Author Contributions: Drs Liu and Yang had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Dong and Tian contributed equally to the study. Drs Liu and Yang contributed equally as senior authors.
An outbreak of new coronavirus SARS-CoV-2 was occurred in Wuhan, China and rapidly spread to other cities and nations. The standard diagnostic approach that widely adopted in the clinic is nucleic acid detection by real-time RT-PCR. However, the false-negative rate of the technique is unneglectable and serological methods are urgently warranted. Here, we presented the colloidal gold-based immunochromatographic (ICG) strip targeting viral IgM or IgG antibody and compared it with real-time RT-PCR. The sensitivity of ICG assay with IgM and IgG combinatorial detection in nucleic acid confirmed cases were 11.1%, 92.9% and 96.8% at the early stage (1-7 days after onset), intermediate stage (8-14 days after onset), and late stage (more than 15 days), respectively. The ICG detection capacity in nucleic acid-negative suspected cases was 43.6%. In addition, the concordance of whole blood samples and plasma showed Cohen's kappa value of 0.93, which represented the almost perfect agreement between two types of samples. In conclusion, serological ICG strip assay in detecting SARS-CoV-2 infection is both sensitive and consistent, which is considered as an excellent supplementary approach in clinical application.
An outbreak of new coronavirus SARS-CoV-2 was occurred in Wuhan, China and rapidly spread to other cities and nations. The standard diagnostic approach that widely adopted in the clinic is nuclear acid detection by real-time RT-PCR. However, the false-negative rate of the technique is unneglectable and serological methods are urgently warranted. Here, we presented the colloidal gold-based immunochromatographic (ICG) strip targeting viral IgM or IgG antibody and compared it with real-time RT-PCR. The sensitivity of ICG assay with IgM and IgG combinatorial detection in nuclear acid confirmed cases were 11.1%, 92.9% and 96.8% at the early stage (1-7 days after onset), intermediate stage (8-14 days after onset), and late-stage (more than 15 days), respectively. The ICG detection capacity in nuclear acid-negative suspected cases was 43.6%. In addition, the consistencies of whole blood samples with plasma were 100% and 97.1% in IgM and IgG strips, respectively. In conclusion, serological ICG strip assay in detecting SARS-CoV-2 infection is both sensitive and consistent, which is considered as an excellent supplementary approach in clinical application.
The antiestrogen fulvestrant (ICI 182,780) causes immobilization of estrogen receptor-␣ (ER␣) in the nuclear matrix accompanied by rapid degradation by the ubiquitin-proteasome pathway. In this study we tested the hypothesis that fulvestrant induces specific nuclear matrix protein-ER␣ interactions that mediate receptor immobilization and turnover. A glutathione S-transferase (GST)-ER␣-activating function-2 (AF2) fusion protein was used to isolate and purify receptor-interacting proteins in cell lysates prepared from human MCF-7 breast cancer cells. After SDS-PAGE and gel excision, mass spectrometry was used to identify two major ER␣-interacting proteins, cytokeratins 8 and 18 (CK8⅐CK18). We determined, using ER␣-activating function-2 mutants, that helix 12 (H12) of ER␣, but not its F domain, is essential for fulvestrant-induced ER␣-CK8 and CK18 interactions. To investigate the in vivo role of H12 in fulvestrant-induced ER␣ immobilization/degradation, transient transfection assays were performed using wild type ER␣, ER␣ with a mutated H12, and ER␣ with a deleted F domain. Of those, only the ER␣ H12 mutant was resistant to fulvestrant-induced immobilization to the nuclear matrix and protein degradation. Fulvestrant treatment caused ER␣ degradation in CK8⅐CK18-positive human breast cancer cells, and CK8 and CK18 depletion by small interference RNAs partially blocked fulvestrant-induced receptor degradation. Furthermore, fulvestrant-induced ER␣ degradation was not observed in CK8 or CK18-negative cancer cells, suggesting that these two intermediate filament proteins are necessary for fulvestrant-induced receptor turnover. Using an ER␣-green fluorescent protein construct in fluorescence microscopy revealed that fulvestrant-induced cytoplasmic localization of newly synthesized receptor is mediated by its interaction with CK8 and CK18. In summary, this study provides the first direct evidence linking ER␣ immobilization and degradation to the nuclear matrix. We suggest that fulvestrant induces ER␣ to interact with CK8 and CK18, drawing the receptor into close proximity to nuclear matrix-associated proteasomes that facilitate ER␣ turnover.Estrogen receptor-␣ (ER␣), 2 a member of the nuclear receptor family, is a ligand-dependent transcription factor that mediates physiological responses to its cognate ligand, 17-estradiol (E2), in estrogen target tissues such as the breast, uterus, and bone (1). Because ER␣ is a shortlived protein (half-life of 4 -5 h), its cellular levels are strictly regulated (2). Although ER␣ turnover is a continuous process (2), dynamic fluctuations in receptor levels, mediated primarily by the ubiquitin-proteasome pathway (3-6), occur in response to changing cellular conditions (7-9). In addition, differing ligands have been demonstrated to exert differential effects on steady-state levels of ER␣ (10, 11). For example, E2 and the "pure" ER␣ antagonists (i.e. ICI 164,384, ICI 182,780, RU 58,668, and ZK-703) (12, 13) induce receptor turnover, whereas the "partial" agonist/antagonist 4-hydroxytamoxif...
Breast cancer susceptibility gene 1 (BRCA1) located at chromosome 17q12-21 is a classic tumor suppressor gene, and has been considered as a significant role in hereditary breast cancers. Moreover, numerous studies demonstrated the methylation status of CpG islands in the promoter regions of BRCA1 gene was aberrant in patients with sporadic breast tumors compared with healthy females or patients with benign diseases. However, these conclusions were not always consistent. Hence, a meta-analysis was performed to get a more precise estimate for these associations. Crude odds ratio with 95% confidence interval were used to assess the association of BRCA1 promoter methylation and the risk or clinicopathologic characteristics of breast cancers under fixed or random effect model. A total of 40 studies were eligible for this present study. We observed the frequency of BRCA1 promoter methylation was statistically significant higher in breast cancers than non-cancer controls. Furthermore, BRCA1 methylation was statistically associated with lymph node metastasis, histological grade 3, ER(-), PR(-), triple-negative phenotype, and decreased or lack levels of BRCA1 protein expression. In conclusion, this study indicated that BRCA1 promoter methylation appeared to be a useful predictive or prognostic biomarker for breast cancers in clinical assessment.
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