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  1. Article ; Online: Latency-Associated Transcript-Derived MicroRNAs in Herpes Simplex Virus Type 1 Target SMAD3 and SMAD4 in TGF-β/Smad Signaling Pathway.

    Shojaei Jeshvaghani, Zahra / Arefian, Ehsan / Asgharpour, Sara / Soleimani, Masoud

    Iranian biomedical journal

    2021  Volume 25, Issue 3, Page(s) 169–179

    Abstract: Background: During its latent infection, hepatic stellate cell (HSV-1) produces only a micro RNA (miRNA) precursor called latency-associated transcript (LAT), which encodes six distinct miRNAs. Recent studies have suggested that some of these miRNAs ... ...

    Abstract Background: During its latent infection, hepatic stellate cell (HSV-1) produces only a micro RNA (miRNA) precursor called latency-associated transcript (LAT), which encodes six distinct miRNAs. Recent studies have suggested that some of these miRNAs could target cellular mRNAs. One of the key cell signaling pathways that can be affected by HSV-1 is the TGF-β/Smad pathway. Herein, we investigated the potential role of the LAT as well as three LAT-derived miRNAs in targeting SMAD3 and SMAD4, as two main mediators in TGF-β/Smad.
    Methods: The selection of LAT-derived miRNAs was based on the search results obtained from an online miRNA prediction tool. HEK293T cells were transfected with each miRNA-expressing lentivector and with the construct-expressing LAT. To survey the effect of LAT on the expression of pro-fibrotic markers, we transfected LX-2 cells with LAT construct. The impact of viral miRNA overexpression on SMADs and fibrotic markers was measured by quantitative PCR and luciferase assays.
    Results: Among the LAT-derived miRNAs, miR-H2, miR-H3, and miR-H4 were selected for the study. Our results demonstrated that while miR-H2 binds to both SMAD mRNAs, miR-H3 and miR-H4 inhibit only the expression of the SMAD4 and SMAD3, respectively. Transfection of the LX-2 with LAT also decreased pro-fibrotic genes expression.
    Conclusion: Our findings display that LAT negatively regulates TGF-β/Smad through targeting SMAD3 and SMAD4 by its miRNAs. These viral miRNAs can also contribute to the development of therapeutic interventions in diseases for which prevention or treatment can be achieved through targeting TGF-β pathway.
    MeSH term(s) Base Sequence ; Cell Survival/genetics ; Gene Expression Regulation ; Genetic Vectors/metabolism ; HEK293 Cells ; Herpesvirus 1, Human/genetics ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Plasmids/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Signal Transduction ; Smad3 Protein/metabolism ; Smad4 Protein/metabolism ; Transforming Growth Factor beta/metabolism
    Chemical Substances MicroRNAs ; RNA, Messenger ; Smad3 Protein ; Smad4 Protein ; Transforming Growth Factor beta ; latency associated transcript, herpes simplex virus-1
    Language English
    Publishing date 2021-05-01
    Publishing country Iran
    Document type Journal Article
    ZDB-ID 2489282-8
    ISSN 2008-823X ; 1028-852X
    ISSN (online) 2008-823X
    ISSN 1028-852X
    DOI 10.29252/ibj.25.3.169
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    Zs.A 6776: Show issues Location:
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  2. Article ; Online: Cytokine signaling converging on

    Kastlmeier, Miriam T / Gonzalez-Rodriguez, Erika / Cabanis, Phoebe / Guenther, Eva M / König, Ann-Christine / Han, Lianyong / Hauck, Stefanie M / See, Fenja / Asgharpour, Sara / Bukas, Christina / Burgstaller, Gerald / Piraud, Marie / Lehmann, Mareike / Hatz, Rudolf A / Behr, Jürgen / Stoeger, Tobias / Hilgendorff, Anne / Voss, Carola

    Frontiers in immunology

    2023  Volume 14, Page(s) 1128239

    Abstract: Introduction: Interstitial lung disease (ILD) is a heterogenous group of lung disorders where destruction and incomplete regeneration of the lung parenchyma often results in persistent architectural distortion of the pulmonary scaffold. Continuous ... ...

    Abstract Introduction: Interstitial lung disease (ILD) is a heterogenous group of lung disorders where destruction and incomplete regeneration of the lung parenchyma often results in persistent architectural distortion of the pulmonary scaffold. Continuous mesenchyme-centered, disease-relevant signaling likely initiates and perpetuates the fibrotic remodeling process, specifically targeting the epithelial cell compartment, thereby destroying the gas exchange area.
    Methods: With the aim of identifying functional mediators of the lung mesenchymal-epithelial crosstalk with potential as new targets for therapeutic strategies, we developed a 3D organoid co-culture model based on human induced pluripotent stem cell-derived alveolar epithelial type 2 cells that form alveolar organoids in presence of lung fibroblasts from fibrotic-ILD patients, in our study referring to cases of pulmonary fibrosis, as well as control cell line (IMR-90).
    Results: While organoid formation capacity and size was comparable in the presence of fibrotic-ILD or control lung fibroblasts, metabolic activity was significantly increased in fibrotic-ILD co-cultures. Alveolar organoids cultured with fibrotic-ILD fibroblasts further demonstrated reduced stem cell function as reflected by reduced Surfactant Protein C gene expression together with an aberrant basaloid-prone differentiation program indicated by elevated Cadherin 2, Bone Morphogenic Protein 4 and Vimentin transcription. To screen for key mediators of the misguided mesenchymal-to-epithelial crosstalk with a focus on disease-relevant inflammatory processes, we used mass spectrometry and characterized the secretome of end stage fibrotic-ILD lung fibroblasts in comparison to non-chronic lung disease (CLD) patient fibroblasts. Out of the over 2000 proteins detected by this experimental approach, 47 proteins were differentially abundant comparing fibrotic-ILD and non-CLD fibroblast secretome. The fibrotic-ILD secretome profile was dominated by chemokines, including CXCL1, CXCL3, and CXCL8, interfering with growth factor signaling orchestrated by Interleukin 11 (IL11), steering fibrogenic cell-cell communication, and proteins regulating extracellular matrix remodeling including epithelial-to-mesenchymal transition. When in turn treating alveolar organoids with IL11, we recapitulated the co-culture results obtained with primary fibrotic-ILD fibroblasts including changes in metabolic activity.
    Conclusion: We identified mediators likely contributing to the disease-perpetuating mesenchymal-to-epithelial crosstalk in ILD. In our alveolar organoid co-cultures, we were able to highlight the importance of fibroblast-initiated aberrant epithelial differentiation and confirmed IL11 as a key player in fibrotic-ILD pathogenesis by unbiased fibroblast secretome analysis.
    MeSH term(s) Humans ; Interleukin-11/metabolism ; Induced Pluripotent Stem Cells ; Lung Diseases, Interstitial/pathology ; Fibroblasts/metabolism ; Fibrosis ; Cell Differentiation
    Chemical Substances Interleukin-11
    Language English
    Publishing date 2023-05-17
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1128239
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Sfrp1 inhibits lung fibroblast invasion during transition to injury-induced myofibroblasts.

    Mayr, Christoph H / Sengupta, Arunima / Asgharpour, Sara / Ansari, Meshal / Pestoni, Jeanine C / Ogar, Paulina / Angelidis, Ilias / Liontos, Andreas / Rodriguez-Castillo, José Alberto / Lang, Niklas J / Strunz, Maximilian / Porras-Gonzalez, Diana / Gerckens, Michael / De Sadeleer, Laurens J / Oehrle, Bettina / Viteri-Alvarez, Valeria / Fernandez, Isis E / Tallquist, Michelle / Irmler, Martin /
    Beckers, Johannes / Eickelberg, Oliver / Stoleriu, Gabriel Mircea / Behr, Jürgen / Kneidinger, Nikolaus / Wuyts, Wim A / Wasnick, Roxana Maria / Yildirim, Ali Önder / Ahlbrecht, Katrin / Morty, Rory E / Samakovlis, Christos / Theis, Fabian J / Burgstaller, Gerald / Schiller, Herbert B

    The European respiratory journal

    2024  Volume 63, Issue 2

    Abstract: Background: Fibroblast-to-myofibroblast conversion is a major driver of tissue remodelling in organ fibrosis. Distinct lineages of fibroblasts support homeostatic tissue niche functions, yet their specific activation states and phenotypic trajectories ... ...

    Abstract Background: Fibroblast-to-myofibroblast conversion is a major driver of tissue remodelling in organ fibrosis. Distinct lineages of fibroblasts support homeostatic tissue niche functions, yet their specific activation states and phenotypic trajectories during injury and repair have remained unclear.
    Methods: We combined spatial transcriptomics, multiplexed immunostainings, longitudinal single-cell RNA-sequencing and genetic lineage tracing to study fibroblast fates during mouse lung regeneration. Our findings were validated in idiopathic pulmonary fibrosis patient tissues
    Measurements and main results: We discovered a transitional fibroblast state characterised by high
    Conclusions: Our study reveals the convergence of spatially and transcriptionally distinct fibroblast lineages into transcriptionally uniform myofibroblasts and identifies SFRP1 as a modulator of TGFβ1-driven fibroblast phenotypes in fibrogenesis. These findings are relevant in the context of therapeutic interventions that aim at limiting or reversing fibroblast foci formation.
    MeSH term(s) Mice ; Animals ; Humans ; Myofibroblasts/metabolism ; Fibroblasts/metabolism ; Lung/metabolism ; Idiopathic Pulmonary Fibrosis/metabolism ; Cell Differentiation ; Transforming Growth Factor beta1/metabolism ; Extracellular Matrix Proteins/metabolism ; Membrane Proteins/genetics ; Membrane Proteins/metabolism
    Chemical Substances Transforming Growth Factor beta1 ; CTHRC1 protein, human ; Extracellular Matrix Proteins ; Sfrp1 protein, mouse ; Membrane Proteins
    Language English
    Publishing date 2024-02-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 639359-7
    ISSN 1399-3003 ; 0903-1936
    ISSN (online) 1399-3003
    ISSN 0903-1936
    DOI 10.1183/13993003.01326-2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2322: Show issues Location:
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    Zs.MO 292: Show issues

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  4. Article ; Online: Transcription factor decoy: a pre-transcriptional approach for gene downregulation purpose in cancer.

    Rad, Seyed Mohammad Ali Hosseini / Langroudi, Lida / Kouhkan, Fatemeh / Yazdani, Laleh / Koupaee, Alireza Nouri / Asgharpour, Sara / Shojaei, Zahra / Bamdad, Taravat / Arefian, Ehsan

    Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine

    2015  Volume 36, Issue 7, Page(s) 4871–4881

    Abstract: Gene therapy as a therapeutic approach has been the dream for many scientists around the globe. Many strategies have been proposed and applied for this purpose, yet the void for a functional safe method is still apparent. Since most of the diseases are ... ...

    Abstract Gene therapy as a therapeutic approach has been the dream for many scientists around the globe. Many strategies have been proposed and applied for this purpose, yet the void for a functional safe method is still apparent. Since most of the diseases are caused by undesirable upregulation (oncogenes) or downregulation (tumor suppressor genes) of genes, major gene therapy's techniques affect gene expression. Most of the methods are used in post-transcriptional level such as RNA inhibitory (RNAi) and splice-switching oligonucleotides (SSOs). RNAi blocks messenger RNA (mRNA) translation by mRNA degradation or interruption between attachments of mRNA with ribosomes' subunits. However, one of the novel methods is the usage of transcription factor targeted decoys. DNA decoys are the new generation of functional gene downregulatory oligonucleotides which compete with specific binding sites of transcription factors. Considering the exponential growth of this technique in both in vitro and in vivo studies, in this paper, we aim to line out the description, design, and application of decoys in research and therapy.
    MeSH term(s) Binding Sites ; Gene Expression Regulation, Neoplastic ; Genetic Therapy ; Humans ; NF-kappa B/genetics ; Neoplasms/genetics ; Neoplasms/therapy ; Oligodeoxyribonucleotides/therapeutic use ; RNA Interference ; RNA, Messenger/genetics ; Transcription Factors/genetics ; Transcription Factors/therapeutic use ; Transcription, Genetic
    Chemical Substances NF-kappa B ; Oligodeoxyribonucleotides ; RNA, Messenger ; Transcription Factors
    Language English
    Publishing date 2015-07
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 605825-5
    ISSN 1423-0380 ; 0289-5447 ; 1010-4283
    ISSN (online) 1423-0380
    ISSN 0289-5447 ; 1010-4283
    DOI 10.1007/s13277-015-3344-z
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    Zs.A 1598: Show issues Location:
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  5. Article: IgG subclass antibodies to three variants of Plasmodium falciparum merozoite surface protein-1 (PfMSP-1₁₉) in an area with unstable malaria transmission in Iran

    Mehrizi, Akram Abouie / Asgharpour, Sara / Salmanian, Ali-Hatef / Djadid, Navid Dinparast / Zakeri, Sedigheh

    Acta tropica. 2011 Aug., v. 119, no. 2-3

    2011  

    Abstract: Plasmodium falciparum remains globally an important cause of mortality and morbidity and despite decades of research, no effective vaccine is available against this deadly parasite. The 19-kDa C-terminal fragment of P. falciparum merozoite surface ... ...

    Abstract Plasmodium falciparum remains globally an important cause of mortality and morbidity and despite decades of research, no effective vaccine is available against this deadly parasite. The 19-kDa C-terminal fragment of P. falciparum merozoite surface protein 1 (PfMSP-1₁₉) is a target for protective immunity against malaria and the major concern in development of vaccine based on this antigen is the presence of polymorphisms. This investigation was designed to evaluate naturally acquired antibodies and antigen-binding avidity of IgG antibodies to three variant forms of PfMSP-1₁₉ antigen (E/TSG/L, E/KNG/F and Q/KNG/L) in malaria individuals who are living in hypoendemic areas in Iran (n=92, 4–75years old). The three variant forms of PfMSP-1₁₉ were expressed in Escherichia coli and IgG isotype composition and avidity of naturally acquired antibodies to the 19-kDa antigen were measured by ELISA assay. Results showed that almost 72% of the studied individuals had positive antibody responses to three PfMSP-1₁₉ variants and the prevalence of responders did not differ significantly (P>0.05). High-avidity IgG (62.7%, 65.7% and 47.76%) and IgG1 (64.2%, 50.75%, and 50.75%) were found in positive sera for E/TSG/L, E/KNG/F and Q/KNG/L variants, respectively. Moreover, the prevalence and titers of IgG1 antibody responses to the three variants increased with age (P<0.05). In summary, individuals in low transmission areas in Iran can develop and maintain equal immune responses with high avidity to the PfMSP-1₁₉ variants (E/TSG/L, E/KNG/F and Q/KNG/L); however, the precise role of the total IgG and its isotypes in protection requires further investigation. These results could support the design of a universal PfMSP-1₁₉-based vaccine.
    Keywords Escherichia coli ; Plasmodium falciparum ; antibodies ; antigens ; enzyme-linked immunosorbent assay ; immune response ; immunoglobulin G ; malaria ; merozoites ; morbidity ; mortality ; parasites ; surface proteins ; vaccine development ; Iran
    Language English
    Dates of publication 2011-08
    Size p. 84-90.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 210415-5
    ISSN 1873-6254 ; 0001-706X
    ISSN (online) 1873-6254
    ISSN 0001-706X
    DOI 10.1016/j.actatropica.2011.04.012
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: IgG subclass antibodies to three variants of Plasmodium falciparum merozoite surface protein-1 (PfMSP-1(19)) in an area with unstable malaria transmission in Iran.

    Mehrizi, Akram Abouie / Asgharpour, Sara / Salmanian, Ali-Hatef / Djadid, Navid Dinparast / Zakeri, Sedigheh

    Acta tropica

    2011  Volume 119, Issue 2-3, Page(s) 84–90

    Abstract: Plasmodium falciparum remains globally an important cause of mortality and morbidity and despite decades of research, no effective vaccine is available against this deadly parasite. The 19-kDa C-terminal fragment of P. falciparum merozoite surface ... ...

    Abstract Plasmodium falciparum remains globally an important cause of mortality and morbidity and despite decades of research, no effective vaccine is available against this deadly parasite. The 19-kDa C-terminal fragment of P. falciparum merozoite surface protein 1 (PfMSP-1(19)) is a target for protective immunity against malaria and the major concern in development of vaccine based on this antigen is the presence of polymorphisms. This investigation was designed to evaluate naturally acquired antibodies and antigen-binding avidity of IgG antibodies to three variant forms of PfMSP-1(19) antigen (E/TSG/L, E/KNG/F and Q/KNG/L) in malaria individuals who are living in hypoendemic areas in Iran (n=92, 4-75 years old). The three variant forms of PfMSP-1(19) were expressed in Escherichia coli and IgG isotype composition and avidity of naturally acquired antibodies to the 19-kDa antigen were measured by ELISA assay. Results showed that almost 72% of the studied individuals had positive antibody responses to three PfMSP-1(19) variants and the prevalence of responders did not differ significantly (P>0.05). High-avidity IgG (62.7%, 65.7% and 47.76%) and IgG1 (64.2%, 50.75%, and 50.75%) were found in positive sera for E/TSG/L, E/KNG/F and Q/KNG/L variants, respectively. Moreover, the prevalence and titers of IgG1 antibody responses to the three variants increased with age (P<0.05). In summary, individuals in low transmission areas in Iran can develop and maintain equal immune responses with high avidity to the PfMSP-1(19) variants (E/TSG/L, E/KNG/F and Q/KNG/L); however, the precise role of the total IgG and its isotypes in protection requires further investigation. These results could support the design of a universal PfMSP-1(19)-based vaccine.
    MeSH term(s) Adolescent ; Adult ; Aged ; Antibodies, Protozoan/blood ; Antibody Affinity ; Child ; Child, Preschool ; Escherichia coli/genetics ; Female ; Humans ; Immunoglobulin G/blood ; Iran/epidemiology ; Malaria, Falciparum/epidemiology ; Malaria, Falciparum/transmission ; Male ; Merozoite Surface Protein 1/immunology ; Middle Aged ; Plasmodium falciparum/immunology ; Recombinant Proteins ; Seroepidemiologic Studies ; Young Adult
    Chemical Substances Antibodies, Protozoan ; Immunoglobulin G ; Merozoite Surface Protein 1 ; Recombinant Proteins
    Language English
    Publishing date 2011-08
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 210415-5
    ISSN 1873-6254 ; 0001-706X
    ISSN (online) 1873-6254
    ISSN 0001-706X
    DOI 10.1016/j.actatropica.2011.04.012
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  7. Article: IgG subclass antibodies to three variants of Plasmodium falciparum merozoite surface protein-1 (PfMSP-1₁₉) in an area with unstable malaria transmission in Iran

    Mehrizi, Akram Abouie / Asgharpour, Sara / Salmanian, Ali-Hatef / Djadid, Navid Dinparast / Zakeri, Sedigheh

    Acta tropica

    Volume v. 119,, Issue no. 2

    Abstract: Plasmodium falciparum remains globally an important cause of mortality and morbidity and despite decades of research, no effective vaccine is available against this deadly parasite. The 19-kDa C-terminal fragment of P. falciparum merozoite surface ... ...

    Abstract Plasmodium falciparum remains globally an important cause of mortality and morbidity and despite decades of research, no effective vaccine is available against this deadly parasite. The 19-kDa C-terminal fragment of P. falciparum merozoite surface protein 1 (PfMSP-1₁₉) is a target for protective immunity against malaria and the major concern in development of vaccine based on this antigen is the presence of polymorphisms. This investigation was designed to evaluate naturally acquired antibodies and antigen-binding avidity of IgG antibodies to three variant forms of PfMSP-1₁₉ antigen (E/TSG/L, E/KNG/F and Q/KNG/L) in malaria individuals who are living in hypoendemic areas in Iran (n=92, 4–75years old). The three variant forms of PfMSP-1₁₉ were expressed in Escherichia coli and IgG isotype composition and avidity of naturally acquired antibodies to the 19-kDa antigen were measured by ELISA assay. Results showed that almost 72% of the studied individuals had positive antibody responses to three PfMSP-1₁₉ variants and the prevalence of responders did not differ significantly (P>0.05). High-avidity IgG (62.7%, 65.7% and 47.76%) and IgG1 (64.2%, 50.75%, and 50.75%) were found in positive sera for E/TSG/L, E/KNG/F and Q/KNG/L variants, respectively. Moreover, the prevalence and titers of IgG1 antibody responses to the three variants increased with age (P<0.05). In summary, individuals in low transmission areas in Iran can develop and maintain equal immune responses with high avidity to the PfMSP-1₁₉ variants (E/TSG/L, E/KNG/F and Q/KNG/L); however, the precise role of the total IgG and its isotypes in protection requires further investigation. These results could support the design of a universal PfMSP-1₁₉-based vaccine.
    Keywords merozoites ; parasites ; surface proteins ; antibodies ; immunoglobulin G ; Plasmodium falciparum ; enzyme-linked immunosorbent assay ; malaria ; Escherichia coli ; mortality ; immune response ; vaccine development ; morbidity ; antigens
    Language English
    Document type Article
    ISSN 0001-706X
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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