Publications by authors named "Xiaoping Sun"

116 Publications

Endoscopic transpapillary gallbladder drainage for management of acute cholecystitis with coagulopathy.

J Int Med Res 2021 Mar;49(3):300060521996912

Department of Urology, Lanzhou University Second Hospital, Lanzhou, Gansu, China.

Acute cholecystitis is a common and frequently occurring disease, and laparoscopic cholecystectomy is the preferred treatment method. Percutaneous transhepatic gallbladder drainage is regarded as the first-line palliative procedure for elderly patients with poor cardiopulmonary function who cannot tolerate general anesthesia. However, for patients with acute cholecystitis who are undergoing treatment with oral antithrombotics or who have abnormal coagulation mechanisms, endoscopic transpapillary gallbladder drainage may be a good choice. Endoscopic transpapillary gallbladder drainage is an endoscopic retrograde cholangiopancreatography-based technique that drains the gallbladder by placing a tube into the cavity of the gallbladder though the cystic gall duct. It is the application of the concept of natural orifice transluminal endoscopic surgery in the biliary system. This technique can not only achieve gallbladder drainage but can also minimize the risk of procedure-induced bleeding. In this paper, we describe a representative case to introduce the key points of this procedure and the associated clinical care, hoping to provide useful information for clinicians and nurses.
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http://dx.doi.org/10.1177/0300060521996912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168036PMC
March 2021

TPTEP1 suppresses high glucose-induced dysfunction in retinal vascular endothelial cells by interacting with STAT3 and targeting VEGFA.

Acta Diabetol 2021 Jun 12;58(6):759-769. Epub 2021 Feb 12.

Department of Endocrinology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, No. 164, Lanxi Road, Shanghai, 200062, China.

Aims: Diabetic retinopathy (DR) is a vascular complication of diabetes mellitus that causes visual impairment and blindness. Long noncoding RNAs (lncRNAs) have been revealed to be involved in biological processes of several diseases including DR. We designed this study to investigate the specific role of TPTEP1 in DR.

Methods: First, we mimicked diabetic conditions with high glucose (HG) stimulation of human retinal vascular endothelial cells (HRVECs) and measured TPTEP1 expression in HG-stimulated HRVECs using RT-qPCR analysis. Then, CCK-8, Transwell, and Matrigel tube formation assays as well as western blot analysis were performed to reveal the biological functions of TPTEP1 in HG-stimulated HRVECs. Subsequently, bioinformatics analysis, RNA pull down, luciferase reporter and ChIP assays as well as western blot analysis evaluated the relationship of TPTEP1, signal transducer and activator of transcription 3 (STAT3) and vascular endothelial growth factor A (VEGFA) in HG-stimulated HRVECs. Finally, to verify the regulation of the TPTEP1/STAT3/VEGFA axis in HG-stimulated HRVECs, rescue experiments were carried out in HG-stimulated HRVECs.

Results: TPTEP1 presented a significant downregulation in HG-stimulated HRVECs. Additionally, TPTEP1 overexpression reduced viability, migration, and angiogenesis in HG-stimulated HRVECs. Moreover, TPTEP1 suppressed phosphorylation and nuclear translocation of STAT3, and thereby downregulated VEGFA mRNA and protein levels. Furthermore, TPTEP1 overexpression-mediated suppression of HG-induced dysfunction in HRVECs was countervailed by STAT3 upregulation or VEGFA upregulation.

Conclusions: TPTEP1 alleviated HG-induced dysfunction in HRVECs via interacting with STAT3 and targeting VEGFA.
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http://dx.doi.org/10.1007/s00592-020-01663-wDOI Listing
June 2021

The complete mitochondrial genome of (Anatidae: Anas).

Mitochondrial DNA B Resour 2020 29;5(3):2207-2208. Epub 2020 May 29.

Collaborative Innovation Center of Sustainable Forestry in Southern China of Jiangsu Province, Nanjing Forestry University, Nanjing, China.

The complete mitochondrial DNA genome of the Eurasian Wigeon, , was mapped by the next-generation sequencing and Mega 7.0. The circular mitogenome (16,596 bp in length) contains 13 protein-coding genes, 2 rRNA genes (12S ribosomal RNA and 16S ribosomal RNA), 22 tRNA genes and a control region. The content of four base pairs of the complete mitochondrial DNA is 28.9% of A, 22.3%of T, 32.7%of C and 16.1% of G. To validate the phylogenetic relationship, 25 published complete mitochondrial genomes of Anseriformesalong with the genome of Terek sandpiper were used to construct the phylogenetic tree.
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http://dx.doi.org/10.1080/23802359.2020.1768920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510573PMC
May 2020

Genetic signatures of high-altitude adaptation and geographic distribution in Tibetan sheep.

Sci Rep 2020 10 27;10(1):18332. Epub 2020 Oct 27.

Lanzhou Institute of Husbandry and Pharmaceutical Sciences of the Chinese Academy of Agricultural Sciences, Jiangouyan Street, Lanzhou, China.

Most sheep breeding programs designed for the tropics and sub-tropics have to take into account the impacts of environmental adaptive traits. However, the genetic mechanism regulating the multiple biological processes driving adaptive responses remains unclear. In this study, we applied a selective sweep analysis by combing 1% top values of F and ZHp on both altitude and geographic subpopulations (APS) in 636 indigenous Tibetan sheep breeds. Results show that 37 genes were identified within overlapped genomic regions regarding F significantly associated with APS. Out of the 37 genes, we found that 8, 3 and 6 genes at chromosomes (chr.) 13, 23 and 27, respectively, were identified in the genomic regions with 1% top values of ZHp. We further analyzed the INDEL variation of 6 genes at chr.27 (X chromosome) in APS together with corresponding orthologs of 6 genes in Capra, Pantholops, and Bos Taurus. We found that an INDEL was located within 5'UTR region of HAG1 gene. This INDEL of HAG1 was strongly associated with the variation of APS, which was further confirmed by qPCR. Sheep breeds carrying "C-INDEL" of HAG1 have significantly greater body weight, shear amount, corpuscular hemoglobin and globulin levels, but lower body height, than those carrying "CA-INDEL" of HAG1. We concluded that "C-INDEL" variation of HAG1 gene confers better hypoxia tolerance in the highlands of Tibetan and explains well geographic distributions in this population. These results contribute to our understanding of adaptive responses to altitude and geographic adaptation in Tibetan sheep populations and will help to guide future conservation programs for Tibetan sheep native to Qinghai-Tibetan Plateau.
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http://dx.doi.org/10.1038/s41598-020-75428-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591910PMC
October 2020

Analysis of dynamic and widespread lncRNA and miRNA expression in fetal sheep skeletal muscle.

PeerJ 2020 22;8:e9957. Epub 2020 Sep 22.

Sheep Breeding Engineering Technology Research Center, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.

The sheep is an economically important animal, and there is currently a major focus on improving its meat quality through breeding. There are variations in the growth regulation mechanisms of different sheep breeds, making fundamental research on skeletal muscle growth essential in understanding the regulation of (thus far) unknown genes. Skeletal muscle development is a complex biological process regulated by numerous genes and non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). In this study, we used deep sequencing data from sheep longissimus dorsi (LD) muscles sampled at day 60, 90, and 120 of gestation, as well as at day 0 and 360 following birth, to identify and examine the lncRNA and miRNA temporal expression profiles that regulate sheep skeletal myogenesis. We stained LD muscles using histological sections to analyse the area and circumference of muscle fibers from the embryonic to postnatal development stages. Our results showed that embryonic skeletal muscle growth can be characterized by time. We obtained a total of 694 different lncRNAs and compared the differential expression between the E60 vs. E90, E90 vs. E120, E120 vs. D0, and D0 vs. D360 lncRNA and gene samples. Of the total 701 known sheep miRNAs we detected, the following showed a wide range of expression during the embryonic stage: miR-2387, miR-105, miR-767, miR-432, and miR-433. We propose that the detected lncRNA expression was time-specific during the gestational and postnatal stages. GO and KEGG analyses of the genes targeted by different miRNAs and lncRNAs revealed that these significantly enriched processes and pathways were consistent with skeletal muscle development over time across all sampled stages. We found four visual lncRNA-gene regulatory networks that can be used to explore the function of lncRNAs in sheep and may be valuable in helping improve muscle growth. This study also describes the function of several lncRNAs that interact with miRNAs to regulate myogenic differentiation.
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http://dx.doi.org/10.7717/peerj.9957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518186PMC
September 2020

SOX4 promotes the growth and metastasis of breast cancer.

Cancer Cell Int 2020 29;20:468. Epub 2020 Sep 29.

Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003 People's Republic of China.

Purpose: Increasing evidence has shown that the transcription factor SOX4 is closely associated with the development and progression of many malignant tumors. However, the effect of SOX4 on breast cancer is unclear. In this study, we purposed to investigate the role of SOX4 in the growth and metastasis in breast cancer and the underlying mechanism. Moreover, the effect of SOX4 on cancer cell resistance to chemotherapeutic agents was also evaluated in vitro and in vivo.

Methods: We used lentivirus technique to ectopically express SOX4 in MDA-MB-231 and SUM149 cells or knockdown SOX4 in BT474 cells, and examined the effect of these changes on various cellular functions. MTT assay was used to determine the cell viability as well as resistance to chemotherapeutic agents. The regulation of SOX4 on epithelial-mesenchymal transition (EMT)-related genes was analyzed using qRT-PCR. The binding of SOX4 to the CXCR7 gene was demonstrated using chromatin immunoprecipitation assay and dual-luciferase reporter activity assay. The effect of SOX4/CXCR7 axis on metastasis was examined using Transwell migration and Matrigel invasion assays. The expression of SOX4/CXCR7 in primary tumors and metastatic foci in lymph nodes was assessed using immunohistochemistry. Cellular morphology was investigated under phase contrast microscope and transmission electron microscopy. Moreover, the effect of SOX4 on tumor growth, metastasis, and resistance to chemotherapy was also studied in vivo by using bioluminescent imaging.

Results: SOX4 increased breast cancer cell viability, migration, and invasion in vitro and enhanced tumor growth and metastasis in vivo. It regulated EMT-related genes and bound to CXCR7 promoter to upregulate CXCR7 transcription. Both SOX4 and CXCR7 were highly expressed in human primary tumors and metastatic foci in lymph nodes. Treatment of breast cancer cells with the CXCR7 inhibitor CCX771 reversed the SOX4 effect on cell migration and invasion. Ectopic expression of SOX4 increased the susceptibility of cells to paclitaxel.

Conclusions: SOX4 plays an important role in the growth and metastasis of breast cancer. SOX4/CXCR7 may serve as potential therapeutic targets for the treatment. Paclitaxel may be a good therapeutic option if the expression level of SOX4 is high.
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http://dx.doi.org/10.1186/s12935-020-01568-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523060PMC
September 2020

Insulinoma-associated protein 1 immunostaining for various types of neuroendocrine tumors on FNA smears.

Cancer Cytopathol 2020 10 23;128(10):725-732. Epub 2020 Jun 23.

Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Insulinoma-associated protein 1 (INSM1) has recently emerged as a reliable nuclear immunostaining marker for detecting neuroendocrine tumors (NETs) in paraffin-embedded surgical samples and cytologic cell blocks, but the reliability of INSM1 staining on cytologic smears is understudied. This study investigated the performance of INSM1 staining on cytologic smears for the detection of various NETs in comparison with chromogranin (CG) and synaptophysin (SYN).

Methods: INSM1, CG, and SYN were stained on cytologic smears of 70 NETs, including 20 pancreatic NETs, 10 lung carcinoid tumors, 11 small cell lung carcinomas (SCLCs), 10 medullary thyroid carcinomas, 10 Merkel cell carcinomas, 4 thymic atypical carcinoid tumors, and 5 olfactory neuroblastomas. The detection rate, the percentage of positive cells, and the staining intensity were recorded.

Results: The overall detection rate of INSM1 (94%) was higher than the rates of CG (79%) and SYN (89%). The detection rate of INSM1 was higher than the rates of CG and SYN in SCLC, Merkel cell carcinoma, and olfactory neuroblastoma; higher than the rate of CG and equal to the rate of SYN in pancreatic NETs and medullary thyroid carcinoma; equal to the rate of CG and higher than the rate of SYN in thymic atypical carcinoid tumors; and equal to the rate of CG and lower than the rate of SYN in lung carcinoid tumors. INSM1 staining was easier to interpret than CG and SYN staining, especially in high-grade NETs.

Conclusions: INSM1 can be reliably stained on cytologic smears and outperforms CG and SYN in the verification of clinically or radiologically suspected NETs.
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http://dx.doi.org/10.1002/cncy.22310DOI Listing
October 2020

High levels of immunoglobulin expression predict shorter overall survival in patients with acute myeloid leukemia.

Eur J Haematol 2020 Oct 9;105(4):449-459. Epub 2020 Jul 9.

Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Objectives: It has been believed that immunoglobulins can only be produced by B lymphocytes and plasma cells. We have previously reported that IgG can be expressed in myeloblasts from patients with acute myeloid leukemia (AML) and plays a role in the proliferation and apoptosis of leukemic cells. However, its clinical impact has not been assessed.

Methods: We assessed the expression of different classes of immunoglobulin in peripheral blood and bone marrow samples from 132 AML patients and correlated the levels of expression with clinicopathologic and molecular genetic features, as well as clinical outcome.

Results: We found that, in addition to IgG, all classes of immunoglobulin are expressed in myeloblasts, including IgG, IgM, IgA, IgD, IgE, Igκ, and Igλ. The levels of IgG expression (coupled with Igκ or Igλ) are higher than those of IgM, IgA, IgD, and IgE. Using receiver operating characteristic (ROC) curve analysis, we identified two distinct groups of AML patients with differential expression of immunoglobulin and different clinical outcomes.

Conclusions: High levels of immunoglobulin expression are associated with monocytic differentiation, multilineage dysplasia, TET2 and KRAS mutations, and poor overall survival. Assessment of immunoglobulin may serve as a useful marker for prognostic stratification and target therapy.
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http://dx.doi.org/10.1111/ejh.13466DOI Listing
October 2020

Role of identified noncoding RNA in erectile dysfunction.

Andrologia 2020 Aug 22;52(7):e13596. Epub 2020 May 22.

Hangzhou Xixi Hospital affiliated to Zhejiang Chinese Medical University, Hangzhou, China.

Erectile dysfunction (ED) is a common male sexual dysfunction and is closely related to many risk factors such as age, chronic diseases and mental disorder. Phosphodiesterase type 5 inhibitor (PDE5i) is recommended as the first-line medicine in therapy, but up to 35% of patients fail to this treatment. Unfortunately, the pathogenesis of ED is still poorly understood. Hence, it has reached the state that researchers should seek for new candidate biomarkers or therapeutic targets. Recent studies have reported that noncoding RNAs (ncRNAs) such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are involved in the pathogenesis process of ED, even in stem cell therapy. In this review, we aim to summarise the mechanisms and functions of identified ncRNAs that are associated with ED.
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http://dx.doi.org/10.1111/and.13596DOI Listing
August 2020

Genome-Wide Association Study of Body Weight Traits in Chinese Fine-Wool Sheep.

Animals (Basel) 2020 Jan 19;10(1). Epub 2020 Jan 19.

Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China.

Body weight is an important economic trait for sheep and it is vital for their successful production and breeding. Therefore, identifying the genomic regions and biological pathways that contribute to understanding variability in body weight traits is significant for selection purposes. In this study, the genome-wide associations of birth, weaning, yearling, and adult weights of 460 fine-wool sheep were determined using resequencing technology. The results showed that 113 single nucleotide polymorphisms (SNPs) reached the genome-wide significance levels for the four body weight traits and 30 genes were annotated effectively, including , , , and . The genes annotated by these SNPs significantly enriched 78 gene ontology terms and 25 signaling pathways, and were found to mainly participate in skeletal muscle development and lipid metabolism. These genes can be used as candidate genes for body weight in sheep, and provide useful information for the production and genomic selection of Chinese fine-wool sheep.
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http://dx.doi.org/10.3390/ani10010170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022301PMC
January 2020

TCR Repertoires of Thymic Conventional and Regulatory T Cells: Identification and Characterization of Both Unique and Shared TCR Sequences.

J Immunol 2020 02 10;204(4):858-867. Epub 2020 Jan 10.

Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;

Thymic regulatory T cells (tTreg) are critical in the maintenance of normal T cell immunity and tolerance. The role of TCR in tTreg selection remains incompletely understood. In this study, we assessed TCRα and TCRβ sequences of mouse tTreg and thymic conventional CD4 T cells (Tconv) by high-throughput sequencing. We identified αβ TCR sequences that were unique to either tTreg or Tconv and found that these were distinct as recognized by machine learning algorithm and by preferentially used amino acid trimers in αβ CDR3 of tTreg. In addition, a proportion of αβ TCR sequences expressed by tTreg were also found in Tconv, and machine learning classified the great majority of these shared αβ TCR sequences as characteristic of Tconv and not tTreg. These findings identify two populations of tTreg, one in which the regulatory T cell fate is associated with unique properties of the TCR and another with TCR properties characteristic of Tconv for which tTreg fate is determined by factors beyond TCR sequence.
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http://dx.doi.org/10.4049/jimmunol.1901006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002224PMC
February 2020

A multi-scale approach to study biochemical and biophysical aspects of resveratrol on diesel exhaust particle-human primary lung cell interaction.

Sci Rep 2019 12 3;9(1):18178. Epub 2019 Dec 3.

Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT, 84322, USA.

Diesel exhaust particles (DEPs) are major air pollutants that lead to numerous human disorders, especially pulmonary diseases, partly through the induction of oxidative stress. Resveratrol is a polyphenol that ameliorates the production of reactive oxygen species (ROS) and delays aging-related processes. Herein we studied the cytoprotective effect of resveratrol on DEP-exposed human lung cells in a factorial experimental design. This work investigates biophysical features including cellular compositions and biomechanical properties, which were measured at the single-cell level using confocal Raman microspectroscopy (RM) and atomic force microscopy (AFM), respectively. Principal component analysis (PCA), hierarchical cluster analysis (HCA) and partial least square regression (PLS) analysis were applied to analyze Raman spectra with and without resveratrol protection. The health status of individual cells could be effectively predicted using an index derived from characteristic Raman spectral peak (e.g., 1006 cm) based on PLS model. AFM measurements indicated that cellular adhesion force was greatly reduced, while Young's modulus was highly elevated in resveratrol treated DEP-exposed cells. Anti-oxidant resveratrol reduced DEP-induced ROS production and suppressed releases of several cytokines and chemokines. These findings suggest resveratrol may enhance resistance of human lung cells (e.g., SAEC) to air pollutants (e.g. DEPs).
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http://dx.doi.org/10.1038/s41598-019-54552-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890693PMC
December 2019

The value of ultrasound for detecting hand fractures: A meta-analysis.

Medicine (Baltimore) 2019 Nov;98(44):e17823

Department of Health Management Center.

Backgrounds: Hand fractures are the second most common upper-extremity fractures. The standard X-ray has shortcomings, such as exposure to radiation. Ultrasound has been reported as an alternative method of detecting hand fractures. In this study, we used meta-analysis to assess the diagnostic value of ultrasound for hand fractures.

Methods: Web of Science, PubMed, Embase, and Cochrane Library databases were searched for relative citations up to June 2019. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the summary receiver operating characteristic curve (AUC), and summary receiver operating characteristic (SROC) curve were estimated.

Results: Seven studies including 842 participants (845 examined hands) met our inclusion criteria. The pooled sensitivity, specificity, PLR, and NLR of ultrasound for detecting hand fractures were 91%, 96%, 20.66, and 0.09, respectively. The pooled DOR was 231.17, indicating a very powerful diagnostic ability of ultrasound. Meta-regression showed that there was no heterogeneity with respect to age, cut-off, the performer of the ultrasound, and the types of hand fractures.

Conclusions: Our results showed that ultrasound had an excellent diagnostic value for hand fractures. In clinic, we proposed using ultrasound as a first-line and radiation-free modality in detecting hand fractures, including phalanx and metacarpal fractures.
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http://dx.doi.org/10.1097/MD.0000000000017823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946312PMC
November 2019

Usefulness of Dual Immunohistochemistry Staining in Detection of Hairy Cell Leukemia in Bone Marrow.

Am J Clin Pathol 2020 02;153(3):322-327

Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.

Objectives: We evaluated efficacy of two dual immunohistochemistry (IHC) staining assays in assessing hairy cell leukemia (HCL) involvement in core biopsies and compared the results with concurrently collected flow cytometric data.

Methods: Overall, 148 patients with HCL (123 male, 25 female; mean age: 59.8 years; range: 25-81 years) had multiparameter flow cytometry performed using CD19, CD20, CD22, CD11c, CD25, CD103, CD123, surface light chains, CD5, and CD23. In parallel, bone marrow IHC was done using PAX5/CD103 and PAX5/tartrate-resistant alkaline phosphatase (TRAP) dual IHC stains.

Results: Overall sensitivity of dual IHC stains was 81.4%, positive predictive value was 100%, and negative predictive value was 81.7%. All IHC-positive cases concurred with flow cytometry data, even when HCL burden was extremely low in the flow cytometry specimens (as low as 0.02% of all lymphoid cells).

Conclusions: Dual IHC stain is a sensitive tool in detecting HCL, even in cases with minimal disease involvement.
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http://dx.doi.org/10.1093/ajcp/aqz171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315001PMC
February 2020

Exploring ecosystem services and scenario simulation in the headwaters of Qiantang River watershed of China.

Environ Sci Pollut Res Int 2019 Dec 27;26(34):34905-34923. Epub 2019 Oct 27.

Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment of the People's Republic of China, Nanjing, 210042, China.

Background: Land use change has a significant impact on ecosystem services in watershed systems. The upper part of Qiantang River, Kaihua Country has experienced land-use changes over the past 15 years, but the effect of these changes on ecosystem services remains unknown.

Objective: This study evaluates land-use changes in response to ecological protection and the effects on ecosystem services.

Methods: Ecosystem services during 2000-2015 are assessed and compared to future land use scenarios in 2025 (business-as-usual, strategic planning, environmental protection, and economic development). These scenarios are identified in collaboration with local stakeholders and used to assess changes in ecosystem services under future scenarios.

Results: Analysis shows that during 2000-2015, the woodland increased by 7335 ha as a result of the "Grain for green" policy, and the built-up land increased by 2259 ha due to urbanization, and these changes affected ecosystem services, such as water yield, nitrogen and phosphorus exports which decreased by 0.29%, 12.45%, and 13.74%, respectively, and soil retention, carbon storage, and habitat quality index increased by 0.05%, 1.36%, and 0.80%, respectively.

Conclusion: Among all the future scenarios, the strategic planning scenario is an optimal land use strategy to balance the demand for urban development, while providing higher levels of ecosystem services.
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http://dx.doi.org/10.1007/s11356-019-06483-2DOI Listing
December 2019

Utility of NKX3.1 Immunostaining in the Detection of Metastatic Prostatic Carcinoma on Fine-Needle Aspiration Smears.

Am J Clin Pathol 2019 09;152(4):495-501

Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston.

Objectives: NK3 homeobox 1 (NKX3.1) has been increasingly used to diagnose metastatic prostatic carcinoma in histologic samples. However, its utility and reliability in cytologic direct smears have not been studied.

Methods: A total of 59 fine-needle aspiration (FNA) cases with a definitive diagnosis of metastatic carcinoma from the prostate were included. The cases were grouped based on different Gleason score in their corresponding primary tumors and morphologic variants. For each case, tumor cells were immunostained with NKX3.1, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP) on cell-transferred smears.

Results: NKX3.1 was strongly and diffusely positive in all 40 metastatic prostatic adenocarcinomas, including those with ductal features, but negative for the 19 small cell carcinoma (SmCC) cases. NKX3.1 had a better detection rate than PSA (13/50, 26%) and PAP (0/47, 0%).

Conclusions: NKX3.1 immunostaining on FNA smears is highly reliable for detecting metastatic prostatic carcinomas of conventional and ductal types but not for SmCC.
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http://dx.doi.org/10.1093/ajcp/aqz063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344246PMC
September 2019

Benralizumab for -Negative Hypereosinophilic Syndrome.

N Engl J Med 2019 04;380(14):1336-1346

From the Laboratory of Parasitic Diseases (F.L.K., F.L., M.M., J.W., L.W., T.B., T.M., B.P., P.Y., P.K., A.D.K.) and Biostatistics Research Branch (M.P.F.), National Institute of Allergy and Infectious Diseases, the Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (H.A., S.K.), and the Laboratory of Pathology, National Cancer Institute (A.P., M.Q.), National Institutes of Health (NIH), and the Departments of Laboratory Medicine (J.H.E., X.S., I.M.) and Transfusion Medicine (S.R.P.), NIH Clinical Center, Bethesda, Washington Adventist Hospital, Takoma Park (T.M.), and MedImmune (N.L., R.K.) and AstraZeneca (P.N., M.G.), Gaithersburg - all in Maryland; the Department of Veteran Affairs, Tennessee Valley Healthcare System, Chattanooga (J.H.E.); and MedImmune, South San Francisco, CA (L.Y.).

Background: Hypereosinophilic syndrome is a group of diseases defined by marked eosinophilia in blood or tissue and eosinophil-related clinical manifestations. Benralizumab is a monoclonal antibody against interleukin-5 receptor α, which is expressed on human eosinophils.

Methods: In this randomized, double-blind, placebo-controlled, phase 2 trial, we administered a series of three monthly subcutaneous injections of either benralizumab (at a dose of 30 mg) or placebo in 20 symptomatic patients who had -negative hypereosinophilic syndrome and an absolute eosinophil count of at least 1000 cells per cubic millimeter; all the patients were receiving stable therapy (drugs or dietary changes) for this disease. This regimen was followed by an open-label phase, during which the patient's background therapy could be tapered as tolerated, and an extension phase. The primary end point of the randomized phase was a reduction of at least 50% in the absolute eosinophil count at week 12.

Results: During the randomized phase, the primary end point occurred in more patients in the benralizumab group than in the placebo group (9 of 10 patients [90%] vs. 3 of 10 patients [30%], P = 0.02). During the open-label phase, clinical and hematologic responses were observed in 17 of 19 patients (89%) and were sustained for 48 weeks in 14 of 19 patients (74%); in the latter group, in 9 of 14 patients (64%), background therapies could be tapered. Bone marrow and tissue eosinophilia were also suppressed with benralizumab therapy. The most common drug-related adverse events, headache and an elevated lactate dehydrogenase level, occurred in 32% of the patients after the first dose of benralizumab and resolved within 48 hours in all patients. Other adverse events occurred with similar frequency in the two groups. Of the many potential predictors of response that were examined, only clinical disease subtype appeared to be associated with the initial response or relapse.

Conclusions: In this small phase 2 trial, patients with -negative hypereosinophilic syndrome who received benralizumab for 12 weeks had lower absolute eosinophil counts than those who received placebo. During the open-label phase, clinical and hematologic responses were sustained for 48 weeks in 74% of the patients. Adverse events did not limit treatment. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov numbers, NCT00001406 and NCT02130882.).
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http://dx.doi.org/10.1056/NEJMoa1812185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557265PMC
April 2019

Molecular constraints on CDR3 for thymic selection of MHC-restricted TCRs from a random pre-selection repertoire.

Nat Commun 2019 03 4;10(1):1019. Epub 2019 Mar 4.

Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, MD, 20852, USA.

The αβ T cell receptor (TCR) repertoire on mature T cells is selected in the thymus, but the basis for thymic selection of MHC-restricted TCRs from a randomly generated pre-selection repertoire is not known. Here we perform comparative repertoire sequence analyses of pre-selection and post-selection TCR from multiple MHC-sufficient and MHC-deficient mouse strains, and find that MHC-restricted and MHC-independent TCRs are primarily distinguished by features in their non-germline CDR3 regions, with many pre-selection CDR3 sequences not compatible with MHC-binding. Thymic selection of MHC-independent TCR is largely unconstrained, but the selection of MHC-specific TCR is restricted by both CDR3 length and specific amino acid usage. MHC-restriction disfavors TCR with CDR3 longer than 13 amino acids, limits positively charged and hydrophobic amino acids in CDR3β, and clonally deletes TCRs with cysteines in their CDR3 peptide-binding regions. Together, these MHC-imposed structural constraints form the basis to shape VDJ recombination sequences into MHC-restricted repertoires.
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http://dx.doi.org/10.1038/s41467-019-08906-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399321PMC
March 2019

Rational "Error Elimination" Approach to Evaluating Molecular Barcoded Next-Generation Sequencing Data Identifies Low-Frequency Mutations in Hematologic Malignancies.

J Mol Diagn 2019 05 20;21(3):471-482. Epub 2019 Feb 20.

Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address:

The emergence of highly sensitive molecular diagnostic approaches, such as droplet digital PCR, has allowed the accurate identification of low-frequency variant alleles in clinical specimens; however, the multiplex capabilities of droplet digital PCR for variant detection are inadequate. The incorporation of molecular barcodes or unique IDs into next-generation sequencing libraries through PCR has enabled the detection of low-frequency variant alleles across multiple genomic regions. However, rational library preparation and sequencing data analytic strategies that integrate molecular barcodes have rarely been applied to clinical settings. In this study, we evaluated the parameters that are crucial in the use of molecular barcodes in next-generation sequencing for genotyping clinical specimens from patients with hematologic malignancies. The uniform incorporation of molecular barcodes into DNA templates through PCR was found to be crucial, and the extent of uniformity was governed by multiple interdependent variables. An error elimination strategy was developed for removing sequencing background errors by using molecular barcode sequence information as an alternative to the conventional error correction approach. This approach was successfully used to identify mutations with frequencies as low as 0.15%, and the clonal heterogeneity of hematologic malignancies was revealed. These findings have implications for elucidating heterogeneity and temporal and spatial clonal evolution, evaluating response to therapy, and monitoring relapse in patients with hematologic malignancies.
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http://dx.doi.org/10.1016/j.jmoldx.2019.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521894PMC
May 2019

Advances in diagnosis of mastocytosis and hypereosinophilic syndrome.

Semin Hematol 2019 01 28;56(1):22-29. Epub 2018 May 28.

Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1508.

Mastocytosis and hypereosinophilic syndrome is very rare neoplastic hematopoietic diseases. Mastocytosis is characterized by expansion and accumulation of clonal tissue mast cells in skin and/or various internal organs, while hypereosinophilic syndrome manifests with an increased number of eosinophils in the peripheral blood and tissue damage. These diseases represent a diagnostic challenge, since they can have overlapping clinical and pathologic features. Recently, great advances in the molecular and immunophenotypic diagnosis of these two entities were achieved, contributing to the new World Health Organization (WHO) classification. The WHO classification of myeloid neoplasms has been revised in 2016 by adding several new entities and refinement of the 2008 WHO classification, in an attempt to incorporate up-to-date clinical, prognostic, morphologic, and molecular genetics data that emerged since 2008. Here we overview the recent advances in disease diagnosis, with a focus on the updated WHO classification, refined diagnostic criteria, and up-to-date molecular findings in these two rare diseases.
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http://dx.doi.org/10.1053/j.seminhematol.2018.05.005DOI Listing
January 2019

Detection of KIT D816V in peripheral blood of children with manifestations of cutaneous mastocytosis suggests systemic disease.

Br J Haematol 2018 12;183(5):775-782

Mast Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

The use of allele-specific quantitative polymerase chain reaction to identify KIT D816V in the peripheral blood of adults with mastocytosis has been reported to have value in the diagnosis, assessment of disease burden and management of this disease. To examine the value of this assay in children with cutaneous manifestations of mastocytosis, we assessed data on 65 patients with all variants of paediatric-onset mastocytosis, including those known to have systemic disease, to correlate KIT mutation status with clinical findings, serum tryptase levels and bone marrow histopathology. We found that KIT D816V was not identified in the peripheral blood of children known to have only cutaneous disease (specificity 100%) but was found in those known to have both cutaneous and systemic/probable systemic disease (sensitivity of 85·2%). These findings were the basis of the development of an algorithm to assist in the decision for when to perform a bone marrow biopsy in children presenting with cutaneous manifestations of mastocytosis.
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http://dx.doi.org/10.1111/bjh.15624DOI Listing
December 2018

Triptolide inhibits Epstein-Barr nuclear antigen 1 expression by increasing sensitivity of mitochondria apoptosis of nasopharyngeal carcinoma cells.

J Exp Clin Cancer Res 2018 Aug 15;37(1):192. Epub 2018 Aug 15.

The State Key Laboratory of Virology, Department of Pathogen Biology, School of Basic Medical Sciences, Hubei Province Key Laboratory of Allergy and Immune-related Diseases, Wuhan University, 185 Eastlake Road, Wuhan, 430071, People's Republic of China.

Background: Epstein-Barr virus (EBV) is widely found in nasopharyngeal carcinoma (NPC) tissue and associated with poor prognosis of patients. EBV nuclear antigen 1 (EBNA1) is expressed in all NPC tumors and plays multiple biological roles in both virus and host cells. Triptolide is a natural product extracted from Tripterygium and shows anti-cancer activities. The goal of this work was to illustrate the anti-cancer effect of triptolide and elucidate a novel anti-apoptotic mechanism of EBNA1 in NPC cells encountered with triptolide.

Methods: In the present study, a CCK-8 assay was used to analyze the proliferation of NPC cells treated with triptolide in a dose- and time-dependent ways. Effects of triptolide on NPC cell cycle and apoptosis were investigated by flow cytometric analysis. EBNA1 expression in mRNA and protein levels was determined by quantitative real-time PCR and Western blot, respectively.

Results: Our results showed that triptolide effectively inhibited proliferation of NPC cells. Triptolide arrested NPC cell cycles in S phase and induced apoptosis through a caspase-9-dependent apoptosis pathway. Low-dose of triptolide reduced the half-life of EBNA1 and significantly decreased EBNA1 expression by promoting the process of proteasome-ubiquitin pathway. Over-expression of EBNA1, which was independent from EBV genome, effectively attenuated the apoptosis induced by triptolide. In addition, triptolide significantly inhibited proliferations of tumors induced by EBV-positive cells in vivo. Furthermore, EBNA1 were expressed in all NPC biopsies of Chinese patients.

Conclusions: In summary, our study provides the evidence that triptolide induces EBNA1 degradation and stimulates NPC apoptosis through mitochondria apoptotic pathway. In addition, EBNA1 assists NPC cells to resist triptolide-induced apoptosis through inhibiting caspase-9-dependent apoptotic pathway.
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http://dx.doi.org/10.1186/s13046-018-0865-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094928PMC
August 2018

Taurocholic acid is an active promoting factor, not just a biomarker of progression of liver cirrhosis: evidence from a human metabolomic study and in vitro experiments.

BMC Gastroenterol 2018 Jul 11;18(1):112. Epub 2018 Jul 11.

Second department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.

Background: Previous studies have indicated that bile acid is associated with progression of liver cirrhosis. However, the particular role of specific bile acid in the development of liver cirrhosis is not definite. The present study aims to identify the specific bile acid and explore its possible mechanisms in promoting liver cirrhosis.

Methods: Thirty two cirrhotic patients and 27 healthy volunteers were enrolled. Age, gender, Child-Pugh classification and serum of patients and volunteers were collected. Liquid chromatography tandem mass spectrometry (LC-MS) was utilized to determine concentrations of 12 bile acids in serum. Principal component analysis, fold change analysis and heatmap analysis were used to identify the most changed bile acid. And pathway analysis was used to identify the most affected pathway in bile acid metabolism. Spearman rank correlation analysis was employed to assess correlation between concentrations of bile acids and Child-Pugh classification. Hepatic stellate cells (LX-2) were cultured in DMEM. LX-2 cells were also co-cultured with HepG2 cells in the transwell chambers. LX-2 cells were treated with Na+/taurocholate in different concentrations. Western blot was used to evaluate the expression of alpha smooth muscle actin (α-SMA), type I collagen, and Toll-like receptor 4 (TLR4) in LX-2 cells.

Results: Concentrations of 12 bile acids in serum of patients and healthy volunteers were determined with LC-MS successively. Principal component analysis, fold change analysis and heatmap analysis identified taurocholic acid (TCA) to be the most changed bile acid. Pathway analysis showed that TCA biosynthesis increased significantly. Spearman rank correlation analysis showed that concentration of TCA in serum of cirrhotic patients was positively associated with Child-Pugh classification. TCA increased the expression of α-SMA, type I collagen, and TLR4 in LX-2 cells. Moreover, the above effect was strengthened when LX-2 cells were co-cultured with HepG2 cells.

Conclusions: Increased TCA concentration in serum of liver cirrhotic patients is mainly due to increased bile acid biosynthesis. TCA is an active promoter of the progression of liver cirrhosis. TCA promoting liver cirrhosis is likely through activating hepatic stellate cells via upregulating TLR4 expression. TCA is a potential therapeutic target for the prevention and treatment of liver cirrhosis.
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http://dx.doi.org/10.1186/s12876-018-0842-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042259PMC
July 2018

The Hsp70 inhibitor 2-phenylethynesulfonamide inhibits replication and carcinogenicity of Epstein-Barr virus by inhibiting the molecular chaperone function of Hsp70.

Cell Death Dis 2018 06 29;9(7):734. Epub 2018 Jun 29.

The State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and Immune-related Diseases, Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China.

Epstein-Barr virus (EBV) can infect cells in latent and lytic period and cause serious disease. Epstein-Barr virus nuclear antigen 1 (EBNA1) is essential for the maintenance of the EBV DNA episome, replication and transcription. 2-phenylethynesulfonamide (PES) is a small molecular inhibitor of Heat shock protein 70 (Hsp70), which can interact with Hsp70 and disrupts its association with co-chaperones and substrate proteins of Hsp70. In our study, we found that PES could decrease the expression of EBNA1, which is independent of effects on EBNA1 transcription or proteasomal degradation pathway. The central glycine-alanine repeats domain was not required for inhibition of EBNA1 expression by PES. Also, PES could reduce the amount of intracellular EBV genomic DNA. PES inhibited proliferation and migration but induced cell cycle arrest and apoptosis of EBV positive cells. In addition, silencing of Hsp70 decreased expression of EBNA1 and the amounts of intracellular EBV genomic DNA, and PES increased this effect on a dose-dependent manner. On the contrast, over-expression of Hsp70 enhanced the expression of EBNA1 and the amounts of intracellular EBV genomic DNA, but PES inhibited this effect on a dose-dependent manner. Furthermore, Hsp70 interacted with EBNA1 but PES interfered this interaction. Our results indicate that PES suppresses replication and carcinogenicity of Epstein-Barr virus via inhibiting the molecular chaperone function of Hsp70.
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http://dx.doi.org/10.1038/s41419-018-0779-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026193PMC
June 2018

The contribution of cause-effect link to representing the core of scientific paper-The role of Semantic Link Network.

PLoS One 2018 21;13(6):e0199303. Epub 2018 Jun 21.

Laboratory of Cyber-Physical-Social Intelligence, Guangzhou University, China.

The Semantic Link Network is a general semantic model for modeling the structure and the evolution of complex systems. Various semantic links play different roles in rendering the semantics of complex system. One of the basic semantic links represents cause-effect relation, which plays an important role in representation and understanding. This paper verifies the role of the Semantic Link Network in representing the core of text by investigating the contribution of cause-effect link to representing the core of scientific papers. Research carries out with the following steps: (1) Two propositions on the contribution of cause-effect link in rendering the core of paper are proposed and verified through a statistical survey, which shows that the sentences on cause-effect links cover about 65% of key words within each paper on average. (2) An algorithm based on syntactic patterns is designed for automatically extracting cause-effect link from scientific papers, which recalls about 70% of manually annotated cause-effect links on average, indicating that the result adapts to the scale of data sets. (3) The effects of cause-effect link on four schemes of incorporating cause-effect link into the existing instances of the Semantic Link Network for enhancing the summarization of scientific papers are investigated. The experiments show that the quality of the summaries is significantly improved, which verifies the role of semantic links. The significance of this research lies in two aspects: (1) it verifies that the Semantic Link Network connects the important concepts to render the core of text; and, (2) it provides an evidence for realizing content services such as summarization, recommendation and question answering based on the Semantic Link Network, and it can inspire relevant research on content computing.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199303PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013162PMC
April 2019

Dexpramipexole as an oral steroid-sparing agent in hypereosinophilic syndromes.

Blood 2018 08 8;132(5):501-509. Epub 2018 May 8.

Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases.

Hypereosinophilic syndromes (HESs) are a heterogeneous group of disorders characterized by peripheral eosinophilia and eosinophil-related end organ damage. Whereas most patients respond to glucocorticoid (GC) therapy, high doses are often necessary, and side effects are common. Dexpramipexole (KNS-760704), an orally bioavailable synthetic aminobenzothiazole, showed an excellent safety profile and was coincidentally noted to significantly decrease absolute eosinophil counts (AECs) in a phase 3 trial for amyotrophic lateral sclerosis. This proof-of-concept study was designed to evaluate dexpramipexole (150 mg orally twice daily) as a GC-sparing agent in HESs. Dual primary end points were (1) the proportion of subjects with ≥50% decrease in the minimum effective GC dose (MED) to maintain AEC <1000/μL and control clinical symptoms, and (2) the MED after 12 weeks of dexpramipexole (MEDD) as a percentage of the MED at week 0. Out of 10 subjects, 40% (95% confidence interval [CI], 12%, 74%) achieved a ≥50% reduction in MED, and the MEDD/MED ratio was significantly <100% (median, 66%; 95% CI, 6%, 98%; = .03). All adverse events were self-limited, and none led to drug discontinuation. Affected tissue biopsy samples in 2 subjects showed normalization of pathology and depletion of eosinophils on dexpramipexole. Bone marrow biopsy samples after 12 weeks of dexpramipexole showed selective absence of mature eosinophils in responders. Dexpramipexole appears promising as a GC-sparing agent without apparent toxicity in a subset of subjects with GC-responsive HESs. Although the exact mechanism of action is unknown, preliminary data suggest that dexpramipexole may affect eosinophil maturation in the bone marrow. This study was registered at www.clinicaltrials.gov as #NCT02101138.
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http://dx.doi.org/10.1182/blood-2018-02-835330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073324PMC
August 2018

Baicalein inhibits growth of Epstein-Barr virus-positive nasopharyngeal carcinoma by repressing the activity of EBNA1 Q-promoter.

Biomed Pharmacother 2018 Jun 5;102:1003-1014. Epub 2018 Apr 5.

Stat Key Laboratory of Virology, Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, PR China; State Key Laboratory of Virology, Wuhan University, Wuhan, 430072, PR China. Electronic address:

Epstein-Barr virus (EBV) can establish a life-long latent infection in the host and is associated with various human malignancies, including nasopharyngeal carcinoma (NPC), the most common cancer originated from nasopharynx. EBV nuclear antigen 1 (EBNA1) is the only viral protein absolutely demanded for segregation, replication, transcription and maintenance of EBV viral genome in host cells. Baicalein, a bioactive flavonoid compound purified from the root of Scutellariae baicaleinsis, displays anti-inflammatory, immunosuppressive, and anti-tumor properties. In this study, the therapeutic effects and functional mechanism of baicalein on EBV-positive human NPC were determined. Cell Counting Kit-8 assays and cell formation colony were performed to investigate that baicalein can suppress proliferation of EBV-infected human NPC cells. Flow cytometric and hoechst 33258 staining results indicated that baicalein induced cell cycle arrest and apoptosis. Western blotting results demonstrated that baicalein down-regulates EBNA1 expression but not reduces the stability and half-life of EBNA1 in EBV-infected NPC cells. Additionally, the mRNA level of EBNA1 was examined by real time-PCR, the activity of EBNA1 Q promoter (Qp) was determined by dual luciferase reporter assay. Considering that transcription factor specificity protein 1 (Sp1) can maintain EBNA1 Qp active. Further analyses also elucidated that baicalein inhibits the expression of Sp1 while knock-down Sp1 by specific shRNAs decreases the expression and transcription levels of EBNA1. Therefore, the results suggested that baicalein may decrease EBNA1 expression level in EBV-positive NPC cells via inhibiting the activity of EBNA1 Q-promoter while over-expression of EBNA1 attenuate the inhibitory effect of baicalein. Finally, it was found that baicalein may strongly reduce growth of tumor in the mouse xenograft model of EBV-positive NPC. These results indicated that baicalein inhibits growth of EBV-positive NPC by repressing the activity of EBNA1 Q-promoter. Baicalein may be used as a therapeutic agent to treat EBV-positive NPC.
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http://dx.doi.org/10.1016/j.biopha.2018.03.114DOI Listing
June 2018

Anti-migraine and anti-depression activities of Tianshu capsule by mediating Monoamine oxidase.

Biomed Pharmacother 2018 Apr 16;100:275-281. Epub 2018 Feb 16.

State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Lianyungang 222001, China. Electronic address:

Background: Tianshu capsule(TSC)is a Chinese patent medicine. It's widely used to treat migraine clinically in China.

Aim Of The Study: In the present study, we investigated anti-migraine and anti-depression activities of TSC using in vivo animal models together with in vitro studies to investigate the mechanism of action.

Materials And Methods: Nitroglycerin (NTG) -induced migraine rat model, rat was given a subcutaneous injection of the NTG suspension (10 mg/kg) once a week for 5 weeks. Behavioral observation was carried out and brain tissues were sampled to determine levels of 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE), monoamine oxidase A (MAO-A), monoamine oxidase B (MAO-B) and tyrosine hydroxylase (TH) by ELISA, in order to evaluate the effect of TSC on migraine progression. Tail suspension test and forced swim test were carried in order to evaluate the effect of TSC on depression progression.

Results: TSC treatments decreased scratch head times significantly in a rat migraine model. Meanwhile, TSC suppressed activities of MAO-A and MAO-B, up-regulated 5-HT, DA and NE expressions in brain tissues. Tail suspension test showed a decrease of immobility time in TSC groups. Furthermore, TSC increased climb times, up-regulated activities of 5-HT, DA and NE in forced swim test mice. Additionally, TSC could attenuate the reduction of 5-HT, DA and NE induced by corticosterone in primary neuronal cells.

Conclusion: TSC could effectively prevent depression, one of the most frequent comorbidities in migraine. It may provide a new target for treating migraine.
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http://dx.doi.org/10.1016/j.biopha.2018.01.171DOI Listing
April 2018

Expression of Programmed Death Ligand 1 (PD-L1) in Posttreatment Primary Inflammatory Breast Cancers and Clinical Implications.

Am J Clin Pathol 2018 Feb;149(3):253-261

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston.

Objectives: Inflammatory breast carcinoma (IBC) is rare but is the most lethal type of breast cancer. Programmed death ligand 1 (PD-L1) expression in IBCs has been understudied.

Methods: In this study, tissue microarrays of 68 IBCs were immunostained with a PD-L1 antibody using an antibody clone (28-8) and detection system approved by the US Food and Drug Administration for selecting patients with non-small cell lung cancer and melanoma for anti-PD-L1 therapy.

Results: Positive PD-L1 expression was found in 25 (36.8%) of 68 samples but was not significantly associated with the clinicopathologic variables examined. Univariate analysis of overall survival (OS) revealed that worse OS was significantly associated with positive PD-L1, negative estrogen receptor, and triple-negative status. The 5-year OS rate was 36.4% for patients with PD-L1-positive IBC and 47.3% for those with PD-L1-negative IBC. In multivariate analyses, PD-L1 status remained a statistically independent predictor of OS.

Conclusions: These findings indicate that PD-L1 inhibitors could potentially improve the clinical outcome of patients with PD-L1-positive IBC.
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http://dx.doi.org/10.1093/ajcp/aqx162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322426PMC
February 2018
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