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  1. Article ; Online: CRESSP: a comprehensive pipeline for prediction of immunopathogenic SARS-CoV-2 epitopes using structural properties of proteins.

    An, Hyunsu / Eun, Minho / Yi, Jawoon / Park, Jihwan

    Briefings in bioinformatics

    2022  Volume 23, Issue 2

    Abstract: The development of autoimmune diseases following SARS-CoV-2 infection, including multisystem inflammatory syndrome, has been reported, and several mechanisms have been suggested, including molecular mimicry. We developed a scalable, comparative ... ...

    Abstract The development of autoimmune diseases following SARS-CoV-2 infection, including multisystem inflammatory syndrome, has been reported, and several mechanisms have been suggested, including molecular mimicry. We developed a scalable, comparative immunoinformatics pipeline called cross-reactive-epitope-search-using-structural-properties-of-proteins (CRESSP) to identify cross-reactive epitopes between a collection of SARS-CoV-2 proteomes and the human proteome using the structural properties of the proteins. Overall, by searching 4 911 245 proteins from 196 352 SARS-CoV-2 genomes, we identified 133 and 648 human proteins harboring potential cross-reactive B-cell and CD8+ T-cell epitopes, respectively. To demonstrate the robustness of our pipeline, we predicted the cross-reactive epitopes of coronavirus spike proteins, which were recognized by known cross-neutralizing antibodies. Using single-cell expression data, we identified PARP14 as a potential target of intermolecular epitope spreading between the virus and human proteins. Finally, we developed a web application (https://ahs2202.github.io/3M/) to interactively visualize our results. We also made our pipeline available as an open-source CRESSP package (https://pypi.org/project/cressp/), which can analyze any two proteomes of interest to identify potentially cross-reactive epitopes between the proteomes. Overall, our immunoinformatic resources provide a foundation for the investigation of molecular mimicry in the pathogenesis of autoimmune and chronic inflammatory diseases following COVID-19.
    MeSH term(s) Algorithms ; Computational Biology/methods ; Cross Reactions/immunology ; Epitopes/chemistry ; Epitopes/immunology ; Epitopes, B-Lymphocyte ; Epitopes, T-Lymphocyte ; Histocompatibility Antigens Class I/chemistry ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Antigens Class II/chemistry ; Histocompatibility Antigens Class II/immunology ; Models, Molecular ; Molecular Mimicry ; Neural Networks, Computer ; Proteome ; Proteomics/methods ; SARS-CoV-2/immunology ; Software ; Structure-Activity Relationship ; Viral Proteins/chemistry ; Viral Proteins/immunology ; Web Browser
    Chemical Substances Epitopes ; Epitopes, B-Lymphocyte ; Epitopes, T-Lymphocyte ; Histocompatibility Antigens Class I ; Histocompatibility Antigens Class II ; Proteome ; Viral Proteins
    Language English
    Publishing date 2022-02-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2068142-2
    ISSN 1477-4054 ; 1467-5463
    ISSN (online) 1477-4054
    ISSN 1467-5463
    DOI 10.1093/bib/bbac056
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Clinical Value of EZH2 in Hepatocellular Carcinoma and Its Potential for Target Therapy.

    Bae, An-Na / Jung, Soo-Jung / Lee, Jae-Ho / Lee, Hyunsu / Park, Seung Gyu

    Medicina (Kaunas, Lithuania)

    2022  Volume 58, Issue 2

    Abstract: Background and objectives: ...

    Abstract Background and objectives:
    MeSH term(s) Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; Enhancer of Zeste Homolog 2 Protein/genetics ; Gene Expression Regulation, Neoplastic ; Hep G2 Cells ; Humans ; Liver Neoplasms/pathology ; Prognosis
    Chemical Substances Biomarkers, Tumor ; EZH2 protein, human (EC 2.1.1.43) ; Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43)
    Language English
    Publishing date 2022-01-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2188113-3
    ISSN 1648-9144 ; 1010-660X
    ISSN (online) 1648-9144
    ISSN 1010-660X
    DOI 10.3390/medicina58020155
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: ROS-Scavenging Lignin-Based Tolerogenic Nanoparticle Vaccine for Treatment of Multiple Sclerosis.

    Phan, Ngoc Man / Nguyen, Thanh Loc / Shin, Hyunsu / Trinh, Thuy An / Kim, Jaeyun

    ACS nano

    2023  Volume 17, Issue 24, Page(s) 24696–24709

    Abstract: Multiple sclerosis (MS) is a demyelinating autoimmune disease, in which the immune system attacks myelin. Although systemic immunosuppressive agents have been used to treat MS, long-term treatment with these drugs causes undesirable side effects such as ... ...

    Abstract Multiple sclerosis (MS) is a demyelinating autoimmune disease, in which the immune system attacks myelin. Although systemic immunosuppressive agents have been used to treat MS, long-term treatment with these drugs causes undesirable side effects such as altered glucose metabolism, insomnia, and hypertension. Herein, we propose a tolerogenic therapeutic vaccine to treat MS based on lignin nanoparticles (LNP) with intrinsic reactive oxygen species (ROS)-scavenging capacity derived from their phenolic moieties. The LNP loaded with autoantigens of MS allowed for inducing tolerogenic DCs with low-level expression of costimulatory molecules while presenting antigenic peptides. Intravenous injection of an LNP-based tolerogenic vaccine into an experimental autoimmune encephalomyelitis (EAE) model led to durable antigen-specific immune tolerance via inducing regulatory T cells (Tregs). Autoreactive T helper type 1 cells, T helper type 17 cells, and inflammatory antigen presentation cells (APCs) were suppressed in the central nervous system (CNS), ameliorating ongoing MS in early and late disease states. Additionally, the incorporation of dexamethasone into an LNP-based tolerogenic nanovaccine could further improve the recovery of EAE mice in the severe chronic stage. As lignin is the most abundant biomass and waste byproduct in the pulping industry, a lignin-based tolerogenic vaccine could be a novel, cost-effective, high-value vaccine platform with potent therapeutic efficiency in treating autoimmune diseases.
    MeSH term(s) Mice ; Animals ; Multiple Sclerosis/drug therapy ; Nanovaccines ; Lignin/therapeutic use ; Reactive Oxygen Species/therapeutic use ; Encephalomyelitis, Autoimmune, Experimental/drug therapy ; Vaccines ; Mice, Inbred C57BL
    Chemical Substances Nanovaccines ; Lignin (9005-53-2) ; Reactive Oxygen Species ; Vaccines
    Language English
    Publishing date 2023-12-05
    Publishing country United States
    Document type Journal Article
    ISSN 1936-086X
    ISSN (online) 1936-086X
    DOI 10.1021/acsnano.3c04497
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Cell Type- and Age-Specific Expression of lncRNAs across Kidney Cell Types.

    Kim, Gyeong Dae / Shin, So-I / Jung, Su Woong / An, Hyunsu / Choi, Sin Young / Eun, Minho / Jun, Chang-Duk / Lee, Sangho / Park, Jihwan

    Journal of the American Society of Nephrology : JASN

    2024  

    Abstract: Background: Accumulated evidence demonstrates that long non-coding RNAs (lncRNAs) regulate cell differentiation and homeostasis, influencing kidney aging and disease. Despite their versatility, the function of lncRNA remains poorly understood due to the ...

    Abstract Background: Accumulated evidence demonstrates that long non-coding RNAs (lncRNAs) regulate cell differentiation and homeostasis, influencing kidney aging and disease. Despite their versatility, the function of lncRNA remains poorly understood due to the lack of a reference map of lncRNA transcriptome in various cell types.
    Methods: In this study, we employed a targeted single-cell RNA sequencing (scRNA-seq) method to enrich and characterize lncRNAs in individual cells. We applied this method to various mouse tissues, including normal and aged kidneys.
    Results: Through tissue-specific clustering analysis, we identified cell type-specific lncRNAs that showed a high correlation with known cell-type marker genes. Furthermore, we constructed gene regulatory networks (GRNs) to explore the functional roles of differentially expressed lncRNAs in each cell type. In the kidney, we observed dynamic expression changes of lncRNAs during aging, with specific changes in glomerular cells. These cell type- and age-specific expression patterns of lncRNAs provide insights into their potential roles in regulating cellular processes, such as immune response and energy metabolism, during kidney aging.
    Conclusions: Our study sheds light on the comprehensive landscape of lncRNA expression and function and provides a valuable resource for future analysis of lncRNAs (https://gist-fgl.github.io/sc-lncrna-atlas/).
    Language English
    Publishing date 2024-04-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.0000000000000354
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 3344: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Clinical Value of EZH2 in Hepatocellular Carcinoma and Its Potential for Target Therapy

    An-Na Bae / Soo-Jung Jung / Jae-Ho Lee / Hyunsu Lee / Seung Gyu Park

    Medicina, Vol 58, Iss 155, p

    2022  Volume 155

    Abstract: Background and objectives: EZH2 is overexpressed in hepatocellular carcinoma (HCC) and is correlated with poor prognosis. However, its clinical significance and molecular mechanism have not been studied in HCC. In this study, clinical and prognostic ... ...

    Abstract Background and objectives: EZH2 is overexpressed in hepatocellular carcinoma (HCC) and is correlated with poor prognosis. However, its clinical significance and molecular mechanism have not been studied in HCC. In this study, clinical and prognostic values of EZH2 was studied using Total Cancer Genome Atlas (TCGA) data and then, these data were confirmed in Huh1 and HepG2 cell lines. Materials and Methods : We used the TCGA database from cBioPortal. In addition, we analyzed EZH2 mRNA levels in HCC cell lines and its correlation with STAT3 and EZH2. Results: According to TCGA, EZH2 had a prognostic value in various cancers, especially in HCC. Furthermore, EZH2 in HCC was correlated with N stage ( p = 0.045) and alpha-fetoprotein (AFP) > 20 ng/mL ( p < 0.01). However, a negative association between EZH2 and age ( p = 0.027) was found. The overall survival result of HCC was significantly poorer in patients with high EZH2 expression. In addition, the recurrence rate was also significantly higher in patients with high expression of EZH2 than those with low expression (χ2 = 16.10, p < 0.001). EZH2 expression was negatively correlated with STAT3 expression among EZH2-associated genes (R = −0.163, p = 0.002). EZH2 expression level was down-regulated to 50% or less compared to the control group treated negative siRNA. MTT assays showed that EZH2-siRNA affected on the viability of HCC cell line significantly. Conclusions: In conclusion, the overexpression of EZH2 was an independent biomarker for poor outcomes of HCC. However, more in vivo studies are required to identify the downstream target genes in HCC to improve our understanding of the biological role of EZH2 in HCC.
    Keywords hepatocellular carcinoma ; EZH2 ; STAT3 ; TCGA ; Medicine (General) ; R5-920
    Subject code 616
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Molecular Mimicry Map (3M) of SARS-CoV-2: Prediction of potentially immunopathogenic SARS-CoV-2 epitopes via a novel immunoinformatic approach

    An, Hyunsu / Park, Jihwan

    bioRxiv

    Abstract: Currently, more than 33 million peoples have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than a million people died from coronavirus disease 2019 (COVID-19), a disease caused by the virus. There have been ... ...

    Abstract Currently, more than 33 million peoples have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than a million people died from coronavirus disease 2019 (COVID-19), a disease caused by the virus. There have been multiple reports of autoimmune and inflammatory diseases following SARS-CoV-2 infections. There are several suggested mechanisms involved in the development of autoimmune diseases, including cross-reactivity (molecular mimicry). A typical workflow for discovering cross-reactive epitopes (mimotopes) starts with a sequence similarity search between protein sequences of human and a pathogen. However, sequence similarity information alone is not enough to predict cross-reactivity between proteins since proteins can share highly similar conformational epitopes whose amino acid residues are situated far apart in the linear protein sequences. Therefore, we used a hidden Markov model-based tool to identify distant viral homologs of human proteins. Also, we utilized experimentally determined and modeled protein structures of SARS-CoV-2 and human proteins to find homologous protein structures between them. Next, we predicted binding affinity (IC50) of potentially cross-reactive T-cell epitopes to 34 MHC allelic variants that have been associated with autoimmune diseases using multiple prediction algorithms. Overall, from 8,138 SARS-CoV-2 genomes, we identified 3,238 potentially cross-reactive B-cell epitopes covering six human proteins and 1,224 potentially cross-reactive T-cell epitopes covering 285 human proteins. To visualize the predicted cross-reactive T-cell and B-cell epitopes, we developed a web-based application “Molecular Mimicry Map (3M) of SARS-CoV-2” (available at https://ahs2202.github.io/3M/). The web application enables researchers to explore potential cross-reactive SARS-CoV-2 epitopes alongside custom peptide vaccines, allowing researchers to identify potentially suboptimal peptide vaccine candidates or less ideal part of a whole virus vaccine to design a safer vaccine for people with genetic and environmental predispositions to autoimmune diseases. Together, the computational resources and the interactive web application provide a foundation for the investigation of molecular mimicry in the pathogenesis of autoimmune disease following COVID-19.
    Keywords covid19
    Publisher BioRxiv; WHO
    Document type Article ; Online
    DOI 10.1101/2020.11.12.344424
    Database COVID19

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  7. Article ; Online: Molecular Mimicry Map (3M) of SARS-CoV-2: Prediction of potentially immunopathogenic SARS-CoV-2 epitopes via a novel immunoinformatic approach

    An, Hyunsu / Park, Jihwan

    bioRxiv

    Abstract: Currently, more than 33 million peoples have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than a million people died from coronavirus disease 2019 (COVID-19), a disease caused by the virus. There have been ... ...

    Abstract Currently, more than 33 million peoples have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than a million people died from coronavirus disease 2019 (COVID-19), a disease caused by the virus. There have been multiple reports of autoimmune and inflammatory diseases following SARS-CoV-2 infections. There are several suggested mechanisms involved in the development of autoimmune diseases, including cross-reactivity (molecular mimicry). A typical workflow for discovering cross-reactive epitopes (mimotopes) starts with a sequence similarity search between protein sequences of human and a pathogen. However, sequence similarity information alone is not enough to predict cross-reactivity between proteins since proteins can share highly similar conformational epitopes whose amino acid residues are situated far apart in the linear protein sequences. Therefore, we used a hidden Markov model-based tool to identify distant viral homologs of human proteins. Also, we utilized experimentally determined and modeled protein structures of SARS-CoV-2 and human proteins to find homologous protein structures between them. Next, we predicted binding affinity (IC50) of potentially cross-reactive T-cell epitopes to 34 MHC allelic variants that have been associated with autoimmune diseases using multiple prediction algorithms. Overall, from 8,138 SARS-CoV-2 genomes, we identified 3,238 potentially cross-reactive B-cell epitopes covering six human proteins and 1,224 potentially cross-reactive T-cell epitopes covering 285 human proteins. To visualize the predicted cross-reactive T-cell and B-cell epitopes, we developed a web-based application "Molecular Mimicry Map (3M) of SARS-CoV-2" (available at https://ahs2202.github.io/3M/). The web application enables researchers to explore potential cross-reactive SARS-CoV-2 epitopes alongside custom peptide vaccines, allowing researchers to identify potentially suboptimal peptide vaccine candidates or less ideal part of a whole virus vaccine to design a safer vaccine for people with genetic and environmental predispositions to autoimmune diseases. Together, the computational resources and the interactive web application provide a foundation for the investigation of molecular mimicry in the pathogenesis of autoimmune disease following COVID-19.
    Keywords covid19
    Language English
    Publishing date 2020-11-12
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2020.11.12.344424
    Database COVID19

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  8. Article ; Online: Pheophorbide A and SN38 conjugated hyaluronan nanoparticles for photodynamic- and cascadic chemotherapy of cancer stem-like ovarian cancer.

    Lee, Junghan / Davaa, Enkhzaya / Jiang, Yixin / Shin, Kyung-Ju / Kim, Min Hye / An, Hyunsu / Kim, Jinho / Cho, Steve K / Yang, Su-Geun

    Carbohydrate polymers

    2022  Volume 289, Page(s) 119455

    Abstract: In this study, we designed photo-triggered reactive oxygen species (ROS)-generating pheophorbide A and ROS-cleavable thioketal-SN38 conjugated hyaluronan-cholesterol nanoparticles (PheoA-SN38-HC NPs). And we observed the combined therapeutic effects of ... ...

    Abstract In this study, we designed photo-triggered reactive oxygen species (ROS)-generating pheophorbide A and ROS-cleavable thioketal-SN38 conjugated hyaluronan-cholesterol nanoparticles (PheoA-SN38-HC NPs). And we observed the combined therapeutic effects of PheoA-SN38-HC NPs against HEY-T30 human ovarian cancer (OC) model. Clinical Proteomic Tumor Analysis Consortium (CPTAC) data showed that the expression of cancer stem cell (CSC) markers (CD44, ALDH1A1, and CD117) is highly associated with poor clinical outcomes in OC patients. We proved that HEY-T30 cells overexpress CSC markers and much more invasive than other cancer cells. Flow cytometry (FACS) and microscopic analysis revealed the active targeting property of PheoA-SN38-HC NPs to CD44+ HEY-T30 cells. Moreover, the combination therapeutic effect of PheoA-SN38-HC NPs was clearly demonstrated against in vitro HEY-T30 cells and an in vivo xenograft mouse model. In particular, the paracrine cytotoxic effect of SN38 probably compensates the locoregional therapeutic limitation of photodynamic therapy.
    MeSH term(s) Animals ; Cell Line, Tumor ; Chlorophyll/analogs & derivatives ; Female ; Humans ; Hyaluronic Acid ; Mice ; Nanoparticles ; Ovarian Neoplasms/drug therapy ; Proteomics ; Reactive Oxygen Species/metabolism
    Chemical Substances Reactive Oxygen Species ; Chlorophyll (1406-65-1) ; Hyaluronic Acid (9004-61-9) ; pheophorbide a (IA2WNI2HO2)
    Language English
    Publishing date 2022-04-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 1501516-6
    ISSN 1879-1344 ; 0144-8617
    ISSN (online) 1879-1344
    ISSN 0144-8617
    DOI 10.1016/j.carbpol.2022.119455
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Investigating the electrical crosstalk effect between pixels in high-resolution organic light-emitting diode microdisplays.

    Kang, Haneul / Hwang, Yeonsu / Kang, Chan-Mo / Kim, Joo Yeon / Joo, Chul Woong / Shin, Jin-Wook / Sim, Soobin / Cho, Hyunsu / Ahn, Dae Hyun / Cho, Nam Sung / Youn, Hyoc Min / An, Young Jae / Kim, Jin Sun / Byun, Chun-Won / Lee, Hyunkoo

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 14070

    Abstract: Organic light-emitting diode (OLED) microdisplays have received great attention owing to their excellent performance for augmented reality/virtual reality devices applications. However, high pixel density of OLED microdisplay causes electrical crosstalk, ...

    Abstract Organic light-emitting diode (OLED) microdisplays have received great attention owing to their excellent performance for augmented reality/virtual reality devices applications. However, high pixel density of OLED microdisplay causes electrical crosstalk, resulting in color distortion. This study investigated the current crosstalk ratio and changes in the color gamut caused by electrical crosstalk between sub-pixels in high-resolution full-color OLED microdisplays. A pixel structure of 3147 pixels per inch (PPI) with four sub-pixels and a single-stack white OLED with red, green, and blue color filters were used for the electrical crosstalk simulation. The results showed that the sheet resistance of the top and bottom electrodes of OLEDs rarely affected the electrical crosstalk. However, the current crosstalk ratio increased dramatically and the color gamut decreased as the sheet resistance of the common organic layer decreased. Furthermore, the color gamut of the OLED microdisplay decreased as the pixel density of the panel increased from 200 to 5000 PPI. Additionally, we fabricated a sub-pixel circuit to measure the electrical crosstalk current using a 3147 PPI scale multi-finger-type pixel structure and compared it with the simulation result.
    Language English
    Publishing date 2023-08-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-41033-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Pheophorbide A and SN38 conjugated hyaluronan nanoparticles for photodynamic- and cascadic chemotherapy of cancer stem-like ovarian cancer

    Lee, Junghan / Davaa, Enkhzaya / Jiang, Yixin / Shin, Kyung-Ju / Kim, Min Hye / An, Hyunsu / Kim, Jinho / Cho, Steve K. / Yang, Su-Geun

    Carbohydrate polymers. 2022 Aug. 01, v. 289

    2022  

    Abstract: In this study, we designed photo-triggered reactive oxygen species (ROS)-generating pheophorbide A and ROS-cleavable thioketal-SN38 conjugated hyaluronan-cholesterol nanoparticles (PheoA-SN38-HC NPs). And we observed the combined therapeutic effects of ... ...

    Abstract In this study, we designed photo-triggered reactive oxygen species (ROS)-generating pheophorbide A and ROS-cleavable thioketal-SN38 conjugated hyaluronan-cholesterol nanoparticles (PheoA-SN38-HC NPs). And we observed the combined therapeutic effects of PheoA-SN38-HC NPs against HEY-T30 human ovarian cancer (OC) model. Clinical Proteomic Tumor Analysis Consortium (CPTAC) data showed that the expression of cancer stem cell (CSC) markers (CD44, ALDH1A1, and CD117) is highly associated with poor clinical outcomes in OC patients. We proved that HEY-T30 cells overexpress CSC markers and much more invasive than other cancer cells. Flow cytometry (FACS) and microscopic analysis revealed the active targeting property of PheoA-SN38-HC NPs to CD44+ HEY-T30 cells. Moreover, the combination therapeutic effect of PheoA-SN38-HC NPs was clearly demonstrated against in vitro HEY-T30 cells and an in vivo xenograft mouse model. In particular, the paracrine cytotoxic effect of SN38 probably compensates the locoregional therapeutic limitation of photodynamic therapy.
    Keywords cytotoxicity ; flow cytometry ; humans ; hyaluronic acid ; mice ; ovarian neoplasms ; photochemotherapy ; proteomics ; reactive oxygen species ; stem cells ; xenotransplantation
    Language English
    Dates of publication 2022-0801
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 1501516-6
    ISSN 1879-1344 ; 0144-8617
    ISSN (online) 1879-1344
    ISSN 0144-8617
    DOI 10.1016/j.carbpol.2022.119455
    Database NAL-Catalogue (AGRICOLA)

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