Sputum Metabolomic Profiling Reveals Metabolic Pathways and Signatures Associated With Inflammatory Phenotypes in Patients With Asthma

Liu Ying,Zhang Xin,Zhang Li,Oliver Brian G,Wang Hong Guang,Liu Zhi Peng,Chen Zhi Hong,Wood Lisa,Hsu Alan Chen-Yu,Xie Min,McDonald Vanessa,Wan Hua Jing,Luo Feng Ming,Liu Dan,Li Wei Min,Wang Gang 대한천식알레르기학회 2022 Allergy, Asthma & Immunology Research Vol.14 No.4

Purpose: The molecular links between metabolism and inflammation that drive different inflammatory phenotypes in asthma are poorly understood. We aimed to identify the metabolic signatures and underlying molecular pathways of different inflammatory asthma phenotypes. Methods: In the discovery set (n = 119), untargeted ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to characterize the induced sputum metabolic profiles of asthmatic patients with different inflammatory phenotypes using orthogonal partial least-squares discriminant analysis (OPLS-DA), and pathway topology enrichment analysis. In the validation set (n = 114), differential metabolites were selected to perform targeted quantification. Correlations between targeted metabolites and clinical indices in asthmatic patients were analyzed. Logistic and negative binomial regression models were established to assess the association between metabolites and severe asthma exacerbations. Results: Seventy-seven differential metabolites were identified in the discovery set. Pathway topology analysis uncovered that histidine metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, linoleic acid metabolism as well as phenylalanine, tyrosine and tryptophan biosynthesis were involved in the pathogenesis of different asthma phenotypes. In the validation set, 24 targeted quantification metabolites were significantly expressed between asthma inflammatory phenotypes. Finally, adenosine 5′-monophosphate (adjusted relative risk [adj RR] = 1.000; 95% confidence interval [CI] = 1.000–1.000; P = 0.050), allantoin (adj RR = 1.000; 95% CI = 1.000–1.000; P = 0.043) and nicotinamide (adj RR = 1.001; 95% CI = 1.000–1.002; P = 0.021) were demonstrated to predict severe asthma exacerbation rates. Conclusions: Different inflammatory asthma phenotypes have specific metabolic profiles in induced sputum. The potential metabolic signatures may identify therapeutic targets in different inflammatory asthma phenotypes.

Fresh Washed Microbiota Transplantation Alters Gut Microbiota Metabolites to Ameliorate Sleeping Disorder Symptom of Autistic Children

Liu Nai-Hua,Liu Hong-Qian,Zheng Jia-Yi,Zhu Meng-Lu,Wu Li-Hao,Pan Hua-Feng,He Xing-Xiang 한국미생물학회 2023 The journal of microbiology Vol.61 No.8

Accumulating studies have raised concerns about gut dysbiosis associating autism spectrum disorder (ASD) and its related symptoms. However, the effect of gut microbiota modification on the Chinese ASD population and its underlying mechanism were still elusive. Herein, we enrolled 24 ASD children to perform the first course of fresh washed microbiota transplantation (WMT), 18 patients decided to participate the second course, 13 of which stayed to participate the third course, and there were 8 patients at the fourth course. Then we evaluated the effects of fresh WMT on these patients and their related symptoms. Our results found that the sleeping disorder symptom was positively interrelated to ASD, fresh WMT significantly alleviated ASD and its sleeping disorder and constipation symptoms. In addition, WMT stably and continuously downregulated Bacteroides/ Flavonifractor/Parasutterella while upregulated Prevotella_9 to decrease toxic metabolic production and improve detoxification by regulating glycolysis/myo-inositol/D-glucuronide/D-glucarate degradation, L-1,2-propanediol degradation, fatty acid β-oxidation. Thus, our results suggested that fresh WMT moderated gut microbiome to improve the behavioral and sleeping disorder symptoms of ASD via decrease toxic metabolic production and improve detoxification. Which thus provides a promising gut ecological strategy for ASD children and its related symptoms treatments.

Indole-3-propionic acid inhibits gut dysbiosis and endotoxin leakage to attenuate steatohepatitis in rats

Ze-Hua Zhao,Feng-Zhi Xin,Yaqian Xue,Zhimin Hu,Yamei Han,Fengguang Ma,Da Zhou,Xiao-Lin Liu,Aoyuan Cui,Zhengshuai Liu,Yuxiao Liu,Jing Gao,Qin Pan,Yu Li,Jian-Gao Fan 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Microbial metabolites have emerged as critical components that mediate the metabolic effects of the gut microbiota. Here, we show that indole-3-propionic acid (IPA), a tryptophan metabolite produced by gut bacteria, is a potent anti-non-alcoholic steatohepatitis (NASH) microbial metabolite. Here, we demonstrate that administration of IPA modulates the microbiota composition in the gut and inhibits microbial dysbiosis in rats fed a high-fat diet. IPA induces the expression of tight junction proteins, such as ZO-1 and Occludin, and maintains intestinal epithelium homeostasis, leading to a reduction in plasma endotoxin levels. Interestingly, IPA inhibits NF-κB signaling and reduces the levels of proinflammatory cytokines, such as TNFα, IL-1β, and IL-6, in response to endotoxin in macrophages to repress hepatic inflammation and liver injury. Moreover, IPA is sufficient to inhibit the expression of fibrogenic and collagen genes and attenuate diet-induced NASH phenotypes. The beneficial effects of IPA on the liver are likely mediated through inhibiting the production of endotoxin in the gut. These findings suggest a protective role of IPA in the control of metabolism and uncover the gut microbiome and liver cross-talk in regulating the intestinal microenvironment and liver pathology via a novel dietary nutrient metabolite. IPA may provide a new therapeutic strategy for treating NASH.

Molecular Cloning and Function Analysis of an Anthocyanidin Synthase Gene from Ginkgo biloba, and Its Expression in Abiotic Stress Responses

Feng Xu,Hua Cheng,Rong Cai,Lin Ling Li,Jie Chang,Jun Zhu,Feng Xia Zhang,Liu Ji Chen,Yan Wang,Shu Han Cheng,Shui Yuan Cheng 한국분자세포생물학회 2008 Molecules and cells Vol.26 No.6

Anthocyanidin synthase (ANS, leucoanthocyanidin oxygenase), a 2-oxoglutarate iron-dependent oxygenase, catalyzed the penultimate step in the biosynthesis of the anthocyanin class of flavonoids, from the colorless leucoanthocyanidins to the colored anthocyanidins. The full-length cDNA and genomic DNA sequences of ANS gene (designated as GbANS) were isolated from Ginkgo biloba for the first time. The full-length cDNA of GbANS contained a 1062-bp open reading frame (ORF) encoding a 354-amino-acid protein. The genomic DNA analysis showed that GbANS gene had three exons and two introns. The deduced GbANS protein showed high identities to other plant ANSs. The conserved amino acids (H-X-D) ligating ferrous iron and residues (R-X-S) participating in 2-oxoglutarate binding were found in GbANS at the similar positions like other ANSs. Southern blot analysis indicated that GbANS belonged to a multi-gene family. The expression analysis by real-time PCR showed that GbANS expressed in a tissue-specific manner in G. biloba. GbANS was also found to be up-regulated by all of the six tested abiotic stresses, UV-B, abscisic acid, sucrose, salicylic acid, cold and ethylene, consistent with the promoter region analysis of GbANS. The recombinant protein was successfully expressed in E. coli strain with pET-28a vector. The in vitro enzyme activity assay by HPLC indicated that recombinant GbANS protein could catalyze the formation the cyanidin from leucocyanidin and conversion of dihydroquercetin to quercetin, suggesting GbANS is a bifunctional enzyme within the anthocyanidin and flavonol biosynthetic pathway.

N-Carbamylglutamate in Combination with Vitamin C Show Synergistic Role to Anti-Heat Stress in Sows

Feng Tao,Bai Jia-hua,Xu Xiao-ling,Huang Zheng,Guo Yong,Liu Yan 한국동물생명공학회(구 한국동물번식학회) 2014 한국동물번식학회 한중일 심포지엄 Vol.2014 No.1

The PR10 gene family is highly expressed in Lilium regale Wilson during Fusarium oxysporum f. sp. lilii infection

Hua He,Diqiu Liu,Nannan Zhang,Wei Zheng,Qing Han,Bo Ji,Feng Ge,Chaoyin Chen 한국유전학회 2014 Genes & Genomics Vol.36 No.4

Pathogenesis-related (PR) proteins play keyroles in plant responses to pathogens and abiotic stresses. In this study, nine novel PR genes were isolated from Liliumregale Wilson, which is a wild lily species of Chinawith high-level resistance to the soilborne fungal pathogenFusarium oxysporum f. sp. lilii, and homology analysisclassified them into the PR10 family. These novel LrPR10swere clustered together with PR10s from monocotyledonsin a phylogenetic tree, moreover, phylogenetic analysisdivided the nine LrPR10s into two groups. The main-chainconformation and folding patterns of the LrPR10s werehighly conserved with other plant PR10s. The expressionpatterns of the nine LrPR10s in L. regale during normaldevelopment were examined by QRT-PCR, and the transcriptionlevels of the LrPR10s were relatively high inroots. Furthermore, QRT-PCR analysis indicated that theexpression levels of LrPR10-1, LrPR10-2, LrPR10-5,LrPR10-6, and LrPR10-7 in L. regale roots were up-regulatedby two or more stress-related signaling moleculesincluding salicylic acid, jasmonic acid, ethylene, and H2O2,while the other four LrPR10s were repressed by these foursignaling molecules. In addition, five members of theLrPR10 gene family including LrPR10-2, LrPR10-4,LrPR10-5, LrPR10-6, LrPR10-7, and LrPR10-9 werestrongly induced by F. oxysporum in resistant L. regalecompared with the susceptible Lilium Oriental hybrid‘Siberia’. The other four LrPR10s were down-regulated byF. oxysporum infection. In summary, our results indicatethat the members of PR10 gene family are involved inL. regale defense responses against F. oxysporum f. sp. lilii.

Laparoscopic left hepatectomy in swine: a safe and feasible technique

Hua Zhang,Tao Liu,Yue Wang,Hai-feng Liu,Jian-tao Zhang,Yan-shuang Wu,Lei Lei,Hong-bin Wang 대한수의학회 2014 JOURNAL OF VETERINARY SCIENCE Vol.15 No.3

A purely laparoscopic four-port approach was created forleft hepatectomy in pigs. A polyethylene loop was placed onthe left two hepatic lobes for traction and lift. Next,penetrating ligation of the lobes using of a double row of silksutures was performed to control bleeding. A direct hepatictransection was completed using a monopolar hook electrodewithout meticulous dissection of the left hepatic vein. Theraw surface of the liver was coagulated and sealed with fibringlue. Lobes were retrieved through an enlarged portal. Laparoscopic hepatic lobectomy was completed in all pigswithout the use of specialized instruments and with a meanoperative time of 179 ± 9 min. No significant perioperativecomplications were observed. The average weight of eachresected lobe was 180 ± 51 g. Complete blood count as well asserum organics and enzyme levels normalized after about 2weeks. During necropsy, adhesion of the hepatic raw surfaceto the gastric wall and omentum were observed. No otherabnormalities were identified. This minimally invasive lefthepatectomy technique in swine could serve as a usefulmodel for investigating liver diseases and regeneration, andoffer preclinical information to improve hepatobiliary surgical procedures.

MTHFR C677T Polymorphism and Pancreatic Cancer Risk: a Meta-analysis

Liu, Xiang-Ming,Liu, Feng-Hua,Tang, Yong,Li, Qiang Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, and the role of the MTHFR C677T polymorphism in pancreatic carcinogenesis is still controversial. Methods: A literature search was performed using Pubmed and CNKI databases for published studies through May 2012. We performed a meta-analysis of all relevant case-control studies that examined the association between MTHFR C677T polymorphism and pancreatic cancer risk. Results: Finally, 9 individual case-control studies with a total of 1,299 pancreatic cancer cases and 2,473 controls were included into this meta-analysis. Results: This metaanalysis showed there was an obvious association between MTHFR C677T polymorphism and pancreatic cancer risk in East Asians (for allele model, OR = 1.67, 95%CI 1.11-2.51; For homozygote model, OR = 2.77, 95%CI 1.40-5.48; for recessive model, OR = 1.96, 95%CI 1.54-2.50; for dominant model, OR = 2.11, 95%CI 1.01-4.41). However, no significant association was found in Caucasians. Conclusions: The MTHFR C677T polymorphism is associated with pancreatic cancer risk, and a race-specific effect may exist in this association. More studies with a larger sample size are needed to further clarify this association.

Selective miRNA Expression Profile in Chronic Myeloid Leukemia K562 Cell-derived Exosomes

Feng, Dan-Qin,Huang, Bo,Li, Jing,Liu, Jing,Chen, Xi-Min,Xu, Yan-Mei,Chen, Xin,Zhang, Hai-Bin,Hu, Long-Hua,Wang, Xiao-Zhong Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of hematopoietic stem cell scarrying the Philadelphia (Ph) chromosome and an oncogenic BCR-ABL1 fusion gene. The tyrosine kinase inhibitor (TKI) of BCR-ABL1 kinase is a treatment of choice for control of CML. Objective: Recent studies have demonstrated that miRNAs within exosomes from cancer cells play crucial roles in initiation and progression. This study was performed to assess miRNAs within exosomes of K562 cells. Methods: miRNA microarray analysis of K562 cells and K562 cell-derived exosomes was conducted with the 6th generation miRCURYTM LNA Array (v.16.0). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also carried out. GO terms and signaling pathways were categorized into 66 classes (including homophilic cell adhesion, negative regulation of apoptotic process, cell adhesion) and 26 signaling pathways (such as Wnt). Results: In exosomes, 49 miRNAs were up regulated as compared to K562 cells, and two of them were further confirmed by quantitative real-time PCR. There are differentially expressed miRNAs between K562 cell derived-exosomes and K562 cells. Conclusion: Selectively expressed miRNAs in exosomes may promote the development of CML via effects on interactions (e.g. adhesion) of CML cells with their microenvironment.

Enhanced x-ray irradiation-induced cancer cell damage by gold nanoparticles treated by a new synthesis method of polyethylene glycol modification

Liu, Chi-Jen,Wang, Chang-Hai,Chien, Chia-Chi,Yang, Tsung-Yeh,Chen, Shin-Tai,Leng, Wei-Hua,Lee, Cheng-Feng,Lee, Kuen-Ho,Hwu, Y,Lee, Yao-Chang,Cheng, Chia-Liang,Yang, Chung-Shi,Chen, Y J,Je, J H,Margari IOP Pub 2008 Nanotechnology Vol.19 No.29

<P>We explored a very interesting gold nanoparticle system—pegylated gold in colloidal solution—and analyzed its uptake by mice colorectal adenocarcinoma CT26 tumor cells and the impact on the cell’s response to x-ray irradiation. We found that exposure to polyethylene glycol (PEG) modified (‘pegylated’) 4.7 ± 2.6 nm gold nanoparticles synthesized by a novel synchrotron-based method enhances the response of CT26 cells to x-ray irradiation. Transmission electron microscopy (TEM) and confocal microscopy revealed that substantial amounts of such nanoparticles are taken up and absorbed by the cells and this conclusion is supported by quantitative induced coupled plasma (ICP) results. Standard tests indicated that the internalized particles are highly biocompatible but strongly enhance the cell damage induced by x-ray irradiation. Synchrotron radiation Fourier transform infrared (SR-FTIR) spectromicroscopy analyzed the chemical aspects of this phenomenon: the appearance of C = O stretching bond spectral features could be used as a marker for cell damage and confirmed the enhancement of the radiation-induced toxicity for cells.</P>