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  • 1
    Online Resource
    Online Resource
    CCR7 Mediates Cell Invasion and Migration in Extrahepatic Cholangiocarcinoma by Inducing Epithelial–Mesenchymal Transition
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 6 ( 2023-03-21), p. 1878-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 6 ( 2023-03-21), p. 1878-
    Abstract: The epithelial–mesenchymal transition (EMT) contributes to the metastatic cascade in various tumors. C-C chemokine receptor 7 (CCR7) interacts with its ligand, chemokine (C-C motif) ligand 19 (CCL19), to promote EMT. However, the association between EMT and CCR7 in extrahepatic cholangiocarcinoma (EHCC) remains unknown. This study aimed to elucidate the prognostic impact of CCR7 expression and its association with clinicopathological features and EMT in EHCC. The association between CCR7 expression and clinicopathological features and EMT status was examined via the immunohistochemical staining of tumor sections from 181 patients with perihilar cholangiocarcinoma. This association was then investigated in TFK-1 and EGI-1 EHCC cell lines. High-grade CCR7 expression was significantly associated with a large number of tumor buds, low E-cadherin expression, and poor overall survival. TFK-1 showed CCR7 expression, and Western blotting revealed E-cadherin downregulation and vimentin upregulation in response to CCL19 treatment. The wound healing and Transwell invasion assays revealed that the activation of CCR7 by CCL19 enhanced the migration and invasion of TFK-1 cells, which were abrogated by a CCR7 antagonist. These results suggest that a high CCR7 expression is associated with an adverse postoperative prognosis via EMT induction and that CCR7 may be a potential target for adjuvant therapy in EHCC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15061878
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 2
    Online Resource
    Online Resource
    Neighborhood Ties Reduced Depressive Symptoms in Older Disaster Survivors: Iwanuma Study, a Natural Experiment
    MDPI AG ; 2020
    In:  International Journal of Environmental Research and Public Health Vol. 17, No. 1 ( 2020-01-03), p. 337-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 17, No. 1 ( 2020-01-03), p. 337-
    Abstract: Objective: As most studies relating to mental health and disasters have employed cross-sectional or follow-up assessments about psychological health with post-disaster information, the association between changes in social ties and mental health remains unclear. We examined the relationship between the changes in survivor neighborhood ties and depressive symptoms before and after a natural disaster. Methods: Participants were 3567 individuals aged ≥65 years living in Iwanuma city who had responded to questionnaires by the Japan Gerontological Evaluation Study both predating the 2011 Great East Japan Earthquake and Tsunami, and 2.5 years afterward. Changes in the depressive symptoms were assessed using the geriatric depression scale (GDS) at the baseline and follow-up survey. Changes in the neighborhood ties were assessed by asking the participants about their interactions with people in their neighborhood. Possible confounders were adjusted in a linear regression model. Results: Among the 3111 participants in this analysis, 1073 (34.5%) had increased GDS score after the disaster. There were 336 (10.8%) individuals who had neighborhood ties before the disaster, but had no ties afterward; their mean GDS score increased from 2.93 points in 2010 to 3.19 points in 2013. Among those who had not had ties before and after the disaster the mean GDS score remained almost stable, from 2.19 points in 2010 to 2.12 points in 2013. The participants with post-disaster ties were significantly less likely to have an increased GDS score compared with those who had not had ties before and after the disaster (β = −0.39; 95% confidence interval: −0.72, −0.06). Conclusions: Increased neighborhood ties after the disaster reduced the risk of depressive symptoms even when survivors suffered disaster damages. The study reinforces the importance of social capital in disaster recovery and suggests to local governments and local communities that fostering horizontal, neighborhood ties may improve disaster preparedness and mental health resilience.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph17010337
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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  • 3
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    Online Resource
    Entomological Assessment of the Status and Risk of Mosquito-borne Arboviral Transmission in Ghana
    MDPI AG ; 2020
    In:  Viruses Vol. 12, No. 2 ( 2020-01-27), p. 147-
    Details
    In: Viruses, MDPI AG, Vol. 12, No. 2 ( 2020-01-27), p. 147-
    Abstract: Entomological surveillance is one of the tools used in monitoring and controlling vector-borne diseases. However, the use of entomological surveillance for arboviral infection vector control is often dependent on finding infected individuals. Although this method may suffice in highly endemic areas, it is not as effective in controlling the spread of diseases in low endemic and non-endemic areas. In this study, we examined the efficiency of using entomological markers to assess the status and risk of arbovirus infection in Ghana, which is considered a non-endemic country, by combining mosquito surveillance with virus isolation and detection. This study reports the presence of cryptic species of mosquitoes in Ghana, demonstrating the need to combine morphological identification and molecular techniques in mosquito surveillance. Furthermore, although no medically important viruses were detected, the importance of insect-specific viruses in understanding virus evolution and arbovirus transmission is discussed. This study reports the first mutualistic relationship between dengue virus and the double-stranded RNA Aedes aegypti totivirus. Finally, this study discusses the complexity of the virome of Aedes and Culex mosquitoes and its implication for arbovirus transmission.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v12020147
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2516098-9
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  • 4
    Online Resource
    Online Resource
    Tumor Growth Suppression of Pancreatic Cancer Orthotopic Xenograft Model by CEA-Targeting CAR-T Cells
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 3 ( 2023-01-18), p. 601-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 3 ( 2023-01-18), p. 601-
    Abstract: Chimeric antigen receptor engineered T cell (CAR-T) therapy has high therapeutic efficacy against blood cancers, but it has not shown satisfactory results in solid tumors. Therefore, we examined the therapeutic effect of CAR-T therapy targeting carcinoembryonic antigen (CEA) in pancreatic adenocarcinoma (PDAC). CEA expression levels on the cell membranes of various PDAC cell lines were evaluated using flow cytometry and the cells were divided into high, medium, and low expression groups. The relationship between CEA expression level and the antitumor effect of anti-CEA-CAR-T was evaluated using a functional assay for various PDAC cell lines; a significant correlation was observed between CEA expression level and the antitumor effect. We created orthotopic PDAC xenograft mouse models and injected with anti-CEA-CAR-T; only the cell line with high CEA expression exhibited a significant therapeutic effect. Thus, the therapeutic effect of CAR-T therapy was related to the target antigen expression level, and the further retrospective analysis of pathological findings from PDAC patients showed a correlation between the intensity of CEA immunostaining and tumor heterogeneity. Therefore, CEA expression levels in biopsies or surgical specimens can be clinically used as biomarkers to select PDAC patients for anti-CAR-T therapy.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15030601
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 5
    Online Resource
    Online Resource
    Retroviral Replicating Vector Toca 511 (Vocimagene Amiretrorepvec) for Prodrug Activator Gene Therapy of Lung Cancer
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 23 ( 2022-11-25), p. 5820-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 23 ( 2022-11-25), p. 5820-
    Abstract: Therapeutic efficacy of retroviral replicating vector (RRV)-mediated prodrug activator gene therapy has been demonstrated in a variety of tumor models, but clinical investigation of this approach has so far been restricted to glioma and gastrointestinal malignancies. In the present study, we evaluated replication kinetics, transduction efficiency, and therapeutic efficacy of RRV in experimental models of lung cancer. RRV delivering GFP as a reporter gene showed rapid viral replication in a panel of lung cancer cells in vitro, as well as robust intratumoral replication and high levels of tumor transduction in subcutaneous and orthotopic pleural dissemination models of lung cancer in vivo. Toca 511 (vocimagene amiretrorepvec), a clinical-stage RRV encoding optimized yeast cytosine deaminase (yCD) which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil (5-FU), showed potent cytotoxicity in lung cancer cells upon exposure to 5-FC prodrug. In vivo, Toca 511 achieved significant tumor growth inhibition following 5-FC treatment in subcutaneous and orthotopic pleural dissemination models of lung cancer in both immunodeficient and immunocompetent hosts, resulting in significantly increased overall survival. This study demonstrates that RRV can serve as highly efficient vehicles for gene delivery to lung cancer, and indicates the translational potential of RRV-mediated prodrug activator gene therapy with Toca 511/5-FC as a novel therapeutic strategy for pulmonary malignancies.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14235820
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 6
    Online Resource
    Online Resource
    Two New Terpenes Isolated from Dictyostelium Cellular Slime Molds
    MDPI AG ; 2020
    In:  Molecules Vol. 25, No. 12 ( 2020-06-23), p. 2895-
    Details
    In: Molecules, MDPI AG, Vol. 25, No. 12 ( 2020-06-23), p. 2895-
    Abstract: We report a protoilludane-type sesquiterpene, mucoroidiol, and a geranylated bicyclogermacranol, firmibasiol, isolated from Dictyostelium cellular slime molds. The methanol extracts of the fruiting bodies of cellular slime molds were separated by chromatographic methods to give these compounds. Their structures have been established by several spectral means. Mucoroidiol and firmibasiol are the first examples of more modified and oxidized terpenoids isolated from cellular slime molds. Mucoroidiol showed moderate osteoclast-differentiation inhibitory activity despite demonstrating very weak cell-proliferation inhibitory activity. Therefore, cellular slime molds produce considerably diverse secondary metabolites, and they are promising sources of new natural product chemistry.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules25122895
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2008644-1
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  • 7
    Online Resource
    Online Resource
    Conjunctival Sac Microbiome in Infectious Conjunctivitis
    MDPI AG ; 2021
    In:  Microorganisms Vol. 9, No. 10 ( 2021-10-04), p. 2095-
    Details
    In: Microorganisms, MDPI AG, Vol. 9, No. 10 ( 2021-10-04), p. 2095-
    Abstract: Acute bacterial conjunctival infections are common, and this study identified the conjunctival bacterial community in infectious conjunctivitis cases seen at the outpatient clinic of Khanh Hoa General Hospital in Nha Trang, Vietnam from October 2016 through December 2017. Conjunctival swabs were collected and tested using conventional culture, PCR, and 16S ribosomal RNA sequencing. The study included 47 randomly selected patients. More than 98% of all DNA reads represented five bacterial phyla. Three of these phyla constituted 92% of all sequences (Firmicutes (35%), Actinobacteria (31%), and Proteobacteria (26%)). At the genus level, there were 12 common genera that constituted about 61% of all sequence reads. Seven of those genera were common (Streptococcus (10%), Cutibacterium (10%), Staphylococcus (7%), Nocardioides (7%), Corynebacterium 1 (5%), Anoxybacillus (5%), and Acinetobacter (5%)), which encompassed 49% of all reads. As for diversity analysis, there was no difference on PERMANOVA analysis (unweighted UniFrac) for sex (p = 0.087), chemosis (p = 0.064), and unclassified eyedrops (p = 0.431). There was a significant difference in cases with bilateral conjunctivitis (p = 0.017) and for using antibiotics (p = 0.020). Of the predominant phyla, Firmicutes had the highest abundance in bacterial conjunctivitis in this study. Pseudomonas as a resident commensal microbiota may have an important role in the prevention of infection.
    Type of Medium: Online Resource
    ISSN: 2076-2607
    URL: Article
    DOI: 10.3390/microorganisms9102095
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720891-6
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