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  • Frontiers Media SA  (38)
  • 1
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    Image_9.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-11-15)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-11-15)
    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a global health concern since 2019. The viral spike protein infects the host by binding to angiotensin-converting enzyme 2 (ACE2) expressed on the cell surface, which is then processed by type II transmembrane serine protease. However, ACE2 does not react to SARS-CoV-2 in inbred wild-type mice, which poses a challenge for preclinical research with animal models, necessitating a human ACE2 (hACE2)-expressing transgenic mouse model. Cytokeratin 18 ( K18 ) promoter-derived hACE2 transgenic mice [B6.Cg-Tg(K18-ACE2)2Prlmn/J] are widely used for research on SARS-CoV-1, MERS-CoV, and SARS-CoV-2. However, SARS-CoV-2 infection is lethal at ≥10 5 PFU and SARS-CoV-2 target cells are limited to type-1 alveolar pneumocytes in K18-hACE2 mice, making this model incompatible with infections in the human lung. Hence, we developed lung-specific SARS-CoV-2 infection mouse models with surfactant protein B ( SFTPB ) and secretoglobin family 1a member 1 ( Scgb1a1 ) promoters. After inoculation of 10 5 PFU of SARS-CoV-2 to the K18-hACE2, SFTPB-hACE2, and SCGB1A1-hACE2 models, the peak viral titer was detected at 2 days post-infection and then gradually decreased. In K18-hACE2 mice, the body temperature decreased by approximately 10°C, body weight decreased by over 20%, and the survival rate was reduced. However, SFTPB-hACE2 and SCGB1A1-hACE2 mice showed minimal clinical signs after infection. The virus targeted type I pneumocytes in K18-hACE2 mice; type II pneumocytes in SFTPB-hACE2 mice; and club, goblet, and ciliated cells in SCGB1A1-hACE2 mice. A time-dependent increase in severe lung lesions was detected in K18-hACE2 mice, whereas mild lesions developed in SFTPB-hACE2 and SCGB1A1-hACE2 mice. Spleen, small intestine, and brain lesions developed in K18-hACE2 mice but not in SFTPB-hACE2 and SCGB1A1-hACE2 mice. These newly developed SFTPB-hACE2 and SCGB1A1-hACE2 mice should prove useful to expand research on hACE2-mediated respiratory viruses.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.1055811
    DOI: 10.3389/fimmu.2022.1055811.s001
    DOI: 10.3389/fimmu.2022.1055811.s002
    DOI: 10.3389/fimmu.2022.1055811.s003
    DOI: 10.3389/fimmu.2022.1055811.s004
    DOI: 10.3389/fimmu.2022.1055811.s005
    DOI: 10.3389/fimmu.2022.1055811.s006
    DOI: 10.3389/fimmu.2022.1055811.s007
    DOI: 10.3389/fimmu.2022.1055811.s008
    DOI: 10.3389/fimmu.2022.1055811.s009
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 2
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    Corrigendum: Mouse models of lung-specific SARS-CoV-2 infection with moderate pathological traits
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-12-2)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-12-2)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2022.1105713
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 3
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    DataSheet_1.pdf
    Frontiers Media SA ; 2023
    In:  Frontiers in Cellular and Infection Microbiology Vol. 13 ( 2023-5-15)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 13 ( 2023-5-15)
    Abstract: Immune-evading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are emerging continuously. The clinical effectiveness of monoclonal antibody agents that exhibit decreased in vitro activity against SARS-CoV-2 variants needs to be elucidated. Methods A nationwide, multicenter, retrospective cohort study was designed to evaluate the effectiveness of regdanvimab, an anti-SARS-CoV-2 monoclonal antibody agent. Regdanvimab was prescribed in South Korea before and after the emergence of the delta variant, against which the in vitro activity of regdanvimab was decreased but present. Mild to moderate coronavirus 2019 (COVID-19) patients with risk factors for disease progression who were admitted within seven days of symptom onset were screened in four designated hospitals between December 2020 and September 2021. The primary outcomes, O 2 requirements and progression to severe disease within 21 days of admission, were compared between the regdanvimab and supportive care groups, with a subgroup analysis of delta variant–confirmed patients. Results A total of 2,214 mild to moderate COVID-19 patients were included, of whom 1,095 (49.5%) received regdanvimab treatment. In the analysis of the total cohort, significantly fewer patients in the regdanvimab group than the supportive care group required O 2 support (18.4% vs. 27.1%, P & lt; 0.001) and progressed to severe disease (4.0% vs. 8.0%, P & lt; 0.001). In the multivariable analysis, regdanvimab was significantly associated with a decreased risk for O 2 support (HR 0.677, 95% CI 0.561–0.816) and progression to severe disease (HR 0.489, 95% CI 0.337–0.709). Among the 939 delta-confirmed patients, O 2 support (21.5% vs. 23.5%, P = 0.526) and progression to severe disease (4.2% vs. 7.3%, P = 0.055) did not differ significantly between the regdanvimab and supportive care groups. In the multivariable analyses, regdanvimab treatment was not significantly associated with a decreased risk for O 2 support (HR 0.963, 95% CI 0.697–1.329) or progression to severe disease (HR 0.665, 95% CI 0.349–1.268) in delta-confirmed group. Conclusions Regdanvimab treatment effectively reduced progression to severe disease in the overall study population, but did not show significant effectiveness in the delta-confirmed patients. The effectiveness of dose increment of monoclonal antibody agents should be evaluated for variant strains exhibiting reduced susceptibility.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    URL: Article
    DOI: 10.3389/fcimb.2023.1192512
    DOI: 10.3389/fcimb.2023.1192512.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2619676-1
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  • 4
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    DataSheet2.xlsx
    Frontiers Media SA ; 2022
    In:  Frontiers in Genetics Vol. 13 ( 2022-9-12)
    Details
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2022-9-12)
    Abstract: Despite recent advancements in our understanding of genetic etiology and its molecular and physiological consequences, it is not yet clear what genetic features determine the inheritance pattern of a disease. To address this issue, we conducted whole exome sequencing analysis to characterize genetic variants in 1,180 Korean patients with neurological symptoms. The diagnostic yield for definitive pathogenic variant findings was 50.8%, after including 33 cases (5.9%) additionally diagnosed by reanalysis. Of diagnosed patients, 33.4% carried inherited variants. At the genetic level, autosomal recessive-inherited genes were characterized by enrichments in metabolic process, muscle organization and metal ion homeostasis pathways. Transcriptome and interactome profiling analyses revealed less brain-centered expression and fewer protein-protein interactions for recessive genes. The majority of autosomal recessive genes were more tolerant of variation, and functional prediction scores of recessively-inherited variants tended to be lower than those of dominantly-inherited variants. Additionally, we were able to predict the rates of carriers for recessive variants. Our results showed that genes responsible for neurodevelopmental disorders harbor different molecular mechanisms and expression patterns according to their inheritance patterns. Also, calculated frequency rates for recessive variants could be utilized to pre-screen rare neurodevelopmental disorder carriers.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fgene.2022.990015
    DOI: 10.3389/fgene.2022.990015.s001
    DOI: 10.3389/fgene.2022.990015.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606823-0
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  • 5
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    DataSheet_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Marine Science Vol. 10 ( 2023-4-3)
    Details
    In: Frontiers in Marine Science, Frontiers Media SA, Vol. 10 ( 2023-4-3)
    Abstract: The hairy snails of the genus Alviniconcha are representative deep-sea hydrothermal vent animals distributed across the Western Pacific and Indian Ocean. Out of six known species in the genus Alviniconcha , only one nominal species of A. marisindica was found in the Indian Ocean from the Carlsberg Ridge (CR), Central Indian Ridge (CIR) to the northern part of Southwest Indian Ridge (SWIR) and Southeast Indian Ridge (SEIR). Recently, the Alviniconcha snails were found at three new vent fields, named Onnare, Onbada, and Onnuri, in the northern CIR, which promotes a more comprehensive phylogeographic study of this species. Here, we examined the phylogeography and connectivity of the Alviniconcha snails among seven vent fields representing the CR and CIR based on DNA sequence data of a mitochondrial COI gene and two protein-coding nuclear genes. Phylogenetic inferences revealed that the Alviniconcha snails of the newly found in the northern CIR and two vent fields of Wocan and Tianxiu in the CR were divergent with the previously identified A. marisindica in the southern CIR and mitochondrial COI data supported the divergence with at least greater than 3% sequence divergence. Population structure analyses based on the three genetic markers detected a phylogeographic boundary between Onnuri and Solitaire that divides the whole snail populations into northern and southern groups with a low migration rate. The high degree of genetic disconnection around the ‘Onnuri’ boundary suggests that the Alviniconcha snails in the Indian Ocean may undergo allopatric speciation. The border may similarly act as a dispersal barrier to many other vent species co-distributed in the CIR. This study would expand understanding the speciation and connectivity of vent species in the Indian Ocean.
    Type of Medium: Online Resource
    ISSN: 2296-7745
    URL: Article
    URL: Article
    DOI: 10.3389/fmars.2023.1139190
    DOI: 10.3389/fmars.2023.1139190.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2757748-X
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  • 6
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    Table_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Endocrinology Vol. 14 ( 2023-8-23)
    Details
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 14 ( 2023-8-23)
    Abstract: Accumulating evidence from other countries indicates potential associations between gout and cardiovascular diseases; however, the associations of gout with cardiovascular diseases, particularly stroke, ischemic heart disease, and heart failure, remain ambiguous in the Korean population. We hypothesized that individuals with gout are at a higher likelihood of stroke, ischemic heart disease, or heart failure. This study expands upon previous research by ensuring a comparable baseline between patient and control groups and analyzing 16 years of data derived from an extensive healthcare database. Methods We selected 22,480 patients with gout and 22,480 control individuals from the Korean National Health Insurance Service-Health Screening Cohort database (2002–2019), and matched them at a 1:1 ratio according to sex, age, income, and residence. A Cox proportional hazard model with weighted overlap was employed to examine the relationship between gout and the risk of stroke, ischemic heart disease, or heart failure after adjustment for several covariates. Results The incidences of stroke, ischemic heart disease, or heart failure in participants with gout were slightly higher than those in controls (stroke: 9.84 vs. 8.41 per 1000 person-years; ischemic heart disease: 9.77 vs. 7.15 per 1000 person-years; heart failure: 2.47 vs. 1.46 per 1000 person-years). After adjustment, the gout group had an 11% (95% confidence interval [CI] = 1.04–1.19), 28% (95% CI = 1.19–1.37), or 64% (95% CI = 1.41–1.91) higher likelihood of experiencing stroke, ischemic heart disease, or heart failure, respectively, than the control group. Conclusion The present findings suggest that individuals with gout in the Korean population, particularly those aged ≥ 60 years, were more likely to have stroke, ischemic heart disease, or heart failure.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    URL: Article
    URL: Article
    DOI: 10.3389/fendo.2023.1195888
    DOI: 10.3389/fendo.2023.1195888.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2592084-4
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  • 7
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    Table_1.xlsx
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-3-16)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-3-16)
    Abstract: Immune checkpoint inhibitor (ICI) is one of the standard treatment strategies in triple negative breast cancer (TNBC). However, the benefit of ICI with chemotherapy is limited in metastatic TNBC. In this study, we evaluated the effect of PD-L1 and LAG-3 expression on tissue microenvironment of mTNBC treated with ICI. Methods We reviewed representative formalin-fixed paraffin embedded specimens from metastatic or archival tumor tissues of TNBCs who treated with PD-1/PD-L1 inhibitors in metastatic setting. We used the Opal multiplex Detection kit with six antibodies (anti-PD-L1, anti-LAG-3, anti-CD68, anti-panCK, anti-CD8, anti-CD107a/LAMP antibody). Results We evaluated the association between LAG-3+cells and survival outcome regarding CK expression. Stromal LAG-3+/CK+ and LAG-3+/CK- cells were not associated with ICI-progression free survival(PFS) (P=0.16). However, LAG-3+ cell distributions in the tumor area impacted on ICI-PFS. A high density of LAG-3+CK+ cells was associated with shorter ICI-PFS compared with low densities of both LAG-3+CK+ and LAG-3+CK- cells (1.9 vs. 3.5 months). In addition, a high density of LAG-3+CK- cells had a relatively longer ICI-PFS compared with other groups (P=0.01). In terms of total area, the pattern of densities of LAG-3+CK+ cells and LAG-3+CK- cells were similar to those in the tumor area In addition, ICI-PFS of LAG-3+CK- and LAG-3+CK+ cell densities in the total area was equal to that in the tumor area. Discussion In conclusion, our findings revealed tumor-intrinsic LAG-3 expression was the resistance mechanism toward PD-1/PD-L1 inhibitors in mTNBCs. Multivariate analysis also suggested that LAG-3 expression in tumor cells was an independent predictive biomarker.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2023.1146934
    DOI: 10.3389/fonc.2023.1146934.s001
    DOI: 10.3389/fonc.2023.1146934.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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    Table1.DOCX
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 14 ( 2023-7-4)
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    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-7-4)
    Abstract: Background: Pulmonary fibrosis (PF) is a progressive lung disease characterized by fibroblast accumulation and collagen deposition, resulting in lung scarring and impaired gas exchange. Current treatments for idiopathic pulmonary fibrosis (IPF) have limited efficacy and significant side effects. Heat shock protein 27 (HSP27) has emerged as a potential therapeutic target for PF due to its involvement in fibrotic processes. However, effective HSP27 inhibitors for PF treatment are still lacking. Methods: To assess the anti-fibrotic effects of NA49, we utilized murine PF models induced by radiation (IR) or bleomycin (BLM). We administered NA49 to the PF mice and evaluated its impact on lung fibrosis progression. We also investigated the molecular mechanisms underlying NA49's effects, focusing on its inhibition of EMT-related signaling pathways. Results: In our study, we evaluated the potential of a novel HSP27 inhibitor, NA49, in preclinical models of PF. NA49 effectively suppressed PF development in radiation and bleomycin-induced PF models. It reduced fibrosis, inhibited NFkB signaling, and downregulated EMT-related molecules. Importantly, we evaluated the safety profile of NA49 by assessing its impact on DNA strand breakage. Compared to previous HSP27 inhibitors, NA49 showed lower levels of DNA damage in human lung epithelial cells, and suggests that NA49 may have reduced toxicity compared to other HSP27 inhibitors. Overall, our results demonstrate that NA49 effectively inhibits PF development in preclinical models. It reduces lung fibrosis, inhibits EMT-related signaling pathways, and exhibits improved safety profiles. These findings highlight the potential of NA49 as a promising candidate for the treatment of PF. Conclusion: NA49 exhibited significant anti-fibrotic effects, inhibiting fibrosis development and EMT-related signaling pathways. Moreover, NA49 showed improved safety profiles compared to previous HSP27 inhibitors.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2023.1203033
    DOI: 10.3389/fphar.2023.1203033.s001
    DOI: 10.3389/fphar.2023.1203033.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 9
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    Table_1.DOCX
    Frontiers Media SA ; 2021
    In:  Frontiers in Neurology Vol. 12 ( 2021-10-18)
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    In: Frontiers in Neurology, Frontiers Media SA, Vol. 12 ( 2021-10-18)
    Abstract: Background: Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disease of the central nervous system that is gradually increasing in prevalence. The etiology of MS remains unknown; however, it is assumed to be caused by a deterioration of autoimmune regulation. Although immunomodulatory agents are a standard treatment option in patients with MS, there is insufficient evidence about their clinical efficacy in symptomatic treatment, and many MS patients resort to complementary and alternative medicine. For this reason, we conducted a scoping review to investigate the current status of the clinical evidence related to traditional East Asian herbal medicine treatment for MS and to inform future research and treatment strategies. Method: A scoping review is an emerging methodology for knowledge synthesis that adopts the Arksey and O'Malley framework. The research question was, “What has been studied about the herbal medicine treatments administered to patients with MS?” Articles published until 2019 were identified in six databases (PubMed, Embase, Cochrane, KoreaMed, NDSL, and OASIS) in March of 2020. Data from the included studies were charted and descriptively analyzed in relation to the study's research questions. Results: Of the 1,445 articles identified, 14 studies were included in this review. Single and serial case reports constituted the majority (42.86%), with 57.14% of studies conducted in China. A total of 20 prescriptions containing 95 herbs were used in the intervention and observational studies. Herbal medicines were effective at improving clinical symptoms of MS and reducing recurrence frequency. The main cause of MS was presumed to be oxidative stress, which enhances inflammation and, consequently, causes neuronal death. Conclusion: Herbal medicines were determined to improve the symptoms of MS and to reduce the frequency of recurrences. This study suggests that herbal medicines are promising and worth pursuing further studies but the state of current evidence is poor. Thus, further, high-quality studies included larger randomized trial are required.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    URL: Article
    DOI: 10.3389/fneur.2021.710769
    DOI: 10.3389/fneur.2021.710769.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2564214-5
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  • 10
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    Effectiveness and safety of herbal medicine Ukgansan for clinical symptoms in Parkinson's disease: A pilot, randomized, assessor-blinded clinical trial
    Frontiers Media SA ; 2022
    In:  Frontiers in Neurology Vol. 13 ( 2022-11-10)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-11-10)
    Abstract: Parkinson's disease (PD) is a neurodegenerative disease in which patients are suffering various symptoms. Previous experimental studies suggested that herbal medicine Ukgansan (UGS) could be beneficial for PD. The aim of this pilot clinical trial was to evaluate the efficacy of UGS for improving clinical symptoms in patients with PD. Methods Sixty patients with idiopathic PD were randomly assigned to receive either UGS plus acupuncture or acupuncture alone for 6 weeks. During the trial, all anti-parkinsonian medications were maintained. Subjects were evaluated for various clinical assessments of PD, including the Movement Disorder Society-Sponsored Revision of the Unified PD Rating Scale (MDS-UPDRS) and the 39-item Parkinson's Disease Questionnaire (PDQ-39), until 12 weeks. Results In MDS-UPDRS between the groups, no significant time x group interaction was found. In the subgroup analysis of participants with anxiety, a significant time x group interaction was found in the PDQ-39 domain of mobility ( P = 0.007), activities of daily living ( P = 0.042), and the PDQ-39 summary index ( P = 0.048). In addition, post-hoc analysis in participants with anxiety showed a significant decrease in the domains of mobility ( P = 0.001) and activities of daily living ( P = 0.013) at week 7. There were no adverse events associated with UGS. Conclusion The additional administration of UGS has the potential to significantly improve the quality of life of PD patients with anxiety. In order to create more definitive evidence, clinical trials with more rigorous methodologies should be conducted in future. Clinical trial registration http://cris.nih.go.kr , identifier: KCT0003444.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    DOI: 10.3389/fneur.2022.1025269
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564214-5
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