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  • 1
    Online Resource
    Online Resource
    Image_6.TIF
    Frontiers Media SA ; 2022
    In:  Frontiers in Microbiology Vol. 13 ( 2022-11-4)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2022-11-4)
    Abstract: Hepatitis C virus (HCV) NS3/4A protease is an attractive target for direct-acting antiviral agents. Real-time tracking of the NS3/4A protease distribution and activity is useful for clinical diagnosis and disease management. However, no approach has been developed that can systemically detect NS3/4A protease activity or distribution. We designed a protease-activatable retention probe for tracking HCV NS3/4A protease activity via positron emission topography (PET) imaging. A cell-penetrating probe was designed that consisted of a cell-penetrating Tat peptide, HCV NS3/4A protease substrate, and a hydrophilic domain. The probe was labeled by fluorescein isothiocyanate (FITC) and 124 I in the hydrophilic domain to form a TAT-ΔNS3/4A- 124 I-FITC probe. Upon cleavage at NS3/4A substrate, the non-penetrating hydrophilic domain is released and accumulated in the cytoplasm allowing PET or optical imaging. The TAT-ΔNS3/4A-FITC probe selectively accumulated in NS3/4A-expressing HCC36 (NS3/4A-HCC36) cells/tumors and HCV-infected HCC36 cells. PET imaging showed that the TAT-ΔNS3/4A- 124 I-FITC probe selectively accumulated in the NS3/4A-HCC36 xenograft tumors and liver-implanted NS3/4A-HCC36 tumors, but not in the control HCC36 tumors. The TAT-ΔNS3/4A- 124 I-FITC probe can be used to represent NS3/4 protease activity and distribution via a clinical PET imaging system allowing. This strategy may be extended to detect any cellular protease activity for optimization the protease-based therapies.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmicb.2022.896588
    DOI: 10.3389/fmicb.2022.896588.s001
    DOI: 10.3389/fmicb.2022.896588.s002
    DOI: 10.3389/fmicb.2022.896588.s003
    DOI: 10.3389/fmicb.2022.896588.s004
    DOI: 10.3389/fmicb.2022.896588.s005
    DOI: 10.3389/fmicb.2022.896588.s006
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587354-4
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  • 2
    Online Resource
    Online Resource
    DataSheet_4.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-12-21)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-12-21)
    Abstract: Drug repurposing is a fast and effective way to develop drugs for an emerging disease such as COVID-19. The main challenges of effective drug repurposing are the discoveries of the right therapeutic targets and the right drugs for combating the disease. Methods Here, we present a systematic repurposing approach, combining Homopharma and hierarchal systems biology networks (HiSBiN), to predict 327 therapeutic targets and 21,233 drug-target interactions of 1,592 FDA drugs for COVID-19. Among these multi-target drugs, eight candidates (along with pimozide and valsartan) were tested and methotrexate was identified to affect 14 therapeutic targets suppressing SARS-CoV-2 entry, viral replication, and COVID-19 pathologies. Through the use of in vitro (EC 50 = 0.4 μM) and in vivo models, we show that methotrexate is able to inhibit COVID-19 via multiple mechanisms. Results Our in vitro studies illustrate that methotrexate can suppress SARS-CoV-2 entry and replication by targeting furin and DHFR of the host, respectively. Additionally, methotrexate inhibits all four SARS-CoV-2 variants of concern. In a Syrian hamster model for COVID-19, methotrexate reduced virus replication, inflammation in the infected lungs. By analysis of transcriptomic analysis of collected samples from hamster lung, we uncovered that neutrophil infiltration and the pathways of innate immune response, adaptive immune response and thrombosis are modulated in the treated animals. Conclusions We demonstrate that this systematic repurposing approach is potentially useful to identify pharmaceutical targets, multi-target drugs and regulated pathways for a complex disease. Our findings indicate that methotrexate is established as a promising drug against SARS-CoV-2 variants and can be used to treat lung damage and inflammation in COVID-19, warranting future evaluation in clinical trials.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.1080897
    DOI: 10.3389/fimmu.2022.1080897.s001
    DOI: 10.3389/fimmu.2022.1080897.s002
    DOI: 10.3389/fimmu.2022.1080897.s003
    DOI: 10.3389/fimmu.2022.1080897.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 3
    Online Resource
    Online Resource
    Presentation1.PPTX
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-4-6)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-4-6)
    Abstract: P2X7 signaling has been explored in adipose tissue because of its potential to promote ATP-activated inflammatory cascades during obesogenic environments. However, limited literature has investigated the role of the P2X7 receptor in lipid metabolism during adipocyte differentiation. This study sought to explore the regulatory roles of P2X7 in adipocytes. This study utilized the in vitro 3T3-L1 differentiation model. Lipid accumulation, intracellular triglyceride, and extracellular glycerol were determined. The selective P2X7 agonist BzATP and antagonist A438079 were administered to investigate the functions of P2X7. We found that the expression of P2X7 and the lipid accumulation increased during adipocyte differentiation from D0 to D4. When administered at D0/D2, A438079 attenuated, while BzATP enhanced the degree of lipid accumulation during adipocyte differentiation. Neither did BzATP and A438079 administration affect the expression of PPARγ and C/EBPα genes that increased at D4. In addition, both intracellular triglyceride and extracellular glycerol levels at D4 were reduced by A438079 treatment and enhanced by BzATP administration. When administered at stage 2 of adipocyte differentiation, BzATP consistently enhanced lipid accumulation and intracellular triglyceride and extracellular glycerol levels without affecting mRNA and protein levels of PPARγ and C/EBPα that increased at D4. However, treating A438079 or BzATP at D4 did not affect intracellular triglyceride formation and extracellular glycerol release in differentiated adipocytes at D7. Notably, BzATP administration at stage 2 exerted a concentration-dependent inhibition on the enhanced expression of PRDM16, PGC-1α, and UCP-1 at D4. Furthermore, BzATP administration at D0/D2 inhibited the protein and mRNA levels of sirtuin-3/5 at D4. BzATP treatment at stage 2 also suppressed the mRNA levels of sirtuin-3/5 genes upregulated by insulin. In conclusion, this study demonstrated P2X7 enhances lipid accumulation during adipogenesis by suppressing the expression of sirtuin-3/5 and the browning genes.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.852858
    DOI: 10.3389/fphar.2022.852858.s001
    DOI: 10.3389/fphar.2022.852858.s002
    DOI: 10.3389/fphar.2022.852858.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 4
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    Online Resource
    Microbial Safety of Dairy Manure Fertilizer Application in Raspberry Production
    Frontiers Media SA ; 2019
    In:  Frontiers in Microbiology Vol. 10 ( 2019-10-2)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 10 ( 2019-10-2)
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    DOI: 10.3389/fmicb.2019.02276
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2587354-4
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  • 5
    Online Resource
    Online Resource
    Data_Sheet_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Marine Science Vol. 8 ( 2021-10-5)
    Details
    In: Frontiers in Marine Science, Frontiers Media SA, Vol. 8 ( 2021-10-5)
    Abstract: The atmospheric partial pressure of CO 2 ( p CO 2 ) has been increasing dramatically since the beginning of the industrial revolution and about 30% of the CO 2 produced by anthropogenic activities was absorbed by the ocean. This led to a perturbation of the seawater carbonate chemistry resulting in a decrease of the average surface ocean pH by 0.1 and termed ocean acidification (OA). Projections suggest that p CO 2 may reach 900 μatm by the end of the twenty-first century lowering the average pH of the surface ocean by 0.4 units. The negative impacts of OA on many species of marine invertebrates such as mollusks, echinoderms, and crustaceans are well documented. However, less attention has been paid to the impacts of low pH on fitness and immune system in crustaceans. Here, we exposed Pacific white shrimps to 3 different pHs (nominal pH 8.0, 7.9, and 7.6) over a 100-days experiment. We found that, even though there were no significant effects on fitness parameters (survival, growth and allometries between length and weight), some immune markers were modified under low pH. A significant decrease in total hemocyte count and phenoloxidase activity was observed in shrimps exposed to pH 7.6 as compared to pH 8.0; and phagocytosis rate significantly decreased with decreasing pH. A significant increase in superoxide production was also observed at pH 7.6 as compared to pH 8.0. All these results suggest that a 100-days exposure to pH 7.6 did not have a direct effect on fitness but lead to a modulation of the immune response.
    Type of Medium: Online Resource
    ISSN: 2296-7745
    URL: Article
    URL: Article
    DOI: 10.3389/fmars.2021.748837
    DOI: 10.3389/fmars.2021.748837.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2757748-X
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  • 6
    Online Resource
    Online Resource
    Table_1.docx
    Frontiers Media SA ; 2019
    In:  Frontiers in Neuroscience Vol. 13 ( 2019-11-26)
    Details
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 13 ( 2019-11-26)
    Type of Medium: Online Resource
    ISSN: 1662-453X
    URL: Article
    URL: Article
    DOI: 10.3389/fnins.2019.01269
    DOI: 10.3389/fnins.2019.01269.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2411902-7
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  • 7
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    Online Resource
    Pyogenic Liver Abscess Risk in Patients With Newly Diagnosed Type 2 Diabetes Mellitus: A Nationwide, Population-Based Cohort Study
    Frontiers Media SA ; 2021
    In:  Frontiers in Medicine Vol. 8 ( 2021-5-12)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2021-5-12)
    Abstract: Background: To date, no comprehensive epidemiological study exists on pyogenic liver abscess (PLA) risk in patients with newly diagnosed type 2 diabetes mellitus (T2DM) worldwide. Methods: We conducted a retrospective cohort study by using data from Taiwan National Health Insurance Research Database (NHIRD) to examine the association between newly diagnosed T2DM and PLA. The T2DM cohort included patients newly diagnosed as having T2DM (ICD-9-CM:250) from 2000 to 2009, with follow-up until December 31, 2011. The comparison cohort was then recruited through 1:4 random frequency matching with the T2DM cohort. Finally, the adjusted hazard ratios for PLA were compared between the T2DM and comparison cohorts, which included 44,728 patients with T2DM and 178,912 patients without DM respectively. Results: In T2DM cohort, 166 patients were diagnosed as having PLA (incidence rate = 5.87 per 10,000 person-years) and in comparison cohort, 238 patients were diagnosed as having PLA (incidence rate = 2.06 per 10,000 person-years). The T2DM cohort exhibited higher PLA risk than did the comparison cohort (hazard ratio = 2.83, 95% confidence interval = 2.32–3.46). Furthermore, the adjusted hazard ratio for PLA risk in T2DM cohort was the highest in those who were younger, man and with duration of DM & lt;2 years. In the T2DM cohort, the most common PLA causative agent was Klebsiella pneumonia (KP). In addition, PLA risk was high in T2DM patients with gallstone and cholecystitis. Compared with comparison cohort, patients with T2DM prescribed acarbose has a lower PLA risk, however glyburide significantly increased PLA risk in T2DM cohort. Conclusion: In patients with newly diagnosed T2DM, PLA risk was high and acarbose might reduce PLA risk.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    DOI: 10.3389/fmed.2021.675345
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2775999-4
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  • 8
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    Online Resource
    Predictors of a Minimal Clinically Important Difference Following Omalizumab Treatment in Adult Patients With Severe Allergic Asthma
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 8 ( 2022-1-3)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2022-1-3)
    Abstract: Several factors have been found to be predictors of a good response following omalizumab treatment in patients with severe allergic asthma (SAA). However, it remains unclear whether clinical characteristics can predict a minimal clinically important difference (MCID) following omalizumab treatment in this population. Therefore, the aim of this study was to investigate the features associated with an MCID following omalizumab treatment in adult patients with SAA. Of the 124 participants enrolled in this retrospective, cross-sectional study, 94, 103, 20 and 53 achieved the MCID following treatment with omalizumab and were considered to be responders of exacerbation reduction (no exacerbation during the 1-year follow-up period or ≧50% reduction in exacerbations from baseline), oral corticosteroid (OCS) sparing (no use of OCS to control asthma during the study period or a reduction of the monthly OCS maintenance dose to & lt;50% of baseline), lung function (an increase of ≧230 ml in the forced expiratory volume in 1 s from baseline) and asthma control (an increase of ≧3 points in the asthma control test score from baseline), respectively. Normal weight [ & lt;25 vs. ≧30 kg/m 2 , odds ratio (OR) = 3.86, p = 0.024] was predictive of a responder of reduction in exacerbations following omalizumab treatment while subjects with a blood eosinophil level of & lt;300 cells/μL ( & lt;300 vs. ≧300 cells/μL, OR = 5.81, p = 0.001) were more likely to exhibit an MCID in OCS sparing. No factor was found to be a predictor of lung function or asthma control. When choosing treatment for adult patients with SAA, our findings may help to select those who may benefit the most from omalizumab treatment.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    DOI: 10.3389/fmed.2021.762318
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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