Mitochondrial citrate accumulation drives alveolar epithelial cell necroptosis in lipopolysaccharide-induced acute lung injury

Yang Hui-Hui,Jiang Hui-Ling,Tao Jia-Hao,Zhang Chen-Yu,Xiong Jian-Bing,Yang Jin-Tong,Liu Yu-Biao,Zhong Wen-Jing,Guan Xin-Xin,Duan Jia-Xi,Zhang Yan-Feng,Liu Shao-Kun,Jiang Jian-Xin,Zhou Yong,Guan Cha-Xi 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Necroptosis is the major cause of death in alveolar epithelial cells (AECs) during acute lung injury (ALI). Here, we report a previously unrecognized mechanism for necroptosis. We found an accumulation of mitochondrial citrate (citratemt) in lipopolysaccharide (LPS)-treated AECs because of the downregulation of Idh3α and citrate carrier (CIC, also known as Slc25a1). shRNA- or inhibitor–mediated inhibition of Idh3α and Slc25a1 induced citratemt accumulation and necroptosis in vitro. Mice with AEC-specific Idh3α and Slc25a1 deficiency exhibited exacerbated lung injury and AEC necroptosis. Interestingly, the overexpression of Idh3α and Slc25a1 decreased citratemt levels and rescued AECs from necroptosis. Mechanistically, citratemt accumulation induced mitochondrial fission and excessive mitophagy in AECs. Furthermore, citratemt directly interacted with FUN14 domain-containing protein 1 (FUNDC1) and promoted the interaction of FUNDC1 with dynamin-related protein 1 (DRP1), leading to excessive mitophagy-mediated necroptosis and thereby initiating and promoting ALI. Importantly, necroptosis induced by citratemt accumulation was inhibited in FUNDC1-knockout AECs. We show that citratemt accumulation is a novel target for protection against ALI involving necroptosis.

Biological characterization of mesenchymal stem cells from bovine umbilical cord

Hui Xiong,Wei Jun Guan,Yue Hui Ma,Chunyu Bai,Shuang Wu,Yuhua Gao,Taofeng Lu,Qingyun Hu 한국통합생물학회 2014 Animal cells and systems Vol.18 No.1

Mesenchymal stem cells (MSCs) are multi-potential cells that are able to proliferate and differentiate into othercell types. Much research has been done on the MSCs from the umbilical cord (UCMSCs) in human, mice, andavian, but little literature has been published about these cells in big livestock. Here, we choose Luxi cattle asthe experimental animal, we describe an external culture of the UCMSCs from it and summarize the biologicalcharacteristics of these cells, e.g., morphologic appearance, surface antigens, colony-forming ability, geneexpression, and differentiation potential were detected via using immunofluorescence and reverse transcriptionpolymerase chain reaction (RT-PCR). The induced cells, osteoblast, lipoblast, hepatocyte, islet cells, andneurocyte were identified by Alizarin red staining, Oil-red-O staining, Periodic acid-schiff staining, andDithizone staining and RT-PCR detection for specific genes. Results suggest that biological characteristics ofthe UCMSCs were similar to those of MSCs previously analyzed. The primary UCMSCs were sub-cultured topassage 32, the UCMSCs expressed gene CD29, CD44, CD73, CD90, and CD166, induced cells illustratedtypical staining, and expressed specific genes, which indicate that the UCMSCs could be a novel alternativesource of MSCs for experimental and clinical applications.

Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells

Xiong, Wei,Jiang, Yong-Xin,Ai, Yi-Qin,Liu, Shan,Wu, Xing-Rao,Cui, Jian-Guo,Qin, Ji-Yong,Liu, Yan,Xia, Yao-Xiong,Ju, Yun-He,He, Wen-Jie,Wang, Yong,Li, Yun-Fen,Hou, Yu,Wang, Li,Li, Wen-Hui Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.8

Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.

Embryoid bodies formation from chicken primordial germ cells

Hui Xiong,Yabin Pu,Qingyun Hu,Zhiqiang Shan,Pengfei Hu,Weijun Guan,Yuehui Ma 한국통합생물학회 2015 Animal cells and systems Vol.19 No.3

Primordial germ cells (PGCs) were demonstrated to be multipotential because of their differentiation ability in all embryonic lineages and because the pluripotential nature of PGCs caters for recent researches on stem cells. PGCs were cultured in suspension to form embryoid bodies (EBs). The characterization of PGCs and EBs was assessed by immunofluorescence technique, reverse transcription-polymerase chain reaction (RT-PCR) and paraffin section for Haematoxylin and Eosin (HE) stain. We established a stable chicken PGC line in vitro and prepared masses of EBs from PGCs. We also demonstrated that PGCs expressed stage-specific and stem cell-specific surface makers: SSEA-1, SSEA-3, Oct4, and Sox2. EBs expressed specific genes from three germ layers: gene AFP from entoderm, gene GATA6 from mesoderm, and gene Sox3 from ectoderm. The HE staining illustrated that EBs developed different cell types; relatively larger EBs (440 μm in diameter) were obtained, which contract rhythmically. We concluded that chicken PGCs were suitable for the formation of EBs. Abundant larger size EBs could be prepared in an effective way with our protocol, which could construct a good animal model and provide a useful clinical platform in studying human embryonic development and cell transplantation field.

淺說唐宋記體古文書寫策略的轉變

웅례휘 ( Li Hui Xiong ) 한국중국산문학회 2014 중국산문연구집간 Vol.4 No.-

Miscellaneous essay is full of literariness, which belongs to a stylistic category of Tang and Song dynasty. In order to enhance its function, strengthen its literariness and enrich its artistic beauty, various attempts in the aspect of "what to write, how to write" have been made, especially the change in writing strategy. For example in this paper, writing strategy of the essay of Han Yu and Liu Zong-yuan has two ways. One is recording and describing. The other is narrating and discussing. But Ou Yang-xiu and Su Shi’s writing strategy is enunciating their theory and expressing their emotion. Through continuous exploration of writing strategy, the change of miscellaneous essay of Tang and Song dynasty makes it more interesting and charming. So we shouldn’t judge their work according to whether it is right or wrong, good or bad.

Parecoxib: an Enhancer of Radiation Therapy for Colorectal Cancer

Xiong, Wei,Li, Wen-Hui,Jiang, Yong-Xin,Liu, Shan,Ai, Yi-Qin,Liu, Rong,Chang, Li,Zhang, Ming,Wang, Xiao-Li,Bai, Han,Wang, Hong,Zheng, Rui,Tan, Jing Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.2

Background: To study the effect of parecoxib, a novel cyclooxygenase-2 selective inhibitor, on the radiation response of colorectal cancer (CRC) cells and its underlying mechanisms. Materials and Methods: Both in vitro colony formation and apoptosis assays as well as in vivo mouse xenograft experiments were used to explore the radiosensitizing effects of parecoxib in human HCT116 and HT29 CRC cells. Results: Parecoxib sensitized CRC cells to radiation in vitro with a sensitivity enhancement ratio of 1.32 for HCT116 cells and 1.15 for HT29 cells at a surviving fraction of 0.37. This effect was partially attributable to enhanced apoptosis induction by parecoxib combined with radiation, as illustrated using an in vitro apoptosis assays. Parecoxib augmented the tumor response of HCT116 xenografts to radiation, achieving growth delay more than 20 days and an enhancement factor of 1.53. In accordance with the in vitro results, parecoxib combined with radiation resulted in less proliferation and more apoptosis in tumors than radiation alone. Radiation monotherapy decreased microvessel density (MVD) and microvessel intensity (MVI), but increased the hypoxia level in xenografts. Parecoxib did not affect MVD, but it increased MVI and attenuated hypoxia. Conclusions: Parecoxib can effectively enhance radiation sensitivity in CRC cells through direct effects on tumor cells and indirect effects on tumor vasculature.

Isolation, Characterization, and Molecular Cloning of the cDNA Encoding a Novel Phytase from Aspergillus niger 113 and High Expression in Pichia pastoris

Xiong, Ai Sheng,Yao, Quan-Hong,Peng, Ri-He,Li, Xian,Fan, Hui-Qin,Guo, Mei-Jin,Zhang, Si-Liang Korean Society for Biochemistry and Molecular Biol 2004 Journal of biochemistry and molecular biology Vol.37 No.3

Phytases catalyze the release of phosphate from phytic acid. Phytase-producing microorganisms were selected by culturing the soil extracts on agar plates containing phytic acid. Two hundred colonies that exhibited potential phytase activity were selected for further study. The colony showing the highest phytase activity was identified as Aspergillus niger and designated strain 113. The phytase gene from A. niger 113 (phyI1) was isolated, cloned, and characterized. The nucleotide and deduced amino acid sequence identity between phyI1 and phyA from NRRL3135 were 90% and 98%, respectively. The identity between phyI1 and phyA from SK-57 was 89% and 96%. A synthetic phytase gene, phyI1s, was synthesized by successive PCR and transformed into the yeast expression vector carrying a signal peptide that was designed and synthesized using P. pastoris biased codon. For the phytase expression and secretion, the construct was integrated into the genome of P. pastoris by homologous recombination. Over-expressing strains were selected and fermented. It was discovered that ~4.2 g phytase could be purified from one liter of culture fluid. The activity of the resulting phytase was 9.5 U/mg. Due to the heavy glycosylation, the expressed phytase varied in size (120, 95, 85, and 64 kDa), but could be deglycosylated to a homogeneous 64 kDa species. An enzymatic kinetics analysis showed that the phytase had two pH optima (pH 2.0 and pH 5.0) and an optimum temperature of $60^{\circ}C$.

Comparison of Leukotriene Receptor Antagonist and Theophylline in Addition to Inhaled Corticosteroid in Adult Asthma: A Meta-Analysis

( Hui Juan Fang ),( Jian Miao Wang ),( Di Jin ),( Yong Cao ),( Yong Jian Xu ),( Wei Ning Xiong ) 한국응용약물학회 2011 Biomolecules & Therapeutics(구 응용약물학회지) Vol.19 No.3

This meta-analysis was performed to evaluate the difference of the therapeutic efficacy and adverse effects of leukotriene receptor antagonist and theophylline added to inhaled corticosteroids in adult asthma. Databases were searched for studies published through Nov, 2010. Randomized-controlled trials containing inhaled corticosteroids plus leukotriene receptor antagonist and inhaled corticosteroids plus sustained-release theophylline for asthma therapy were selected. For each report, data were extracted to the outcomes analyzed: mean change in morning peak expiratory flow, mean change in evening peak expiratory flow, mean change in morning forced expiratory volume in 1 sec, mean change in daily short bete2-agonist use, asthma exacerbation and adverse effects. Four assessable trials including 182 asthmatic patients were identified. Inhaled corticosteroids plus leukotriene receptor antagonist was superior to inhaled corticosteroids plus theophylline therapy in improving morning peak expiratory flow in asthmatics (mean difference 19.08 [95% confidence interval 13.37-23.79] l/min, p<0.001) and morning forced expiratory volume in 1 sec in asthmatics (mean difference 0.09 [95% confidence interval 0.03-0.14] liter, p=0.001). In evening peak expiratory flow, daily short bete2-agonist use, asthma exacerbation and adverse effects, there was no significant difference between these two therapies (All p>0.05). Our meta-analysis showed that the combination of inhaled corticosteroids plus leukotriene receptor antagonist resulted in more improvement in both peak expiratory flow and forced expiratory volume in 1 sec in the morning than inhaled corticosteroids plus sustained-release theophylline in adult asthmatics. Further trials are necessary to evaluate the dominant effects of the former combination.

Canonical Transient Receptor Potential Channels and Their Link with Cardio/Cerebro-Vascular Diseases

( Xiong Xiao ),( Hui-xia Liu ),( Kuo Shen ),( Wei Cao ),( Xiao-qiang Li ) 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.5

The canonical transient receptor potential channels (TRPCs) constitute a series of nonselective cation channels with variable degrees of Ca²⁺selectivity. TRPCs consist of seven mammalian members, TRPC1, TRPC2, TRPC3, TRPC4, TRPC5, TRPC6, and TRPC7, which are further divided into four subtypes, TRPC1, TRPC2, TRPC4/5, and TRPC3/6/7. These channels take charge of various essential cell functions such as contraction, relaxation, proliferation, and dysfunction. This review, organized into seven main sections, will provide an overview of current knowledge about the underlying pathogenesis of TRPCs in cardio/cerebrovascular diseases, including hypertension, pulmonary arterial hypertension, cardiac hypertrophy, atherosclerosis, arrhythmia, and cerebrovascular ischemia reperfusion injury. Collectively, TRPCs could become a group of drug targets with important physiological functions for the therapy of human cardio/cerebro-vascular diseases.

Single-cell RNA sequencing reveals B cell–related molecular biomarkers for Alzheimer’s disease

Xiong Liu-Lin,Xue Lu-Lu,Du Ruo-Lan,Niu Rui-Ze,Chen Li,Chen Jie,Hu Qiao,Tan Ya-Xin,Shang Hui-Fang,Liu Jia,Yu Chang-Yin,Wang Ting-Hua 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

In recent years, biomarkers have been integrated into the diagnostic process and have become increasingly indispensable for obtaining knowledge of the neurodegenerative processes in Alzheimer’s disease (AD). Peripheral blood mononuclear cells (PBMCs) in human blood have been reported to participate in a variety of neurodegenerative activities. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 in the early stage, 2 in the late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease in B cells was detected in the blood of AD patients. Furthermore, we further examined PBMCs from 43 AD patients and 41 normal subjects by fluorescence activated cell sorting (FACS), and combined with correlation analysis, we found that the reduction in B cells was closely correlated with the patients’ Clinical Dementia Rating (CDR) scores. To confirm the role of B cells in AD progression, functional experiments were performed in early-stage AD mice in which fibrous plaques were beginning to appear; the results demonstrated that B cell depletion in the early stage of AD markedly accelerated and aggravated cognitive dysfunction and augmented the Aβ burden in AD mice. Importantly, the experiments revealed 18 genes that were specifically upregulated and 7 genes that were specifically downregulated in B cells as the disease progressed, and several of these genes exhibited close correlation with AD. These findings identified possible B cell-based AD severity, which are anticipated to be conducive to the clinical identification of AD progression.