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  1. Article: [Association between insomnia and type 2 diabetes: A two-sample Mendelian rando-mization study].

    Ma, Yujia / Lu, Ranli / Zhou, Zechen / Li, Xiaoyi / Yan, Zeyu / Wu, Yiqun / Chen, Dafang

    Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences

    2024  Volume 56, Issue 1, Page(s) 174–178

    Abstract: Objective: To explore the robust relationship between insomnia and type 2 diabetes mellitus by two-sample Mendelian randomization analysis to overcome confounding factors and reverse causality in observational studies.: Methods: We identified strong, ...

    Abstract Objective: To explore the robust relationship between insomnia and type 2 diabetes mellitus by two-sample Mendelian randomization analysis to overcome confounding factors and reverse causality in observational studies.
    Methods: We identified strong, independent single nucleotide polymorphisms (SNPs) of insomnia from the most up to date genome wide association studies (GWAS) within European ancestors and applied them as instrumental variable to GWAS of type 2 diabetes mellitus. After excluding SNPs that were significantly associated with smoking, physical activity, alcohol consumption, educational attainment, obesity, or type 2 diabetes mellitus, we assessed the impact of insomnia on type 2 diabetes mellitus using inverse variance weighting (IVW) method. Weighted median and MR-Egger regression analysis were also conducted to test the robustness of the association. We calculated the
    Results: We selected 248 SNPs independently associated with insomnia at the genome-wide level (
    Conclusion: Insomnia is a risk factor of type 2 diabetes mellitus, which has positively effects on type 2 diabetes mellitus. Our study provides further rationale for indivi-duals at risk for diabetes to keep healthy lifestyle.
    MeSH term(s) Humans ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/genetics ; Sleep Initiation and Maintenance Disorders/genetics ; Genome-Wide Association Study ; Reproducibility of Results ; Risk Factors ; Polymorphism, Single Nucleotide ; Mendelian Randomization Analysis
    Language Chinese
    Publishing date 2024-02-06
    Publishing country China
    Document type English Abstract ; Journal Article
    ZDB-ID 2452593-5
    ISSN 1671-167X
    ISSN 1671-167X
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Morphometric Analysis of Rat Prostate Development: Roles of MEK/ERK and Rho Signaling Pathways in Prostatic Morphogenesis.

    Hu, Wen-Yang / Afradiasbagharani, Parivash / Lu, Ranli / Liu, Lifeng / Birch, Lynn A / Prins, Gail S

    Biomolecules

    2021  Volume 11, Issue 12

    Abstract: The molecular mechanisms underlying prostate development can provide clues for prostate cancer research. It has been demonstrated that MEK/ERK signaling downstream of androgen-targeted FGF10 signaling directly induces prostatic branching during ... ...

    Abstract The molecular mechanisms underlying prostate development can provide clues for prostate cancer research. It has been demonstrated that MEK/ERK signaling downstream of androgen-targeted FGF10 signaling directly induces prostatic branching during development, while Rho/Rho-kinase can regulate prostate cell proliferation. MEK/ERK and Rho/Rho kinase regulate myosin light chain kinase (MLCK), and MLCK regulates myosin light chain phosphorylation (MLC-P), which is critical for cell fate, including cell proliferation, differentiation, and apoptosis. However, the roles and crosstalk of the MEK/ERK and Rho/Rho kinase signaling pathways in prostatic morphogenesis have not been examined. In the present study, we used numerical and image analysis to characterize lobe-specific rat prostatic branching during postnatal organ culture and investigated the roles of FGF10-MEK/ERK and Rho/Rho kinase signaling pathways in prostatic morphogenesis. Prostates exhibited distinctive lobe-specific growth and branching patterns in the ventral (VP) and lateral (LP) lobes, while exogenous FGF10 treatment shifted LP branching towards a VP branching pattern. Treatment with inhibitors of MEK1/2, Rho, Rho kinase, or MLCK significantly inhibited VP growth and blocked branching morphogenesis, further supporting critical roles for MEK/ERK and Rho/Rho kinase signaling pathways in prostatic growth and branching during development. We propose that MLCK-regulated MLC-P may be a central downstream target of both signaling pathways in regulating prostate morphogenesis.
    MeSH term(s) Animals ; Cell Differentiation ; Cell Proliferation ; Fibroblast Growth Factor 10/metabolism ; Gene Expression Regulation, Developmental ; MAP Kinase Signaling System ; Male ; Morphogenesis ; Organ Culture Techniques ; Prostate/growth & development ; Prostate/metabolism ; Rats ; rho-Associated Kinases/metabolism
    Chemical Substances Fgf10 protein, rat ; Fibroblast Growth Factor 10 ; rho-Associated Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2021-12-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom11121829
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Stem cells from a malignant rat prostate cell line generate prostate cancers

    Hu, Wen-Yang / Liu, Li-Feng / Afradiasbagharani, Parivash / Lu, Ran-Li / Chen, Zhen-Long / Hu, Dan-Ping / Birch, Lynn A / Prins, Gail S

    American journal of clinical and experimental urology

    2022  Volume 10, Issue 6, Page(s) 377–389

    Abstract: Cancer stem cells (CSCs) are resistant to conventional cancer therapies, permitting the repopulation of new tumor growth and driving disease progression. Models for testing prostate CSC-propagated tumor growth are presently limited yet necessary for ... ...

    Abstract Cancer stem cells (CSCs) are resistant to conventional cancer therapies, permitting the repopulation of new tumor growth and driving disease progression. Models for testing prostate CSC-propagated tumor growth are presently limited yet necessary for therapeutic advancement. Utilizing the congenic nontumorigenic NRP152 and tumorigenic NRP154 rat prostate epithelial cell lines, the present study investigated the self-renewal, differentiation, and regenerative abilities of prostate stem/progenitor cells and developed a CSC-based PCa model. NRP154 cells expressed reduced levels of tumor suppressor caveolin-1 and increased p-Src as compared to NRP152 cells. Gene knockdown of caveolin-1 in NRP152 cells upregulated p-Src, implicating their role as potential oncogenic mediators in NRP154 cells. A FACS-based Hoechst exclusion assay revealed a side population of stem-like cells (0.1%) in both NRP152 and NRP154 cell lines. Using a 3D Matrigel culture system, stem cells from both cell lines established prostaspheres at a 0.1% efficiency through asymmetric self-renewal and rapid proliferation of daughter progenitor cells. Spheres derived from both cell lines contained CD117
    Language English
    Publishing date 2022-12-25
    Publishing country United States
    Document type Journal Article
    ISSN 2330-1910
    ISSN 2330-1910
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Keratin Profiling by Single-Cell RNA-Sequencing Identifies Human Prostate Stem Cell Lineage Hierarchy and Cancer Stem-Like Cells.

    Hu, Wen-Yang / Hu, Dan-Ping / Xie, Lishi / Nonn, Larisa / Lu, Ranli / Abern, Michael / Shioda, Toshihiro / Prins, Gail S

    International journal of molecular sciences

    2021  Volume 22, Issue 15

    Abstract: Single prostate stem cells can generate stem and progenitor cells to form prostaspheres in 3D culture. Using a prostasphere-based label retention assay, we recently identified keratin 13 ( ...

    Abstract Single prostate stem cells can generate stem and progenitor cells to form prostaspheres in 3D culture. Using a prostasphere-based label retention assay, we recently identified keratin 13 (
    MeSH term(s) Adult ; Cells, Cultured ; Humans ; Keratins/metabolism ; Male ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Primary Cell Culture ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology ; RNA/metabolism ; Single-Cell Analysis ; Young Adult
    Chemical Substances RNA (63231-63-0) ; Keratins (68238-35-7)
    Language English
    Publishing date 2021-07-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22158109
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Per- and polyfluoroalkyl substances target and alter human prostate stem-progenitor cells.

    Hu, Wen-Yang / Lu, Ranli / Hu, Dan Ping / Imir, Ozan Berk / Zuo, Qianying / Moline, Dan / Afradiasbagharani, Parivash / Liu, Lifeng / Lowe, Scott / Birch, Lynn / Griend, Donald J Vander / Madak-Erdogan, Zeynep / Prins, Gail S

    Biochemical pharmacology

    2021  Volume 197, Page(s) 114902

    Abstract: Per- and polyfluorinated alkyl substances (PFAS) are a large family of widely used synthetic chemicals that are environmentally and biologically persistent and present in most individuals. Chronic PFAS exposure have been linked to increased prostate ... ...

    Abstract Per- and polyfluorinated alkyl substances (PFAS) are a large family of widely used synthetic chemicals that are environmentally and biologically persistent and present in most individuals. Chronic PFAS exposure have been linked to increased prostate cancer risk in occupational settings, however, underlying mechanisms have not been interrogated. Herein we examined exposure of normal human prostate stem-progenitor cells (SPCs) to 10 nM PFOA or PFOS using serial passage of prostasphere cultures. Exposure to either PFAS for 3-4 weeks increased spheroid numbers and size indicative of elevated stem cell self-renewal and progenitor cell proliferation. Transcriptome analysis using single-cell RNA sequencing (scRNA-seq) showed 1) SPC expression of PPARs and RXRs able to mediate PFAS effects, 2) the emergence of a new cell cluster of aberrantly differentiated luminal progenitor cells upon PFOS/PFOA exposure, and 3) enrichment of cancer-associated signaling pathways. Metabolomic analysis of PFAS-exposed prostaspheres revealed increased glycolytic pathways including the Warburg effect as well as strong enrichment of serine and glycine metabolism which may promote a pre-malignant SPC fate. Finally, growth of in vivo xenografts of tumorigenic RWPE-2 human prostate cells, shown to contain cancer stem-like cells, was markedly enhanced by daily PFOS feeding to nude mice hosts. Together, these findings are the first to identify human prostate SPCs as direct PFAS targets with resultant reprogrammed transcriptomes and metabolomes that augment a preneoplastic state and may contribute to an elevated prostate cancer risk with chronic exposures.
    MeSH term(s) Animals ; Environmental Pollutants/toxicity ; Fluorocarbons/toxicity ; Humans ; Male ; Mice ; Mice, Nude ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/pathology ; Prostate/drug effects ; Prostate/pathology ; Stem Cells/drug effects ; Stem Cells/pathology ; Xenograft Model Antitumor Assays/methods ; Young Adult
    Chemical Substances Environmental Pollutants ; Fluorocarbons
    Language English
    Publishing date 2021-12-27
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 208787-x
    ISSN 1873-2968 ; 0006-2952
    ISSN (online) 1873-2968
    ISSN 0006-2952
    DOI 10.1016/j.bcp.2021.114902
    Database MEDical Literature Analysis and Retrieval System OnLINE

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