The results of this meta-analysis confirm that NUDT15 c.415C>T may be an important predictor of thiopurine-induced leukocytopenia in Asians. Genotype targeting of NUDT15 c.415C>T before initiating thiopurine treatment may be useful to limit leukocytopenia.
The telomeric protein TRF2, involving in telomeric and extratelomeric DNA damage response, has been previously reported to facilitate multidrug resistance (MDR) in gastric cancer cells by interfering ATM-dependent DNA damage response induced by anticancer drugs. Rap1 is the TRF2-interacting protein in the shelterin complex. Complex formation between Rap1 and TRF2 is essential for their function in telomere and end protection. Here we focus on the effects of Rap1 on TRF2 function in DNA damage response induced by anticancer drugs. Both Rap1 and TRF2 expression were upregulated in SGC7901 and its MDR variant SGC7901/VCR after etoposide treatment, which was more marked in SGC7901/VCR than in SGC7901. Rap1 silencing by siRNA in SGC7901/VCR partially reversed the etoposide resistance. And Rap1 silencing partially reversed the TRF2-mediated resistance to etoposide in SGC7901. Rap1 silencing did not affect the TRF2 upregulation induced by etoposide, but eliminated the inhibition effect of TRF2 on ATM expression and ATM phosphorylation at serine 1981 (ATM pS1981). Furthermore, phosphorylation of ATM targets, including γH2AX and serine 15 (S15) on p53, were increased in Rap1 silencing cells in response to etoposide. Thus, we confirm that Rap1, interacting with TRF2 in the shelterin complex, also has an important role in TRF2-mediated DNA damage response in gastric cancer cells treated by etoposide.
ABSTRACT. The aim of this study was to investigate the association between four single nucleotide polymorphisms in NR3C1 (Tth111I, BclI, ER22/23EK, and N363S), which encode the glucocorticoid receptor, and asthma susceptibility in patients from the Henan Province of China. Three hundred and twenty-eight patients with asthma and 60 healthy volunteers were recruited to this study. The target SNPs were genotyped by polymerase chain reaction (PCR)-high resolution melting and PCR-restriction fragment length polymorphism. The frequencies of the AA (8.84%) and GG (30.79%) genotypes of Tth111I were higher, and that of the AG genotype was lower (60.37%), in the asthma patients compared to that seen in healthy controls (5.00, 26.67, and 68.33%, respectively). On the other hand, asthma patients showed higher frequencies of the AA genotype (78.05%) of N363S, and lower frequencies of the AG and GG genotypes (15.55 and 6.40%), compared to healthy volunteers (71.67, 18.33, and 10.00%, respectively). Neither of these differences were found to be statistically significant. Moreover, we observed no significant differences in the genotype or allele frequencies of the BclI and ER22/23EK SNPs between the patient and control groups. In conclusion, SNPs in NR3C1 were not significantly associated with asthma in patients from the Henan Province. Patients showed higher frequencies of the AA and GG genotypes of Tth111I and the AA genotype of the N363S SNP compared to healthy volunteers, although these differences were not significant.
Background and objective: The outbreak of COVID-19 has become a global health concern. In this study, we evaluate the effectiveness and safety of convalescent plasma therapy in patients with severe and critically ill COVID-19. Methods: Sixteen COVID-19 patients received transfusion of anti-COVID-19 antibody-positive convalescent plasma. The main outcome was time for viral nucleic acid amplification (NAA) test turning negative. Clinical laboratory parameters were measured at the baseline (d0) before plasma transfusion, and day 1 (d1), day 3 (d3) after transfusion as well. Results: Among the 16 patients, 10 of them had a consistently positive result of viral NAA test before convalescent plasma transfusion. Eight patients (8/10) became negative from day 2 to day 8 after transfusion. Severe patients showed a shorter time for NAA test turning negative after transfusion (mean rank 2.17 vs 5.90, P = 0.036). Two critically ill patients transfused plasma with lower antibody level remained a positive result of NAA test. CRP level demonstrated a decline 1 day after convalescent plasma treatment, compared with the baseline (P = 0.017). No adverse events were observed during convalescent plasma transfusion. Conclusions: Viral NAA test of most patients with COVID-19 who received convalescent plasma transfusion turned negative on the 2nd to 8th days after transfusion, and the negative time of severe patients was shorter than that of critically ill patients.
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