RESUMO
Objectives: Patients who are undergoing dialysis due to end-stage kidney disease are susceptible to greater coronavirus disease 2019 (COVID-19) complications. While vaccination is seen as the most effective tactic against COVID-19, the dialysis population usually has impaired immune responses to vaccination. Owing to the global vaccine supply shortage in the early phase of the COVID-19 pandemic, hemodialysis patients in Taiwan were administered homologous ChAdOx1 nCoV-19/ChAdOx1 nCoV-19 at 12-week intervals, with a third booster shot of mRNA-1273 given 12 weeks after the second dose. We assessed the antibody responses of these patients to this extended-interval dosing protocol. Materials and Methods: A total of 168 hemodialysis patients (mean age: 67 ± 13 years) without prior COVID-19 infection were vaccinated between June 16, 2021, and January 5, 2022, and followed until February 10, 2022. The primary outcome was seroconversion with an antispike immunoglobulin G (IgG) antibody level ≥50 arbitrary units (AU)/mL at 4 weeks after the administration of an mRNA-1273 booster shot. The secondary outcome was the level of antispike IgG antibodies. Multivariable linear regression models were used to evaluate the associations between the baseline characteristics and the antispike IgG level. Results: A total of 163 (97.0%) patients reached the primary endpoint, with antibody levels after the third booster dose of mRNA-1273 being significantly higher than those after the second dose of ChAdOx1 nCoV-19 (median IgG titer 12,007 [4394-23,860] vs. 846 [interquartile range 295-2114] AU/mL; P < 0.001). Patients who were male, older, had a higher body mass index, had a lower total lymphocyte count, and used immunosuppressants had lower antibody levels. Conclusion: A third booster dose of mRNA-1273 after two consecutive priming doses of ChAdOx1 nCoV-19 with extended intervals resulted in adequate humoral immune responses among hemodialysis patients.
RESUMO
Objective: To investigate the role of platelet derived growth factor receptor alpha (PDGFRα) on bidirectional differentiation of glioma-associated oncogene homolog 1-positive mesenchymal stem cells (Gli1+-MSC). Methods: Breeding double reporter transgenic mice ROSAmT/mG/Gli1-CreERt2/PDGFRαfl (Experimental group) and ROSAmT/mG/Gli1-CreERt2 (Control group), 20 mice in each of the two groups at four weeks of age were selected, MSC were isolated from the mouse aortic epithelium. After tamoxifen inducement, the two groups of Gli1+-MSC were screened by green fluorescent protein (GFP) labeling and flow cytometry sorting. PDGFRα was conditionally knocked out in the experimental group, and the control group Gli1+-MSC expressed PDGFRα normally. The two groups of Gli1+-MSC were subjected to adipogenic induction and fibrogenic induction, the Western blotting was performed to detect PDGFRα, adipocyte markers [perilipin and CCAAT/enhancer binding protein alpha (C/EBPα)] and fibrogenic markers [alpha smooth muscle actin (α-SMA) and fibroblast-specific protein 1 (FSP-1)] and semi-quantitative analysis was performed. The degree of cellular adipose differentiation after bidirectional induction of Gli1+-MSC in both groups was observed by oil red O staining and analyzed semi-quantitatively. Results: After tamoxifen induction, Gli1+-MSC could be accurately isolated from flow cytometry by GFP labeling. Via adipogenic differentiation, the expression of PDGFRα in the experimental group (0.017±0.002) was significantly lower than that in the control group (0.184±0.012) (t=25.48，P=0.002). The protein expressions of perilipin (3.138±0.414) and C/EBPα (3.565±0.289) were significantly higher than those in the control group (2.312±0.218 and 2.179±0.103, respectively) (t=6.21，P=0.025；t=6.69，P=0.022). Thus, the knock-out of PDGFRα enhanced the adipogenic differentiation ability of Gli1+-MSC. After fibrogenesis induction, the protein expressions of PDGFRα, α-SMA and FSP-1 in the experimental group (0.030±0.001, 0.932±0.177 and 0.276±0.020, respectively) were significantly lower than those in the control group (0.439±0.006, 1.352±0.170 and 0.835±0.097, respectively) (t=149.40, P<0.001; t=66.38,P<0.001; t=11.41,P<0.08). This suggested that the knock-out of PDGFRα significantly inhibited Gli1+-MSC differentiation toward fibroblasts. After bidirectional induction, significantly less adipocyte formation was seen in the control group and more in the experimental group. Quantitative analysis showed that the amount of oil red O staining in the experimental group (0.461±0.042) was significantly higher than that in the control group (0.017±0.007) after bidirectional induction (t=23.20, P<0.01). Conclusions: PDGFRα plays an important role in the regulation of bidirectional differentiation of vascular adventitial Gli1+-MSC.
