Peking Union Medical College Hospital

About: Peking Union Medical College Hospital is a healthcare organization based out in Beijing, China. It is known for research contribution in the topics: Medicine & Population. The organization has 15996 authors who have published 16018 publications receiving 226505 citations.

Long-term persistence of robust antibody and cytotoxic T cell responses in recovered patients infected with SARS coronavirus.

Abstract: Most of the individuals infected with SARS coronavirus (SARS-CoV) spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.

Screening and identification of linear B-cell epitopes and entry-blocking peptide of severe acute respiratory syndrome (SARS)-associated coronavirus using synthetic overlapping peptide library

Abstract: A 10-mer overlapping peptide library has been synthesized for screening and identification of linear B-cell epitopes of severe acute respiratory syndrome associated coronavirus (SARS-CoV), which spanned the major structural proteins of SARS-CoV. One hundred and eleven candidate peptides were positive according to the result of PEPscan, which were assembled into 22 longer peptides. Five of these peptides showed high cross-immunoreactivities (approximately 66.7 to 90.5%) to SARS convalescent patients' sera from the severest epidemic regions of the China mainland. Most interestingly, S(471-503), a peptide located at the receptor binding domain (RBD) of SARS-CoV, could specifically block the binding between the RBD and angiotensin-converting enzyme 2, resulting in the inhibition of SARS-CoV entrance into host cells in vitro. The study demonstrated that S(471-503) peptide was a potential immunoantigen for the development of peptide-based vaccine or a candidate for further drug evaluation against the SARS-CoV virus-cell fusion.

CD146-HIF-1α hypoxic reprogramming drives vascular remodeling and pulmonary arterial hypertension.

Abstract: Pulmonary arterial hypertension (PAH) is a vascular remodeling disease of cardiopulmonary units. No cure is currently available due to an incomplete understanding of vascular remodeling. Here we identify CD146-hypoxia-inducible transcription factor 1 alpha (HIF-1α) cross-regulation as a key determinant in vascular remodeling and PAH pathogenesis. CD146 is markedly upregulated in pulmonary artery smooth muscle cells (PASMCs/SMCs) and in proportion to disease severity. CD146 expression and HIF-1α transcriptional program reinforce each other to physiologically enable PASMCs to adopt a more synthetic phenotype. Disruption of CD146-HIF-1α cross-talk by genetic ablation of Cd146 in SMCs mitigates pulmonary vascular remodeling in chronic hypoxic mice. Strikingly, targeting of this axis with anti-CD146 antibodies alleviates established pulmonary hypertension (PH) and enhances cardiac function in two rodent models. This study provides mechanistic insights into hypoxic reprogramming that permits vascular remodeling, and thus provides proof of concept for anti-remodeling therapy for PAH through direct modulation of CD146-HIF-1α cross-regulation.

Circular RNA profiling reveals circEXOC6B and circN4BP2L2 as novel prognostic biomarkers in epithelial ovarian cancer.

Abstract: Circular RNAs (circRNAs) are regarded as a novel class of widespread endogenous non-coding RNAs, which may play important roles in tumorigenesis by regulating gene expression. Nevertheless, the characterization of circRNAs in epithelial ovarian cancer (EOC) remains largely unknown. This study aimed to investigate circRNA expression profiles in EOC. A total of 54 EOC specimens and 54 normal ovarian tissues (controls) were collected. circRNA-sequencing based circRNA expression profiles were identified in 4 EOC specimens and compared with 4 normal ovarian tissues. circRNA-sequencing data were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in the 54 EOC specimens and 54 normal ovarian tissues. The association between differentially expressed circRNAs and various clinicopathological features of EOC was determined using a non-parametric test. Univariate analysis was performed using the log-rank test. A total of 4,388 circRNAs (2,556 up- and 1,832 downregulated; fold change of ≥2 and P<0.05) were identified to be differentially expressed in the EOC specimens compared with the normal ovarian tissues. Of these, the levels of 6 circRNAs (circBNC2, circEXOC6B, circFAM13B, circN4BP2L2, circRHOBTB3 and circCELSR1) were confirmed by RT-qPCR. Our data further indicated that these 6 circRNAs were associated with various clinicopathological features of EOC. More importantly, we found that circEXOC6B and circN4BP2L2 may act as novel prognostic biomarkers in patients with EOC. On the whole, the results of this study indicate that differentially expressed circRNAs may participate in the pathogenesis of EOC and may thus have potential for use as novel diagnostic and prognostic biomarkers for EOC. Future experiments with larger sample sizes are required to verify the current findings and illuminate the regulatory mechanisms of action of circRNAs in the tumorigenesis of EOC.

Vitamin D binding protein variants associate with asthma susceptibility in the Chinese han population

Abstract: Background Asthma is a genetically heterogeneous disease. Polymorphisms of genes encoding components of the vitamin D pathway have been reported to associate with the risk of asthma. We have previously demonstrated that vitamin D status was associated with lung function in Chinese asthma patients. In this study, we tested whether polymorphisms of genes encoding for vitamin D receptor (VDR), vitamin D 25-hydroxylase (CYP2R1) and vitamin D binding protein (GC) were associated with asthma in the Chinese Han population.