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- Passos, Vania, et al.
(författare)
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Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons
- 2024
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Ingår i: Journal of Medical Virology. - : John Wiley & Sons. - 0146-6615 .- 1096-9071. ; 96:2
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory coronavirus 2 (SARS-CoV-2) causes neurological disease in the peripheral and central nervous system (PNS and CNS, respectively) of some patients. It is not clear whether SARS-CoV-2 infection or the subsequent immune response are the key factors that cause neurological disease. Here, we addressed this question by infecting human induced pluripotent stem cell-derived CNS and PNS neurons with SARS-CoV-2. SARS-CoV-2 infected a low number of CNS neurons and did not elicit a robust innate immune response. On the contrary, SARS-CoV-2 infected a higher number of PNS neurons. This resulted in expression of interferon (IFN) λ1, several IFN-stimulated genes and proinflammatory cytokines. The PNS neurons also displayed alterations characteristic of neuronal damage, as increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and α-synuclein, and lower levels of cytoskeletal proteins. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neuronal damage, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS. Our results provide a basis to study coronavirus disease 2019 (COVID-19) related neuronal pathology and to test future preventive or therapeutic strategies.
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2. |
- Zhang, Cong, et al.
(författare)
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Association of Metabolic Syndrome with Macular Thickness and Volume in Older Adults : A Population-Based Optical Coherence Tomography Study
- 2024
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Ingår i: Metabolic Syndrome and Related Disorders. - 1540-4196 .- 1557-8518. ; 22:2, s. 141-150
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Tidskriftsartikel (refereegranskat)abstract
- Background: To explore the associations of the metabolic syndrome (MetS) and individual components with macular thickness and volume among rural-dwelling Chinese older adults.Methods: This population-based cross-sectional study included 705 participants (age ≥60 years) derived from the MIND-China study. In 2018–2019, we collected data through face-to-face interview, clinical examination, optical coherence tomography (OCT) examination, and blood test. We measured macular thickness and volume using spectral-domain OCT. MetS was defined following the International Diabetes Federation (IDF) criteria, the IDF/American Heart Association (AHA) criteria, the National Cholesterol Education Program-Adult Treatment Panel III criteria, and the Chinese Diabetes Society (CDS) criteria. Data were analyzed with multivariable general linear models.Results: MetS was significantly associated with thinner macula in central (multivariable-adjusted β = −5.29; 95% confidence interval: −9.31 to −1.26), parafoveal (−2.85; −5.73 to 0.04) and perifoveal regions (−4.37; −6.79 to −1.95) when using the IDF criteria, in the perifoveal regions (−3.82; −6.18 to −1.47) when using the IDF/AHA criteria, and in the central region (−5.63; −10.25 to −1.02) when using the CDS criteria, and with reduced macular volume when using the IDF (−0.16; −0.26 to −0.07) and IDF/AHA (−0.13; −0.22 to −0.04) criteria. In the parafoveal region, the IDF-defined MetS was significantly associated with thinner retina in men (β = −6.25; −10.94 to −1.56) but not in women. Abdominal obesity (−2.83; −5.41 to −0.25) and elevated fasting blood glucose (−2.65; −5.08 to −0.21) were associated with thinner macular thickness in the perifoveal region.Conclusion: MetS is associated with macular thinning and reduced macular volume among rural-dwelling older adults, and the associations vary by the defining criteria of MetS.
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