Biology subjects

Shu, B.

Publications and source records attributed to Shu, B..

5 recordsLinked to original sources

bioRxiv2025

Epidermal stem cell-derived extracellular vesicles induce fibroblasts mesenchymal-epidermal transition to alleviate hypertrophic scar via the miR-200s/ZEBs axis

Hypertrophic scar (HS) is a prevalent yet unresolved wound healing complication characterized by persistent hyperactive and proliferative fibroblasts, leading to excessive extracellular matrix (ECM) synthesis and collagen contraction. Our previous studies have identified epidermal stem cells (ESCs) as critical for wound healing and HS remodeling, with its extracellular vesicles (EVs) playing a vital role. However, the specific mechanisms remain unclear. In this study, we first discovered that ESC-EVs could effectively induce the mesenchymal-epidermal transition (MET) of HS fibroblasts (HSFs) and inhibit their biological activity. Furthermore, by next-generation sequencing and multiplexed CRISPR/Cas9 system, we elucidated that this therapeutic effect is mediated by the miR-200 family (miR-200s) encapsulated in ESC-EVs, which targeted and inhibited ZEB1 and ZEB2 in HSFs. This vital role and mechanism have been thoroughly validated in both in vitro cell experiments and in vivo rat tail HS (RHS) models. These findings not only shed light on a previously unidentified mechanism of ESC-EVs for HS, but also provide potential novel targets and strategies for its precise treatment.

cell biology↗

bioRxiv2022

CryoEM structures of the multimeric secreted NS1, a major factor for dengue hemorrhagic fever

Dengue virus infection can cause dengue hemorrhagic fever (DHF). Dengue NS1 is multifunctional: the intracellular dimeric NS1 (iNS1) forms part of the viral replication complex, the extracellular multi-oligomeric secreted NS1 (sNS1) is a major factor contributing to DHF. The structure of the iNS1 is well studied but not sNS1. Here we show the tetrameric (stable and loose conformation) and hexameric structures of sNS1. Stability of the stable and loose tetramers is determined by the conformation of their N-terminal domain - elongated {beta}-sheet or {beta}-roll. Binding of an anti-NS1 Fab breaks the loose tetrameric and hexameric sNS1 into dimers, whereas the stable tetramer remains largely unbound. Our results show detailed quaternary organization of different oligomeric states of sNS1 and will contribute towards the design of dengue therapeutics.

molecular biology↗

bioRxiv2020

Transient high glucose causes delayed wound healing by the DNMT1-mediated Ang-1/NF-κB pathway

The progression of diabetic complications does not halt despite termination of hyperglycemia, suggesting a "metabolic memory" phenomenon. However, whether metabolic memory exists in and affects the healing of diabetic wounds, as well as the underlying molecular mechanisms, remain unclear. In this study, we found that wound healing was delayed and angiogenesis was decreased in diabetic mice, despite normalization of glycemic control. Thus, we hypothesized that transient hyperglycemic spikes may be a risk factor for diabetic wound healing. We showed that transient hyperglycemia caused persistent damage to the vascular endothelium. Transient hyperglycemia directly upregulated DNMT1 expression, leading to the hypermethylation of Ang-1 and reduced Ang-1 expression, which, in turn, induced long-lasting activation of nuclear factor (NF)-{kappa}B and subsequent endothelial dysfunction. An in vivo study further showed that inhibition of DNMT1 promoted angiogenesis and accelerated diabetic wound healing by regulating the Ang-1/NF-{kappa}B signaling pathway. These results highlight the dramatic and long-lasting effects of transient hyperglycemic spikes on wound healing and suggest that DNMT1 is a novel target for diabetic vascular complications.

cell biology↗

bioRxiv2019

Detection and discrimination of influenza B Victoria lineage deletion variant viruses by real-time RT-PCR

Influenza B viruses have two genetically and antigenically distinct lineages, B/Victoria/2/1987-like (VIC) and B/Yamagata/16/1988-like (YAM) viruses, that emerged in the 1980s and co-circulate annually during the influenza season. During the 2016-2017 influenza season, influenza B/VIC lineage variant viruses emerged with two (K162N163) or three (K162N163D164) amino acid (AA) deletions in the hemagglutinin protein. Hemagglutination inhibition assays demonstrate that these deletion variant influenza B/VIC viruses are antigenically distinct from each other and from the progenitor B/VIC virus that lacks the deletion. Therefore, there are currently four antigenically distinct HA proteins expressed by influenza B co-circulating: B/YAM, B/VIC V1A (no deletion), B/VIC V1A.1 (two-AA deletion), and B/VIC V1A.2 and V1A.3 (three-AA deletion). The prevalence of these viruses differs across geographic regions, making it critical to have a sensitive, rapid diagnostic assay(s) that detect and distinguish these Influenza B variant viruses during surveillance. Here, we present a real time RT-PCR assay that targets the influenza B/VIC deletion region in the HA gene and detects and distinguishes the influenza B/VIC V1A, B/VIC V1A.1, B/VIC V1A.2 and B/VIC V1A.3 variant viruses, with no cross-reactivity. This assay can be run as a multiplex reaction, allowing for increased testing efficiency and reduced cost. Coupling this assay with the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel Influenza B Lineage Genotyping Kit results in rapid detection and characterization of circulating influenza B viruses. Having accurate and detailed surveillance information on these distinct Influenza B variant viruses will provide insight into the prevalence and geographic distribution and could aid in vaccine recommendations.

molecular biology↗

bioRxiv2019

Droplet-digital Cas13a assay enables direct single-molecule microRNA quantification

The direct quantification of microRNA at the single-molecule level is still challenging. Herein, we developed a droplet-digital Cas13a assay (ddCA) as a general approach for the amplification-free and absolute quantification of single unlabeled miRNA molecules with single-nucleotide specificity. We demonstrate its simplicity, precise quantification capability, excellent specificity and broad applicability by analyzing microRNAs from synthetic and cell lines-derived materials.

biochemistry↗