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  1. Article ; Online: Ensemble methods of rank-based trees for single sample classification with gene expression profiles.

    Lu, Min / Yin, Ruijie / Chen, X Steven

    Journal of translational medicine

    2024  Volume 22, Issue 1, Page(s) 140

    Abstract: Building Single Sample Predictors (SSPs) from gene expression profiles presents challenges, notably due to the lack of calibration across diverse gene expression measurement technologies. However, recent research indicates the viability of classifying ... ...

    Abstract Building Single Sample Predictors (SSPs) from gene expression profiles presents challenges, notably due to the lack of calibration across diverse gene expression measurement technologies. However, recent research indicates the viability of classifying phenotypes based on the order of expression of multiple genes. Existing SSP methods often rely on Top Scoring Pairs (TSP), which are platform-independent and easy to interpret through the concept of "relative expression reversals". Nevertheless, TSP methods face limitations in classifying complex patterns involving comparisons of more than two gene expressions. To overcome these constraints, we introduce a novel approach that extends TSP rules by constructing rank-based trees capable of encompassing extensive gene-gene comparisons. This method is bolstered by incorporating two ensemble strategies, boosting and random forest, to mitigate the risk of overfitting. Our implementation of ensemble rank-based trees employs boosting with LogitBoost cost and random forests, addressing both binary and multi-class classification problems. In a comparative analysis across 12 cancer gene expression datasets, our proposed methods demonstrate superior performance over both the k-TSP classifier and nearest template prediction methods. We have further refined our approach to facilitate variable selection and the generation of clear, precise decision rules from rank-based trees, enhancing interpretability. The cumulative evidence from our research underscores the significant potential of ensemble rank-based trees in advancing disease classification via gene expression data, offering a robust, interpretable, and scalable solution. Our software is available at https://CRAN.R-project.org/package=ranktreeEnsemble .
    MeSH term(s) Humans ; Transcriptome ; Software ; Neoplasms/genetics ; Oncogenes ; Algorithms
    Language English
    Publishing date 2024-02-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 2118570-0
    ISSN 1479-5876 ; 1479-5876
    ISSN (online) 1479-5876
    ISSN 1479-5876
    DOI 10.1186/s12967-024-04940-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Experimental study on the axial tensile properties of polypropylene fiber reinforced concrete.

    Zhang, Xutao / Yin, Ruijie / Chen, Yunjuan / Lou, Chao

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 16383

    Abstract: In order to study the axial tensile properties of polypropylene fiber reinforced concrete, an axial tensile test device for concrete is developed in this paper. The device is composed of three parts: rigid frame, spherical hinge and puller, and specimen ... ...

    Abstract In order to study the axial tensile properties of polypropylene fiber reinforced concrete, an axial tensile test device for concrete is developed in this paper. The device is composed of three parts: rigid frame, spherical hinge and puller, and specimen fabrication part. The test device can accurately measure the tensile strength and peak tensile strain of concrete, and perfectly solves the eccentricity problem of concrete specimens under tension. It can measure the post peak segment tensile strain, such that the whole process tensile stress-strain curve can be obtained. The axial tensile test of polypropylene fiber concrete was carried out using the above test device, and the results show that the tensile strength of concrete can be clearly improved by adding polypropylene fiber, which makes the tensile failure of concrete show certain plastic characteristics. The test results show that with the increase in fiber content, the tensile strength of concrete increases first and then decreases. The effects of polypropylene fiber content and curing age on the tensile properties of concrete were studied and the optimum polypropylene fiber content was determined. When the fiber content is 0.9 kg/m
    Language English
    Publishing date 2023-09-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-43723-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: TGF-β2-induced alterations of m6A methylation in hTERT RPE-1 cells.

    Li, Xue / Zhao, Xueru / Yin, Ruijie / Yuan, Min / Zhang, Yongya / Li, Xiaohua

    Experimental eye research

    2024  Volume 241, Page(s) 109839

    Abstract: N6-methyladenosine (m6A) is a major type of RNA modification implicated in various pathophysiological processes. Transforming growth factor β2 (TGF-β2) induces epithelial-mesenchymal transition (EMT) in retinal pigmental epithelial (RPE) cells and ... ...

    Abstract N6-methyladenosine (m6A) is a major type of RNA modification implicated in various pathophysiological processes. Transforming growth factor β2 (TGF-β2) induces epithelial-mesenchymal transition (EMT) in retinal pigmental epithelial (RPE) cells and promotes the progression of proliferative vitreoretinopathy (PVR). However, the role of m6A methylation in the EMT of human telomerase reverse transcriptase (hTERT) retinal pigmental epithelium (RPE)-1 cells has not been clarified. Here, we extracted RNA from RPE cells subjected to 0 or 20 ng/mL TGF-β2 for 72 h and identified differentially methylated genes (DMGs) by m6A-Seq and differentially expressed genes (DEGs) by RNA-Seq. We selected the genes related to EMT by conjoint m6A-Seq/RNA-Seq analysis and verified them by qRT-PCR. We then confirmed the function of m6A methylation in the EMT of RPE cells by knocking down the methyltransferase METTL3 and the m6A reading protein YTHDF1. Sequencing yielded 5814 DMGs and 1607 DEGs. Conjoint analysis selected 467 genes altered at the m6A and RNA levels that are closely associated with the EMT-related TGF-β, AGE-RAGE, PI3K-Akt, P53, and Wnt signaling pathways. We also identified ten core EMT genes ACTG2, BMP6, CDH2, LOXL2, SNAIL1, SPARC, BMP4, EMP3, FOXM1, and MYC. Their RNA levels were evaluated by qRT-PCR and were consistent with the sequencing results. We observed that METTL3 knockdown enhanced RPE cell migration and significantly upregulated the EMT markers N-cadherin (encoded by CDH2), fibronectin (FN), Snail family transcription repressor (SLUG), and vimentin. However, YTHDF1 knockdown had the opposite effects and decreased both cell migration and the N-cadherin, FN, and SLUG expression levels. The present study clarified TGF-β2-induced m6A- and RNA-level differences in RPE cells, indicated that m6A methylation might regulate EMT marker expression, and showed that m6A could regulate TGF-β2-induced EMT.
    MeSH term(s) Humans ; Transforming Growth Factor beta2/genetics ; Transforming Growth Factor beta2/pharmacology ; Transforming Growth Factor beta2/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Retinal Pigment Epithelium/metabolism ; Vitreoretinopathy, Proliferative/genetics ; Vitreoretinopathy, Proliferative/metabolism ; Epithelial-Mesenchymal Transition ; Methylation ; Cadherins/genetics ; Cadherins/metabolism ; RNA/genetics ; RNA/metabolism ; Methyltransferases/metabolism ; Membrane Glycoproteins/metabolism ; Adenine/analogs & derivatives
    Chemical Substances Transforming Growth Factor beta2 ; 6-methyladenine (W7IBY2BGAX) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Cadherins ; RNA (63231-63-0) ; METTL3 protein, human (EC 2.1.1.62) ; Methyltransferases (EC 2.1.1.-) ; EMP3 protein, human ; Membrane Glycoproteins ; Adenine (JAC85A2161)
    Language English
    Publishing date 2024-02-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 80122-7
    ISSN 1096-0007 ; 0014-4835
    ISSN (online) 1096-0007
    ISSN 0014-4835
    DOI 10.1016/j.exer.2024.109839
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Age Distribution of 4526 Surgically Excised Specimens of Eye Tumors by Histopathological Examination in China.

    Li, Xiaohua / Ying, Guishuang / Liu, Xiaohui / Yuan, Min / Yin, Ruijie

    Frontiers in bioscience (Landmark edition)

    2022  Volume 27, Issue 4, Page(s) 132

    Abstract: Background: Cumulative evidence suggests that the risk of eye tumors varies among different age groups and populations. The purpose of the present study was to assess the age distribution of eye tumors in China.: Methods: In this retrospective study, ...

    Abstract Background: Cumulative evidence suggests that the risk of eye tumors varies among different age groups and populations. The purpose of the present study was to assess the age distribution of eye tumors in China.
    Methods: In this retrospective study, the age distribution of various types of eye tumors was analyzed on surgically excised and histologically confirmed specimens obtained from 4492 patients (4526 eyes), collected between 2001 and 2017.
    Results: Of the 4526 specimens, 3156 eyes (69.7%) had benign eye tumors, while 1370 eyes (30.3%) had malignant tumors. The age-specific incidence of eye tumors was characterized by a bimodal distribution, one peak occurred at age 0-9 years (19.7%) and the other at 50-59 years (14.7%) of age. Malignant eyelid tumors were very rare under the age of 20 years, but increased to 78% of all eyelid tumors by the age of 70 years. Children aged 0-9 years old were 6.5 times as likely to have a malignant eye tumor (95% CI, 4.1-10.4) as those aged 10-19 years. The age-related variation of eye tumors was also observed in the top ten categories of both benign (
    Conclusions: These results showed that age is a major factor determining the type of eye tumor, confirmed by histopathological analysis.
    MeSH term(s) Age Distribution ; Child ; Child, Preschool ; China/epidemiology ; Eye Neoplasms/epidemiology ; Eye Neoplasms/surgery ; Eyelid Neoplasms/epidemiology ; Eyelid Neoplasms/pathology ; Humans ; Infant ; Infant, Newborn ; Retrospective Studies
    Language English
    Publishing date 2022-04-18
    Publishing country Singapore
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2704569-9
    ISSN 2768-6698 ; 2768-6698
    ISSN (online) 2768-6698
    ISSN 2768-6698
    DOI 10.31083/j.fbl2704132
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Alterations of the m

    Zhao, Xueru / Li, Xue / Li, Lingke / Zhang, Yongya / Wu, Fei / Yin, Ruijie / Yuan, Min / Li, Xiaohua

    Frontiers in bioscience (Landmark edition)

    2023  Volume 28, Issue 7, Page(s) 148

    Abstract: Background: N6-methyladenosine (m6A) participates in diverse physiological processes and contributes to many pathological conditions. Epithelial-mesenchymal transition (EMT) of retinal pigmental epithelial (RPE) cells plays an essential role in retinal- ... ...

    Abstract Background: N6-methyladenosine (m6A) participates in diverse physiological processes and contributes to many pathological conditions. Epithelial-mesenchymal transition (EMT) of retinal pigmental epithelial (RPE) cells plays an essential role in retinal-related diseases, and transforming growth factor β2 (TGF-β2) is known to induce EMT
    Methods: RNA-seq and MeRIP-seq were performed to analyze changes at the mRNA and m6A levels after TGF-β2 treatment of human ARPE-19 cells. mRNA levels and total m6A levels were subsequently validated.
    Results: Sequencing revealed 929 differentially expressed genes and 7328 differentially methylated genes after TGF-β2 treatment. Conjoint analysis identified 290 genes related to microtubule cytoskeleton, focal adhesion, ECM-receptor interaction, cell division, cell cycle, AGE-RAGE, PI3K-Akt and cGMP-PKG pathways. Further analysis revealed that 12 EMT-related genes were altered at the mRNA and m6A levels after TGF-β2 treatment (
    Conclusions: This study revealed the transcriptional profiling of m6A modification induced by TGF-β2 in RPE cells. Novel connections were discovered between m6A modification and TGF-β2-induced EMT, suggesting that m6A may play crucial roles in the EMT process.
    MeSH term(s) Humans ; Epithelial-Mesenchymal Transition ; Transforming Growth Factor beta2/pharmacology ; Retinal Pigment Epithelium/cytology ; Cell Line ; RNA-Seq ; Methylation ; Adenosine/analogs & derivatives
    Chemical Substances Transforming Growth Factor beta2 ; N-methyladenosine (CLE6G00625) ; Adenosine (K72T3FS567)
    Language English
    Publishing date 2023-08-01
    Publishing country Singapore
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2704569-9
    ISSN 2768-6698 ; 2768-6698
    ISSN (online) 2768-6698
    ISSN 2768-6698
    DOI 10.31083/j.fbl2807148
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Effective Extraction of Bisphenol Compounds from Milk with Stable Zr(IV)-Based Metal-Organic Framework Particles.

    Li, Tong / Wang, Ruiguo / Yin, Ruijie / Xu, Hongyan / Han, Xiaoxu / Du, Qiuling / Cheng, Jie / Lin, Zhenyu / Wang, Peilong

    Journal of agricultural and food chemistry

    2023  Volume 71, Issue 10, Page(s) 4272–4280

    Abstract: Bisphenol compounds (BPs) have recently been the subject of growing interest due to their wide use in industrial and consumer products. Besides their adverse effects on human endocrine system, effective extraction of BPs and their elimination from ... ...

    Abstract Bisphenol compounds (BPs) have recently been the subject of growing interest due to their wide use in industrial and consumer products. Besides their adverse effects on human endocrine system, effective extraction of BPs and their elimination from complex sample matrix are still significant challenges in food analysis. Herein, a novel Zr(IV)-based metal-organic framework (MOF), named BUT-16, has been synthesized and utilized for the extraction and enrichment of BPs in milk samples. Bisphenol A (BPA), one of the highest production volume BPs, is used as a model molecule. The uptake capacity for BPA can reach up to 48 mg/g, and the adsorption rate is rapid (∼10 min), because of the larger surface area and cooperation of multiple functionalities of BUT-16. Employing BUT-16 in solid-phase extraction, coupled with ultra-performance liquid chromatography-tandem mass spectrometry detection, we generated a rapid, facile, and robust method for the enrichment and detection of trace BPA and its 12 substitutes in milk samples. After optimization, the limits of detection and quantification for BPs can be achieved as low as 0.05 and 0.2 ng/mL, respectively. Without the correction of the isotopic internal standard, the average recoveries of BPs at the different spiked concentrations varied from 63.8 to 120.6%, with a satisfactory precision (RSD ≤ 8.2%). Furthermore, the proposed method was successfully applied to the detection of BPs in real milk samples, and the results were in accordance with those of methods reported previously.
    MeSH term(s) Humans ; Animals ; Milk/chemistry ; Metal-Organic Frameworks ; Tandem Mass Spectrometry/methods ; Chromatography, Liquid/methods ; Benzhydryl Compounds/analysis ; Solid Phase Extraction ; Chromatography, High Pressure Liquid
    Chemical Substances Metal-Organic Frameworks ; bisphenol A (MLT3645I99) ; Benzhydryl Compounds
    Language English
    Publishing date 2023-03-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 241619-0
    ISSN 1520-5118 ; 0021-8561
    ISSN (online) 1520-5118
    ISSN 0021-8561
    DOI 10.1021/acs.jafc.2c09085
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  7. Article ; Online: International Nosocomial Infection Control Consortium (INICC) report of health care-associated infections, data summary of 25 countries for 2014 to 2023, Surgical Site Infections Module.

    Rosenthal, Victor Daniel / Yin, Ruijie / Jin, Zhilin / Alkhawaja, Safaa Abdulaziz / Zuñiga-Chavarria, Maria Adelia / Salgado, Estuardo / El-Kholy, Amani / Zuniga Moya, Julio C / Patil, Priyanka / Nadimpalli, Gita / Pattabhiramarao, Rao Nadimpalli / Zala, Dolatsinh / Villegas-Mota, Isabel / Ider, Bat-Erdene / Tumu, Nellie / Duszynska, Wieslawa / Nguyet, Le Thi Thu / Nair, Pravin K / Memish, Ziad A

    American journal of infection control

    2024  

    Abstract: Background: Surgical site infection (SSI) rates are higher in low-resource countries (LRC) than in high-income counterparts.: Methods: Prospective cohort study using the INICC Surveillance Online System, from 116 hospitals in 75 cities across 25 ... ...

    Abstract Background: Surgical site infection (SSI) rates are higher in low-resource countries (LRC) than in high-income counterparts.
    Methods: Prospective cohort study using the INICC Surveillance Online System, from 116 hospitals in 75 cities across 25 Latin-American, Asian, Eastern-European, and Middle-Eastern countries: Argentina, Bahrain, Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Egypt, Honduras, India, Kosovo, Kuwait, Lebanon, Mexico, Mongolia, Pakistan, Papua New Guinea, Philippines, Poland, Romania, Saudi Arabia, Thailand, Turkey, Venezuela, Vietnam. CDC/NHSN definitions were applied. Surgical procedures (SPs) were categorized according to the International Classification of Diseases criteria.
    Results: From 2014 to 2023, we collected data on 1,251 SSIs associated with 56,617 SPs. SSI rates were significantly higher in SPs of INICC compared to CDC/NHSN data: hip prosthesis (3.68% vs 0.67%, relative risk [RR]=5.46, 95% confidence interval [CI]=3.71-8.03, P<.001), knee prosthesis (2.02% vs 0.58%, RR=3.49, 95% CI=1.87-6.49, P<.001), coronary artery bypass (4.16% vs 1.37%, RR=3.03, 95% CI=2.35-3.91, P<.001), peripheral vascular bypass (15.69% vs 2.93%, RR=5.35, 95% CI=2.30-12.48, P<.001), abdominal aortic aneurysm repair (8.51% vs 2.12%, RR=4.02, 95% CI=2.11-7.65, P<.001), spinal fusion (6.47% vs 0.70%, RR=9.27, 95% CI=6.21-13.84, P<.001), laminectomy (2.68% vs 0.72%, RR=3.75, 95% CI=2.36-5.95, P<.001), among others.
    Conclusions: Elevated SSI rates in LRCs emphasize the need for effective interventions.
    Language English
    Publishing date 2024-04-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 392362-9
    ISSN 1527-3296 ; 0196-6553
    ISSN (online) 1527-3296
    ISSN 0196-6553
    DOI 10.1016/j.ajic.2024.04.007
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  8. Article ; Online: Determinants and Temporal Trends of Dual Antiplatelet Therapy After Mild Noncardioembolic Stroke.

    Del Brutto, Victor J / Yin, Ruijie / Gardener, Hannah / Ying, Hao / Gutierrez, Carolina M / Jameson, Angus M / Rose, David Z / Alkhachroum, Ayham / Foster, Dianne / Dong, Chuanhui / Ancheta, Selina / Sur, Nicole B / Gordon Perue, Gillian / Rundek, Tatjana / Asdaghi, Negar / Sacco, Ralph L / Romano, Jose G

    Stroke

    2023  Volume 54, Issue 10, Page(s) 2552–2561

    Abstract: Background: Short-term dual antiplatelet therapy (DAPT) reduces early stroke recurrence after mild noncardioembolic ischemic stroke (NCIS). We aim to evaluate temporal trends and determinants of DAPT prescription after mild NCIS in the Florida Stroke ... ...

    Abstract Background: Short-term dual antiplatelet therapy (DAPT) reduces early stroke recurrence after mild noncardioembolic ischemic stroke (NCIS). We aim to evaluate temporal trends and determinants of DAPT prescription after mild NCIS in the Florida Stroke Registry, a statewide registry across Get With The Guidelines-Stroke participating hospitals.
    Methods: In this cross-sectional analysis of a cohort study, we included patients with mild NCIS (National Institutes of Health Stroke Scale score ≤3) who were potentially eligible for DAPT across 168 Florida Stroke Registry participating hospitals between January 2010 and September 2022. Using antiplatelet prescription as the dependent variable (DAPT versus single antiplatelet therapy), we fit logistic regression models adjusted for patient-related factors, hospital-related factors, clinical presentation, vascular risk factors, and ischemic stroke subtype, to obtain adjusted odds ratios (aORs) with 95% CIs.
    Results: From 283 264 Florida Stroke Registry ischemic stroke patients during the study period, 109 655 NCIS were considered eligible. Among these, 37 058 patients with National Institutes of Health Stroke Scale score >3 were excluded, resulting in a sample of 72 597 mild NCIS (mean age 68±14 years; female 47.3%). Overall, 24 693 (34.0%) patients with mild NCIS were discharged on DAPT and 47 904 (66.0%) on single antiplatelet therapy. DAPT prescription increased from 25.7% in 2010 to 52.8% in 2022 (
    Conclusions: Despite a temporal trend increase in DAPT prescription after mild NCIS, we found substantial underutilization of evidence-based DAPT associated with significant disparities in stroke care.
    MeSH term(s) Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Platelet Aggregation Inhibitors/therapeutic use ; Aspirin/therapeutic use ; Clopidogrel/therapeutic use ; Cohort Studies ; Cross-Sectional Studies ; Stroke/drug therapy ; Stroke/epidemiology ; Stroke/chemically induced ; Ischemic Stroke/drug therapy ; Drug Therapy, Combination ; Treatment Outcome
    Chemical Substances Platelet Aggregation Inhibitors ; Aspirin (R16CO5Y76E) ; Clopidogrel (A74586SNO7)
    Language English
    Publishing date 2023-09-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80381-9
    ISSN 1524-4628 ; 0039-2499 ; 0749-7954
    ISSN (online) 1524-4628
    ISSN 0039-2499 ; 0749-7954
    DOI 10.1161/STROKEAHA.123.043769
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  9. Article ; Online: Dose-dependent effects of lead induced gut injuries: An in vitro and in vivo study.

    Yu, Leilei / Yu, Yaqi / Yin, Ruijie / Duan, Hui / Qu, Dingwu / Tian, Fengwei / Narbad, Arjan / Chen, Wei / Zhai, Qixiao

    Chemosphere

    2020  Volume 266, Page(s) 129130

    Abstract: Lead (Pb) toxicity has been widely studied, but its dose-dependent toxic effects on the gut remain unclear, therefore, the aim of this study was to evaluate the effects of different doses of Pb exposure on the gut microbiota and gut barrier in vitro and ... ...

    Abstract Lead (Pb) toxicity has been widely studied, but its dose-dependent toxic effects on the gut remain unclear, therefore, the aim of this study was to evaluate the effects of different doses of Pb exposure on the gut microbiota and gut barrier in vitro and in vivo. The HT-29 cell model was used to determine the Pb-induced effects on cell viability, reactive oxygen species (ROS), and tight junction proteins (TJPs) in vitro, and C57BL/6 mice models exposed to 0, 20, 100, 500, and 1000 mg/kg Pb were used to investigate the Pb-induced dose-dependent effects on the gut microbiota, TJP expression, and colon histopathology. Our results showed that the exposure of HT-29 cells to 8 mM Pb decreased cell viability by 50%, elevated ROS levels by 200%, and suppressed the expression of the TJPs, zonula occludens-1 (ZO-1) and occludin by 23% and 35%, respectively. Consistently, Pb-exposed mice showed significant increases in colon tissue damage and inflammation and reductions in ZO-1 mRNA levels in a dose-dependent manner. The occludin mRNA levels decreased in the 500 and 1000 mg/kg groups. At the genus level, the relative abundance of Coprococcus and Oscillospira decreased and that of Lactobacillus increased in linear manner with the Pb exposure dose. PICRUSt analysis based on 16S rRNA sequencing revealed Pb dose-dependent alterations in metabolism through the gut microbiota. These findings suggest that Pb exposure can not only disrupt the barrier by generating oxidative stress, but can also induce gut dysbiosis, colon tissue damage, and gut inflammation in a dose-dependent manner.
    MeSH term(s) Animals ; Gastrointestinal Microbiome ; Lead/toxicity ; Mice ; Mice, Inbred C57BL ; Occludin ; RNA, Ribosomal, 16S
    Chemical Substances Occludin ; RNA, Ribosomal, 16S ; Lead (2P299V784P)
    Language English
    Publishing date 2020-11-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 120089-6
    ISSN 1879-1298 ; 0045-6535 ; 0366-7111
    ISSN (online) 1879-1298
    ISSN 0045-6535 ; 0366-7111
    DOI 10.1016/j.chemosphere.2020.129130
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  10. Article ; Online: Histone deacetylase inhibitor attenuates experimental fungal keratitis in mice.

    Li, Xiaohua / Yuan, Min / Yin, Ruijie / Liu, Xiaohui / Zhang, Yu / Sun, Shengtao / Han, Lei / He, Shikun

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 9859

    Abstract: Fungal keratitis is one of the leading causes of blindness of infected corneal diseases, but the pathogenesis of fungal keratitis is not fully understood and therefore the treatment of the disease by medication is still under investigation. In the ... ...

    Abstract Fungal keratitis is one of the leading causes of blindness of infected corneal diseases, but the pathogenesis of fungal keratitis is not fully understood and therefore the treatment of the disease by medication is still under investigation. In the current study, we sought to study the effect of HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) on experimental fungal keratitis in mice. SAHA (25 mg/kg) (n = 30) or vehicle (DMSO) (n = 30) was delivered through intraperitoneal injection (IP) 24 hours after the fungal inoculation, and the same amount of SAHA injection or DMSO was followed at day 2. The expression of histone H3 (H3), acetylated histone H3 (AC-H3), histone deacetylase 1 (HDAC)1, tumor necrosis factor-α (TNFα), and Toll-like receptor 4 (TLR4) in surgically excised specimens from the patients and mice with fungal keratitis were detected by immunohistochemistry. The expression of mRNAs for Interleukin-1β (IL-1β), TNFα, and TLR4 were evaluated in the corneas of the mice with fungal infection and the control corneas by real-time PCR. The quantification of IL-1β and TNFα in the corneas of the mice with fungal infection was determined by ELISA. The inhibitory effect of SAHA on mice fungal keratitis was revealed by GMS and H&E staining. We found that the downregulation of histone acetylation and upregulation of HDAC1 expression were associated with the increased inflammation response in fungal keratitis not only in humans but also in experimental animals. SAHA was able to inhibit experimental fungal keratitis in mouse by suppressing TLR4 and inflammatory cytokines such as TNFα and IL-1β; the inhibition of HDAC may be a potential therapeutic approach for the treatment of fungal keratitis.
    MeSH term(s) Acetylation ; Adult ; Aged ; Animals ; Cytokines/metabolism ; Dimethyl Sulfoxide/pharmacology ; Disease Models, Animal ; Eye Infections, Fungal/drug therapy ; Eye Infections, Fungal/metabolism ; Female ; Histone Deacetylase 1/antagonists & inhibitors ; Histone Deacetylase Inhibitors/pharmacology ; Histones/metabolism ; Humans ; Keratitis/drug therapy ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Toll-Like Receptor 4/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Vorinostat/pharmacology
    Chemical Substances Cytokines ; Histone Deacetylase Inhibitors ; Histones ; Toll-Like Receptor 4 ; Tumor Necrosis Factor-alpha ; Vorinostat (58IFB293JI) ; Histone Deacetylase 1 (EC 3.5.1.98) ; Dimethyl Sulfoxide (YOW8V9698H)
    Language English
    Publishing date 2019-07-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-46361-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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