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- 2019
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Tidskriftsartikel (refereegranskat)
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- Zhou, Wei, et al.
(författare)
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Global Biobank Meta-analysis Initiative : Powering genetic discovery across human disease
- 2022
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Ingår i: Cell Genomics. - : Elsevier. - 2666-979X. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.
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- Chen, Yan-Ting, et al.
(författare)
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Biomimetic Platelet Nanomotors for Site-Specific Thrombolysis and Ischemic Injury Alleviation
- 2023
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 15:27, s. 32967-32983
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Tidskriftsartikel (refereegranskat)abstract
- Due to the mortality associated with thrombosis and its highrecurrence rate, there is a need to investigate antithrombotic approaches.Noninvasive site-specific thrombolysis is a current approach being used; however,its usage is characterized by the following limitations: low targeting efficiency, poorability to penetrate clots, rapid half-life, lack of vascular restoration mechanisms,and risk of thrombus recurrence that is comparable to that of traditionalpharmacological thrombolysis agents. Therefore, it is vital to develop an alternativetechnique that can overcome the aforementioned limitations. To this end, a cottonball-shaped platelet (PLT)-mimetic self-assembly framework engineered with aphototherapeutic poly(3,4-ethylenedioxythiophene) (PEDOT) platform has beendeveloped. This platform is capable of delivering a synthetic peptide derived fromhirudin P6 (P6) to thrombus lesions, forming P6@PEDOT@PLT nanomotors fornoninvasive site-specific thrombolysis, effective anticoagulation, and vascularrestoration. Regulated by P-selectin mediation, the P6@PEDOT@PLT nanomotors target the thrombus site and subsequentlyrupture under near-infrared (NIR) irradiation, achieving desirable sequential drug delivery. Furthermore, the movement ability ofthe P6@PEDOT@PLT nanomotors under NIR irradiation enables effective penetration deep into thrombus lesions, enhancingbioavailability. Biodistribution analyses have shown that the administered P6@PEDOT@PLT nanomotors exhibit extendedcirculation time and metabolic capabilities. In addition, the photothermal therapy/photoelectric therapy combination cansignificantly augment the effectiveness (ca. 72%) of thrombolysis. Consequently, the precisely delivered drug and the resultantphototherapeutic-driven heat-shock protein, immunomodulatory, anti-inflammatory, and inhibitory plasminogen activator inhibitor1 (PAI-1) activities can restore vessels and effectively prevent rethrombosis. The described biomimetic P6@PEDOT@PLTnanomotors represent a promising option for improving the efficacy of antithrombotic therapy in thrombus-related illnesses.
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- Tsai, Pei-I, et al.
(författare)
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Fak56 functions downstream of integrin alphaPS3betanu and suppresses MAPK activation in neuromuscular junction growth.
- 2008
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Ingår i: Neural development. - : Springer Science and Business Media LLC. - 1749-8104. ; 3, s. 26-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Focal adhesion kinase (FAK) functions in cell migration and signaling through activation of the mitogen-activated protein kinase (MAPK) signaling cascade. Neuronal function of FAK has been suggested to control axonal branching; however, the underlying mechanism in this process is not clear. RESULTS: We have generated mutants for the Drosophila FAK gene, Fak56. Null Fak56 mutants display overgrowth of larval neuromuscular junctions (NMJs). Localization of phospho-FAK and rescue experiments suggest that Fak56 is required in presynapses to restrict NMJ growth. Genetic analyses imply that FAK mediates the signaling pathway of the integrin alphaPS3betanu heterodimer and functions redundantly with Src. At NMJs, Fak56 downregulates ERK activity, as shown by diphospho-ERK accumulation in Fak56 mutants, and suppression of Fak56 mutant NMJ phenotypes by reducing ERK activity. CONCLUSION: We conclude that Fak56 is required to restrict NMJ growth during NMJ development. Fak56 mediates an extracellular signal through the integrin receptor. Unlike its conventional role in activating MAPK/ERK, Fak56 suppresses ERK activation in this process. These results suggest that Fak56 mediates a specific neuronal signaling pathway distinct from that in other cellular processes.
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- Chiang, Yueh-Tao, et al.
(författare)
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Emergence of a butterfly: the life experiences of type 1 diabetes Taiwanese patients during the 16-25 years old transition period.
- 2020
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Ingår i: International journal of qualitative studies on health and well-being. - : Informa UK Limited. - 1748-2631. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To explore the life experiences of patients with type 1 diabetes transition from adolescence into adulthood in Taiwan.Methods: Descriptive phenomenological design was used. Fourteen participants were individually interviewed using a semi-structured interview.Results: The life experiences of patients with type 1 diabetes transition from adolescence into adulthood experience a metamorphosis from awareness of responsibility to figuring out a way to care for themselves. Six themes emerged: (1) hibernation: awareness of responsibility; (2) emergence: attempts to take responsibility; (3) perseverance: encountering difficulties; (4)anxiety: multiple worries; (5) hesitation: back-and-forth," and (6) exit: finding a way out."Conclusions: During the transition phase, the participants experienced the trials of various situations. Regardless of whether they are able to independently bear the responsibilities of self-management, they all hope to turn around the challenges of disease control and take ownership of their disease. Like a butterfly that emerges from a cocoon, they hoped to overcome the dangers of taking flight through trial and error and navigating the world. The results of this study can serve as a reference for clinical care and developing localized intervention strategies targeted to the transition period between adolescence and young adulthood.
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