Background: While a small number of studies have shown that the booster vaccination was able to provide additional serologic protection in transplant population, evidence on whether immunogenicity elicited provides actual protection from symptomatic Omicron infection is unclear.Methods: CoVaKT was a prospective non-interventional study assessing the serologic efficacy and safety of a booster dose of SARS-CoV-2 vaccinations in COVID-19 infection nave renal transplant recipients (RTRs).To further evaluate the clinical effectiveness of the vaccine, we collected data on the incidence and severity of subsequent breakthrough infections which all occurred during the Omicron surge and evaluated the association between post-booster anti-spike antibody level and clinical outcomes.Vaccine-induced SARS-CoV-specific antibody was quantified through Abbott SARS-CoV-2 immunoglobulin G (IgG) II Quant assay.Results: A total of 287 RTRs who had standard doses of the COVID-19 vaccine were enrolled.After the booster mRNA vaccine dose, the seropositivity rate increased from 57.1% (164/287) to 82.2% (236/287).Median antibody titer also was significantly increased (62.3 to 1,382.8AU/mL, P<0.01).Factors associated with negative antibody response were shorter duration since transplantation, lower hemoglobin, lower estimated glomerular filtration rate, high tacrolimus trough concentration, mycophenolate mofetil or mycophenolic acid use and having two doses of ChAdOX1-S during the primary vaccination.Sixty-five patients (22.6%) had breakthrough COVID-19 infection within 4 months after the booster vaccination, of which 12 patients needed admission.The median time to infection was 83 days.Factors associated with infection in the multivariable logistic regression model were post-booster anti-spike IgG <400 AU/mL (odds ratio [OR], 3.55; 95% confidence interval [CI], 1.99-6.32;P<0.01), and having received living donor transplantation (OR, 1.97; 95% CI, 1.03-3.75;P=0.04).Low post-booster antibody level (IgG <200 AU/mL) was also a risk factor for severe disease (OR, 22.9; 95% CI, 2.27-231.6;P=0.01). Conclusions:The COVID-19 mRNA booster vaccination was immunogenically effective in RTRs, and a higher anti-spike IgG level post-boost provided protection against both breakthrough infection and severe COVID-19 disease.
During the first trimester of pregnancy, trophoblastic E-cadherin expression is down-regulated, thereby allowing extravillous trophoblasts (EVTs) to acquire the potential for migration and invasiveness. The aim of the present study was to investigate the role of OSM on the migration and proliferation of EVT cell line HTR8/SVneo with regard to its effects on the expression of E-cadherin and STAT3 activation.We investigated the effects of OSM on RNA and protein expression of E-cadherin by real time RT-PCR analyses, western blotting, and indirect immunofluorescence staining in HTR8/SVneo cells, as well as the effects on cell migration and proliferation. The selective signal transducer and activator of transcription (STAT)3 inhibitor, stattic, and STAT3 siRNA were used to investigate STAT3 activation by OSM.OSM significantly reduced RNA and protein expression of E-cadherin. Indirect immunofluorescence staining of HTR8/SVneo cells also revealed the down-regulation of E-cadherin, compared with the controls. OSM-stimulated cell migration was attenuated by anti-gp130 antibodies. OSM-induced STAT3 phosphorylation, and the down-regulation of E-cadherin by OSM treatment was restored by stattic and STAT3 siRNA. In addition, OSM-stimulated migration and proliferation were significantly suppressed by STAT3 inhibition.This study suggests that OSM stimulates the migration and proliferation of EVTs during the first trimester of pregnancy through the down-regulation of E-cadherin. In addition, this study suggests that the effects of OSM on migration and proliferation are related to STAT3 activation, which is important in trophoblast invasiveness.
Our previous studies have shown that oncostatin M (OSM) promotes trophoblast invasion activity through increased enzyme activity of matrix metalloproteinase (MMP)-2 and -9. We further investigated OSM-induced intracellular signaling mechanisms associated with these events in the immortalized human trophoblast cell line HTR8/SVneo.We investigated the effects of OSM on RNA and protein expression of MMP-2 and -9 in the first-trimester extravillous trophoblast cell line (HTR8/SVneo) via Western blot. The selective signal transducer and activator of transcription (STAT)3 inhibitor, stattic, STAT3 siRNA, and extracellular signal-regulated kinase (ERK) siRNA were used to investigate STAT3 and ERK activation by OSM. The effects of STAT3 and ERK inhibitors on OSM-induced enzymatic activities of MMP-2 and -9 and invasion activity were further determined via Western blot and gelatin zymography.OSM-induced MMP-2 and -9 protein expression was significantly suppressed by STAT3 inhibition with stattic and STAT3 siRNA silencing, whereas the ERK1/2 inhibitor (U0126) and ERK silencing significantly suppressed OSM-induced MMP-2 protein expression. OSM-induced MMP-2 and MMP-9 enzymatic activities were significantly decreased by stattic pretreatment. The increased invasion activity induced by OSM was significantly suppressed by STAT3 and ERK1/2 inhibition, though to a greater extent by STAT3 inhibition.Both STAT3 and ERK signaling pathways are involved in OSM-induced invasion activity of HTR8/SVneo cells. Activation of STAT3 appears to be critical for the OSM-mediated increase in invasiveness of HTR8/SVneo cells.
= Abstract = Purpose : Idiopathic nephrotic syndrome (NS) can be clinically classified as steroid-sensitive and steroid-resistant. The detailed mechanism of glucocorticoid action in NS is currently unknown. Methods : In this study, we investigated 3 known single nucleotide polymorphisms (SNPs) (ER22/23EK, N363S, and BclI) of the glucocorticoid receptor gene (the NR3C1 gene) in 190 children with NS using polymerase chain reaction-restriction fragment length polymorphism and analyzed the correlation between the genotypes and clinicopathologic features of the patients. Results : Eighty patients (42.1%) were initial steroid nonresponders, of which 31 (16.3% of the total) developed end-stage renal disease during follow-up. Renal biopsy findings of 133 patients were available, of which 36 (31.9%) showed minimal changes in NS and 77 (68.1%) had focal segmental glomerulosclerosis. The distribution of the BclI genotypes was com- parable between the patient and control groups, and the G allele frequencies in both the groups were almost the same. The ER22/23EK and N363S genotypes were homogenous as ER/ER and NN, respectively, in all the patients and in 100 control subjects. The BclI genotype showed no correlation with the NS onset age, initial steroid responsiveness, renal pathologic findings, or progression to end-stage renal disease. Conclusion : These data suggested that the ER22/23EK, N363S, and BclI SNPs in the NR3C1 gene do not affect the development of NS, initial steroid responsiveness, renal pathologic lesion, and progression to end-stage renal disease in Korean children with NS. (Korean J Pediatr 2009;52:1260-1266)
In this study, an assay to quantify the presence of magnesium ions with a chemosensor of bispicolylamine covalently attached to coumarin as a fluorephore was developed using a ratiometric fluorescence enhancement approach. Upon treatment with magnesium ions, the fluorescence wavelength of the chemosensor at 367 nm was shifted to 413 nm and the intensity was also enhanced. The formation of a 1:2 complex between the chemosensor and magnesium ions was confirmed based on the spectral changes of UV–vis, fluorescence and NMR as well as Job's plot. An appreciable enhancement in the luminescence intensity for the emission band at 413 nm was evident when magnesium ions were added progressively. The maximum wavelength and intensity of the emission of the complex with Mg2+ were discriminated from those of other metal ions, such as Ca2+ and Zn2+.
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