Biology subjects

Leng, B.

Publications and source records attributed to Leng, B..

4 recordsLinked to original sources

bioRxiv2026

Pharmacological up-regulation of CALM1 restore endothelial cells in intracranial aneurysm pathogenesis

Subarachnoid hemorrhage (SAH) resulted from intracranial aneurysm (IA) rupture is an especially severe form of stroke. Endothelial dysfunction represents the initiating event of IA pathogenesis. Understanding the role of endothelial cells (ECs) underlying formation of IAs is helpful to seek for pharmaceutical treatment strategy. Based on single-cell RNA sequencing, proteomics, and metabolic analysis, we discovered a change in cell population in IA samples, majorly in ECs and macrophages (MPs). Abnormal ECs exhibit senescence and death in IA samples, which is absent in the control arterial samples. Cross-analysis of multi-omics revealed that CALM1, a calcium detector involved in mechanotransduction, is downregulated in the abnormal ECs. CALM1 knockdown leads to senescence and inhibits the proliferation and maturation of ECs under turbulent flow. Through high-throughput virtual screening, this work identified compound ZC04329651 as a potent CALM1 activator in maintaining the stability of endothelial cell junctions and attenuating cellular senescence. Thus, our findings showed compound ZC04329651 up-regulate the expression of CALM1 to restore ECs, which maybe a promising pharmacological treatment strategy for IAs.

cell biology↗

bioRxiv2024

STING contributes to pulmonary hypertension by targeting the interferon and BMPR2 signaling through regulating F2RL3

Rational/ObjectivesPulmonary hypertension (PH) is an incurable disease characterized by pulmonary arterial remodeling. Endothelial injury and inflammation are the key triggers of the disease initiation. Recent findings suggest that STING (stimulator of interferon genes) activation plays a critical role in the endothelial dysfunction and interferon signaling. Here, we investigated the involvement of STING in the pathogenesis of PH. MethodsPH patients and rodent PH model samples, Sugen5416/hypoxia (SuHx) PH model, and pulmonary artery endothelial cells (PAECs) were used to evaluate the hypothesis. Measurement and Main ResultsThe cyclic GMP-AMP (cGAS)-STING signaling pathway was activated in the lung tissues from rodent PH models and PH patients, and the TNF- induced PAECs in vitro. In particular, STING significantly elevated in the endothelial cell in PH disease settings. In SuHx mouse model, genetic knockout or pharmacological inhibition of STING prevented the progression of PH. Functionally, knockdown of STING reduced the proliferation and migration in PAECs. Mechanistically, STING transcriptional regulates its binding partner F2RL3 through STING-NF-{kappa}B axis, which activated the interferon signaling and repressed the BMPR2 signaling both in vitro and in vivo. Further analysis revealed that F2RL3 expression was increased in PH settings and identified negative feedback regulation of F2RL3/BMPR2 signaling. Accordingly, a positive correlation of expression levels between STING and F2RL3/ interferon-stimulated genes (ISGs) was observed in vivo. ConclusionsOur findings suggest that STING activation in PAECs plays a critical role in the pathobiology of PH. Targeting STING may be a promising therapeutic strategy for preventing the development of PH.

cell biology↗

bioRxiv2020

Study on β-Chitosan against the binding of SARS-CoV-2S-RBD/ACE2

SARS-CoV-2 invades human respiratory epithelial cells via an interaction between its spike RBD protein (SARS-CoV-2 S-RBD) and the host cell receptor angiotensin converting enzyme II (ACE2). Blocking this interaction provides a potent approach to preventing and controlling SARS-CoV-2 infection. In this work, the ability of {beta}-chitosan to block the binding interaction between SARS-CoV-2 S-RBD and ACE2 was investigated. The inhibitory effect of {beta}-chitosan on inflammation induced by the SARS-CoV-2 S-RBD was also studied. Native-PAGE analysis indicated that {beta}-chitosan could bind with ACE2 and the SARS-CoV-2 S-RBD and a conjugate of {beta}-chitosan and ACE2 could no longer bind with the SARS-CoV-2 S-RBD. HPLC analysis suggested that a conjugate of {beta}-chitosan and the SARS-CoV-2 S-RBD displayed high binding affinity without dissociation under high pressure (40 MPa) compared with that of {beta}-chitosan and ACE2. Furthermore, immunofluorescent staining of Vero E6 cells and lungs from hACE2 mice showed that the presence of {beta}-chitosan prevented SARS-CoV-2 S-RBD from binding to ACE2. Meanwhile, {beta}-chitosan could dramatically suppress the inflammation caused by the presence of the SARS-CoV-2 S-RBD both in vitro and vivo. Moreover, the decreased expression of ACE2 caused by {beta}-chitosan treatment was restored by addition of TAPI-1, an inhibitor of the transmembrane protease ADAM17. Our findings demonstrated that {beta}-chitosan displays an antibody-like function capable of neutralizing the SARS-CoV-2 S-RBD and effectively preventing the binding of the SARS-CoV-2 S-RBD to ACE2. Moreover, ADAM17 activation induced by {beta}-chitosan treatment can enhance the cleavage of the extracellular domain of ACE2, releasing the active ectodomain into the extracellular environment, which can prevent the binding, internalization, and degradation of ACE2 bound to the SARS-CoV-2 S-RBD and thus diminish inflammation. Our study provides an alternative avenue for preventing SARS-CoV-2 infection using {beta}-chitosan.

cell biology↗

bioRxiv2019

MATRIEX Imaging: Multi-Area Two-photon Real-time In-vivo Explorer

Two-photon laser scanning microscopy, originally developed since 1990s1, has been widely applied for biomedical research in recent decades, particularly popular among neuroscientists for studying neural functions in vivo2. However, it is typically restricted to one imaging area that is orthogonal to the optical axis. Here, we demonstrate a novel multi-axis optical conjugation method that enables two-photon imaging at single-cell resolution simultaneously in multiple areas at different depths, each of which could have a view diameter of ~200 m and could be largely freely targeted within a zone up to 12-mm diameter. For example, we show simultaneous imaging of neuronal activities in the primary visual cortex (V1), the primary motor cortex (M1) and the hippocampal CA1 region of awake mice. This method can be readily implemented on a single conventional two-photon microscope to enable multi-area exploration of neuronal activities in vivo.

neuroscience↗