Publications by authors named "Xiaokang Wu"

29 Publications

  • Page 1 of 1

Circ_PIP5K1A regulates cisplatin resistance and malignant progression in non-small cell lung cancer cells and xenograft murine model via depending on miR-493-5p/ROCK1 axis.

Respir Res 2021 Sep 18;22(1):248. Epub 2021 Sep 18.

The Public Health, Xi'an Jiaotong University Health Science Center, No.76 Yanta West Road, Xi'an, 710061, Shaanxi Province, China.

Background: Chemoresistance limits the therapeutic effect of cisplatin (DDP) on non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) function as important regulators in chemoresistance. This study aimed to explore the regulation of circRNA Phosphatidylinositol-4-Phosphate 5-Kinase Type 1 Alpha (circ_PIP5K1A) in DDP resistance.

Methods: The expression analysis of circ_PIP5K1A, micoRNA-493-5p (miR-493-5p) and Rho Associated Coiled-Coil Containing Protein Kinase 1 (ROCK1) was conducted through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell sensitivity was determined using 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell proliferation and cell viability were evaluated by colony formation assay and MTT assay, respectively. Cell cycle and apoptosis detection was performed via flow cytometry. Cell motility was examined by transwell migration or invasion assay. Dual-luciferase reporter assay was applied to confirm the target binding. ROCK1 protein level was assayed via Western blot. In vivo assay was carried out using xenograft model in mice.

Results: Circ_PIP5K1A level was abnormally increased in DDP-resistant NSCLC tissues and cells. Silencing circ_PIP5K1A reduced DDP resistance, proliferation, cell cycle progression and cell motility in DDP-resistant NSCLC cells. Circ_PIP5K1A directly interacted with miR-493-5p in NSCLC cells. The function of circ_PIP5K1A was dependent on the negative regulation of miR-493-5p. MiR-493-5p directly targeted ROCK1 and circ_PIP5K1A regulated the ROCK1 level via acting as a sponge of miR-493-5p. Overexpression of miR-493-5p inhibited chemoresistance and cancer progression by downregulating ROCK1 expression in DDP-resistant NSCLC cells. Circ_PIP5K1A regulated DDP sensitivity in vivo via the miR-493-5p/ROCK1 axis.

Conclusion: These findings suggested that circ_PIP5K1A upregulated the ROCK1 expression to promote DDP resistance and cancer progression in NSCLC by sponging miR-493-5p.
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http://dx.doi.org/10.1186/s12931-021-01840-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8449484PMC
September 2021

The Novel Interplay between Commensal Gut Bacteria and Metabolites in Diet-Induced Hyperlipidemic Rats Treated with Simvastatin.

J Proteome Res 2021 Aug 9. Epub 2021 Aug 9.

Department of Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.

Hyperlipidemia is one kind of metabolic syndrome for which the treatment commonly includes simvastatin (SV). Individuals vary widely in statin responses, and growing evidence implicates gut microbiome involvement in this variability. However, the associated molecular mechanisms between metabolic improvement and microbiota composition following SV treatment are still not fully understood. In this study, combinatory approaches using ultrahigh-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF MS/MS)-based metabolomic profiling, PCR-denaturing gradient gel electrophoresis (PCR-DGGE), quantitative PCR (qPCR), and 16S rRNA gene sequencing-based gut microbiota profiling were performed to investigate the interplay of endogenous metabolites and the gut microbiota related to SV treatment. A total of 6 key differential endogenous metabolites were identified that affect the metabolism of amino acids (phenylalanine and tyrosine), unsaturated fatty acids (linoleic acid and 9-hydroxyoctadecadienoic acid (9-HODE)), and the functions of gut microbial metabolism. Moreover, a total of 22 differentially abundant taxa were obtained following SV treatment. Three bacterial taxa were identified to be involved in SV treatment, namely, , , and . These findings suggested that the phenylalanine and tyrosine-associated amino acid metabolism pathways, as well as the linoleic acid and 9-HODE-associated unsaturated fatty acid metabolism pathways, which are involved in gut flora interactions, might be potential therapeutic targets for improvement in SV hypolipidemic efficacy. The mass spectrometric data have been deposited to MassIVE (https://massive.ucsd.edu/ProteoSAFe/static/massive.jsp). Username: MSV000087842_reviewer. Password: hardworkingzsr.
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http://dx.doi.org/10.1021/acs.jproteome.1c00252DOI Listing
August 2021

Bioprinting of dual ECM scaffolds encapsulating limbal stem/progenitor cells in active and quiescent statuses.

Biofabrication 2021 08 13;13(4). Epub 2021 Aug 13.

Department of NanoEngineering, University of California San Diego, La Jolla, CA 92093, United States of America.

Limbal stem cell deficiency and corneal disorders are among the top global threats for human vision. Emerging therapies that integrate stem cell transplantation with engineered hydrogel scaffolds for biological and mechanical support are becoming a rising trend in the field. However, methods for high-throughput fabrication of hydrogel scaffolds, as well as knowledge of the interaction between limbal stem/progenitor cells (LSCs) and the surrounding extracellular matrix (ECM) are still much needed. Here, we employed digital light processing (DLP)-based bioprinting to fabricate hydrogel scaffolds encapsulating primary LSCs and studied the ECM-dependent LSC phenotypes. The DLP-based bioprinting with gelatin methacrylate (GelMA) or hyaluronic acid glycidyl methacrylate (HAGM) generated microscale hydrogel scaffolds that could support the viability of the encapsulated primary rabbit LSCs (rbLSCs) in culture. Immunocytochemistry and transcriptional analysis showed that the encapsulated rbLSCs remained active in GelMA-based scaffolds while exhibited quiescence in the HAGM-based scaffolds. The primary human LSCs encapsulated within bioprinted scaffolds showed consistent ECM-dependent active/quiescent statuses. Based on these results, we have developed a novel bioprinted dual ECM 'Yin-Yang' model encapsulating LSCs to support both active and quiescent statues. Our findings provide valuable insights towards stem cell therapies and regenerative medicine for corneal reconstruction.
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http://dx.doi.org/10.1088/1758-5090/ac1992DOI Listing
August 2021

Exosomally derived Y RNA fragment alleviates hypertrophic cardiomyopathy in transgenic mice.

Mol Ther Nucleic Acids 2021 Jun 20;24:951-960. Epub 2021 Apr 20.

Smidt Heart Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.

Cardiosphere-derived cell exosomes (CDC) and YF1, a CDC-derived non-coding RNA, elicit therapeutic bioactivity in models of myocardial infarction and hypertensive hypertrophy. Here we tested the hypothesis that YF1, a 56-nucleotide Y RNA fragment, could alleviate cardiomyocyte hypertrophy, inflammation, and fibrosis associated with hypertrophic cardiomyopathy (HCM) in transgenic mice harboring a clinically relevant mutation in cardiac troponin I (cTnI). By quantitative PCR, YF1 was detectable in bone marrow, spleen, liver, and heart 30 min after intravenous (i.v.) infusion. For efficacy studies, mice were randomly allocated to receive i.v. YF1 or vehicle, monitored for ambulatory and cardiac function, and sacrificed at 4 weeks. YF1 (but not vehicle) improved ambulation and reduced cardiac hypertrophy and fibrosis. In parallel, peripheral mobilization of neutrophils and proinflammatory monocytes was decreased, and fewer macrophages infiltrated the heart. RNA-sequencing of macrophages revealed that YF1 confers substantive and broad changes in gene expression, modulating pathways associated with immunological disease and inflammatory responses. Together, these data demonstrate that YF1 can reverse hypertrophic and fibrotic signaling pathways associated with HCM, while improving function, raising the prospect that YF1 may be a viable novel therapeutic candidate for HCM.
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http://dx.doi.org/10.1016/j.omtn.2021.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141670PMC
June 2021

Black carbon concentration in the central Himalayas: Impact on glacier melt and potential source contribution.

Environ Pollut 2021 Apr 23;275:116544. Epub 2021 Jan 23.

International Centre for Integrated Mountain Development (ICIMOD), GPO Box 3226, Kathmandu, Nepal. Electronic address:

This study discusses year-long (October 2016-September 2017) observations of atmospheric black carbon (BC) mass concentration, its source and sector contributions using a chemical transport model at a high-altitude (28°12'49.21″N, 85°36'33.77″E, 4900 masl) site located near the Yala Glacier in the central Himalayas, Nepal. During a field campaign, fresh snow samples were collected from the surface of the Yala Glacier in May 2017, which were analysed for BC and water-insoluble organic carbon mass concentration in order to estimate the scavenging ratio and surface albedo reduction. The maximum BC mass concentration in the ambient atmosphere (0.73 μg m) was recorded in the pre-monsoon season. The BC and water-insoluble organic carbon analysed from the snow samples were in the range of 96-542 ng g and 152-827 ng g, respectively. The source apportionment study using the absorption Ångström exponent from in situ observations indicated approximately 44% contribution of BC from biomass-burning sources and the remainder from fossil-fuel sources during the entire study period. The source contribution study, using model data sets, indicated ∼14% contribution of BC from open-burning and ∼77% from anthropogenic sources during the study period. Our analysis of regional contributions of BC indicated that the highest contribution was from both Nepal and India combined, followed by China, while the rest was distributed among the nearby countries. The surface snow albedo reduction, estimated by an online model - Snow, Ice, and Aerosol Radiation - was in the range of 0.8-3.8% during the pre-monsoon season. The glacier mass balance analysis suggested that BC contributed to approximately 39% of the total mass loss in the pre-monsoon season.
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http://dx.doi.org/10.1016/j.envpol.2021.116544DOI Listing
April 2021

Rapid bioprinting of conjunctival stem cell micro-constructs for subconjunctival ocular injection.

Biomaterials 2021 01 23;267:120462. Epub 2020 Oct 23.

Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA; Materials Science and Engineering Program, University of California San Diego, La Jolla, CA, 92093, USA; Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA. Electronic address:

Ocular surface diseases including conjunctival disorders are multifactorial progressive conditions that can severely affect vision and quality of life. In recent years, stem cell therapies based on conjunctival stem cells (CjSCs) have become a potential solution for treating ocular surface diseases. However, neither an efficient culture of CjSCs nor the development of a minimally invasive ocular surface CjSC transplantation therapy has been reported. Here, we developed a robust in vitro expansion method for primary rabbit-derived CjSCs and applied digital light processing (DLP)-based bioprinting to produce CjSC-loaded hydrogel micro-constructs for injectable delivery. Expansion medium containing small molecule cocktail generated fast dividing and highly homogenous CjSCs for more than 10 passages in feeder-free culture. Bioprinted hydrogel micro-constructs with tunable mechanical properties enabled the 3D culture of CjSCs while supporting viability, stem cell phenotype, and differentiation potency into conjunctival goblet cells. These hydrogel micro-constructs were well-suited for scalable dynamic suspension culture of CjSCs and were successfully delivered to the bulbar conjunctival epithelium via minimally invasive subconjunctival injection. This work integrates novel cell culture strategies with bioprinting to develop a clinically relevant injectable-delivery approach for CjSCs towards the stem cell therapies for the treatment of ocular surface diseases.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719077PMC
January 2021

Enhanced sustainable green revolution yield via nitrogen-responsive chromatin modulation in rice.

Science 2020 02;367(6478)

State Key Laboratory of Plant Cell and Chromosome Engineering, Institute of Genetics and Developmental Biology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing 100101, China.

Because environmentally degrading inorganic fertilizer use underlies current worldwide cereal yields, future agricultural sustainability demands enhanced nitrogen use efficiency. We found that genome-wide promotion of histone H3 lysine 27 trimethylation (H3K27me3) enables nitrogen-induced stimulation of rice tillering: APETALA2-domain transcription factor NGR5 (NITROGEN-MEDIATED TILLER GROWTH RESPONSE 5) facilitates nitrogen-dependent recruitment of polycomb repressive complex 2 to repress branching-inhibitory genes via H3K27me3 modification. NGR5 is a target of gibberellin receptor GIBBERELLIN INSENSITIVE DWARF1 (GID1)-promoted proteasomal destruction. DELLA proteins (characterized by the presence of a conserved aspartate-glutamate-leucine-leucine-alanine motif) competitively inhibit the GID1-NGR5 interaction and explain increased tillering of green revolution varieties. Increased NGR5 activity consequently uncouples tillering from nitrogen regulation, boosting rice yield at low nitrogen fertilization levels. NGR5 thus enables enhanced nitrogen use efficiency for improved future agricultural sustainability and food security.
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http://dx.doi.org/10.1126/science.aaz2046DOI Listing
February 2020

Evaluation and accurate diagnoses of pediatric diseases using artificial intelligence.

Nat Med 2019 03 11;25(3):433-438. Epub 2019 Feb 11.

Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Artificial intelligence (AI)-based methods have emerged as powerful tools to transform medical care. Although machine learning classifiers (MLCs) have already demonstrated strong performance in image-based diagnoses, analysis of diverse and massive electronic health record (EHR) data remains challenging. Here, we show that MLCs can query EHRs in a manner similar to the hypothetico-deductive reasoning used by physicians and unearth associations that previous statistical methods have not found. Our model applies an automated natural language processing system using deep learning techniques to extract clinically relevant information from EHRs. In total, 101.6 million data points from 1,362,559 pediatric patient visits presenting to a major referral center were analyzed to train and validate the framework. Our model demonstrates high diagnostic accuracy across multiple organ systems and is comparable to experienced pediatricians in diagnosing common childhood diseases. Our study provides a proof of concept for implementing an AI-based system as a means to aid physicians in tackling large amounts of data, augmenting diagnostic evaluations, and to provide clinical decision support in cases of diagnostic uncertainty or complexity. Although this impact may be most evident in areas where healthcare providers are in relative shortage, the benefits of such an AI system are likely to be universal.
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http://dx.doi.org/10.1038/s41591-018-0335-9DOI Listing
March 2019

iTRAQ-Based Differential Proteomic Analysis Reveals the Pathways Associated with Tigecycline Resistance in Acinetobacter baumannii.

Cell Physiol Biochem 2018 27;51(3):1327-1339. Epub 2018 Nov 27.

Background/aims: Acinetobacter baumannii is an aerobic and Gram-negative bacterial pathogen with high morbidity and mortality. It remains a serious public health problem arising from its multidrug-resistant and extensive antibiotic resistance spectrum.

Methods: In the present study, iTRAQ coupled with 2D LC-MS/MS was used to evaluate the proteome in standard Acinetobacter baumannii standard strains and tigecycline-resistant strains.

Results: A total of 3639 proteins were identified and 961 proteins were identified to be differentially expressed in tigecycline-resistant Acinetobacter baumannii strains compared to the standard strains. 506 (52.6%) proteins were up-regulated and 455 (47.4%) proteins were down-regulated. Based on the GO enrichment analysis and KEGG pathway analysis, we concluded that most differentially expressed proteins were associated with stress responses, cellular component organization, proteins synthesis, degradation and function. Moreover, β-lactam resistance, the longevity regulating pathway and other related pathways were also involved in the regulation of tigecycline-resistant Acinetobacter baumannii. The differential expression of key proteins were evaluated by transcript analysis using quantitative RT-PCR.

Conclusion: These results may provide new insights into the mechanisms of drug resistance in Acinetobacter baumannii.
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http://dx.doi.org/10.1159/000495551DOI Listing
January 2019

Molecular Alteration Analysis of Human Gut Microbial Composition in Graves' disease Patients.

Int J Biol Sci 2018 7;14(11):1558-1570. Epub 2018 Sep 7.

Department of Microbiology and Immunology, Key Laboratory of Environment and Genes Related to Diseases of Chinese Ministry of Education, School of Medicine, Xi'an Jiaotong University, Xi'an, China.

The gut microbial association with host co-existence is critical for body homeostasis and pathogenicity. Graves' disease (GD) is an autoimmune disease manifested with hyperthyroidism and ophthalmopathy. However, we hypothesized that gut bacteria could affect an important role in GD pathogenicity. The current study aim was to characterize and investigate the intestinal bacterial composition of GD qualitatively and quantitatively. 27 GD and 11 healthy controls were enrolled for fecal sample collection. The PCR-DGGE of 16S rRNA gene by targeting V3 region and Real-time PCR for , were performed. High-throughput sequencing of 16S rRNA gene with the V3+V4 site was perormed on Hiseq2500 platform on randomly 20 selected samples. The relative analysis of richness indices and diversity illustrated lesser diversification of intestinal bacteria in GD patients in contrast to controls. The data statistics shows the alteration in phyla of GD as compared to control. At the family taxonomic level, the relative abundance of Prevotellaceae and Pasteurellaceae were significantly higher in patients, while Enterobacteriaceae, Veillonellaceae, and Rikenellaceae were significantly lower in the diseased group as compared to control. At the genus level, a significant raised in genera count of the diseased group were while significantly decreased in the genera of the GD group were and The modulation in intestinal bacterial composition was checked at species level particularly abundance was raised in GD. The outcomes of the current study are aligned with the proposed hypothesis of gut microbial dysbiosis in GD. Statistically, alpha indices and differential abundance analyses of each intestinal bacterial community were significantly changed in GD. Therefore, the current study may provide a new insight into the GD pathogenesis and, in turn, explore its contribution in possible treatments.
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http://dx.doi.org/10.7150/ijbs.24151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158725PMC
September 2019

Serum CK 18-M30 reflect liver pathological severity during NAFLD progression in a rat model.

Pathol Res Pract 2018 Nov 20;214(11):1778-1786. Epub 2018 Aug 20.

Department of Laboratory, The Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, PR China. Electronic address:

Background: CK 18-M30 was increased in patients with NAFLD. However, little is known about the relationship between CK 18-M30 and NAFLD progression. We aimed to analyze the variety of CK 18-M30 and other metabolism indices during NAFLD progression. Meanwhile, we aimed to investigate the correlation between CK 18-M30 and liver pathology during NAFLD progression.

Materials And Methods: Rats were fed with high sucrose and high fat diet for building NAFLD models. We detected liver pathology by hematoxylin-eosin (HE) staining. We also detected serum CK 18-M30 and metabolism indices including liver enzymes, serum lipids and glycometabolism indices.

Results: The aggravating degree of liver pathology appeared with prolonged feeding period. The relevance of CK 18-M30 to the severity of liver pathology were higher relative to other indices.

Conclusion: Our results suggested the significance of CK 18-M30 in the progression of NAFLD and provided new evidence for the early diagnosis and prognostic estimation of NAFLD.
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http://dx.doi.org/10.1016/j.prp.2018.08.016DOI Listing
November 2018

Overexpression of α3, β3 and γ2 chains of laminin-332 is associated with poor prognosis in pancreatic ductal adenocarcinoma.

Oncol Lett 2018 Jul 9;16(1):199-210. Epub 2018 May 9.

Division of Hepatobiliary and Pancreatic Surgery, Jinhua Municipal Central Hospital, Jinhua, Zhejiang 321000, P.R. China.

Pancreatic ductal adenocarcinoma (PDA) is a worldwide health problem. Early diagnosis and assessment may enhance the quality of life and survival of patients. The present study investigated the potential correlations between the gene and protein expression of laminin-332 (LM-332 or laminin-5) and clinicopathological factors as well as evaluating its influence on the survival of patients with PDA. The expression of LM-332 subunit mRNAs in pancreatic carcinoma specimens from 37 patients was investigated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Using immunohistochemical methods, the protein expressions of the three chains of LM-322 (LNα3, LNβ3 and LNγ2) were determined in 96 pancreatic carcinoma specimens, for association analysis with clinicopathological characteristics from patient data. The results of the prognosis analysis of three mRNAs expression datasets were validated in The Cancer Genome Atlas datasets. RT-qPCR results indicated that the overall relative values of LNα3 and LNγ2 mRNAs were increased in pancreatic carcinoma compared with the control. In immunostaining analyses LNα3 and LNγ2 expression was observed in all tumor tissues from the 96 patient samples. The expression levels of LNα3, LNβ3 and LNγ2 were associated with each other. LNα3 and LNγ2 positivity was significantly associated with differentiation, depth of invasion and advanced stage (P<0.05). The samples were classified into three groups: Basement membrane (B) type, cytoplasmic (C) type and mixed (M) type, according to their LNγ2 immunohistochemical expression patterns. The B type correlated significantly with differentiation (P=0.010) and the M type was significantly associated with hepatic metastasis (P=0.031). Patients with B-type LNγ2 demonstrated significantly better outcomes than patients with the C or M type (P=0.012 and P=0.003, respectively). Overexpression of the α3, β3 and γ2 chains of LM-332 may serve an important role in the progression and prognosis of PDA.
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http://dx.doi.org/10.3892/ol.2018.8678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006395PMC
July 2018

Liu et al. reply.

Nature 2018 04;556(7699):E3-E4

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.

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http://dx.doi.org/10.1038/nature26150DOI Listing
April 2018

Identifying Medical Diagnoses and Treatable Diseases by Image-Based Deep Learning.

Cell 2018 02;172(5):1122-1131.e9

Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 510005 Guangzhou, China; Shiley Eye Institute, Institute for Engineering in Medicine, Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.

The implementation of clinical-decision support algorithms for medical imaging faces challenges with reliability and interpretability. Here, we establish a diagnostic tool based on a deep-learning framework for the screening of patients with common treatable blinding retinal diseases. Our framework utilizes transfer learning, which trains a neural network with a fraction of the data of conventional approaches. Applying this approach to a dataset of optical coherence tomography images, we demonstrate performance comparable to that of human experts in classifying age-related macular degeneration and diabetic macular edema. We also provide a more transparent and interpretable diagnosis by highlighting the regions recognized by the neural network. We further demonstrate the general applicability of our AI system for diagnosis of pediatric pneumonia using chest X-ray images. This tool may ultimately aid in expediting the diagnosis and referral of these treatable conditions, thereby facilitating earlier treatment, resulting in improved clinical outcomes. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/j.cell.2018.02.010DOI Listing
February 2018

Molecular estimation of alteration in intestinal microbial composition in Hashimoto's thyroiditis patients.

Biomed Pharmacother 2017 Nov 10;95:865-874. Epub 2017 Sep 10.

Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China. Electronic address:

The gut microbiota has a crucial effect on human health and physiology. Hypothyroid Hashimoto's thyroiditis (HT) is an autoimmune disorder manifested with environmental and genetic factors. However, it is hypothesized that intestinal microbes might play a vital role in the pathogenesis of HT. The aim of current was to investigate and characterize the gut microbial composition of HT patients both quantitatively and qualitatively. The fecal samples from 29 HT patients and 12 healthy individuals were collected. The PCR-DGGE targeted V3 site of 16S rRNA gene and real time PCR for Bifidobacterium Lactobacillus, Bacteroides vulgatus and Clostridium leptum were performed. Pyrosequencing of 16S rRNA gene with V4 location was performed on 20 randomly selected samples. The comparative analysis of diversity and richness indices revealed diversification of gut microbiota in HT as compared to control. The statistical data elucidate the alterations in phyla of HT patients which was also affirmed at the family level. We observed the declined abundance of Prevotella_9 and Dialister, while elevated genera of the diseased group included Escherichia-Shigella and Parasutterella. The alteration in gut microbial configuration was also monitored at the species level, which showed an increased abundance of E. coli in HT. Therefore, the current study is in agreement with the hypothesis that HT patients have intestinal microbial dysbiosis. The taxa statistics at species-level along with each gut microbial community were modified in HT. Thus, the current study may offer the new insights into the treatment of HT patients, disease pathway, and mechanism.
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http://dx.doi.org/10.1016/j.biopha.2017.08.101DOI Listing
November 2017

Molecular Characterization Of Fecal Microbiota Of Healthy Chinese Tobacco Smoker Subjects In Shaanxi Province, Xi'an China.

J Ayub Med Coll Abbottabad 2017 Jan-Mar;29(1):3-7

Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, China.

Background: Tobacco Smoking, most commonly, can cause the diseases affecting the lungs and heart. Human gut microbiota plays a key role to decide the health status of the host. Current study aimed to characterize the gut microbiota of healthy Chinese tobacco smokers and to study the alteration in diversity and similarity of gut microbiota, with comparison of healthy non-smokers.

Methods: Fecal samples were collected from fourteen healthy tobacco smokers and six from healthy non-smoker individuals. PCR-denaturing gradient gel electrophoresis, with universal primers focusing V3 region of the 16S rRNA gene, was done to characterize the overall gut microbial composition of healthy tobacco smokers in comparison with healthy non-smoker subjects and some strongly dominant gel bands were excised for sequencing. Real time PCR was also performed to evaluate the copy numbers of some dominant bacteria of intestinal flora.

Results: The results indicated that gut microbial diversity in tobacco smoker group was lower than non-smoker controls. Furthermore, similarity index comparison also indicated that it was lower in inter-group than intra-group, which showed that gut microbial composition was changed in tobacco smoker group. Sequencing results also indicated a change in bacterial composition between both groups. We also observed that in tobacco smoker group, there was a significant reduction in Bifidobacterium and non-significant increase in Bacteroides vulgatus, while nonsignificant decrease in Lactobacillus and clostridium leptum sub group, respectively.

Conclusions: It can be concluded that in healthy Chinese tobacco smoker group, there is a notable alteration in the molecular characterization of gut microbiota.
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April 2019

Probiotics may delay the progression of nonalcoholic fatty liver disease by restoring the gut microbiota structure and improving intestinal endotoxemia.

Sci Rep 2017 03 28;7:45176. Epub 2017 Mar 28.

Department of Laboratory, The Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.

Gut-derived bacterial lipopolysaccharide (LPS) and subsequent hepatic toll-like receptor 4 (TLR4) activation have been recognized to be involved in the onset of diet-induced nonalcoholic fatty liver disease (NAFLD), but little is known about the variation of LPS and TLR4 during the progression of NAFLD. Probiotics were able to inhibit proliferation of harmful bacteria and improve gastrointestinal barrier function. However, it's unclear whether LPS/TLR4 is involved in the protection effect of probiotics on NAFLD. In this study, we described characteristic of gut microbiota structure in the progression of NAFLD, and we also analyzed the relationship between gut microbiota and LPS/TLR4 in this process. Furthermore, we applied probiotics intervention to investigate the effect of probiotics on gut flora structure, intestinal integrity, serum LPS, liver TLR4 and liver pathology. Our results showed that serum LPS and liver TLR4 were highly increased during progression of NAFLD, with gut flora diversity and gut mircobiological colonization resistance (B/E) declining. Furthermore, probiotics could improve gut microbiota structure and liver pathology. Probiotics could also downregulate serum LPS and liver TLR4. Our results suggested that both gut flora alteration and endotoxemia may be involved in the progression of NAFLD. Probiotics may delay the progression of NAFLD via LPS/TLR4 signaling.
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http://dx.doi.org/10.1038/srep45176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368635PMC
March 2017

Re-emerging of rabies in Shaanxi province, China, from 2009 to 2015.

J Med Virol 2017 09 15;89(9):1511-1519. Epub 2017 Jun 15.

The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

To explore the epidemiological, phylogeographic, and migration characteristics of human rabies in Shaanxi province, China from 2009 to 2015. The collected data were described and the sequenced glycoprotein (G) and nucleoprotein (N) genes were implemented to estimate the evolutionary rates and phylogeographic patterns using BEAST v.1.8.2. A total of 269 rabies cases were reported and 70.26% of the cases were male and 61.71% were between the ages of 19-59. The majority of the cases were farmers (83.27%). The estimated evolutionary rate of the N genes was 2.4 × 10 substitutions/site/year and the G genes was 3.4 × 10 . The time of the most recent common ancestor (TMRCA) was estimated around 1990. We detected viral migration paths from Sichuan, Guizhou, and Hunan to Hanzhong prefecture of Shaanxi and then spreaded to Xi'an and other prefectures. The main population affected by rabies virus was male adult farmers. The evolution rate of rabies viruses in Shaanxi was similar with the prior results reported by others and the ancestor virus should be circulating in neighboring province Sichuan around 1990 and then transmitted to Shaanxi. Promptly standard wound treatment and timely post-exposure prophylaxis should be compulsory for the dog-bitten victims.
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http://dx.doi.org/10.1002/jmv.24769DOI Listing
September 2017

Mutation Changes in the preC/Core Promoter in HBeAg-Positive Patients With Chronic Hepatitis B During Interferon Therapy.

Medicine (Baltimore) 2016 Feb;95(5):e2657

From the Department of Laboratory (YG, XW, XW, NX); Department of Digestive, The Second Affiliated Hospital (XL); and Department of Immunology and Pathogenic Biology, Health Science Center, Xi'an Jiaotong University, Xi'an, People's Republic of China (LH, JX).

To study the changes in 3 mutations related with hepatitis B e antigen (HBeAg) in patients with HBeAg-positive chronic hepatitis B (CHB) during interferon therapy.HBeAg seroconversion is a major therapeutic milestone for patients with HBeAg-positive CHB. The precore mutation G1896A and the basal core promoter mutations A1762T/G1764A are 3 important mutations that affect the expression of HBeAg; however, the change of these 3 mutations in CHB patients during interferon therapy has not yet been evaluated.Sixty-four treatment-naive patients with HBeAg-positive CHB were treated with interferon for 48 weeks and followed up for 24 weeks. Serum samples were collected from all of the participants at different time points and then subjected to viral DNA extraction. The precore and basal core promoter sequences were determined using nested PCR and direct sequencing. The treatment outcomes were confirmed both at the end of therapy and the follow-up period, and the results were compared between patients with mutant and wild-type virus.No significant difference in HBeAg loss and HBeAg seroconversion was observed between patients with mutant versus wild-type virus although the portion of patients who achieved HBeAg loss/seroconversion with mutant virus was a little higher than in patients with wild-type virus. Once a mutation exists, it is not replaced with the wild-type sequence during interferon therapy and follow-up; moreover, our results show that mutants stably coexist with the wild-type virus during interferon therapy.This study shows the changes in 3 mutations affecting the expression of HBeAg during interferon therapy. However, additional studies with a larger sample size and more sensitive detection methods are needed to uncover the underlying mechanism and clinical significance of these results.
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http://dx.doi.org/10.1097/MD.0000000000002657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748907PMC
February 2016

MicroRNA-27b suppresses Helicobacter pylori-induced gastric tumorigenesis through negatively regulating Frizzled7.

Oncol Rep 2016 Apr 18;35(4):2441-50. Epub 2016 Jan 18.

Department of Immunology and Pathogenic Biology, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

MicroRNAs (miRNAs) are novel tools for cancer therapy. Frizzled7 (FZD7) is an important co-receptor in the WNT signaling pathway. The WNT signaling pathway is aberrantly activated in Helicobacter pylori (H. pylori)‑infected gastric cancer cells. However, the role of FZD7 in H. pylori‑induced gastric tumorigenesis remains unknown. In this study, we investigated the potential role of FZD7 in H. pylori-induced gastric tumorigenesis and validated the possibility that targeting of FZD7 by specific miRNA inhibits H. pylori-induced gastric tumorigenesis. First, we found that FZD7 was significantly induced by H. pylori infection in a dose- and time-dependent manner. Knockdown of FZD7 by FZD7 small interfering RNA effectively inhibited H. pylori infection-induced cell proliferation of gastric cancer cells. We found that microRNA-27b (miR-27b) was the predicted miRNA for FZD7 and that miR-27b negatively regulated FZD7 expression by targeting the 3'-untranslated region of FZD7. Furthermore, miR-27b overexpression significantly inhibited H. pylori infection-induced cell proliferation and WNT signaling pathway activation in gastric cancer cells. Restoration of FZD7 expression significantly attenuated the inhibitory effect of miR-27b overexpression on cell proliferation and WNT signaling pathway activation. Collectively, our study suggests that FZD7 triggered by H. pylori infection contributes to the H. pylori infection-induced cell proliferation that links the WNT. Thus, miR-27b may be a promising molecular target for the treatment of the disease.
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http://dx.doi.org/10.3892/or.2016.4572DOI Listing
April 2016

A novel missense mutation in collagenous domain of EDA gene in a Chinese family with X-linked hypohidrotic ectodermal dysplasia.

J Genet 2015 Mar;94(1):115-9

Stomatology Clinic, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, People's Republic of China.

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http://dx.doi.org/10.1007/s12041-015-0474-4DOI Listing
March 2015

Nested PCR-denaturing gradient gel electrophoresis analysis of human skin microbial diversity with age.

Microbiol Res 2014 Sep-Oct;169(9-10):686-92. Epub 2014 Mar 1.

Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, Yanta West Road No. 76, 710061 Xi'an, China. Electronic address:

To determine whether the composition and structure of skin microbiota differ with age, cutaneous bacteria were isolated from the axillary fossa of 37 healthy human adults in two age groups (old people and young adults). Bacterial genomic DNA was extracted and characterized by nested PCR-denaturing gradient gel electrophoresis (PCR-DGGE) with primers specifically targeting V3 region of the 16S rRNA gene. The excised gel bands were sequenced to identify bacterial categories. The total bacteria, Staphylococcus spp., Staphylococcus epidermidis and Corynebacterium spp. were further enumerated by quantitative PCR. There were no significant differences in the species diversity profiles between age groups. The similarity index was lower across age groups than that it was intra-group. This indicates that the composition of skin flora is more similar to others of the same age than across age groups. While Staphylococcus spp. and Corynebacterium spp. were the dominant bacteria in both groups, sequencing and quantitative PCR revealed that skin bacterial composition differed by age. The copy number of total bacteria and Corynebacterium spp. were significantly lower in younger subjects, whereas there were no statistical differences in the quantity of Staphylococcus spp. and Staphylococcus epidermidis. These results suggest that the skin flora undergo both quantitative and qualitative changes related to aging.
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http://dx.doi.org/10.1016/j.micres.2014.02.008DOI Listing
March 2015

Molecular characterization of skin microbiota between cancer cachexia patients and healthy volunteers.

Microb Ecol 2014 Apr 9;67(3):679-89. Epub 2014 Jan 9.

Department of Immunology and Pathogenic Biology, Molecular Bacteriology Laboratory, Key Laboratory of Environment and Genes Related to Diseases of Chinese Ministry of Education, School of Medicine, Xi'an Jiaotong University, Yanta West Road No. 76, 710061, Xi'an, Shaanxi Province, China.

Systemic inflammation contributes to both the development of cancer and of cachexia. The microenvironment of bacterial habitats might be changed during the progression of cancer cachexia. The aim of this study was to quantitatively and qualitatively compare the composition of the skin microbiota between cancer cachexia patients and healthy volunteers. Cutaneous bacteria were swabbed at the axillary fossa of 70 cancer cachexia patients and 34 healthy individuals from China. Nested-PCR-denaturing gradient gel electrophoresis (PCR-DGGE) with primers specifically targeting V3 region and quantitative PCR (qPCR) for total bacteria, Corynebacterium spp., Staphylococcus spp., and Staphylococcus epidermidis were performed on all samples. Barcoded 454 pyrosequencing of the V3-V4 regions was performed on 30 randomly selected samples. By comparing diversity and richness indices, we found that the skin microbiome of cachectic cancer patients is less diverse than that of healthy participants, though these differences were not significant. The main microbes that reside on human skin were divided into four phyla: Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes. Staphylococcus spp. and Corynebacterium spp. were the dominant bacteria at the genus level. Significantly fewer Corynebacterium spp. had been observed in cachexia patients compared to healthy subjects. These results suggest that the presence of cancer and cachexia alters human skin bacterial communities. Understanding the changes in microbiota during cancer cachexia may lead to new insights into the syndrome.
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http://dx.doi.org/10.1007/s00248-013-0345-6DOI Listing
April 2014

An improved susceptibility test based on Amberlite reveals the potential antilisterial activity of fosfomycin in vitro.

Can J Microbiol 2013 Apr 4;59(4):252-9. Epub 2013 Feb 4.

Department of Immunology and Pathogenic Biology, College of Medicine, Xi'an Jiaotong University, 76 West Yanta Road, Xi'an 710061, P.R. China.

Listeria monocytogenes is resistant to fosfomycin in vitro but is susceptible in vivo due to increased expression of positive regulator factor A (PrfA) and its dependent factor, hexose phosphate transporter (Hpt), upon infection of host cells. Amberlite, a polymeric adsorbent resin, could induce PrfA-dependent gene expression and thus, in theory, improve the sensitivity of L. monocytogenes to fosfomycin in vitro. In the current study, an improved susceptibility test based on Amberlite was developed using reference strains. Thirty-five clinical isolates were further examined to verify those preliminary results. Briefly, Amberlite increased in vitro fosfomycin sensitivity of all strains. Optimal Amberlite concentrations, as evaluated through the expression of phospholipase B (PlcB) and Hpt, were 10% and 15% (w/v) in agar media and 3% (w/v) in broth media. Mueller-Hinton (MH) medium, tryptone soya (TS) medium, and brain heart infusion (BHI) medium were used to verify the results in the control strains using agar dilution and broth micro- and macro-dilution methods. Better listerial growth was shown in TS and BHI than in MH. Both broth dilution methods yielded lower minimal inhibitory concentration (MIC) of fosfomycin than the agar dilution method. The MIC of fosfomycin for 35 clinical isolates was 2-32 μg/mL, suggesting improved susceptibility. In conclusion, in vitro sensitivity of L. monocytogenes to fosfomycin was substantially improved in the presence of 3% Amberlite-supplemented TSB or BHIB and the broth microdilution method. This improved method revealed the potential antilisterial activity of fosfomycin in vitro and could facilitate the therapy of listeriosis using fosfomycin.
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http://dx.doi.org/10.1139/cjm-2012-0742DOI Listing
April 2013

Increase ICAM-1 and LFA-1 expression by cerebrospinal fluid of subarachnoid hemorrhage patients: involvement of TNF-α.

Brain Res 2013 May 30;1512:89-96. Epub 2013 Mar 30.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.

Subarachnoid hemorrhage (SAH) is a frequent occurrence in cerebrovascular accidents, and inflammation occurs in the subarachnoid space after SAH. Arachnoid cells have the capability to present antigens and active T-lymphocytes after stimulation by cerebrospinal fluid (CSF). However, the effect of CSF on T-lymphocytes and arachnoid cell adhesion was not clearly understood. In this study, we used ELISA to detected tumor necrosis factor-α (TNF-α) content in CSF of SAH patients. CSF or recombinant TNF-α were applied on arachnoid cells and T-lymphoctes, and RT-PCR and western blotting were performed to determine the expression of intercellular adhesion molecule-1 (ICAM-1) in arachnoid cells and Lymphocyte Function-Associated Antigen-1 (LFA-1) in T-lymphocytes, respectively. Meanwhile, the Matrix Metal Proteinase-9 (MMP-9) expression in these cells was also determined. We found that the content of TNF-α in the CSF was significantly increased in the CSF of SAH patients (from 22 ± 8 pg/mL of healthy people to 436-450 pg/mL of SAH patients). Treatement with CSF could increase the expression of ICAM-1 in arachnoid cells and that of LFA-1 in T-lymphocytes, mainly through the increased levels of TNF-α. We also found that the co-culture of arachnoid cells and T-lymphocytes increased the expression of MMP-9 in both cells through the interaction of ICAM-1 of and LFA-1. All of these results suggested that arachnoid cells are involved in the T-lymphocytes invasion in the subarachnoid space after SAH.
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http://dx.doi.org/10.1016/j.brainres.2013.03.041DOI Listing
May 2013

Molecular characterization of fecal microbiota in patients with viral diarrhea.

Curr Microbiol 2011 Sep 8;63(3):259-66. Epub 2011 Jul 8.

Department of Immunology and Pathogenic Biology, Molecular Bacteriology Laboratory, Key Laboratory of Environment and Genes Related to Diseases of Chinese Ministry of Education, School of Medicine, Xi'an Jiaotong University, 76 Yanta West Road, Xi'an, Shaanxi 710061, China.

The study provides molecular analyses of fecal microbiota of diarrhea patients infected with four different types of viruses. Fecal specimens from 52 patients with viral diarrhea (13 each of adenovirus, norovirus, rotavirus, and astrovirus) and six healthy individuals were collected and etiological viral agent was confirmed by enzyme immunoassay and specific PCR. To assess the changes in microbial diversity in patients with viral diarrhea, DNA from stool were extracted and characterized by PCR-denaturing gradient gel electrophoresis (DGGE) with universal primers specific for the V3 region of 16S rRNA gene. The strongest bands of the DGGE profiling were excised and sequenced to identify the dominant groups. Bacteroides vulgatus, Bifidobacterium, and Lactobacillus genera were also enumerated by real time PCR. The results revealed that bacterial diversity and similarity in feces from viral diarrhea groups were significantly lower (mean H'/ H'(max) 0.89-0.94, 29-43, respectively) as compared with those of healthy individuals (mean H'/ H'(max) 1.36, 59, respectively). Sequencing of dominant bands affirmed that diarrhea groups were mainly comprised of phylum Firmicutes, such as genera Enterococcus, Peptostreptococcaceae incertae sedi, Streptococcus, Weissella, and Clostridium, and opportunistically pathogenic genus Shigella, while dominant group in healthy individuals was phylum Bacteroidetes. Copy number of Bacteroides vulgatus, Bifidobacterium, and Lactobacillus genera was also reduced significantly in viral diarrhea groups as compared to healthy group. It is concluded that opportunistic pathogens increases, while other species of commensal microbiota decrease significantly in the viral diarrhea patients and dysbacteriosis is dependent on type of virus infection.
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http://dx.doi.org/10.1007/s00284-011-9972-7DOI Listing
September 2011

Characterization and transfer of antibiotic resistance in lactic acid bacteria from fermented food products.

Curr Microbiol 2011 Mar 7;62(3):1081-9. Epub 2011 Jan 7.

Department of Immunology and Pathogenic Biology, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.

The study provides phenotypic and molecular analyses of the antibiotic resistance in lactic acid bacteria (LAB) from fermented foods in Xi'an, China. LAB strains (n = 84) belonging to 16 species of Lactobacillus (n = 73), and Streptococcus thermophilus (n = 11) were isolated and identified by sequencing their 16S rRNA gene. All strains were susceptible to ampicillin, bacitracin, and cefsulodin, and intrinsically resistant to nalidixic acid, kanamycin, and vancomycin (except L. bulgaricus, L. acidophilus, and S. thermophilus, which were susceptible to vancomycin). Some strains had acquired resistance for penicillin (n = 2), erythromycin (n = 9), clindamycin (n = 5), and tetracycline (n = 14), while resistance to gentamycin, ciprofloxacin, streptomycin, and chloramphenicol was species dependent. Minimum inhibitory concentrations presented in this study will help to review microbiological breakpoints for some of the species of Lactobacillus. The erm(B) gene was detected from two strains of each of L. fermentum and L. vaginalis, and one strain of each of L. plantarum, L. salivarius, L. acidophilus, L. animalis, and S. thermophilus. The tet genes were identified from 12 strains of lactobacilli from traditional foods. This is the first time, the authors identified tet(S) gene from L. brevis and L. kefiri. The erm(B) gene from L. fermentum NWL24 and L. salivarius NWL33, and tet(M) gene from L. plantarum NWL22 and L. brevis NWL59 were successfully transferred to Enterococcus faecalis 181 by filter mating. It was concluded that acquired antibiotic resistance is well dispersed in fermented food products in Xi'an, China and its transferability to other genera should be monitored closely.
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http://dx.doi.org/10.1007/s00284-010-9856-2DOI Listing
March 2011

Molecular characterisation of the faecal microbiota in patients with type II diabetes.

Curr Microbiol 2010 Jul 20;61(1):69-78. Epub 2010 Jan 20.

Department of Immunology and Pathogenic Biology, Molecular Bacteriology Laboratory, Key Laboratory of Environment and Genes Related to Diseases of Chinese Ministry of Education, School of Medicine, Xi'an Jiaotong University, 710061, Xi'an, Shaanxi Province, People's Republic of China.

The investigation provides molecular analyses of the faecal microbiota in type 2 diabetic patients. In order to characterise the gut microbiota in diabetic patients and to assess whether there are changes in the diversity and similarity of gut microbiota in diabetic patients when compared with healthy individuals, bacterial DNAs from 16 type 2 diabetic patients and 12 healthy individuals were extracted from faecal samples and characterised by PCR-denaturing gradient gel electrophoresis (DGGE) with primers specifically targeting V3 region of the 16S rRNA gene, as well as been sequenced for excised gel bands. The counts of Bacteroides vulgatus, Clostridium leptum subgroup and Bifidobacterium genus were assessed using quantitative PCR. By comparing species diversity profiles of two groups, we observed that there were no significant differences between diabetic and healthy group, although a few diabetic individuals (D6, D8) exhibited a remarkable decrease in species profiles. As for the similarity index, it was lower in inter-group than that in intra-group, which showed that the composition of gut microbiota in diabetic group might be changed due to diabetes status. Sequencing results also revealed that bacterial composition of diabetic group was different from that of the healthy group. B. vulgatus and Bifidobacterium genus were low represented in the microbiota of diabetic group, and the significant decrease was observed for Bifidobacterium by real-time PCR. Taken together, in this work we observed the characterisation of gut microbiota in diabetic patients, which suggests that the gut microbiota of diabetes patients have some changes associated with occurrence and development of diabetes.
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http://dx.doi.org/10.1007/s00284-010-9582-9DOI Listing
July 2010

Protective effects of a new metalloporphyrin on paraquat-induced oxidative stress and apoptosis in N27 cells.

Acta Biochim Biophys Sin (Shanghai) 2008 Feb;40(2):125-32

School of Life Science and Technology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200092, China.

Paraquat (PQ, 1,1'-dimethyl-4,4'-bipyridinium), a widely-used herbicide, has been suggested as a potential etiologic factor for the development of Parkinson's disease. In recent years, many studies have focused on the mechanism(s) of PQ neurotoxicity. In this study, we examined the neuroprotective effect of manganese (III) meso-tetrakis (N,N'-diethylimidazolium) porphyrin (MnTDM), a superoxide dismutase/catalase mimetic, on PQ-induced oxidative stress and apoptosis in 1RB3AN27 (N27) cells, a dopaminergic neuronal cell line. The results indicated that MnTDM significantly attenuated PQ-induced loss of cell viability, glutathione depletion, and reactive oxygen species production. MnTDM also ameliorated PQ-induced morphological nuclear changes of apoptosis and increased rates of apoptosis. In addition, our data provide direct evidence that MnTDM suppressed PQ-induced caspase-3 cleavage, possibly a key event of PQ neurotoxicity. These observations suggested that oxidative stress and apoptosis are implicated in PQ-induced neurotoxicity and this toxicity could be prevented by MnTDM. These findings also proposed a novel therapeutic approach for Parkinson's disease and other disorders associated with oxidative stress.
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http://dx.doi.org/10.1111/j.1745-7270.2008.00386.xDOI Listing
February 2008
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