role of PGRN in the pathogenesis of HBV infection.
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http://dx.doi.org/10.1016/j.cyto.2016.05.026DOI Listing
September 2016

HER2 Targeting Peptides Screening and Applications in Tumor Imaging and Drug Delivery.

Theranostics 2016 28;6(8):1261-73. Epub 2016 May 28.

1. CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China;; 2. CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China;

Herein, computational-aided one-bead-one-compound (OBOC) peptide library design combined with in situ single-bead sequencing microarray methods were successfully applied in screening peptides targeting at human epidermal growth factor receptor-2 (HER2), a biomarker of human breast cancer. As a result, 72 novel peptides clustered into three sequence motifs which are PYL***NP, YYL***NP and PPL***NP were acquired. Particularly one of the peptides, P51, has nanomolar affinity and high specificity for HER2 in ex vivo and in vivo tests. Moreover, doxorubicin (DOX)-loaded liposome nanoparticles were modified with peptide P51 or P25 and demonstrated to improve the targeted delivery against HER2 positive cells. Our study provides an efficient peptide screening method with a combination of techniques and the novel screened peptides with a clear binding site on HER2 can be used as probes for tumor imaging and targeted drug delivery.
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http://dx.doi.org/10.7150/thno.14302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4893650PMC
October 2017
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