Publications by authors named "Yonghong Xiong"

6 Publications

  • Page 1 of 1

MMP-12 siRNA improves the homeostasis of the small intestine and metabolic dysfunction in high-fat diet feeding-induced obese mice.

Biomaterials 2021 11 11;278:121183. Epub 2021 Oct 11.

State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, PR China. Electronic address:

The changes of small intestinal homeostasis have been recognized to contribute essentially to the obese development. However, the core small intestinal regulator which mediates over-nutrient impacts on the homeostasis of the small intestines remains elusive. Here, we identify the MMP-12 as such a responsive factor in mouse small intestines. Taking advantages of the nano delivery system, we demonstrate that small intestine-specific MMP-12 knockdown alleviates high-fat diet feeding-induced metabolic disorders and improves intestinal homeostasis in mice, including a significant decrease in lipid transportation, bile acid reabsorption, and inflammation. In parallel, the small intestinal integrity is recovered and the gut microbiota composition is reversed towards that under normal diet feeding. Mechanistically, MMP-12, differing from its traditional elastolytic function, acts as a transcriptional factor to activate Fabp4 transcription through epigenetic modification. In translational medicine, clinical applications of our nanosystem and therapeutic interventions targeting MMP-12 will benefit patients with obesity and associated diseases.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121183DOI Listing
November 2021

Host Gasdermin D restrains systemic endotoxemia by capturing Proteobacteria in the colon of high-fat diet-feeding mice.

Gut Microbes 2021 Jan-Dec;13(1):1946369

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.

Gasdermin D (GSDMD) functions as a key pyroptotic executor through its secreted N-terminal domain (GSDMD-N). However, the functional relevance and mechanistic basis of the precise roles of host colonic GSDMD in high-fat diet (HFD)-induced gut dysbiosis and systemic endotoxemia remain elusive. In this study, we demonstrate that HFD feeding triggers GSDMD-N secretion of both T-lymphocytes and enterocytes in mouse colons. GSDMD deficiency aggravates HFD-induced systemic endotoxemia, gut barrier impairment, and colonic inflammation. More importantly, active GSDMD-N kills the phylum via directly interacting with Cardiolipin. Mechanistically, we identify that the Glu236 (a known residue for GSDMD protein cleavage) is a important site for the bacterial recognition of GSDMD. Collectively, our findings explain the mechanism by which colonic GSDMD-N maintains low levels of HFD-induced metabolic endotoxemia. A GSDMD-N mimetic containing an exposed Glu236 site could be an attractive strategy for the treatment of HFD-induced metabolic endotoxemia.
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http://dx.doi.org/10.1080/19490976.2021.1946369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288038PMC
July 2021

Mechanism of N-acetylcysteine in alleviating diabetic myocardial ischemia reperfusion injury by regulating PTEN/Akt pathway through promoting DJ-1.

Biosci Rep 2020 06;40(6)

Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.

Ischemic heart disease is the main cardiovascular complication of diabetes patients which is mainly caused by oxidative stress. DJ-1 is the key regulator for myocardial protection through inhibiting phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and activating Akt (also known as PKB or protein kinase B). This research is to investigate whether the antioxidant N-acetylcysteine (NAC) could alleviate diabetic myocardial ischemia/reperfusion (I/R) injury by the protective molecule DJ-1. DJ-1 in rat myocardial H9c2 cells and cardiac tissue was respectively knocked down by siRNA and adeno-associated virus (AAV). From the present study, it could be found that compared with high glucose (HG)-normal (N)/DM group, hypoxia/reoxygenation (H/R) or I/R injury can aggravate oxidative stress injury and apoptosis rate of myocardial cells, inhibit the expression of Bcl-2, activate the BAX and cleaved caspase-3 (c-caspase-3) protein and PTEN/Akt pathway. However, in the groups of HG-N, DM, HG-N+I/R and DM+I/R, NAC can significantly reduce oxidative stress injury and apoptosis rate of myocytes, promote the Bcl-2 and DJ-1 molecules, inhibit BAX and c-caspase-3 protein and PTEN/Akt pathway. Compared with HG-N+I/R+NAC and DM+I/R+NAC groups, the oxidative stress injury, apoptosis rate of myocardial cells and heart tissues increased after the knockdown of DJ-1, the expression of Bcl-2 and DJ-1 were inhibited, the BAX and c-caspase-3 expression was increased, and PTEN/Akt pathway was activated. Taken together, the findings suggest that NAC can reduce I/R injury in diabetic myocardium by up-regulating the PTEN/Akt pathway through the level of DJ-1.
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http://dx.doi.org/10.1042/BSR20192118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273917PMC
June 2020

Trace Elements, PPARs, and Metabolic Syndrome.

Int J Mol Sci 2020 Apr 9;21(7). Epub 2020 Apr 9.

State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China.

Metabolic syndrome (MetS) is a constellation of metabolic derangements, including central obesity, insulin resistance, hypertension, glucose intolerance, and dyslipidemia. The pathogenesis of MetS has been intensively studied, and now many factors are recognized to contribute to the development of MetS. Among these, trace elements influence the structure of proteins, enzymes, and complex carbohydrates, and thus an imbalance in trace elements is an independent risk factor for MetS. The molecular link between trace elements and metabolic homeostasis has been established, and peroxisome proliferator-activated receptors (PPARs) have appeared as key regulators bridging these two elements. This is because on one hand, PPARs are actively involved in various metabolic processes, such as abdominal adiposity and insulin sensitivity, and on the other hand, PPARs sensitively respond to changes in trace elements. For example, an iron overload attenuates hepatic mRNA expression of ; zinc supplementation is considered to recover the DNA-binding activity of PPAR-α, which is impaired in steatotic mouse liver; selenium administration downregulates mRNA expression of , thereby improving lipid metabolism and oxidative status in the liver of high-fat diet (HFD)-fed mice. More importantly, PPARs' expression and activity are under the control of the circadian clock and show a robust 24 h rhythmicity, which might be the reasons for the side effects and the clinical limitations of trace elements targeting PPARs. Taken together, understanding the casual relationships among trace elements, PPARs' actions, and the pathogenesis of MetS is of great importance. Further studies are required to explore the chronopharmacological effects of trace elements on the diurnal oscillation of PPARs and the consequent development of MetS.
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http://dx.doi.org/10.3390/ijms21072612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177711PMC
April 2020

Ferroptosis Is Involved in Diabetes Myocardial Ischemia/Reperfusion Injury Through Endoplasmic Reticulum Stress.

DNA Cell Biol 2020 Feb 6;39(2):210-225. Epub 2019 Dec 6.

Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, P.R. China.

Myocardial ischemic disease affects the prognosis in perioperative patients. Diabetes can aggravate myocardial injury. The purpose of this research is to investigate the effect of ferroptosis in the process of diabetes mellitus (DM) myocardial ischemia/reperfusion (I/R) injury (IRI). Endoplasmic reticulum stress (ERS) is investigated whether aggravates cardiomyocytes injury. Rat DM+I/R (DIR), cell high glucose (HG), hypoxia reoxygenation (H/R), and high-glucose H/R (HH/R) models were established. Ferroptosis inhibitor Ferrostatin-1, ferroptosis agonist Erastin, ERS inhibitor Salubrinal, and ERS agonist Tunicamycin were administered. Serum creatine kinase-MB (CK-MB), cell viability, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), and cellular ferrous ion concentration were examined. The level of ACSL4, GPX4, ATF4, CHOP, BCL-2, and BAX was detected. Myocardial tissue pathological change was detected by hematoxylin-eosin staining. Cardiac function was monitored by invasive hemodynamic measurements. Evans Blue-triphenyltetrazolium chloride double staining was used to detect the myocardial infarct size. In DM+sham (DS) (or HG) and I/R (or H/R) models, cardiomyocytes were injured accompanied by increased level of ferroptosis and ERS. Moreover, the cell injury was more serious in rat DIR or cell HH/R models. Inhibition of ferroptosis in DIR model could reduce ERS and myocardial injury. Inhibition of ferroptosis in H9c2 cells HG, H/R, and HH/R models could reduce cell injury. Erastin could aggravate ERS and cell injury by stimulating ferroptosis in HH/R cell model. Meanwhile, inhibition of ERS could alleviate ferroptosis and cell injury. Ferroptosis is involved in DIR injury that is related to ERS. Moreover, inhibition of ferroptosis can alleviate DIR injury, which may provide a therapeutic regent for myocardial ischemic disease.
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http://dx.doi.org/10.1089/dna.2019.5097DOI Listing
February 2020

Complete mitochondrial genome of (Passeriformes: Corvidae).

Mitochondrial DNA B Resour 2018 Jun 18;3(2):691-692. Epub 2018 Jun 18.

The institute of Bioinformatics, College of Life Sciences, Anhui Normal University, Wuhu, China.

The complete mitochondrial genome of is 16930 bp in length. It was predicted to contain 13 PCGs, 22 genes, and 2 genes, and a putative control region. All of the PCGs initiated with ATG, except for which began with GTG and began with ATA, while stopped by three types of stop codons. Phylogenetic analysis showed that and the other species of Corvidae were monophyletic group in this study. And the monophyly of the genus was strongly supported. Moreover, our results also support a sister-group relationship between Corvidae and Muscicapidae.
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http://dx.doi.org/10.1080/23802359.2018.1481782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7800095PMC
June 2018
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