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  • 1
    In: Journal of Nanobiotechnology, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2023-10-10)
    Abstract: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is still one of the top killers worldwide among infectious diseases. The escape of Mtb from immunological clearance and the low targeting effects of anti-TB drugs remain the substantial challenges for TB control. Iron is particularly required for Mtb growth but also toxic for Mtb in high dosages, which makes iron an ideal toxic decoy for the ‘iron-tropic’ Mtb. Here, a macrophage-targeted iron oxide nanoparticles (IONPs)-derived IONPs-PAA-PEG-MAN nanodecoy is designed to augment innate immunological and drug killings against intracellular Mtb. IONPs-PAA-PEG-MAN nanodecoy exhibits preferential uptake in macrophages to significantly increase drug uptake with sustained high drug contents in host cells. Moreover, it can serve as a specific nanodecoy for the ‘iron-tropic’ Mtb to realize the localization of Mtb contained phagosomes surrounding the drug encapsulated nanodecoys and co-localization of Mtb with the drug encapsulated nanodecoys in lysosomes, where the incorporated rifampicin (Rif) can be readily released under acidic lysosomal condition for enhanced Mtb killing. This drug encapsulated nanodecoy can also polarize Mtb infected macrophages into anti-mycobacterial M1 phenotype and enhance M1 macrophage associated pro-inflammatory cytokine (TNF-α) production to trigger innate immunological responses against Mtb. Collectively, Rif@IONPs-PAA-PEG-MAN nanodecoy can synergistically enhance the killing efficiency of intracellular Mtb in in vitro macrophages and ex vivo monocyte-derived macrophages, and also significantly reduce the mycobacterial burdens in the lung of infected mice with alleviated pathology. These results indicate that Rif@IONPs-PAA-PEG-MAN nanodecoy may have a potential for the development of more effective therapeutic strategy against TB by manipulating augmented innate immunity and drug killings. Graphic Abstract
    Type of Medium: Online Resource
    ISSN: 1477-3155
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2100022-0
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  • 2
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  European Journal of Medical Research Vol. 27, No. 1 ( 2022-12)
    In: European Journal of Medical Research, Springer Science and Business Media LLC, Vol. 27, No. 1 ( 2022-12)
    Abstract: As one of the most common primary headaches in clinical practice, migraine affects the learning ability and life quality of college students worldwide, posing a heavy burden on individuals and society. This study aims to investigate the incidence of migraine among Chinese medical college students and to explore its characteristics and typical triggers. Method From July 2019 to July 2020, North Sichuan Medical College in Sichuan province, China preliminarily screened migraine cases using ID-Migraine through cluster sampling. College students with positive ID-Migraine results would be included in this study if they were further diagnosed with migraine by neurologists based on ICHD-3. After the ethical review, patients’ personal and headache information would be collected, and the frequency, severity, onset time, and related triggers of migraine would be measured. Results The preliminary screening covered 8783 college students. The overall prevalence rate of migraine is 6.57%, 5.90% in men and 6.77% in women. The prevalence rate of migraine is higher for students in the first and second grades (8.01%, 8.05%), and students with a family history of migraine are more likely to suffer from migraine (OR = 1.509, 95% CI 1.060–2.148, P  = 0.022  〈  0.005). Staying up late ( n  = 329, 57.01%), stress ( n  = 319, 55.29%), catch a cold ( n  = 313, 54.25%) and sleep disorders ( n  = 302, 52.34%) are the common triggers. Conclusion Migraine is common among college students in North Sichuan Medical College. The incidence is higher among lower grade students, female students, and students with a family history of migraine. Improving sleep quality and reducing stress may be effective in relieving migraines.
    Type of Medium: Online Resource
    ISSN: 2047-783X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2129989-4
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2024
    In:  Frontiers in Oncology Vol. 14 ( 2024-6-27)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 14 ( 2024-6-27)
    Abstract: In the field of radiation therapy for brain metastases, whole-brain hippocampus-avoidance treatment is commonly employed. this study aims to examine the impact of different head tilt angles on the dose distribution in the whole-brain target area and organs at risk. It also aims to determine the head tilt angle to achieve optimal radiation therapy outcomes. Methods CT images were collected from 8 brain metastases patients at 5 different groups of head tilt angle. The treatment plans were designed using the volumetric modulated arc therapy (VMAT) technique. The 5 groups of tilt angle were as follows: [0°,10°), [10°,20°), [20°,30°), [30°,40°), and [40°,45°]. The analysis involved assessing parameters such as the uniformity index, conformity index, average dose delivered to the target, dose coverage of the target, hot spots within the target area, maximum dose, and average dose received by organs at risk. Additionally, the study evaluated the correlation between hippocampal dose and other factors, and established linear regression models. Results Significant differences in dosimetric results were observed between the [40°,45°] and [0°,10°) head tilt angles. The [40°,45°] angle showed significant differences compared to the [0°,10°) angle in the average dose in the target area (31.49 ± 0.29 Gy vs. 31.99 ± 0.29 Gy, p=0.016), dose uniformity (1.20 ± 0.03 vs. 1.24 ± 0.03, p=0.016), hotspots in the target area (33.64 ± 0.35 Gy vs. 34.42 ± 0.49 Gy, p=0.016), maximum hippocampal dose (10.73 ± 0.36 Gy vs. 11.66 ± 0.59 Gy, p=0.008), maximum dose in the lens (2.82 ± 1.10 Gy vs. 4.99 ± 0.16 Gy, p=0.016), and average dose in the lens (1.93 ± 0.29 Gy vs. 4.22 ± 0.26 Gy, p=0.008). There is a moderate correlation between the maximum dose in the hippocampi and the PTV length (r=0.49, p=0.001). Likewise, the mean dose in the hippocampi is significantly correlated with the hippocampi length (r=0.34, p=0.04). Conclusion The VMAT plan with a head tilt angle of [40°,45°] met all dose constraints and demonstrated improved uniformity of the target area while reducing the dose to organs at risk. Furthermore, the linear regression models suggest that increasing the head tilt angle within the current range of [0°,45°] is likely to lead to a decrease in the average hippocampal dose.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2649216-7
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-2-26)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-2-26)
    Abstract: It remains undefined whether a subset of CD4+ T cells can function as fast-acting cells to control Mycobacterium tuberculosis (Mtb) infection. Here we show that the primary CD4+CD161+ T-cell subset, not CD4+CD161-, in unexposed healthy humans fast acted as unconventional T cells capable of inhibiting intracellular Mtb and BCG growth upon exposure to infected autologous and allogeneic macrophages or lung epithelial A549 cells. Such inhibition coincided with the ability of primary CD4+CD161+ T cells to rapidly express/secrete anti-TB cytokines including IFN-γ, TNF-α, IL-17, and perforin upon exposure to Mtb. Mechanistically, blockades of CD161 pathway, perforin or IFN-γ by blocking mAbs abrogated the ability of CD4+CD161+ T cells to inhibit intracellular mycobacterial growth. Pre-treatment of infected macrophages with inhibitors of autophagy also blocked the CD4+CD161+ T cell-mediated growth inhibition of mycobacteria. Furthermore, adoptive transfer of human CD4+CD161+ T cells conferred protective immunity against mycobacterial infection in SCID mice. Surprisingly, CD4+CD161+ T cells in TB patients exhibited a loss or reduction of their capabilities to produce perforin/IFN-γ and to inhibit intracellular growth of mycobacteria in infected macrophages. These immune dysfunctions were consistent with PD1/Tim3 up-regulation on CD4+CD161+ T cells in active tuberculosis patients, and the blockade of PD1/Tim3 on this subset cells enhanced the inhibition of intracellular mycobacteria survival. Thus, these findings suggest that a fast-acting primary CD4+CD161+T-cell subset in unexposed humans employs the CD161 pathway, perforin, and IFN-γ/autophagy to inhibit the growth of intracellular mycobacteria, thereby distinguishing them from the slow adaptive responses of conventional CD4+ T cells. The presence of fast-acting CD4+CD161+ T-cell that inhibit mycobacterial growth in unexposed humans but not TB patients also implicates the role of these cells in protective immunity against initial Mtb infection.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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