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  1. Article ; Online: Hippo signaling and histone methylation control cardiomyocyte cell cycle re-entry through distinct transcriptional pathways

    Zhenhe Zhang / Miles Freeman / Yiqiang Zhang / Danny El-Nachef / George Davenport / Allison Williams / W. Robb MacLellan

    PLoS ONE, Vol 18, Iss

    2023  Volume 2

    Abstract: Aims Accumulating data demonstrates that new adult cardiomyocytes (CMs) are generated throughout life from pre-existing CMs, although the absolute magnitude of CM self-renewal is very low. Modifying epigenetic histone modifications or activating the ... ...

    Abstract Aims Accumulating data demonstrates that new adult cardiomyocytes (CMs) are generated throughout life from pre-existing CMs, although the absolute magnitude of CM self-renewal is very low. Modifying epigenetic histone modifications or activating the Hippo-Yap pathway have been shown to promote adult CM cycling and proliferation. Whether these interventions work through common pathways or act independently is unknown. For the first time we have determined whether lysine demethylase 4D (KDM4D)-mediated CM-specific H3K9 demethylation and Hippo pathways inhibition have additive or redundant roles in promoting CM cell cycle re-entry. Methods and results We found that activating Yap1 in cultured neonatal rat ventricular myocytes (NRVM) through overexpressing Hippo pathway inhibitor, miR-199, preferentially increased S-phase CMs, while H3K9me3 demethylase KDM4D preferentially increased G2/M markers in CMs. Together KDM4D and miR-199 further increased total cell number of NRVMs in culture. Inhibition of Hippo signaling via knock-down of Salvador Family WW Domain Containing Protein 1 (Sav1) also led to S-phase reactivation and additional cell cycle re-entry was seen when combined with KDM4D overexpression. Inducible activating KDM4D (iKDM4D) in adult transgenic mice together with shRNA mediated knock-down of Sav1 (iKDM4D+Sav1-sh) resulted in a significant increase in cycling CMs compared to either intervention alone. KDM4D preferentially induced expression of genes regulating late (G2/M) phases of the cell cycle, while miR-199 and si-Sav1 preferentially up-regulated genes involved in G1/S phase. KDM4D upregulated E2F1 and FoxM1 expression, whereas miR-199 and si-Sav1 induced Myc. Using transgenic mice over-expressing KDM4D together with Myc, we demonstrated that KDM4D/Myc significantly increased CM cell cycling but did not affect cardiac function. Conclusions KDM4D effects on CM cell cycle activity are additive with the Hippo-Yap1 pathway and appear to preferentially regulate different cell cycle regulators. This may ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 500
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Hippo signaling and histone methylation control cardiomyocyte cell cycle re-entry through distinct transcriptional pathways.

    Zhenhe Zhang / Miles Freeman / Yiqiang Zhang / Danny El-Nachef / George Davenport / Allison Williams / W Robb MacLellan

    PLoS ONE, Vol 18, Iss 2, p e

    2023  Volume 0281610

    Abstract: Aims Accumulating data demonstrates that new adult cardiomyocytes (CMs) are generated throughout life from pre-existing CMs, although the absolute magnitude of CM self-renewal is very low. Modifying epigenetic histone modifications or activating the ... ...

    Abstract Aims Accumulating data demonstrates that new adult cardiomyocytes (CMs) are generated throughout life from pre-existing CMs, although the absolute magnitude of CM self-renewal is very low. Modifying epigenetic histone modifications or activating the Hippo-Yap pathway have been shown to promote adult CM cycling and proliferation. Whether these interventions work through common pathways or act independently is unknown. For the first time we have determined whether lysine demethylase 4D (KDM4D)-mediated CM-specific H3K9 demethylation and Hippo pathways inhibition have additive or redundant roles in promoting CM cell cycle re-entry. Methods and results We found that activating Yap1 in cultured neonatal rat ventricular myocytes (NRVM) through overexpressing Hippo pathway inhibitor, miR-199, preferentially increased S-phase CMs, while H3K9me3 demethylase KDM4D preferentially increased G2/M markers in CMs. Together KDM4D and miR-199 further increased total cell number of NRVMs in culture. Inhibition of Hippo signaling via knock-down of Salvador Family WW Domain Containing Protein 1 (Sav1) also led to S-phase reactivation and additional cell cycle re-entry was seen when combined with KDM4D overexpression. Inducible activating KDM4D (iKDM4D) in adult transgenic mice together with shRNA mediated knock-down of Sav1 (iKDM4D+Sav1-sh) resulted in a significant increase in cycling CMs compared to either intervention alone. KDM4D preferentially induced expression of genes regulating late (G2/M) phases of the cell cycle, while miR-199 and si-Sav1 preferentially up-regulated genes involved in G1/S phase. KDM4D upregulated E2F1 and FoxM1 expression, whereas miR-199 and si-Sav1 induced Myc. Using transgenic mice over-expressing KDM4D together with Myc, we demonstrated that KDM4D/Myc significantly increased CM cell cycling but did not affect cardiac function. Conclusions KDM4D effects on CM cell cycle activity are additive with the Hippo-Yap1 pathway and appear to preferentially regulate different cell cycle regulators. This may ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 500
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Different internal fixation methods for Hoffa-like fractures of the tibial plateau

    Hang Xue / Junrong Deng / Zhenhe Zhang / Samuel Knoedler / Adriana C. Panayi / Leonard Knoedler / Bobin Mi / Mengfei Liu / Guandong Dai / Guohui Liu

    Frontiers in Medicine, Vol

    a finite element analysis

    2023  Volume 10

    Abstract: Due to the low incidence of posteromedial tibial plateau fractures and limited clinical data available, the optimal treatment for this type of fracture remains to be established. This type of fracture, also known as Hoffa-like fracture of the tibial ... ...

    Abstract Due to the low incidence of posteromedial tibial plateau fractures and limited clinical data available, the optimal treatment for this type of fracture remains to be established. This type of fracture, also known as Hoffa-like fracture of the tibial plateau, shares a similar mechanism of injury with the Hoffa fracture of the femoral condyle. In the field of orthopedics, finite element analysis is considered a valuable method to guide clinical decision-making. In this study, four methods used for internal fixation of Hoffa-like fractures of the tibial plateau were compared using computer simulation and applying a finite element method (FEM). The methods compared were lateral L-plate fixation alone (Model A); lateral L-plate combined with posterior anti-slip plate (reconstruction plate/T-plate) fixation (Model B); lateral L-plate combined with posterior hollow nail fixation of the fracture block (Model C); and lateral L-plate combined with anterior hollow nail fixation of the fracture (Model D). The maximum displacement of the model and the maximum stress of the internal fixation material were analyzed by applying an axial load of 2,500 N. The results showed that, in the normal bone model, the maximum displacement of the fracture in Model A was 0.60032 mm, with improved stability through the addition of posterior lateral plate fixation in Model B and reduction of the displacement to 0.38882 mm. The maximum displacement in Model C and Model D was comparable, amounting to 0.42345 mm and 0.42273 mm, respectively. Maximum stress was 1235.6 MPa for Model A, 84.724 MPa for Model B, 99.805 MPa for Model C, and 103.19 MPa for Model D. In the internal fixation analysis of the osteoporotic fracture model, we observed patterns similar to the results of the normal bone model. The results indicated that Model B yielded the overall best results in the treatment of Hoffa-like fractures of the tibial plateau. The orthopedic surgeon may wish to implement these insights into the perioperative algorithm, thereby refining and ...
    Keywords finite element analysis ; tibial plateau fracture ; Hoffa fracture ; posteromedial split ; internal fixation ; Medicine (General) ; R5-920
    Subject code 550
    Language English
    Publishing date 2023-07-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Enhanced tissue regeneration through immunomodulation of angiogenesis and osteogenesis with a multifaceted nanohybrid modified bioactive scaffold

    Hang Xue / Zhenhe Zhang / Ze Lin / Jin Su / Adriana C. Panayi / Yuan Xiong / Liangcong Hu / Yiqiang Hu / Lang Chen / Chenchen Yan / Xudong Xie / Yusheng Shi / Wu Zhou / Bobin Mi / Guohui Liu

    Bioactive Materials, Vol 18, Iss , Pp 552-

    2022  Volume 568

    Abstract: Major traumatic tissue defects are common clinical problems often complicated by infection and local vascular dysfunction, processes which hinder the healing process. Although local application of growth factors or stem cells through various tissue ... ...

    Abstract Major traumatic tissue defects are common clinical problems often complicated by infection and local vascular dysfunction, processes which hinder the healing process. Although local application of growth factors or stem cells through various tissue engineering techniques are promising methods for the repair of tissue defects, limitations in their clinical application exist. Herein, we synthesized multifaceted nanohybrids composed of Quaternized chitosan (QCS), Graphene oxide (GO), and Polydopamine (PDA; QCS-GO-PDA). Covalent grafting of QCS and GO at a mass ratio of 5:1 (5QCS-1GO) displayed excellent biocompatibility and enhanced osteogenic ability, while addition of PDA (5QCS-1GO-PDA) reduced the level of reactive oxygen species (ROS). 5QCS-1GO-PDA was able to achieve wound tissue regeneration by reducing the inflammatory response and enhancing angiogenesis. Furthermore, Polylactic acid/hydroxyapatite (PLA/HA) composite scaffolds were printed using Selective Laser Sintering (SLS) and the hybrid nanomaterial (5QCS-1GO-PDA) was used to coat the PLA/HA scaffold (5QCS-1GO-PDA@PLA/HA) to be used for rapid bone regeneration. 5QCS-1GO-PDA not only improved angiogenesis and osteogenic differentiation, but also induced M2-type polarization of macrophages and promoted bone regeneration via the BMP2/BMPRs/Smads/Runx2 signaling pathway. The bidirectional enhanced healing ability of the multifaceted nanohybrids 5QCS-1GO-PDA provides a promising method of effectively treating tissue defects.
    Keywords Multifunctional nanohybrids ; Quaternary chitosan ; Polydopamine ; Angiogenesis ; Tissue regeneration ; Materials of engineering and construction. Mechanics of materials ; TA401-492 ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher KeAi Communications Co., Ltd.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: Analysis of gene expression and regulation implicates C2H9orf152 has an important role in calcium metabolism and chicken reproduction

    Liu, Long / Chan Yang / Daoqing Gong / Tuoyu Geng / Yanfeng Fan / Zhenhe Zhang / Zhonghua Ning / Zhuocheng Hou

    Animal reproduction science. 2017 Jan., v. 176

    2017  

    Abstract: The reproductive system of a female bird is responsible for egg production. The genes highly expressed in oviduct are potentially important. From RNA-seq analysis, C2H9orf152 (an orthologous gene of human C9orf152) was identified as highly expressed in ... ...

    Abstract The reproductive system of a female bird is responsible for egg production. The genes highly expressed in oviduct are potentially important. From RNA-seq analysis, C2H9orf152 (an orthologous gene of human C9orf152) was identified as highly expressed in chicken uterus. To infer its function, we obtained and characterized its complete cDNA sequence, determined its spatiotemporal expression, and probed its transcription factor(s) through pharmaceutical approach. Data showed that the complete cDNA sequence was 1468bp long with a 789bp of open reading frame. Compared to other tested tissues, this gene was highly expressed in the oviduct and liver tissues, especially uterus. Its expression in uterus was gradually increased during developmental and reproductive periods, which verified its involvement in the growth and maturity of reproductive system. In contrast, its expression was not significant different between active and quiescent uterus, suggesting the role of C2H9orf152 in reproduction is likely due to its long-term effect. Moreover, based on its 5′-flanking sequence, Foxd3 and Hnf4a were predicted as transcription factors of C2H9orf152. Using berberine or retinoic acid (which can regulate the activities of Hnf4a and Foxd3, respectively), we demonstrated suppression of C2H9orf152 by the chemicals in chicken primary hepatocytes. As retinoic acid regulates calcium metabolism, and Hnf4a is a key nuclear factor to liver, these findings suggest that C2H9orf152 is involved in liver function and calcium metabolism of reproductive system. In conclusion, C2H9orf152 may have a long-term effect on chicken reproductive system by regulating calcium metabolism, suggesting this gene has an important implication in the improvement of egg production and eggshell quality.
    Keywords berberine ; calcium ; chickens ; complementary DNA ; egg production ; egg shell quality ; gene expression regulation ; genes ; hepatocytes ; humans ; liver ; liver function ; long term effects ; metabolism ; open reading frames ; oviducts ; retinoic acid ; sequence analysis ; sexual maturity ; tissues ; transcription factors ; uterus
    Language English
    Dates of publication 2017-01
    Size p. 1-10.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 429674-6
    ISSN 1873-2232 ; 0378-4320
    ISSN (online) 1873-2232
    ISSN 0378-4320
    DOI 10.1016/j.anireprosci.2016.11.002
    Database NAL-Catalogue (AGRICOLA)

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