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  • 1
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    Application of Traditional Vaccine Development Strategies to SARS-CoV-2
    American Society for Microbiology ; 2023
    In:  mSystems Vol. 8, No. 2 ( 2023-04-27)
    Details
    In: mSystems, American Society for Microbiology, Vol. 8, No. 2 ( 2023-04-27)
    Abstract: Over the past 150 years, vaccines have revolutionized the relationship between people and disease. During the COVID-19 pandemic, technologies such as mRNA vaccines have received attention due to their novelty and successes. However, more traditional vaccine development platforms have also yielded important tools in the worldwide fight against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A variety of approaches have been used to develop COVID-19 vaccines that are now authorized for use in countries around the world. In this review, we highlight strategies that focus on the viral capsid and outwards, rather than on the nucleic acids inside. These approaches fall into two broad categories: whole-virus vaccines and subunit vaccines. Whole-virus vaccines use the virus itself, in either an inactivated or an attenuated state. Subunit vaccines contain instead an isolated, immunogenic component of the virus. Here, we highlight vaccine candidates that apply these approaches against SARS-CoV-2 in different ways. In a companion article (H. M. Rando, R. Lordan, L. Kolla, E. Sell, et al., mSystems 8:e00928-22, 2023, https://doi.org/10.1128/mSystems.00928-22 ), we review the more recent and novel development of nucleic acid-based vaccine technologies. We further consider the role that these COVID-19 vaccine development programs have played in prophylaxis at the global scale. Well-established vaccine technologies have proved especially important to making vaccines accessible in low- and middle-income countries. Vaccine development programs that use established platforms have been undertaken in a much wider range of countries than those using nucleic acid-based technologies, which have been led by wealthy Western countries. Therefore, these vaccine platforms, though less novel from a biotechnological standpoint, have proven to be extremely important to the management of SARS-CoV-2. IMPORTANCE The development, production, and distribution of vaccines is imperative to saving lives, preventing illness, and reducing the economic and social burdens caused by the COVID-19 pandemic. Vaccines that use cutting-edge biotechnology have played an important role in mitigating the effects of SARS-CoV-2. However, more traditional methods of vaccine development that were refined throughout the 20th century have been especially critical to increasing vaccine access worldwide. Effective deployment is necessary to reducing the susceptibility of the world’s population, which is especially important in light of emerging variants. In this review, we discuss the safety, immunogenicity, and distribution of vaccines developed using established technologies. In a separate review, we describe the vaccines developed using nucleic acid-based vaccine platforms. From the current literature, it is clear that the well-established vaccine technologies are also highly effective against SARS-CoV-2 and are being used to address the challenges of COVID-19 globally, including in low- and middle-income countries. This worldwide approach is critical for reducing the devastating impact of SARS-CoV-2.
    Type of Medium: Online Resource
    ISSN: 2379-5077
    URL: Article
    DOI: 10.1128/msystems.00927-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 2844333-0
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  • 2
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    The Coming of Age of Nucleic Acid Vaccines during COVID-19
    American Society for Microbiology ; 2023
    In:  mSystems Vol. 8, No. 2 ( 2023-04-27)
    Details
    In: mSystems, American Society for Microbiology, Vol. 8, No. 2 ( 2023-04-27)
    Abstract: In the 21st century, several emergent viruses have posed a global threat. Each pathogen has emphasized the value of rapid and scalable vaccine development programs. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has made the importance of such efforts especially clear. New biotechnological advances in vaccinology allow for recent advances that provide only the nucleic acid building blocks of an antigen, eliminating many safety concerns. During the COVID-19 pandemic, these DNA and RNA vaccines have facilitated the development and deployment of vaccines at an unprecedented pace. This success was attributable at least in part to broader shifts in scientific research relative to prior epidemics: the genome of SARS-CoV-2 was available as early as January 2020, facilitating global efforts in the development of DNA and RNA vaccines within 2 weeks of the international community becoming aware of the new viral threat. Additionally, these technologies that were previously only theoretical are not only safe but also highly efficacious. Although historically a slow process, the rapid development of vaccines during the COVID-19 crisis reveals a major shift in vaccine technologies. Here, we provide historical context for the emergence of these paradigm-shifting vaccines. We describe several DNA and RNA vaccines in terms of their efficacy, safety, and approval status. We also discuss patterns in worldwide distribution. The advances made since early 2020 provide an exceptional illustration of how rapidly vaccine development technology has advanced in the last 2 decades in particular and suggest a new era in vaccines against emerging pathogens. IMPORTANCE The SARS-CoV-2 pandemic has caused untold damage globally, presenting unusual demands on but also unique opportunities for vaccine development. The development, production, and distribution of vaccines are imperative to saving lives, preventing severe illness, and reducing the economic and social burdens caused by the COVID-19 pandemic. Although vaccine technologies that provide the DNA or RNA sequence of an antigen had never previously been approved for use in humans, they have played a major role in the management of SARS-CoV-2. In this review, we discuss the history of these vaccines and how they have been applied to SARS-CoV-2. Additionally, given that the evolution of new SARS-CoV-2 variants continues to present a significant challenge in 2022, these vaccines remain an important and evolving tool in the biomedical response to the pandemic.
    Type of Medium: Online Resource
    ISSN: 2379-5077
    URL: Article
    DOI: 10.1128/msystems.00928-22
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 2844333-0
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  • 3
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    DDRE-31. EVALUATION OF HIGHLY POTENT AND SELECTIVE SINGLE-MOLECULE DUAL EGFR/PI3K INHIBITORS IN ADULT AND PEDIATRIC HIGH-GRADE GLIOMA
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii68-ii68
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii68-ii68
    Abstract: High grade gliomas (HGG) carry poor prognosis with median survival rates under 15 months post diagnosis. Due to dysregulation of kinase signaling pathways within these tumors, targeted kinase inhibition has been considered as a promising clinical strategy. However in HGG, many single-agent inhibitors of EGFR or PI3K have shown limited response due to activation of compensatory signaling. Single-molecule multikinase inhibitors may decrease resistance, present a single pharmacokinetic dosage profile, and reduce risks of multi-agent toxicities, supporting this strategy over dual drug combination approaches. To test this concept, a panel of inhibitors exploiting known binding modes of structurally-related ATP binding site inhibitors of EGFR/PI3K were synthesized and characterized. Of these, MTX-241 was least likely to act as a substrate for drug efflux proteins such as P-glycoprotein. Treatment of MTX-241 in a panel of eight human adult and pediatric HGG lines showed strong cytotoxic potency measured by growth inhibitory activity, with IC50s in the & lt; 10 µM range. Tumor selectivity of MTX-241 was observed, with normal human astrocytes (NHA) nearly insensitive to MTX-241 even at & gt;100 µM. MTX-241 was significantly more potent than clinically relevant inhibitors targeting EGFR/RTKs (gefitinib, lapatinib, dasatinib, imatinib) or PI3K (alpelisib, idelalisib). Synthesis and evaluation of a new series of compounds based on MTX-241 structure, but optimized for improved stability is ongoing. Our data suggests that a dual inhibitor of EGFR and PI3K, represents a viable therapeutic strategy in adult and pediatric HGG. Future studies will focus on evaluation of in vivo efficacy in tumor bearing mouse models.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa215.276
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2094060-9
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  • 4
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    Heated fennel therapy promotes the recovery of gastrointestinal function in patients after complex abdominal surgery: A single-center prospective randomized controlled trial in China
    Elsevier BV ; 2020
    In:  Surgery Vol. 168, No. 5 ( 2020-11), p. 793-799
    Details
    In: Surgery, Elsevier BV, Vol. 168, No. 5 ( 2020-11), p. 793-799
    Type of Medium: Online Resource
    ISSN: 0039-6060
    URL: Article
    DOI: 10.1016/j.surg.2020.05.040
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2018278-8
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  • 5
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    Polyadenylation of Histone H3.1 mRNA Promotes Cell Transformation by Displacing H3.3 from Gene Regulatory Elements
    Elsevier BV ; 2019
    In:  SSRN Electronic Journal
    Details
    In: SSRN Electronic Journal, Elsevier BV
    Type of Medium: Online Resource
    ISSN: 1556-5068
    URL: Article
    DOI: 10.2139/ssrn.3490279
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2019
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  • 6
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    Abstract 5857: Isorhapontigenin inhibits triple-negative breast cancer via activating NRF2-mediated pathway
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 5857-5857
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 5857-5857
    Abstract: Breast cancer is the most prevalent cancer among women worldwide, and is the second leading cause of cancer mortality among women. Triple-negative breast cancers (TNBCs; ER-/PR-/HER2-) are highly aggressive tumors with poor prognosis. Due to lack of these specific receptors, TNBCs cannot be treated with hormone therapies or anti-HER2 targeted therapies. Chemotherapy, combined with surgery and radiation therapy, is the primary strategy for treating TNBCs. Thus, discovery and evaluation of new alternative medications targeting triple-negative breast cancer is of tremendous importance for reducing breast cancer mortality. Isorhapontigenin (ISO), a new derivative of stilbene isolated from Chinese herb Gnetum Cleistostachyun, exhibits a strong inhibitory effect on human bladder cancers. However, its anticancer activity with respect to breast cancer remains unclear. In the present study, we investigated the potential anticancer effect of ISO on TNBCs. ISO treatment inhibited the proliferation and anchorage-independent growth of 4T1 cells, a murine triple-negative breast cancer cell line, in a dose-dependent manner. In addition, the results from wound healing and Transwell invasion assay indicated significantly reduced cell migration and invasion in ISO-treated cells. Moreover, we performed the whole transcriptome analysis using RNA-seq to elucidate the molecules and pathways that mediate ISO's anticancer activity. A total of 1972 differentially expressed genes were identified in ISO-treated cells. IPA analysis revealed that the top canonical pathway altered by ISO is NRF2-mediated pathway. ISO-induced NRF2 activation was further confirmed by nuclear translocation of NRF2 protein and upregulation of NRF2 downstream target genes (GSTA1, GSTM1, HMOX1, and NQO1). In summary, our study is the first to demonstrate that ISO inhibits breast cancer cell growth and invasion, in part, by activating NRF2-mediated signaling pathway. Our results provide a novel mechanism for ISO-induced anticancer effect, and strongly support ISO as a promising therapeutic agent for triple-negative breast cancers. Citation Format: Yusha Zhu, Anthony Murphy, Thomas Kluz, Bo Li, Max Costa, Chuanshu Huang, Hong Sun. Isorhapontigenin inhibits triple-negative breast cancer via activating NRF2-mediated pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5857.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2018-5857
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 7
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    18F-Sodium Fluoride PET as a Diagnostic Modality for Metabolic, Autoimmune, and Osteogenic Bone Disorders: Cellular Mechanisms and Clinical Applications
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 12 ( 2021-06-17), p. 6504-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 12 ( 2021-06-17), p. 6504-
    Abstract: In a healthy body, homeostatic actions of osteoclasts and osteoblasts maintain the integrity of the skeletal system. When cellular activities of osteoclasts and osteoblasts become abnormal, pathological bone conditions, such as osteoporosis, can occur. Traditional imaging modalities, such as radiographs, are insensitive to the early cellular changes that precede gross pathological findings, often leading to delayed disease diagnoses and suboptimal therapeutic strategies. 18F-sodium fluoride (18F-NaF)-positron emission tomography (PET) is an emerging imaging modality with the potential for early diagnosis and monitoring of bone diseases through the detection of subtle metabolic changes. Specifically, the dissociated 18F- is incorporated into hydroxyapatite, and its uptake reflects osteoblastic activity and bone perfusion, allowing for the quantification of bone turnover. While 18F-NaF-PET has traditionally been used to detect metastatic bone disease, recent literature corroborates the use of 18F-NaF-PET in benign osseous conditions as well. In this review, we discuss the cellular mechanisms of 18F-NaF-PET and examine recent findings on its clinical application in diverse metabolic, autoimmune, and osteogenic bone disorders.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22126504
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
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    RUNX2/miR‑31/SATB2 pathway in nickel‑induced BEAS‑2B cell transformation
    Spandidos Publications ; 2021
    In:  Oncology Reports Vol. 46, No. 2 ( 2021-06-07)
    Details
    In: Oncology Reports, Spandidos Publications, Vol. 46, No. 2 ( 2021-06-07)
    Type of Medium: Online Resource
    ISSN: 1021-335X , 1791-2431
    URL: Journal
    URL: Article
    DOI: 10.3892/or
    DOI: 10.3892/or.2021.8105
    Language: Unknown
    Publisher: Spandidos Publications
    Publication Date: 2021
    detail.hit.zdb_id: 1222484-4
    detail.hit.zdb_id: 2120548-6
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  • 9
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    Social innovation in health, community engagement, financing and outcomes: qualitative analysis from the social innovation in health initiative
    BMJ ; 2022
    In:  BMJ Innovations Vol. 8, No. 3 ( 2022-07), p. 216-223
    Details
    In: BMJ Innovations, BMJ, Vol. 8, No. 3 ( 2022-07), p. 216-223
    Abstract: Social innovation in health is a community-engaged process that links social change and health improvement, drawing on the diverse strengths of local individuals and institutions. However, there are few studies that examine community engagement, financing and outcomes. The purpose of this study is to use a qualitative descriptive analysis to assess 40 social innovations in health identified through a global open call. Methods This qualitative analysis examined social innovation case studies from low- and middle-income countries identified by a global social innovation network. A crowdsourcing open call identified projects and key components of each social innovation were evaluated by an independent panel. We used a US Centers for Disease Control and Prevention framework to measure community engagement as shared leadership, collaboration, involvement, consultation or informing. We used descriptive statistics to examine key aspects of community engagement, financing, health outcomes and non-health outcomes. Results Data from 40 social innovations were examined. Social innovations were from Africa (21/40), Asia (11/40), and Latin America and the Caribbean (8/40). Community engagement was diverse and robust across the cases and 60% (24/40) had either shared leadership or collaboration. Financing for social innovation came from research grants (23), national or provincial government support (15), revenues from sales (13), donations (13) and local government support (10). Social innovations reported health and non-health outcomes. Conclusion Our data demonstrate social innovations had robust community engagement. Innovative financing mechanisms provide mechanisms for sustaining social innovations. Further research on health and non-health outcomes of social innovation is needed.
    Type of Medium: Online Resource
    ISSN: 2055-8074 , 2055-642X
    URL: Article
    DOI: 10.1136/bmjinnov-2021-000902
    Language: English
    Publisher: BMJ
    Publication Date: 2022
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  • 10
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    The universality of eAREs in animal feces suggesting that eAREs function possibly in horizontal gene transfer
    ScopeMed ; 2023
    In:  Journal of Advanced Veterinary and Animal Research Vol. 10, No. 1 ( 2023), p. 103-
    Details
    In: Journal of Advanced Veterinary and Animal Research, ScopeMed, Vol. 10, No. 1 ( 2023), p. 103-
    Abstract: Objectives: This study aimed to pinpoint the universality of extracellular antimicrobial resistance elements (eAREs) and compare the contents of eAREs with those of intracellular AREs (iAREs) in animal feces, thus laying a foundation for the further analysis of the horizontal transfer of antimicrobial resistance genes (ARGs) in the animal guts. Materials and Methods: Extracellular DNAs were isolated from the fecal samples of Pavo cristatus (n = 18), Ursus thibetanus (n = 2), two breeds of broilers (n = 21 and 11, respectively), and from the contents of rabbit intestines (n = 5). eAREs were detected by PCR technology. iAREs in P. cristatus and broiler feces were also detected and compared with the corresponding eAREs. In addition, some gene cassettes of class 1 integrons were sequenced and analyzed. Results: The results showed that eAREs exist in animal feces and intestinal contents. In this study, different eAREs were detected from animal feces and intestinal contents, and tetA, tetB, sul1, sul2, class 1 integron, and IncFIB presented the highest detection rates. The detection rates of certain eAREs were significantly higher than those of parallel iAREs. The integral cassettes with intact structures were found in eAREs, and the cassettes carried ARGs. Conclusions: The presented study here sheds light on the presence of eAREs in animal feces or guts, and eAREs may play an important role in the horizontal gene transfer of ARGs.
    Type of Medium: Online Resource
    ISSN: 2311-7710
    URL: Journal
    URL: Article
    DOI: 10.5455/javar.
    DOI: 10.5455/javar.2023.j658
    Language: Unknown
    Publisher: ScopeMed
    Publication Date: 2023
    detail.hit.zdb_id: 2766493-4
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