Publications by authors named "Xiaoyan Qu"

75 Publications

Prognostic value of circulating clonal plasma cells in newly diagnosed multiple myeloma.

Hematology 2021 Dec;26(1):510-517

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, People's Republic of China.

Objectives: Multiple myeloma (MM) involves a clinically and biologically heterogeneous malignancy of plasma cells. It is difficult to predict the prognosis of MM. The presence of circulating clonal plasma cells (CPC) has been associated with a worse prognosis in patients with MM.

Methods: This study retrospectively analysed CPC in 108 newly diagnosed MM patients by 8-colour flow cytometry to investigate their value for predicting the outcome and combined the level of CPC with the revised International Staging System (R-ISS) to stratify the MM patients according to risk.

Results: CPC were detected in 58/108 patients (53.7%). The optimum cut-off for the prediction of overall survival was determined to be 0.105%. Patients with higher R-ISS stages seemed to harbour more CPC. A level of CPC≥0.105% was an independent risk factor for adverse outcomes (<0.001). The combination of the R-ISS staging system and level of CPC was used to stratify MM patients according to risk, and the combination of R-ISS stage III and a level of CPC≥0.105% defined the ultra-high-risk group.

Conclusion: This study suggests that a high proportion of CPC is associated with aggressive disease and that the use of the current R-ISS system in conjunction with assessment of the level of CPC may facilitate the stratification of newly diagnosed MM patients into clinically relevant prognostic subgroups.
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http://dx.doi.org/10.1080/16078454.2021.1948208DOI Listing
December 2021

Pure erythroid leukemia subsequent to acute myelomonocytic leukemia: A case report.

Medicine (Baltimore) 2021 Apr;100(15):e25528

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Hematology of Nanjing Medical University.

Rationale: Pure erythroid leukemia is a rare subcategory of acute myeloid leukemia characterized by predominant immature erythroid population. Its occurrence subsequent to acute myelomonocytic leukemia has not been reported before. We reported this rare case to call attention because it may pose a diagnostic challenge.

Patients Concerns: A 54-year-old female patient presented to our hospital in March 2018 with symptoms of easy fatigability.

Diagnosis: Bone marrow aspiration was hypercellular showing 67.2% blasts mainly including moderate myeloblasts and monoblasts. There was mild dysplasia with some cells having round, oval, or bizarre nuclei which containing 1 to 3 nucleolus. Erythroid lineage was hypoplasia and mature erythrocytes were generally normal. Conventional cytogenetics of bone marrow cells revealed complex karyotype (44, XX, del (5) (q14q34) del (5) (q14q34), del (14) t (11;14) (q10; q10), -16, del (17), -18[10]).

Interventions: The patient was treated with second line chemotherapy but did not respond.

Qutcomes: She died of cardiopulmonary failure 19days after starting of therapy.

Lessons: This unexpected and relatively uncommon occurrence was associated with a universally rapid and fatal clinical course with survival measured in <2 months despite intensive chemotherapy. We call attention to this rare phenomenon because it may pose a diagnostic challenge.
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http://dx.doi.org/10.1097/MD.0000000000025528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052012PMC
April 2021

Sinomenine Inhibits the Growth of Ovarian Cancer Cells Through the Suppression of Mitosis by Down-Regulating the Expression and the Activity of CDK1.

Onco Targets Ther 2021 5;14:823-834. Epub 2021 Feb 5.

Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, People's Republic of China.

Introduction: Ovarian cancer is one of the most common gynecological cancers worldwide. While, therapies against ovarian cancer have not been completely effective, sinomenine has been proved to have anti-tumor activity in various cancer cells. However, study of its anti-ovarian cancer effect is still rare, and the underlying mechanism has not been elucidated. Therefore, we aim to explore the mechanism of sinomenine anti-ovarian cancer.

Materials And Methods: The effect of anti-ovarian cancer HeyA8 cells was analyzed by CCK8 and colony formation assay. The mechanism of sinomenine anti-ovarian cancer was explored via high throughput RNA-seq, and then the target mRNA and protein expression were verified by real-time PCR and Western blot, respectively.

Results: We found that the proliferation and clone formation ability of ovarian cancer HeyA8 cells were markedly reduced by 1.56 mM sinomenine. The transcriptome analysis showed that 2679 genes were differentially expressed after sinomenine treatment in HeyA8 cells, including 1323 down-regulated genes and 1356 up-regulated genes. Gene ontology and KEGG pathway enrichment indicated that differential expression genes (DEGs) between the groups of sinomenine and DMSO-treated HeyA8 cells were mainly involved in the process of the cell cycle, such as kinetochore organization, chromosome segregation, and DNA replication. Strikingly, the top 18 ranked degree genes in the protein-protein interaction (PPI) network were mainly involved in the process of mitosis, such as sister chromatid segregation, condensed chromosome, and microtubule cytoskeleton organization. Moreover, real-time PCR results showed consistent expression trends of DEGs with transcriptome analysis. The results of Western blot showed the expression level of CDK1, which was the highest degree gene in PPI and the main regulator controlling the process of mitosis, and the levels of phosphorylated P-CDK (Thr161) and P-Histone H3 (Ser10) were decreased after being treated with sinomenine.

Conclusion: Our results demonstrated that sinomenine inhibited the proliferation of HeyA8 cells through suppressing mitosis by down-regulating the expression and the activity of CDK1. The study may provide a preliminary research basis for the application of sinomenine in anti-ovarian cancer.
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http://dx.doi.org/10.2147/OTT.S284261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873025PMC
February 2021

Fine particulate matter inhibits phagocytosis of macrophages by disturbing autophagy.

FASEB J 2020 12 30;34(12):16716-16735. Epub 2020 Oct 30.

Center for Translational Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, China.

Mounting evidence from epidemiological and clinical studies has revealed marked correlations between the air pollutant fine particulate matter (FPM) and respiratory diseases. FPM reaches distal airways and deposits in alveolar regions where it can act directly on alveolar macrophages. However, the detailed effect of FPM on the physiological function of alveolar macrophages and the underlying mechanisms remain unclear. In this study, we showed that exposing THP-1-derived macrophages to FPM led to autophagy dysfunction. FPM activated the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway, which promoted the expression of autophagy-related 2A (ATG2A) and reactive oxygen species generation. The overexpression of ATG2A enhanced the synthesis of autophagic membranes, and the excessive production of reactive oxygen species caused autophagy flux inhibition through disrupting the lysosomal activity. More importantly, FPM impaired the phagocytic ability of macrophages on Escherichia coli and apoptotic neutrophils. Finally, we showed that restoring autophagy rescued the impairment of phagocytic ability induced by FPM. In summary, these results reveal the molecular mechanism of autophagy dysfunction caused by FPM and provide a novel approach to resolve the impaired function of macrophages in respiratory diseases induced by FPM.
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http://dx.doi.org/10.1096/fj.202000657RDOI Listing
December 2020

Clinical significance of CD200 expression in newly diagnosed multiple myeloma patients and dynamic changing during treatment.

Leuk Lymphoma 2021 03 27;62(3):709-715. Epub 2020 Oct 27.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.

The aim of our study was to determine the impact of CD200 expression in newly diagnosed myltiple myeloma (MM) patients. CD200 patients had significantly shorter median overall survival time (OS) than CD200 patients (41.0 months not reached,  = .009). The ratio of CD4 to CD8 T cells was lower in CD200 patients and this reduction was significantly related to the increase of CD8 T cells ( = .021). Moreover, we analyzed dynamic changes of CD200 expression in 47 CD200 patients during treatment. Thirty-eight (80.9%) patients switched to CD200 during treatment. Those patients had a favorable survival compared with the others (median OS, 65.0 32.0 months,  < .001; median PFS, 29.0 11.5 months,  = .027). We concluded that CD200 expression is an independent marker for MM prognostic estimation during treatment.
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http://dx.doi.org/10.1080/10428194.2020.1839653DOI Listing
March 2021

Low absolute CD4 T cell counts in peripheral blood predict poor prognosis in patients with newly diagnosed multiple myeloma.

Leuk Lymphoma 2020 08 23;61(8):1869-1876. Epub 2020 Apr 23.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.

The T lymphocyte system plays an active role in tumor immunosurveillance in multiple myeloma (MM), and abnormal T lymphocyte populations are often observed in patients with MM. In the current study, we evaluated the prognostic impact of abnormal T lymphocyte subset distributions in patients with newly diagnosed MM (NDMM). Between December 2012 to October 2016, 110 NDMM patients were included in this study. Multiparameter flow cytometry was applied to quantitatively analysis the peripheral blood T lymphocyte subsets, including CD4 T cell, CD8 T cell, and CD4/CD8 ratio. Survival analyses were performed based on the patients' clinical data and the quantity of T lymphocyte subsets. The median follow-up time was 27.0 months (range, 2.5-66). Baseline percentages and absolute CD4 T cell counts and the CD4/CD8 ratio were positively correlated with both overall survival (OS) and progression-free survival (PFS) according to Kaplan-Meier curves ( < .05). In the multivariate COX analysis, lower CD4 T cell count was an independent unfavorable factor in predicting both OS ( = .016) and PFS ( = .010). Furthermore, lower CD4/CD8 ratio was an independent adverse prognostic factor for shorter PFS ( = .017). These results suggested that T lymphocyte subsets were crucial indicators in correlation with MM patients' prognosis. Low CD4 T cell counts and CD4/CD8 ratio were independent unfavorable prognostic predictors for patients with MM at diagnosis.
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http://dx.doi.org/10.1080/10428194.2020.1751840DOI Listing
August 2020

The phospholipase A effector PlaA from Legionella pneumophila: expression, purification and crystallization.

Acta Crystallogr F Struct Biol Commun 2020 Mar 2;76(Pt 3):138-144. Epub 2020 Mar 2.

School of Life Sciences, Anhui University, 111 Jiulong Road, Hefei, Anhui 230601, People's Republic of China.

Legionella pneumophila encodes an extracellular secreted phospholipase A named PlaA that is translocated by the type II secretion system. It plays an essential role in maintaining the integrity of Legionella-containing vacuoles in L. pneumophila pathogenesis. Here, it is shown that PlaA has a main lysophospholipase activity to hydrolyze fatty-acyl groups in lysophospholipids. Although it has a very low phospholipase A activity to catalyze the hydrolysis of fatty-acyl groups in phospholipids, PlaA can bind phospholipids such as 1,2-dipalmitoylphosphatidylcholine with a dissociation constant of 11.1 µM. Sequence-alignment analysis combined with activity assays revealed that PlaA contains a distinct substrate-binding site among the known structures of the phospholipase A family, implying that PlaA may present a novel mechanism for substrate recognition. Native PlaA and its selenomethionine (SeMet)-substituted form were purified and crystallized by vapour diffusion in hanging drops at 296 K. Diffraction data were collected to a resolution of 2.0 Å for native PlaA protein and to a resolution of 2.7 Å for SeMet-substituted PlaA protein. The crystals of native PlaA belonged to the monoclinic space group P2, while the crystals of SeMet-substituted PlaA belonged to the primitive orthorhombic space group P222. Initial phases for PlaA were obtained from SeMet SAD data sets.
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http://dx.doi.org/10.1107/S2053230X20002149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057347PMC
March 2020

Pharmacogenetic investigation of efficacy response to mepolizumab in eosinophilic granulomatosis with polyangiitis.

Rheumatol Int 2020 Aug 3;40(8):1301-1307. Epub 2020 Feb 3.

Genetics, GlaxoSmithKline, Upper Providence, PA, USA.

Treatment of patients with the rare disease eosinophilic granulomatosis with polyangiitis (EGPA) with mepolizumab, a monoclonal antibody to interleukin-5 (IL-5) that reduces blood eosinophil counts, as an add-on therapy to glucocorticoid treatment, results in more accrued weeks in remission, reductions in glucocorticoid use and reductions in relapse rate. However, treatment response varies across a continuum. Therefore, to investigate if large genetic effects could identify responders, the impact of genetic variants on efficacy in EGPA subjects taking mepolizumab and glucocorticoids was assessed in this post hoc study. Using linear regression and a negative binomial model, genetic variant association with three endpoints (accrued duration of remission, average oral glucocorticoid dose, and frequency of relapse) was tested in 61 EGPA subjects dosed with mepolizumab from MIRRA, a phase 3 trial. Candidate gene and genome-wide approaches were used. The candidate gene analysis was designed to investigate drug target effects with eight gene regions selected that were focused on the intersection of the glucocorticoid response (steroidal response) and IL-5 response mechanisms and recognizing potential overlap between EGPA and severe eosinophilic asthma diseases for which mepolizumab is used. The sample size was insufficient to enable testing of rare variants for effects. No genetic variant from either the candidate gene analysis or the GWAS associated with any endpoint. Thresholds to declare significance were p < 0.0008 (candidate variant) and p < 2.5 × 10 (genome-wide) analyses. Large genetic effects on mepolizumab-treatment response were not identified which could help differentiate responders from non-responders.
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http://dx.doi.org/10.1007/s00296-020-04523-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316687PMC
August 2020

A two-dimensional zinc(II)-based metal-organic framework for fluorometric determination of ascorbic acid, chloramphenicol and ceftriaxone.

Mikrochim Acta 2020 01 17;187(2):136. Epub 2020 Jan 17.

AnHui Province Key Laboratory of Chemistry for Inorganic/Organic Hybrid Functionalized Materials, Institutes of Physical Science and Information Technology Key Laboratory of Structure and Functional Regulation of Hybrid Materials of Ministry of Education, Anhui University, Hefei, 230601, People's Republic of China.

A two-dimensional zinc(II)-based metal-organic framework [Zn • (BA) • (BBI)] was synthesized from 1,2-benzenediacetic acid and 1,1'-(1,4-butanediyl) bis(imidazole) via a solvothermal reaction. The crystal exhibits good chemical stability in the pH range from 2 to 12, and strong fluorescence with excitation/emission maxima of 270/290 nm. The crystal is shown to by a viable fluorescent probe for the detection of ascorbic acid (AA) and the antibiotics chloramphenicol (CHL) and ceftriaxone (CRO). Fluorescence intensity of crystal dispersion is significantly quenched with increasing concentrations of AA/CHL/CRO. Quenching occurs even in the presence of other substances. The assay is fast (5 s) and has a low detection limit (1.6 ppb for AA, 12 ppb for CHL and 3.9 ppb for CRO). The crystal still has a good quenching effect on AA/CHL/CRO after washing and using for five times. The response of the probe is related to the interplay between the MOF and analytes via energy absorption competition. Graphical abstractSchematic diagram of preparing Zn • (BA) • (BBI) and responding to target analytes. BA: 1,2-phenyldiacetic acid; BBI: 1,1'-(1,4-butanediyl)bis(imidazole); Zn • (BA) • (BBI): Crystal chemical formula.
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http://dx.doi.org/10.1007/s00604-019-3979-3DOI Listing
January 2020

Construction of high quality ultrathin lanthanide oxyiodide nanosheets for enhanced CT imaging and anticancer drug delivery to efficient cancer theranostics.

Biomaterials 2020 02 5;230:119670. Epub 2019 Dec 5.

School of Materials Science and Engineering, National Institute for Advanced Materials, Tianjin Key Lab for Rare Earth Materials and Applications, Center for Rare Earth and Inorganic Functional Materials, Nankai University, Tianjin, 300350, China; Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Rare Earth Materials Chemistry and Applications, PKU-HKU Joint Laboratory in Rare Earth Materials and Bioinorganic Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China; College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China.

Two-dimensional (2D) ultrathin nanomaterials have shown extensive attention and potential biomedical applications in cancer theranostics. Herein, for the first time, we report the synthesis of monodisperse ultrathin lanthanum oxyiodide (LaOI) nanosheets with a thickness of merely 3 nm based on a facile wet chemistry strategy. By tuning the solvent composition and molar ratios of the precursors, we can modulate the shape and thickness of the nanosheets. Furthermore, a series of ultrathin lanthanide oxyiodides are synthesized by this method with tunable morphology. LaOI nanosheets as drug delivery platform showed ultrahigh anticancer doxorubicin (DOX) loading capacity (300 wt%) and pH-responsive release behaviour, as well as excellent cellular biocompatibility and efficiently intracellular nucleus delivery of DOX. LaOI with low dose DOX demonstrate enhanced cancer cell killing ability in vitro compared with DOX. The intravenous melanoma model shows that LaOI with low dose (1 mg mL) could significantly inhibit the tumor growth without side toxicity, relative to pure DOX. In addition, LaOI nanosheets also act as high resolution contrast agent for enhanced X-ray computed tomography imaging relative to the commercial iohexol. In summary, the LaOI nanosheets could serve as a competitive safe and low dose drug delivery platform for highly efficiently cancer imaging and therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119670DOI Listing
February 2020

Surface functionalized quantum dots as biosensor for highly selective and sensitive detection of ppb level of propafenone.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Feb 28;227:117709. Epub 2019 Oct 28.

Frontier Institute of Science and Technology, Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, State Key Laboratory for Manufacturing Systems Engineering, Instrument Analysis Center, Xi'an Jiaotong University, Xi'an, 710000, China. Electronic address:

Monodispersed CdTe quantum dots (QDs) were prepared by using thioglycolic acid as surfactants in aqueous solution. The thioglycolic acid was chemically adsorbed on the surface of CdTe QDs that enables the QDs positively charged. In week acidic media, propafenone is positively charged, which can combine with the CdTe QDs to form larger ion-association complex via electrostatic attraction and hydrogen bond. Moreover, the formed ion-association complex could increase the intensity of resonance Rayleigh scattering (RRS), second-order scattering (SOS) and frequency doubling-scattering (FDS) of CdTe QDs, and quench the CdTe QDs fluorescence. Importantly, under optimal experimental conditions, the increased RRS, SOS and FDS intensity, and quenched fluorescence intensity of CdTe QDs were in direct proportion to the propafenone concentration in a certain range, respectively. Among them, the RRS method exhibited the highest sensitivity. In a wide concentration range of propafenone from 0.003 to 7.0 μg mL, the detection limit could reach 0.96 ng mL, which was much lower than previously reported methods. To simulate practical applications, the possible foreign interfering substances were also investigated, such as common ions, amino acid, and glucide. The proposed method here is rapid, sensitive and shows promising application for detection of ppb level of propafenone in human serum.
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http://dx.doi.org/10.1016/j.saa.2019.117709DOI Listing
February 2020

Quantum dots mediated fluorescent "turn-off-on" sensor for highly sensitive and selective sensing of protein.

Colloids Surf B Biointerfaces 2020 Jan 20;185:110599. Epub 2019 Oct 20.

Frontier Institute of Science and Technology, Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, State Key Laboratory for Manufacturing Systems Engineering, Instrument Analysis Center, Xi'an Jiaotong University, Xi'an 710000, China. Electronic address:

We described a highly sensitive and selective strategy for sensing of human serum albumin (HSA) by constructing a reversible fluorescent "turn-off-on" sensor. Monodispersed cadmium telluride quantum dots (CdTe QDs) were synthesized by using a simple aqueous phase synthesis method, which exhibited strong green fluorescence. The CdTe QDs fluorescence was first quenched using resveratrol through dynamic quenching type, that is to say, excited states CdTe QDs collided with resveratrol. HSA can cooperate with resveratrol to dissociate CdTe QDs/resveratrol, leading to the recovered fluorescence of CdTe QDs. Therefore, a facile reversible fluorescent "turn-off-on" sensor can be developed for HSA detection. In a wide concentration range of HSA (0.0237-100 μg mL), the detection limit could reach 6.898 ng mL, which was much lower than previously reported values, indicating high sensitivity. Meanwhile, this strategy was successfully applied to the synthetic samples and demonstrated ideal selectivity. Moreover, the mechanisms of the interactions among QDs, resveratrol, and HSA were also investigated. The proposed strategy for HSA determination based on the constructed reversible fluorescent "turn-off-on" sensor suggests great promising in fluorescent sensing.
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http://dx.doi.org/10.1016/j.colsurfb.2019.110599DOI Listing
January 2020

Cardiomyocyte Homeodomain-Interacting Protein Kinase 2 Maintains Basal Cardiac Function via Extracellular Signal-Regulated Kinase Signaling.

Circulation 2019 11 4;140(22):1820-1833. Epub 2019 Oct 4.

Division of Cardiovascular Medicine (Y.G., J.Y.S., Z.Z., Y.-J.N., T.F., H.L.), Vanderbilt University Medical Center, Nashville, TN.

Background: Cardiac kinases play a critical role in the development of heart failure, and represent potential tractable therapeutic targets. However, only a very small fraction of the cardiac kinome has been investigated. To identify novel cardiac kinases involved in heart failure, we used an integrated transcriptomics and bioinformatics analysis and identified Homeodomain-Interacting Protein Kinase 2 (HIPK2) as a novel candidate kinase. The role of HIPK2 in cardiac biology is unknown.

Methods: We used the Expression2Kinase algorithm for the screening of kinase targets. To determine the role of HIPK2 in the heart, we generated cardiomyocyte (CM)-specific HIPK2 knockout and heterozygous mice. Heart function was examined by echocardiography, and related cellular and molecular mechanisms were examined. Adeno-associated virus serotype 9 carrying cardiac-specific constitutively active MEK1 (TnT-MEK1-CA) was administrated to rescue cardiac dysfunction in CM-HIPK2 knockout mice.

Results: To our knowledge, this is the first study to define the role of HIPK2 in cardiac biology. Using multiple HIPK2 loss-of-function mouse models, we demonstrated that reduction of HIPK2 in CMs leads to cardiac dysfunction, suggesting a causal role in heart failure. It is important to note that cardiac dysfunction in HIPK2 knockout mice developed with advancing age, but not during development. In addition, CM-HIPK2 knockout mice and CM-HIPK2 heterozygous mice exhibited a gene dose-response relationship of CM-HIPK2 on heart function. HIPK2 expression in the heart was significantly reduced in human end-stage ischemic cardiomyopathy in comparison to nonfailing myocardium, suggesting a clinical relevance of HIPK2 in cardiac biology. In vitro studies with neonatal rat ventricular CMscorroborated the in vivo findings. Specifically, adenovirus-mediated overexpression of HIPK2 suppressed the expression of heart failure markers, and , at basal condition and abolished phenylephrine-induced pathological gene expression. An array of mechanistic studies revealed impaired extracellular signal-regulated kinase 1/2 signaling in HIPK2-deficient hearts. An in vivo rescue experiment with adeno-associated virus serotype 9 TnT-MEK1-CA nearly abolished the detrimental phenotype of knockout mice, suggesting that impaired extracellular signal-regulated kinase signaling mediated apoptosis as the key factor driving the detrimental phenotype in CM-HIPK2 knockout mice hearts.

Conclusions: Taken together, these findings suggest that CM-HIPK2 is required to maintain normal cardiac function via extracellular signal-regulated kinase signaling.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.040740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219521PMC
November 2019

Genetic effects on efficacy to fluticasone propionate/salmeterol treatment in COPD.

Respir Med 2019 08 29;155:51-53. Epub 2019 Jun 29.

GlaxoSmithKline, King of Prussia, PA, USA.

Purpose: No studies have investigated genetic effects on quality of life (QoL) measurements like improvements in the St George's Respiratory Questionnaire (SGRQ) scores for chronic obstructive pulmonary disease treatments with fluticasone propionate/salmeterol (FSC). Therefore, in addition to testing genetic effects on change from baseline in trough forced expiratory volume in 1 s (FEV), genetic associations that may predict SGRQ response to FSC treatment were investigated in this analysis.

Methods: This post hoc exploratory genome-wide genetic analysis included subjects from 10 clinical trials: NCT01772134, NCT01772147, NCT00633217, NCT01817764, NCT01879410, NCT01822899, NCT01323621, NCT01342913, NCT01323634, and NCT01706328. The Genetics Analysis Population (subjects who provided written consent, a blood sample for genetic research, and were successfully genotyped) included 2005/2900 subjects in the intent-to-treat sample, who received FSC, for testing association with change from baseline in trough FEV and 1188/2005 subjects for testing SGRQ responses (change from baseline SGRQ score and categorical response by SGRQ score with Responders achieving >4 unit decrease at end of study treatment).

Main Findings: One locus on chromosome 20 with seven variants with low minor allele frequencies significantly associated with change from baseline SGRQ score. The binary SGRQ response provided similar trends for association but did not attain genome-wide significance levels. No genetic association was detected with change from baseline in trough FEV.

Conclusions: Common variants are unlikely to play a role in response to FSC.
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http://dx.doi.org/10.1016/j.rmed.2019.06.023DOI Listing
August 2019

A tetrameric protein scaffold as a nano-carrier of antitumor peptides for cancer therapy.

Biomaterials 2019 06 6;204:1-12. Epub 2019 Mar 6.

Institute of Human Virology and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. Electronic address:

A major pharmacological barrier to peptide therapeutics is their susceptibility to proteolytic degradation and poor membrane permeability, which, in principle, can be overcome by nanoparticle-based delivery technologies. Proteins, by definition, are nano materials and have been clinically proven as an efficient delivery vehicle for small molecule drugs. Here we describe the design of a protein-based peptide drug carrier derived from the tetramerization domain of the chimeric oncogenic protein Bcr/Abl of chronic myeloid leukemia. A dodecameric peptide inhibitor of the p53-MDM2/MDMX interaction, termed PMI, was grafted to the N-terminal helical region of Bcr/Abl tetramer. To antagonize intracellular MDM2/MDMX for p53 activation, we extended this protein, Bcr/Abl, by a C-terminal Arg-repeating hexapeptide to facilitate its cellular uptake. The resultant tetrameric protein Bcr/Abl-R6 adopted an alpha-helical conformation in solution and bound to MDM2 at an affinity of 32 nM. Bcr/Abl-R6 effectively induced apoptosis of HCT116 p53 cells in vitro in a p53-dependent manner and potently inhibited tumor growth in a nude mouse xenograft model by stabilizing p53 in vivo. Our protein-based delivery strategy thus provides a clinically viable solution to p53-inspired anticancer therapy and is likely applicable to the development of many other peptide therapeutics to target a great variety of intracellular protein-protein interactions responsible for disease initiation and progression.
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http://dx.doi.org/10.1016/j.biomaterials.2019.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441627PMC
June 2019

Fibulin-3 Has Anti-Tumorigenic Activities in Cutaneous Squamous Cell Carcinoma.

J Invest Dermatol 2019 08 6;139(8):1798-1808.e5. Epub 2019 Feb 6.

Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address:

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Several previous studies have shown that fibulin-3 participates in the occurrence and development of various tumors; however, its role in cSCC remains unknown. In the present study, we observed that the expression of fibulin-3 was downregulated in cSCC tissues compared with normal skin tissues, which was due to fibulin-3 promoter methylation. In vitro, knockdown of fibulin-3 in cSCC cell lines A431 and SCL-1 cells promoted cell proliferation, protected cells against apoptosis and enhanced migration and invasion abilities. Conversely, overexpression of fibulin-3 inhibited cell proliferation by promoting growth arrest during the G1/S phase transition, induced apoptosis, and reduced migration and invasion abilities. These anticarcinogenic effects of fibulin-3 were associated with inhibition of the AKT signaling pathway. Through a mouse xenograft model, we found that fibulin-3 overexpression inhibited the cSCC tumor growth in vivo. Our results suggest that fibulin-3 has anti-tumorigenic activities in cSCC. Downregulation of fibulin-3 is involved in cSCC development and it may serve as a novel therapeutic target of this disease.
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http://dx.doi.org/10.1016/j.jid.2019.01.022DOI Listing
August 2019

RhoA/ROCK/ARHGAP26 signaling in the eutopic and ectopic endometrium is involved in clinical characteristics of adenomyosis.

J Int Med Res 2018 Dec 2;46(12):5019-5029. Epub 2018 Nov 2.

3 Department of Gynecology and Obstetrics, Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Objective: This study aimed to investigate RhoA, RhoA-associated coiled-coil containing protein kinase (ROCK) 1, ROCK2, and Rho GTPase-activating protein 26 (ARHGAP26) expression in the eutopic endometrium (EU) and ectopic endometrium (EC), and examine their relationships with the clinical characteristics of adenomyosis.

Methods: Twenty patients with adenomyosis who underwent laparoscopy were recruited. Protein and mRNA expression of RhoA, ROCK1, ROCK2, and ARHGAP26 in EU and EC of patients with adenomyosis and in control endometrium without adenomyosis (CE) was detected.

Results: ROCK1, ROCK2, and RhoA mRNA expression in EU was significantly higher than that in CE, and was highest in EC. ARHGAP26 mRNA expression in EC and EU was significantly lower than that in CE. ROCK1, ROCK2, and RhoA protein expression in EC and EU was significantly higher than that in CE. ARHGAP26 protein expression in EC and EU was significantly lower than that in CE. ROCK1, ROCK2, and RhoA gene and protein expression was positively associated and ARHGAP26 was negatively associated with the severity of menorrhagia and menstrual capacity in adenomyosis.

Conclusions: RhoA, ROCK1, and ROCK2 expression is upregulated, and ARHGAP26 expression is downregulated in adenomyosis. The RhoA/ROCK-mediated signaling pathway is associated with dysmenorrhea and menstrual capacity in adenomyosis.
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http://dx.doi.org/10.1177/0300060518789038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300968PMC
December 2018

Association between the HMGB1/TLR4 signaling pathway and the clinicopathological features of ovarian cancer.

Mol Med Rep 2018 Sep 10;18(3):3093-3098. Epub 2018 Jul 10.

Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.

In the present study, the expression levels of high‑mobility group protein B1 (HMGB1), Toll‑like receptor 4 (TLR4), nuclear factor (NF)‑κB and tumor necrosis factor (TNF)‑α in malignant epithelial ovarian cancer (MEOC) were investigated in regards to several clinicopathological characteristics. A total of 20 patients with MEOC who underwent surgery were recruited in the present study. The mRNA and protein expression of HMGB1, TLR4, NF‑κB and TNF‑α was determined in patients with MEOC and compared with expression levels in 20 patients diagnosed with benign ovarian cysts (BOC). It was demonstrated that the mRNA and protein expression of HMGB1, TLR4, NF‑κB and TNF‑α in MEOC was significantly increased, compared with the BOC group (P<0.01). The gene and protein expression of HMGB1, TLR4, NF‑κB and TNF‑α was significantly increased in the advanced tumor stage and poorly differentiated group (P<0.01). The present study suggested that the HMGB1/TLR4 signaling pathway was overactive in MEOC, and was associated with MEOC tumor cell proliferation, invasion and metastasis. Furthermore, this may have been mediated via NF‑κB signaling.
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http://dx.doi.org/10.3892/mmr.2018.9271DOI Listing
September 2018

Long Noncoding RNAs and mRNA Regulation in Peripheral Blood Mononuclear Cells of Patients with Chronic Obstructive Pulmonary Disease.

Mediators Inflamm 2018 13;2018:7501851. Epub 2018 Mar 13.

Center for Translational Medicine, Frontier Institute of Science and Technology, and The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.

Background: Inflammation plays a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD). We evaluated the lncRNA and mRNA expression profile of peripheral blood mononuclear cells (PBMCs) from healthy nonsmokers, smokers without airflow limitation, and COPD patients.

Methods: lncRNA and mRNA profiling of PBMCs from 17 smokers and 14 COPD subjects was detected by high-throughput microarray. The expression of dysregulated lncRNAs was validated by qPCR. The lncRNA targets in dysregulated mRNAs were predicted and the GO enrichment was analyzed. The regulatory role of lncRNA on expression and consequently the effect on PBMC recruitment were investigated by siRNA knockdown and chemotaxis analysis.

Results: We identified 158 differentially expressed lncRNAs in PBMCs from COPD subjects compared with smokers. The dysregulated expression of 5 selected lncRNAs , , , , and , was validated. The GO enrichment showed that leukocyte migration, immune response, and apoptosis are the main enriched processes that previously reported to be involved in the pathogenesis of COPD. The regulatory role of on expression and consequently the effect on PBMC recruitment was confirmed.

Conclusion: This study may provide clues for further studies targeting lncRNAs to control inflammation in COPD.
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http://dx.doi.org/10.1155/2018/7501851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872599PMC
September 2018

Branched Glycerol-Based Copolymer with Ultrahigh p65 siRNA Delivery Efficiency for Enhanced Cancer Therapy.

ACS Appl Mater Interfaces 2018 Feb 24;10(5):4471-4480. Epub 2018 Jan 24.

Department of Biomedical Engineering, University of Michigan, Department of Biologic and Materials Sciences, Macromolecular Science and Engineering Center, Department of Materials Science and Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.

The small interfering RNA (siRNA) is emerging as a potential therapeutic for the treatment of various diseases because of the targeted gene silencing capability. The suppression of p65 expression has shown great potential in various cancer treatments. However, various substantial obstacles limit its clinical applications, including low cellular uptake, instability, and cytotoxicity of delivery vehicles. We show a highly branched and biocompatible glycerol-based copolymer (HBGC) to effectively deliver siRNA for excellent p65 gene silencing and safe lung cancer treatment in vitro and in vivo. HBGCs could be synthesized through a facile and modular one-spot Michael addition. HBGCs effectively protect siRNA in serum, enhance cellular uptake of siRNA, and show negligible cytotoxicity in various cells (A549, HeLa, HepG2, and C2C12). Additionally, the HBGC-siRNA complex potently downregulates the p65 expression in A549 cancer cells (almost the highest value of 96% in reported references) and enhances the cellular apoptosis compared to that of commercial transfection agents polyethyleneimine 25 kDa and Lipofectamine 2000. The HBGC-siRNA complex demonstrated significantly increased accumulation in the tumor sites and enhanced downregulation of p65 gene and cancer cell apoptosis. Furthermore, the tumor growth could be significantly inhibited in a subcutaneous lung tumor model with negligible adverse effects.
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http://dx.doi.org/10.1021/acsami.7b17109DOI Listing
February 2018

MDR1 polymorphisms affect the outcome of Chinese multiple myeloma patients.

Biomed Pharmacother 2017 Nov 7;95:743-748. Epub 2017 Sep 7.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China; Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 210029, China. Electronic address:

Objective: To illustrate the association of MDR1 (Multidrug Resistance 1) polymorphisms at loci 1236, 2677, 3435 and the prognosis of multiple myeloma (MM) in Jiangsu population.

Methods: A total of 129 MM patients were recruited from Jiangsu Province, China. The DNA was extracted from white blood cells (WBC) of peripheral blood and was amplified by polymerase chain reaction-allele specific primers (PCR-ASP). MDR1 polymorphisms at 3 loci were analyzed by electrophoresis followed by photograph or DNA direct sequencing. The association between the MDR1 and clinical outcomes were calculated by Graphpad and SPSS.

Results: MDR1 alleles at locus C1236T with T had significant lower calcium level in MM patients compared with C. The genotype CT had a significantly prolonged progress free survival (PFS) compared genotype CC at locus C1236T (median time: 48 months vs. 28 months, respectively; p=0.0062; HR=0.21; 95%CI0.061-0.715) while patients carrying T allele (CT and TT) at locus C3435T had a longer PFS than patients without T allele (CC) (median time: 60 months vs. 29 months, respectively; p=0.038; HR=0.508; 95%CI 0.264-0.978). And a borderline significance was found in haplotype at loci 2677-3435 and PFS. No significant findings were revealed between OS and MDR1 polymorphisms.

Conclusion: MDR1 polymorphisms could affect the prognosis of multiple myeloma whereas more samples and a longer follow-up are also needed.
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http://dx.doi.org/10.1016/j.biopha.2017.08.142DOI Listing
November 2017

The Expression of Toll-like receptors in eutopic and ectopic endometrium and its implication in the inflammatory pathogenesis of adenomyosis.

Sci Rep 2017 08 4;7(1):7365. Epub 2017 Aug 4.

Department of Gynecology and Obstetrics, Yangpu Hospital, Tongji University School of Medicine, 450 Teng Yue Road, Shanghai, 200090, China.

In this study, we investigated the expression profiles of Toll-like receptors(TLRs) in eutopic endometrium(EU) and ectopic endometrium(EC) and its implication in the inflammatory pathogenesis of adenomyosis. Thirty adenomyosis patients who underwent laparoscopy were recruited in this study. We tested the mRNA and protein expression of TLRs, and the mRNA expression of IL-6 and IL-8 in EU and EC of adenomyosis patients, and control endometrium without adenomyosis(CE). We found that the mRNA expression of IL-6 and IL-8 in EU was significantly higher than that in CE, and was the highest in EC (P < 0.01). The mRNA and protein expression of TLRs were higher in EU, with the expression of TLR1-6, 8 and 9 being significantly higher in EU than in CE, and were the highest in EC (except TLR6) (P < 0.05 or P < 0.01). Pearson correlation analysis showed that the expression of TLR1, 2, 4, 5 and 9 in EU and EC was positively correlated with that of IL-6 and IL-8 (P < 0.00139). This study suggested that adenomyosis was a state of inflammatory pathology. High expression of TLRs in EU and EC were positively correlated with IL-6 and IL-8, which may be involved in the inflammatory pathogenesis of adenomyosis.
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http://dx.doi.org/10.1038/s41598-017-07859-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544718PMC
August 2017

Uterine-Sparing Laparoscopic Pelvic Plexus Ablation, Uterine Artery Occlusion, and Partial Adenomyomectomy for Adenomyosis.

J Minim Invasive Gynecol 2017 Sep - Oct;24(6):940-945. Epub 2017 May 24.

Department of Obstetrics and Gynecology, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China; Institute of Gynecologic Minimally Invasive Medicine, Tongji University School of Medicine, Shanghai, China. Electronic address:

Study Objective: To evaluate safety, feasibility, and long-term clinical effects of adding laparoscopic pelvic plexus ablation to uterine-sparing procedures (uterine artery occlusion and partial adenomyomectomy) for adenomyosis.

Design: A prospective controlled study (Canadian Task Force classification II-1).

Setting: A teaching hospital.

Patients: A total of 112 patients with symptomatic adenomyosis were eligible for uterine-sparing laparoscopy.

Interventions: Laparoscopic pelvic plexus ablation, uterine artery occlusion, and partial adenomyomectomy.

Measurements And Main Results: After the exclusion of patients with malignant tumors or those lost to follow-up, 102 women underwent laparoscopic uterine artery occlusion and partial adenomyomectomy; 50 of these patients also had laparoscopic uterine pelvic plexus ablation (group A) with the remaining 52 patients serving as the control group (group B). Other than operative time (107.0 ± 15.4 vs 98.9 ± 20.2 minutes, p = .02), there were no statistical differences regarding other operative parameters between groups A and B. Relief of severe dysmenorrhea (Visual Analogue Scale score ≥ 7) at 36 months was higher in group A than in group B (100% vs 76.9%, p < .01). No patient suffered constipation or uroschesis in either group.

Conclusion: Adding laparoscopic uterine pelvic plexus ablation to laparoscopic uterine artery occlusion and partial adenomyomectomy was more effective in relieving dysmenorrhea.
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http://dx.doi.org/10.1016/j.jmig.2017.04.027DOI Listing
March 2018

CA125 modified by PLT and NLR improves the predictive accuracy of adenomyosis-derived pelvic dense adhesion.

Medicine (Baltimore) 2017 May;96(19):e6880

Department of Gynecology and Obstetrics, Yangpu Hospital, Tongji University School of Medicine Department of Gynecology and Obstetrics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Institute of Gynecological Minimal Invasive Medicine, Tongji University School of Medicine, Shanghai, China.

To explore the value of serum levels of CA125, platelet count (PLT), neutrophil-lymphocyte ratio (NLR), and modified CA125 markers CA125a and CA125b in predicting pelvic dense adhesion (PDA) associated with adenomyosis, CA125a = lg(CA125 × PLT × 10), CA125b = lg(CA125 × NLR).This retrospective study included 304 patients who underwent surgery for adenomyosis. Correlations of serum levels of CA125, PLT, NLR, and modified CA125 markers with adenomyosis-derived PDA were analyzed by Logistic regression. Receiver operating characteristic curve was applied to assess the utility of these parameters for predicting PDA.All the parameters including CA125, PLT, NLR, and modified CA125 markers were positively correlated with PDA (P < .05 or P < .01). More importantly, CA125a was more specific (85.03% vs. 83.00%) and more sensitive (47.56% vs. 47.47%) than CA125 alone for the prediction of PDA, and CA125b could also improve the predictive specificity of PDA (53.13% vs. 47.47%).Serum CA125, PLT, and NLR were all closely correlated with PDA in adenomyosis patients. CA125 modified by PLT and NLR could further improve the predictive accuracy of adenomyosis-derived PDA, thus providing more meaningful references for better-informed decisions about the mode of surgical access for the clinical treatment of adenomyosis.
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http://dx.doi.org/10.1097/MD.0000000000006880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428624PMC
May 2017

Activation of the Amino Acid Response Pathway Blunts the Effects of Cardiac Stress.

J Am Heart Assoc 2017 May 9;6(5). Epub 2017 May 9.

Heart Failure Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapy Area GlaxoSmithKline, King of Prussia, PA.

Background: The amino acid response (AAR) is an evolutionarily conserved protective mechanism activated by amino acid deficiency through a key kinase, general control nonderepressible 2. In addition to mobilizing amino acids, the AAR broadly affects gene and protein expression in a variety of pathways and elicits antifibrotic, autophagic, and anti-inflammatory activities. However, little is known regarding its role in cardiac stress. Our aim was to investigate the effects of halofuginone, a prolyl-tRNA synthetase inhibitor, on the AAR pathway in cardiac fibroblasts, cardiomyocytes, and in mouse models of cardiac stress and failure.

Methods And Results: Consistent with its ability to inhibit prolyl-tRNA synthetase, halofuginone elicited a general control nonderepressible 2-dependent activation of the AAR pathway in cardiac fibroblasts as evidenced by activation of known AAR target genes, broad regulation of the transcriptome and proteome, and reversal by l-proline supplementation. Halofuginone was examined in 3 mouse models of cardiac stress: angiotensin II/phenylephrine, transverse aortic constriction, and acute ischemia reperfusion injury. It activated the AAR pathway in the heart, improved survival, pulmonary congestion, left ventricle remodeling/fibrosis, and left ventricular function, and rescued ischemic myocardium. In human cardiac fibroblasts, halofuginone profoundly reduced collagen deposition in a general control nonderepressible 2-dependent manner and suppressed the extracellular matrix proteome. In human induced pluripotent stem cell-derived cardiomyocytes, halofuginone blocked gene expression associated with endothelin-1-mediated activation of pathologic hypertrophy and restored autophagy in a general control nonderepressible 2/eIF2α-dependent manner.

Conclusions: Halofuginone activated the AAR pathway in the heart and attenuated the structural and functional effects of cardiac stress.
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http://dx.doi.org/10.1161/JAHA.116.004453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524058PMC
May 2017

Eutopic/ectopic endometrial apoptosis initiated by bilateral uterine artery occlusion: A new therapeutic mechanism for uterus-sparing surgery in adenomyosis.

PLoS One 2017 13;12(4):e0175511. Epub 2017 Apr 13.

Department of Obstetrics and Gynaecology, Yangpu Hospital, Tongji University School of Medicine, Shanghai, PR China.

The objective of the present study was to investigate differences in the expression of apoptosis-related factors in the eutopic and ectopic endometrium (EuE/EE) in women with adenomyosis before and after laparoscopic bilateral uterine artery occlusion (LUAO). Ten patients with uterine adenomyosis who received LUAO were selected as the research subjects, from whom EuE and EE tissues were obtained before and after LUAO and detected for the expression of apoptosis-related molecules in EuE and EE by PT-PCR and Western blot, and changes in the mitochondrial structure by electron microscopy. Normal endometrial stromal cells (NESC), and EuE/EE stromal cells in women with adenomyosis were cultured in a 1% O2, 5% CO2 incubator to establish a physical anoxia state in an in vitro stromal cell model. The expression of apoptosis-related molecules was observed at 0, 6, 12, 24 and 48h of hypoxic. The results showed that the expression of apoptosis-related factors in EuE and EE were increased significantly after LUAO and under hypoxic conditions in vitro, suggesting that transient ischemia and hypoxia were involved in the apoptosis of adenomysis lesions, and that uterine artery occlusion could remove adenomyosis lesions on tissue/cell level by cytoreduction, thus reaching the goal of treating adenomyosis effectively.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175511PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391022PMC
April 2017

Bioinformatic analysis of microRNA and mRNA Regulation in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease.

Respir Res 2017 01 5;18(1). Epub 2017 Jan 5.

Center for Translational Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, Shaanxi province, China.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive, irreversible chronic inflammatory disorder typified by increased recruitment of monocytes, lymphocytes and neutrophils. Because of this, as well as the convenience of peripheral blood nuclear cells (PBMCs) assessments, miRNA profiling of PBMCs has drawn increasing attention in recent years for various disease. Therefore, we analyzed miRNA and mRNA profiles to understand their regulatory network between COPD subjects versus smokers without airflow limitation.

Methods: miRNA and mRNA profiling of PBMCs from pooled 17 smokers and 14 COPD subjects was detected by high-throughput microarray. The expression of dysregulated miRNAs were validated by q-PCR. The miRNA targets in dysregulated mRNAs were predicted and the pathway enrichment was analyzed.

Results: miRNA microarray showed that 8 miRNAs were up-regulated and 3 miRNAs were down-regulated in COPD subjects compared with smokers; the upregulation of miR-24-3p, miR-93-5p, miR-320a and miR-320b and the downregulation of miR-1273 g-3p were then validated. Bioinformatic analysis of regulatory network between miRNA and mRNA showed that NOD and TLR were the most enriched pathways. miR-24-3p was predicted to regulate IL-18, IL-1β, TNF, CCL3 and CCL4 and miR-93-5p to regulate IκBα.

Conclusions: The expression of miRNA and mRNA were dysregulated in PBMCs of COPD patients compared with smokers without airflow limitation. The regulation network between the dysregulated miRNA and mRNA may provide potential therapeutic targets for COPD.
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http://dx.doi.org/10.1186/s12931-016-0486-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217451PMC
January 2017

Genetic landscape of a case of extraovarian peritoneal serous papillary carcinoma.

Oncol Lett 2016 Oct 2;12(4):2395-2402. Epub 2016 Aug 2.

Department of Pathology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, P.R. China.

The present report aimed to study genetic alterations underlying extraovarian peritoneal serous papillary carcinoma (EPSPC), which have not previously been systematically investigated. A case of EPSPC was identified, and its genetic alterations were assessed by combining comparative genomic hybridization and whole-exome sequencing technologies to investigate the genomic landscape, including copy number variations and mutations in EPSPC. It was found that a large number of germline mutations were present, which may have predisposed the patient to the occurrence of this disease. Copy number gains were found in a range of chromosomes, including 4q, 5q, 8q, 10q, 15q, 16p, 18q, 20p, 20q and Xq. Large-scale copy number loss occurred in chromosomes 2p, 13q, 16q, 17p and 17q. Through use of whole-exome sequencing, germline mutations were widely found that were associated with cancer development, including mutations in the BRCA1, DNA repair associated (BRCA1), BRCA2, tumor protein 53, erb-b2 receptor tyrosine kinase 2, matrix metalloproteinases and ADAM metallopeptidase domain-containing genes. In addition, 165 somatic mutations, including 52 missense mutations and 7 short insertions or deletions, were also identified. In summary, the EPSPC was undergoing profound genomic rearrangement and somatic mutation, which may have led to its initiation and development, and the present study discussed the genetic basis of this highly malignant cancer.
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http://dx.doi.org/10.3892/ol.2016.4933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038161PMC
October 2016

Health Effects Associated with Wastewater Treatment, Reuse, and Disposal.

Water Environ Res 2016 Oct;88(10):1823-55

Pacific Advanced Civil Engineering, Inc., 17520 Newhope Street, Suite 200, Fountain Valley, CA 92708, USA.

A review of the literature published in 2015 on topics relating to public and environmental health risks associated with wastewater treatment, reuse, and disposal is presented. This review is divided into the following sections: wastewater management, microbial hazards, chemical hazards, wastewater treatment, wastewater reuse, agricultural reuse in different regions, greywater reuse, wastewater disposal, hospital wastewater, industrial wastewater, and sludge and biosolids.
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http://dx.doi.org/10.2175/106143016X14696400495776DOI Listing
October 2016

LPS/TLR4-mediated stromal cells acquire an invasive phenotype and are implicated in the pathogenesis of adenomyosis.

Sci Rep 2016 Feb 22;6:21416. Epub 2016 Feb 22.

Department of Obstetrics and Gynecology, Yangpu Hospital, Tongji University School of Medicine, Tengyue Road 450#, Shanghai, 200090, China.

The present study tested whether the LPS/TLR4 signal pathway in endometrial stromal cells is essential for the pathogenesis of adenomyosis. We tested the expression of TLR4, MD2 in the endometrium without adenomyosis (CE), the eutopic endometrium with adenomyosis (EuE) and the ectopic endometrium with adenomyosis (EE). We isolated the stromal cells from CE, EuE and EE (CESC, EuESC, EESC), treated with lipopolysaccharide (LPS) and TLR4 antagonist and detected the cell viability. And we also measured the key protein of the TLR4 signal pathway and inflammatory proliferation and invasive growth of experimental cells. We found that the viability of experimental cells treated with LPS was significantly greater than that of the non-treated cells, blocked by the TLR4 antagonist VIPER. TLR4 signal pathway and inflammatory proliferation and invasive growth of experimental cells stimulated by LPS, and it was inhibited by VIPER. This study suggested that stromal cells were activated by the TLR4 signalling pathway, which processed the cellular inflammatory proliferation and invasive growth involved in the pathogenesis of adenomyosis.
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http://dx.doi.org/10.1038/srep21416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761971PMC
February 2016
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