Biology subjects

Jiang, X.-M.

Publications and source records attributed to Jiang, X.-M..

3 recordsLinked to original sources

bioRxiv2025

Niacin protects against vascular calcification via enhanced SIRT1 and SIRT6 signaling and promoted VSMC autophagy

BackgroundVascular calcification (VC) is a common pathologic state that often accompanies calcium-phosphorus metabolism disorder and chronic kidney diseases (CKDs) in aging individuals. Vascular smooth muscle cell (VSMC) has been widely acknowledged as one of the main cell types that involved in this process. Niacin, a lipid-lowering reagent, has been demonstrated to be beneficial in atherosclerotic disease. The correlation and mechanism between niacin and vascular calcification have not been reported so far. Methods and resultsRCS analysis based on large clinical databases indicated that diet that riches in niacin can protect against abdominal artery calcification (AAC). Our data showed that niacin treatment remarkably reduced VSMC osteogenic differentiation and senescence-associated markers under osteogenic stimulation. Moreover, niacin treatment alleviated CKD and vitamin D3-induced vascular calcification in C57BL/6J mice. Mechanistically, we for the first time demonstrated that niacin supplementation inhibited vascular calcification via maintaining both Sirtuin 1 (SIRT1) and Sirtuin 6 (SIRT6) levels. Moreover, we verified that niacin activated SIRT1 and SIRT6 promoted VSMC autophagy flux. ConclusionsThese findings may help to develop novel therapeutic strategies in the treatment and prevention of vascular calcification.

cell biology↗

bioRxiv2021

An angiosperm NLR atlas reveals that NLR gene reduction is associated with ecological specialization and signal transduction component deletion

Nucleotide-binding site-leucine-rich repeat receptor (NLR) genes comprise the largest family of plant disease resistance genes. NLR genes are phylogenetically divided into the TNL, CNL, and RNL subclasses. NLR copy numbers and subclass composition vary tremendously across angiosperm genomes. However, the evolutionary associations between genomic NLR content and plant lifestyle, or between NLR content and signal transduction components, are poorly characterized due to limited genome availability. Here, we established an angiosperm NLR atlas (ANNA, http://compbio.nju.edu.cn/app/ANNA/), which includes NLR genes from over 300 angiosperm genomes. Using ANNA, we revealed that NLR copy numbers differ up to 66-fold among closely related species due to rapid gene loss and gain. Interestingly, NLR contraction was associated with adaptations to aquatic, parasitic, and carnivorous lifestyles. The convergent NLR reduction in aquatic plants resembles the long-term evolutionary silence of NLR genes in green algae before the colonization of land. A co-evolutionary pattern between NLR subclasses and plant immune-pathway components was also identified, suggesting that immune pathway deficiencies may drive TNL loss. Finally, we recovered a conserved TNL lineage that may function independently of the RNL pathway. Our findings provide new insights into the evolution of NLR genes in the context of plant lifestyles and genome content variation.

plant biology↗

bioRxiv2020

Structure-Based Design, Synthesis and Biological Evaluation of Peptidomimetic Aldehydes as a Novel Series of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease

SARS-CoV-2 is the etiological agent responsible for the COVID-19 outbreak in Wuhan. Specific antiviral drug are urgently needed to treat COVID-19 infections. The main protease (Mpro) of SARS-CoV-2 is a key CoV enzyme that plays a pivotal role in mediating viral replication and transcription, which makes it an attractive drug target. In an effort to rapidly discover lead compounds targeting Mpro, two compounds (11a and 11b) were designed and synthesized, both of which exhibited excellent inhibitory activity with an IC50 value of 0.05 M and 0.04 M respectively. Significantly, both compounds exhibited potent anti-SARS-CoV-2 infection activity in a cell-based assay with an EC50 value of 0.42 M and 0.33 M, respectively. The X-ray crystal structures of SARS-CoV-2 Mpro in complex with 11a and 11b were determined at 1.5 [A] resolution, respectively. The crystal structures showed that 11a and 11b are covalent inhibitors, the aldehyde groups of which are bound covalently to Cys145 of Mpro. Both compounds showed good PK properties in vivo, and 11a also exhibited low toxicity which is promising drug leads with clinical potential that merits further studies.

biochemistry↗