37 results on '"Hongyu Ru"'
Search Results
2. Detection of gut microbiota and pathogen produced N-acyl homoserine in host circulation and tissues
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Jingchuan Xue, Liang Chi, Pengcheng Tu, Yunjia Lai, Chih-Wei Liu, Hongyu Ru, and Kun Lu
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Microbial ecology ,QR100-130 - Abstract
Abstract Recent studies suggest that quorum-sensing molecules may play a role in gut microbiota-host crosstalk. However, whether microbiota produces quorum-sensing molecules and whether those molecules can trans-kingdom transport to the host are still unknown. Here, we develop a UPLC-MS/MS-based assay to screen the 27 N-acyl homoserine lactones (AHLs) in the gut microbiota and host. Various AHL molecules are exclusively detected in the cecal contents, sera and livers from conventionally-raised mice but cannot be detected in germ-free mice. Pathogen-produced C4-HSL is detected in the cecal contents and sera of Citrobacter rodentium (C. rodentium)-infected mice, but not found in uninfected controls. Moreover, C. rodentium infection significantly increases the level of multiple AHL molecules in sera. Our findings demonstrate that both commensal and pathogenic bacteria, can produce AHLs that can be detected in host bodies, suggesting that quorum-sensing molecules could be a group of signaling molecules in trans-kingdom microbiota-host crosstalk.
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- 2021
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3. A Black Raspberry-Rich Diet Protects From Dextran Sulfate Sodium-Induced Intestinal Inflammation and Host Metabolic Perturbation in Association With Increased Aryl Hydrocarbon Receptor Ligands in the Gut Microbiota of Mice
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Pengcheng Tu, Liang Chi, Xiaoming Bian, Bei Gao, Hongyu Ru, and Kun Lu
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black raspberry (Rubus occidentalis) ,gut microbiota ,aryl hydrocarbon receptor (AHR) ,metabolomics ,inflammation ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Dietary modulation of the gut microbiota recently received considerable attention, and ligand activation of aryl hydrocarbon receptor (AHR) plays a pivotal role in intestinal immunity. Importantly, black raspberry (BRB, Rubus occidentalis) is associated with a variety of beneficial health effects. We aim to investigate effects of a BRB-rich diet on dextran sulfate sodium (DSS)-induced intestinal inflammation and to determine whether its consequent anti-inflammatory effects are relevant to modulation of the gut microbiota, especially its production of AHR ligands. A mouse model of DSS-induced intestinal inflammation was used in the present study. C57BL/6J mice were fed either AIN-76A or BRB diet. Composition and functions of the gut microbiota were assessed by 16S rRNA sequencing and comparative metagenome analysis. Metabolic profiles of host and the gut microbiome were assessed by serum and fecal metabolomic profiling and identification. BRB diet was found to ameliorate DSS-induced intestinal inflammation and host metabolic perturbation. BRB diet also protected from DSS-induced perturbation in diversity and composition in the gut microbiota. BRB diet promoted AHR ligand production by the gut microbiota, as revealed by increased levels of fecal AHR activity in addition to increased levels of two known AHR ligands, hemin and biliverdin. Accordingly, enrichment of bacterial genes and pathways responsible for production of hemin and biliverdin were found, specific gut bacteria that are highly correlated with abundances of hemin and biliverdin were also identified. BRB dietary intervention ameliorated intestinal inflammation in mice in association with promotion of AHR ligand production by the gut microbiota.
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- 2022
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4. High-Resolution Metabolomics of 50 Neurotransmitters and Tryptophan Metabolites in Feces, Serum, and Brain Tissues Using UHPLC-ESI‑Q Exactive Mass Spectrometry
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Yunjia Lai, Chih-Wei Liu, Liang Chi, Hongyu Ru, and Kun Lu
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Chemistry ,QD1-999 - Published
- 2021
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5. Association between anesthesia duration and outcome in dogs with surgically treated acute severe spinal cord injury caused by thoracolumbar intervertebral disk herniation
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Joe Fenn, Hongyu Ru, Nick D. Jeffery, Sarah Moore, Andrea Tipold, Franz J. Soebbeler, Adriano Wang‐Leandro, Christopher L. Mariani, Peter J. Early, Karen R. Muñana, and Natasha J. Olby
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canine ,extrusion ,hemilaminectomy ,prognosis ,surgery ,Veterinary medicine ,SF600-1100 - Abstract
Abstract Background Retrospective research recently identified a possible relationship between duration of surgery and outcome in severely affected dogs treated surgically for acute thoracolumbar intervertebral disk herniation (TL‐IVDH). Hypothesis That increased duration of surgery is associated with poorer outcome in dogs with absent pain perception treated surgically for TL‐IVDH. Animals Two hundred ninety‐seven paraplegic dogs with absent pain perception surgically treated for acute TL‐IVDH. Methods Retrospective cohort study. Medical records of 5 institutions were reviewed. Inclusion criteria were paraplegia with absence of pain perception, surgical treatment of TL‐IVDH, and 1‐year postoperative outcome (ambulatory: yes or no). Canine data, outcome, and surgery and total anesthesia duration were retrieved. Results In this study, 183/297 (61.6%) dogs were ambulatory within 1 year, 114 (38.4%) dogs failed to recover, including 74 dogs (24.9%) euthanized because of progressive myelomalacia. Median anesthesia duration in dogs that regained ambulation within 1 year of surgery (4.0 hours, interquartile range [IQR] 3.2‐5.1) was significantly shorter than those that did not (4.5 hours, IQR 3.7‐5.6, P = .01). Multivariable logistic regression demonstrated a significant negative association between both duration of surgery and total anesthesia time and ambulation at 1 year when controlling for body weight and number of disk spaces operated on. Conclusions and Clinical Importance Findings support a negative association between increased duration of anesthesia and outcome in this group of dogs. However, the retrospective nature of the data does not imply a causal relationship.
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- 2020
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6. Metabolite Profiling of the Gut Microbiome in Mice with Dietary Administration of Black Raspberries
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Pengcheng Tu, Xiaoming Bian, Liang Chi, Jingchuan Xue, Bei Gao, Yunjia Lai, Hongyu Ru, and Kun Lu
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Chemistry ,QD1-999 - Published
- 2020
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7. Risk factors associated with progressive myelomalacia in dogs with complete sensorimotor loss following intervertebral disc extrusion: a retrospective case-control study
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Aude Castel, Natasha J. Olby, Hongyu Ru, Christopher L. Mariani, Karen R. Muñana, and Peter J. Early
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Ascending-descending myelomalacia ,Spinal cord injury ,Intervertebral disk disease ,Paraplegia ,Veterinary medicine ,SF600-1100 - Abstract
Abstract Background Progressive myelomalacia (PMM) is a usually fatal complication of acute intervertebral disc extrusion (IVDE) in dogs but its risk factors are poorly understood. The objective of this retrospective case-control study was to identify risk factors for PMM by comparing dogs with complete sensorimotor loss following IVDE that did and did not develop the disease after surgery. We also investigated whether any risk factors for PMM influenced return of ambulation. Medical records of client-owned dogs with paraplegia and loss of pain perception that underwent surgery for IVDE from 1998 to 2016, were reviewed. Dogs were categorized as PMM yes or no based on clinical progression or histopathology. Walking outcome at 6 months was established. Signalment, onset and duration of signs (categorized), steroids, non-steroidal anti-inflammatory drugs (yes or no), site of IVDE (lumbar intumescence or thoracolumbar) and longitudinal extent of IVDE were retrieved and their associations with PMM and walking outcome were examined using logistic regression. Results One hundred and ninety seven dogs were included, 45 with and 152 without PMM. A 6-month-outcome was available in 178 dogs (all 45 PMM dogs and 133 control dogs); 86 recovered walking (all in the control group). Disc extrusions at the lumbar intumescence were associated with PMM (p = 0.01, OR: 3.02, CI: 1.3–7.2). Surgery performed more than 12 h after loss of ambulation was associated with PMM (OR = 3.4; CI = 1.1–10.5, p = 0.03 for 12-24 h and OR = 4.6; CI = 1.3–16.6, p = 0.02 for the > 24 h categories when compared with the ≤12 h category). Treatment with corticosteroids was negatively associated with PMM (OR: 3.1; CI: 1.3–7.6, p = 0.01). The only variable to affect walking outcome was longitudinal extent of IVDE (OR = 2.6; CI = 1.3–5.3, p = 0.006). Conclusion Dogs with lumbar intumescence IVDE are at increased risk of PMM. Timing of surgery and corticosteroid use warrant further investigations. PMM and recovery of walking are influenced by different factors.
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- 2019
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8. Studies of xenobiotic-induced gut microbiota dysbiosis: from correlation to mechanisms
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Liang Chi, Pengcheng Tu, Hongyu Ru, and Kun Lu
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gut microbiota ,xenobiotics ,dysbiosis ,host–microbiota interactions ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Environmental chemicals can alter gut microbial community composition, known as dysbiosis. However, the gut microbiota is a highly dynamic system and its functions are still largely underexplored. Likewise, it is unclear whether xenobiotic exposure affects host health through impairing host–microbiota interactions. Answers to this question not only can lead to a more precise understanding of the toxic effects of xenobiotics but also can provide new targets for the development of new therapeutic strategies. Here, we aim to identify the major challenges in the field of microbiota-exposure research and highlight the need to exam the health effects of xenobiotic-induced gut microbiota dysbiosis in host bodies. Although the changes of gut microbiota frequently co-occur with the xenobiotic exposure, the causal relationship of xenobiotic-induced microbiota dysbiosis and diseases is rarely established. The high dynamics of the gut microbiota and the complex interactions among exposure, microbiota, and host, are the major challenges to decipher the specific health effects of microbiota dysbiosis. The next stage of study needs to combine various technologies to precisely assess the xenobiotic-induced gut microbiota perturbation and the subsequent health effects in host bodies. The exposure, gut microbiota dysbiosis, and disease outcomes have to be causally linked. Many microbiota–host interactions are established by previous studies, including signaling metabolites and response pathways in the host, which may use as start points for future research to examine the mechanistic interactions of exposure, gut microbiota, and host health. In conclusion, to precisely understand the toxicity of xenobiotics and develop microbiota-based therapies, the causal and mechanistic links of exposure and microbiota dysbiosis have to be established in the next stage study.
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- 2021
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9. International lineages of Salmonella enterica serovars isolated from chicken farms, Wakiso District, Uganda.
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Takiyah Ball, Daniel Monte, Awa Aidara-Kane, Jorge Matheu, Hongyu Ru, Siddhartha Thakur, Francis Ejobi, and Paula Fedorka-Cray
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Medicine ,Science - Abstract
The growing occurrence of multidrug-resistant (MDR) Salmonella enterica in poultry has been reported with public health concern worldwide. We reported, recently, the occurrence of Escherichia coli and Salmonella enterica serovars carrying clinically relevant resistance genes in dairy cattle farms in the Wakiso District, Uganda, highlighting an urgent need to monitor food-producing animal environments. Here, we present the prevalence, antimicrobial resistance, and sequence type of 51 Salmonella isolates recovered from 379 environmental samples from chicken farms in Uganda. Among the Salmonella isolates, 32/51 (62.7%) were resistant to at least one antimicrobial, and 10/51 (19.6%) displayed multiple drug resistance. Through PCR, five replicon plasmids were identified among chicken Salmonella isolates including IncFIIS 17/51 (33.3%), IncI1α 12/51 (23.5%), IncP 8/51 (15.7%), IncX1 8/51 (15.7%), and IncX2 1/51 (2.0%). In addition, we identified two additional replicons through WGS (Whole Genome Sequencing; ColpVC and IncFIB). A significant seasonal difference between chicken sampling periods was observed (p = 0.0017). We conclude that MDR Salmonella highlights the risks posed to animals and humans. Implementing a robust, integrated surveillance system will aid in monitoring MDR zoonotic threats.
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- 2020
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10. Characterization of the Functional Changes in Mouse Gut Microbiome Associated with Increased Akkermansia muciniphila Population Modulated by Dietary Black Raspberries
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Pengcheng Tu, Xiaoming Bian, Liang Chi, Bei Gao, Hongyu Ru, Thomas J. Knobloch, Christopher M. Weghorst, and Kun Lu
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Chemistry ,QD1-999 - Published
- 2018
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11. Profound perturbation induced by triclosan exposure in mouse gut microbiome: a less resilient microbial community with elevated antibiotic and metal resistomes
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Bei Gao, Pengcheng Tu, Xiaoming Bian, Liang Chi, Hongyu Ru, and Kun Lu
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Triclosan ,Gut microbiome ,Antibiotic resistance ,Metal resistance ,Resistome ,Triclosan resistance ,Therapeutics. Pharmacology ,RM1-950 ,Toxicology. Poisons ,RA1190-1270 - Abstract
Abstract Background Environmental chemical-induced perturbations of gut microbiome are associated with a series of adverse health outcomes. The effects of triclosan on human health have been controversial in recent years. The purpose of this study is to investigate the functional impact of triclosan on the mouse gut microbiome and the link between triclosan exposure and resistomes in gut bacteria. Methods We combined 16S rRNA gene sequencing and shotgun metagenomics sequencing to examine the compositional and functional impact of triclosan exposure on the gut microbiota of C57BL/6 mice. Results 16S rRNA sequencing results revealed that 13-week triclosan exposure in drinking water induced significant perturbations in mouse gut bacterial assemblages with distinct trajectories compared to controls. Metagenomics sequencing results indicated a remarkable enrichment of gut bacterial genes related to triclosan resistance, stress response, antibiotic resistance and heavy metal resistance. Conclusions Triclosan exposure has a profound impact on the mouse gut microbiome by inducing perturbations at both compositional and functional levels. To our best knowledge, this is the first evidence regarding the functional alterations of gut microbiome induced by triclosan exposure, which may provide novel mechanistic insights into triclosan exposure and associated diseases.
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- 2017
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12. Tissue-specific changes in size and shape of the ligaments and tendons of the porcine knee during post-natal growth.
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Stephanie G Cone, Hope E Piercy, Emily P Lambeth, Hongyu Ru, Jorge A Piedrahita, Jeffrey T Spang, Lynn A Fordham, and Matthew B Fisher
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Medicine ,Science - Abstract
Prior studies have analyzed growth of musculoskeletal tissues between species or across body segments; however, little research has assessed the differences in similar tissues within a single joint. Here we studied changes in the length and cross-sectional area of four ligaments and tendons, (anterior cruciate ligament, patellar tendon, medial collateral ligament, lateral collateral ligament) in the tibiofemoral joint of female Yorkshire pigs through high-field magnetic resonance imaging throughout growth. Tissue lengths increased by 4- to 5-fold from birth to late adolescence across the tissues while tissue cross-sectional area increased by 10-20-fold. The anterior cruciate ligament and lateral collateral ligament showed allometric growth favoring change in length over change in cross-sectional area while the patellar tendon and medial collateral ligament grow in an isometric manner. Additionally, changes in the length and cross-sectional area of the anterior cruciate ligament did not increase as much as in the other ligaments and tendon of interest. Overall, these findings suggest that musculoskeletal soft tissue morphometry can vary within tissues of similar structure and within a single joint during post-natal growth.
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- 2019
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13. Gut Microbiome Response to Sucralose and Its Potential Role in Inducing Liver Inflammation in Mice
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Xiaoming Bian, Liang Chi, Bei Gao, Pengcheng Tu, Hongyu Ru, and Kun Lu
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artificial sweetener ,sucralose ,gut microbiota ,metabolomics ,inflammation ,Physiology ,QP1-981 - Abstract
Sucralose is the most widely used artificial sweetener, and its health effects have been highly debated over the years. In particular, previous studies have shown that sucralose consumption can alter the gut microbiota. The gut microbiome plays a key role in processes related to host health, such as food digestion and fermentation, immune cell development, and enteric nervous system regulation. Inflammation is one of the most common effects associated with gut microbiome dysbiosis, which has been linked to a series of human diseases, such as diabetes and obesity. The aim of this study was to investigate the structural and functional effects of sucralose on the gut microbiota and associated inflammation in the host. In this study, C57BL/6 male mice received sucralose in their drinking water for 6 months. The difference in gut microbiota composition and metabolites between control and sucralose-treated mice was determined using 16S rRNA gene sequencing, functional gene enrichment analysis and metabolomics. Inflammatory gene expression in tissues was analyzed by RT-PCR. Alterations in bacterial genera showed that sucralose affects the gut microbiota and its developmental dynamics. Enrichment of bacterial pro-inflammatory genes and disruption in fecal metabolites suggest that 6-month sucralose consumption at the human acceptable daily intake (ADI) may increase the risk of developing tissue inflammation by disrupting the gut microbiota, which is supported by elevated pro-inflammatory gene expression in the liver of sucralose-treated mice. Our results highlight the role of sucralose-gut microbiome interaction in regulating host health-related processes, particularly chronic inflammation.
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- 2017
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14. The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice.
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Xiaoming Bian, Liang Chi, Bei Gao, Pengcheng Tu, Hongyu Ru, and Kun Lu
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Medicine ,Science - Abstract
Artificial sweeteners have been widely used in the modern diet, and their observed effects on human health have been inconsistent, with both beneficial and adverse outcomes reported. Obesity and type 2 diabetes have dramatically increased in the U.S. and other countries over the last two decades. Numerous studies have indicated an important role of the gut microbiome in body weight control and glucose metabolism and regulation. Interestingly, the artificial sweetener saccharin could alter gut microbiota and induce glucose intolerance, raising questions about the contribution of artificial sweeteners to the global epidemic of obesity and diabetes. Acesulfame-potassium (Ace-K), a FDA-approved artificial sweetener, is commonly used, but its toxicity data reported to date are considered inadequate. In particular, the functional impact of Ace-K on the gut microbiome is largely unknown. In this study, we explored the effects of Ace-K on the gut microbiome and the changes in fecal metabolic profiles using 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics. We found that Ace-K consumption perturbed the gut microbiome of CD-1 mice after a 4-week treatment. The observed body weight gain, shifts in the gut bacterial community composition, enrichment of functional bacterial genes related to energy metabolism, and fecal metabolomic changes were highly gender-specific, with differential effects observed for males and females. In particular, ace-K increased body weight gain of male but not female mice. Collectively, our results may provide a novel understanding of the interaction between artificial sweeteners and the gut microbiome, as well as the potential role of this interaction in the development of obesity and the associated chronic inflammation.
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- 2017
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15. Towards Mass Spectrometry-Based Chemical Exposome: Current Approaches, Challenges, and Future Directions
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Jingchuan Xue, Yunjia Lai, Chih-Wei Liu, and Hongyu Ru
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chemical exposome ,biomonitoring ,environmental monitoring ,mass spectrometry ,disease ,bioinformatics ,Chemical technology ,TP1-1185 - Abstract
The proposal of the “exposome” concept represents a shift of the research paradigm in studying exposure-disease relationships from an isolated and partial way to a systematic and agnostic approach. Nevertheless, exposome implementation is facing a variety of challenges including measurement techniques and data analysis. Here we focus on the chemical exposome, which refers to the mixtures of chemical pollutants people are exposed to from embryo onwards. We review the current chemical exposome measurement approaches with a focus on those based on the mass spectrometry. We further explore the strategies in implementing the concept of chemical exposome and discuss the available chemical exposome studies. Early progresses in the chemical exposome research are outlined, and major challenges are highlighted. In conclusion, efforts towards chemical exposome have only uncovered the tip of the iceberg, and further advancement in measurement techniques, computational tools, high-throughput data analysis, and standardization may allow more exciting discoveries concerning the role of exposome in human health and disease.
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- 2019
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16. Serum Metabolomics Identifies Altered Bioenergetics, Signaling Cascades in Parallel with Exposome Markers in Crohn’s Disease
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Yunjia Lai, Jingchuan Xue, Chih-Wei Liu, Bei Gao, Liang Chi, Pengcheng Tu, Kun Lu, and Hongyu Ru
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Inflammatory Bowel Disease ,Crohn’s Disease ,Serum Metabolomics ,docosahexaenoic acid ,Tryptophan Metabolism ,ergothioneine ,gut microbiota ,Exposome ,Organic chemistry ,QD241-441 - Abstract
Inflammatory bowel disease (IBD) has stimulated much interest due to its surging incidences and health impacts in the U.S. and worldwide. However, the exact cause of IBD remains incompletely understood, and biomarker is lacking towards early diagnostics and effective therapy assessment. To tackle these, the emerging high-resolution mass spectrometry (HRMS)-based metabolomics shows promise. Here, we conducted a pilot untargeted LC/MS metabolomic profiling in Crohn’s disease, for which serum samples of both active and inactive cases were collected, extracted, and profiled by a state-of-the-art compound identification workflow. Results show a distinct metabolic profile of Crohn’s from control, with most metabolites downregulated. The identified compounds are structurally diverse, pointing to important pathway perturbations ranging from energy metabolism (e.g., β-oxidation of fatty acids) to signaling cascades of lipids (e.g., DHA) and amino acid (e.g., L-tryptophan). Importantly, an integral role of gut microbiota in the pathogenesis of Crohn’s disease is highlighted. Xenobiotics and their biotransformants were widely detected, calling for massive exposomic profiling for future cohort studies as such. This study endorses the analytical capacity of untargeted metabolomics for biomarker development, cohort stratification, and mechanistic interpretation; the findings might be valuable for advancing biomarker research and etiologic inquiry in IBD.
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- 2019
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17. Effects of the Artificial Sweetener Neotame on the Gut Microbiome and Fecal Metabolites in Mice
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Liang Chi, Xiaoming Bian, Bei Gao, Pengcheng Tu, Yunjia Lai, Hongyu Ru, and Kun Lu
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neotame ,gut microbiome ,metabolomics ,artificial sweeteners ,Organic chemistry ,QD241-441 - Abstract
Although artificial sweeteners are widely used in food industry, their effects on human health remain a controversy. It is known that the gut microbiota plays a key role in human metabolism and recent studies indicated that some artificial sweeteners such as saccharin could perturb gut microbiome and further affect host health, such as inducing glucose intolerance. Neotame is a relatively new low-caloric and high-intensity artificial sweetener, approved by FDA in 2002. However, the specific effects of neotame on gut bacteria are still unknown. In this study, we combined high-throughput sequencing and gas chromatography–mass spectrometry (GC-MS) metabolomics to investigate the effects of neotame on the gut microbiome and fecal metabolite profiles of CD-1 mice. We found that a four-week neotame consumption reduced the alpha-diversity and altered the beta-diversity of the gut microbiome. Firmicutes was largely decreased while Bacteroidetes was significantly increased. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis also indicated that the control mice and neotame-treated mice have different metabolic patterns and some key genes such as butyrate synthetic genes were decreased. Moreover, neotame consumption also changed the fecal metabolite profiles. Dramatically, the concentrations of multiple fatty acids, lipids as well as cholesterol in the feces of neotame-treated mice were consistently higher than controls. Other metabolites, such as malic acid and glyceric acid, however, were largely decreased. In conclusion, our study first explored the specific effects of neotame on mouse gut microbiota and the results may improve our understanding of the interaction between gut microbiome and neotame and how this interaction could influence the normal metabolism of host bodies.
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- 2018
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18. Systematic review and meta-analysis of birth weight and perfluorohexane sulfonate exposures: examination of sample timing and study confidence.
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Hongyu Ru, Lee, Alexandra L., Rappazzo, Kristen M., Dzierlenga, Michael, Radke, Elizabeth, Bateson, Thomas F., and Wright, J. Michael
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- 2024
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19. A Black Raspberry-Rich Diet Protects From Dextran Sulfate Sodium-Induced Intestinal Inflammation and Host Metabolic Perturbation in Association With Increased Aryl Hydrocarbon Receptor Ligands in the Gut Microbiota of Mice
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Pengcheng, Tu, Liang, Chi, Xiaoming, Bian, Bei, Gao, Hongyu, Ru, and Kun, Lu
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Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism ,Food Science - Abstract
Dietary modulation of the gut microbiota recently received considerable attention, and ligand activation of aryl hydrocarbon receptor (AHR) plays a pivotal role in intestinal immunity. Importantly, black raspberry (BRB, Rubus occidentalis) is associated with a variety of beneficial health effects. We aim to investigate effects of a BRB-rich diet on dextran sulfate sodium (DSS)-induced intestinal inflammation and to determine whether its consequent anti-inflammatory effects are relevant to modulation of the gut microbiota, especially its production of AHR ligands. A mouse model of DSS-induced intestinal inflammation was used in the present study. C57BL/6J mice were fed either AIN-76A or BRB diet. Composition and functions of the gut microbiota were assessed by 16S rRNA sequencing and comparative metagenome analysis. Metabolic profiles of host and the gut microbiome were assessed by serum and fecal metabolomic profiling and identification. BRB diet was found to ameliorate DSS-induced intestinal inflammation and host metabolic perturbation. BRB diet also protected from DSS-induced perturbation in diversity and composition in the gut microbiota. BRB diet promoted AHR ligand production by the gut microbiota, as revealed by increased levels of fecal AHR activity in addition to increased levels of two known AHR ligands, hemin and biliverdin. Accordingly, enrichment of bacterial genes and pathways responsible for production of hemin and biliverdin were found, specific gut bacteria that are highly correlated with abundances of hemin and biliverdin were also identified. BRB dietary intervention ameliorated intestinal inflammation in mice in association with promotion of AHR ligand production by the gut microbiota.
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- 2022
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20. Neonatal Cranial Ultrasound Findings Among Infants Born Extremely Preterm: Associations With Neurodevelopmental Outcomes at Ten Years of Age
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Irina L. Mokrova, Jennifer Check, Karl C.K. Kuban, Stephen R. Hooper, Lynn A. Fordham, Elizabeth N. Allred, T. Michael O'Shea, Alan Leviton, Hongyu Ru, Rebecca C. Fry, Hudson P. Santos, Heather Campbell, Nigel Paneth, Hernan Jara, Laurie M. Douglass, Jean A. Frazier, Robert M. Joseph, and Kyle Roell
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Male ,Pediatrics ,medicine.medical_specialty ,Critical Care ,Infant, Premature, Diseases ,Article ,Cerebral palsy ,Cohort Studies ,03 medical and health sciences ,Epilepsy ,0302 clinical medicine ,Leukoencephalopathies ,030225 pediatrics ,Medicine ,Humans ,030212 general & internal medicine ,Cognitive impairment ,Child ,Cerebral Intraventricular Hemorrhage ,business.industry ,Extremely preterm ,Age Factors ,Infant, Newborn ,medicine.disease ,Echoencephalography ,United States ,Hospitalization ,Cranial ultrasound ,Intraventricular hemorrhage ,Increased risk ,Neurodevelopmental Disorders ,Infant, Extremely Premature ,Pediatrics, Perinatology and Child Health ,Female ,business ,Birth cohort - Abstract
OBJECTIVE: To examine the association between neonatal cranial ultrasound abnormalities among infants born extremely preterm and neurodevelopmental outcomes at ten years of age. STUDY DESIGN: In a multi-center birth cohort of infants born at < 28 weeks’ gestation, 889 of 1198 survivors were evaluated for neurological, cognitive, and behavioral outcomes at 10 years of age. Sonographic markers of white matter damage (WMD) included echolucencies in the brain parenchyma and moderate to severe ventricular enlargement. Neonatal cranial ultrasound findings were classified as: intraventricular hemorrhage (IVH) without WMD, IVH with WMD, WMD without IVH, and neither IVH nor WMD. RESULTS: WMD without IVH was associated with an increased risk of cognitive impairment (OR 3.5, 95% CI 1.7, 7.4), cerebral palsy (OR 14.3, 95% CI 6.5, 31.5), and epilepsy (OR 6.9; 95% CI 2.9, 16.8). Similar associations were found for WMD accompanied by IVH. Isolated IVH was not significantly associated these outcomes. CONCLUSIONS: Among children born extremely preterm, cranial ultrasound abnormalities, particularly those indicative of WMD, are predictive of neurodevelopmental impairments at 10 years of age. The strongest associations were found with cerebral palsy.
- Published
- 2021
21. Role of LECT2 in exacerbating atopic dermatitis: insight from in vivo and in vitro models via NF-κB signaling pathway
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Zhifang Liu, Xinyu Jiang, Keyu Zhao, Hongyu Ruan, Yizhao Ma, Yuhan Ma, Qiongyan Zhou, Jing Zhang, Xiaoyan Sun, Wenxue Ma, and Suling Xu
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LECT2 ,atopic dermatitis ,NF-κB signaling pathway ,inflammatory cytokines ,skin barrier proteins ,therapeutic target ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Leukocyte cell-derived chemotaxin 2 (LECT2) is linked to various immune diseases. Previously, we reported that serum LECT2 levels correlate with disease severity in atopic dermatitis (AD) patients. To investigate the role of LECT2 in AD and elucidate its potential mechanisms, we used LECT2 to treat an AD mouse model induced by 1-Chloro-2,4-dinitrobenzene (DNCB) in LECT2 knockout (KO) and wild-type (WT) mice, and an AD cell model using TNF-α/IFN-γ-induced HaCaT cells. Inflammatory factors and barrier proteins were analyzed by histology, immunohistochemistry, RT-qPCR, ELISA, and Western Blot. Activation of the NF-κB signaling pathway was evaluated by Western Blot and immunofluorescence. In the AD mouse model, LECT2 treatment increased epidermal and dermal thickness, mast cell infiltration, and downregulated barrier proteins. Inflammatory factors were increased in skin lesions and serum. In the AD cell model, LECT2 decreased barrier protein levels and increased inflammatory factor levels, enhancing NF-κB P65 nuclear translocation. These results indicate that LECT2 exacerbates AD-like responses by dysregulating the NF-κB signaling pathway, highlighting its potential as a therapeutic target for AD management.
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- 2024
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22. Characterization of the Functional Changes in Mouse Gut Microbiome Associated with Increased Akkermansia muciniphila Population Modulated by Dietary Black Raspberries
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Christopher M. Weghorst, Kun Lu, Bei Gao, Pengcheng Tu, Xiaoming Bian, Hongyu Ru, Thomas J. Knobloch, and Liang Chi
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2. Zero hunger ,0301 basic medicine ,Genetics ,education.field_of_study ,General Chemical Engineering ,digestive, oral, and skin physiology ,030106 microbiology ,Population ,General Chemistry ,Biology ,Health benefits ,Vitamin biosynthesis ,Carbohydrate metabolism ,biology.organism_classification ,digestive system ,Gut microbiome ,lcsh:Chemistry ,03 medical and health sciences ,Human health ,030104 developmental biology ,lcsh:QD1-999 ,Gut bacteria ,education ,Akkermansia muciniphila - Abstract
Gut microbiome plays an essential role in host health through host–gut microbiota metabolic interactions. Desirable modulation of beneficial gut bacteria, such as Akkermansia muciniphila, can confer health benefits by altering microbiome-related metabolic profiles. The purpose of this study is to examine the effects of a black raspberry-rich diet to reshape the gut microbiome by selectively boosting A. muciniphila population in C57BL/6J mice. Remarkable changes of the mouse gut microbiome were revealed at both compositional and functional levels with an expected increase of A. muciniphila in concert with a profound impact on multiple gut microbiome-related functions, including vitamin biosynthesis, aromatic amino acid metabolism, carbohydrate metabolism, and oxidative stress. These functional alterations in the gut microbiome by an easily accessed freeze-dried black raspberry-supplemented diet may provide novel insights on the improvement of human health via gut microbiome modulation.
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- 2018
23. Tissue-specific changes in size and shape of the ligaments and tendons of the porcine knee during post-natal growth
- Author
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Lynn A. Fordham, Jeffrey T Spang, Hongyu Ru, Matthew B. Fisher, Emily P. Lambeth, Stephanie G. Cone, Hope E. Piercy, and Jorge A. Piedrahita
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Knee Joint ,Swine ,Isometric exercise ,Diagnostic Radiology ,Tendons ,0302 clinical medicine ,Skeletal Joints ,Pig Models ,Medicine and Health Sciences ,Anterior Cruciate Ligament ,Musculoskeletal System ,030222 orthopedics ,0303 health sciences ,Medial collateral ligament ,Multidisciplinary ,medicine.diagnostic_test ,Radiology and Imaging ,Anatomy ,Animal Models ,musculoskeletal system ,Magnetic Resonance Imaging ,Tendon ,medicine.anatomical_structure ,Experimental Organism Systems ,Connective Tissue ,Organ Specificity ,Ligament ,Medicine ,Female ,Research Article ,musculoskeletal diseases ,Imaging Techniques ,Anterior cruciate ligament ,Science ,Biology ,Research and Analysis Methods ,03 medical and health sciences ,Diagnostic Medicine ,Patellar Ligament ,medicine ,Tissue specific ,Animals ,030304 developmental biology ,Ligaments ,Morphometry ,Biology and Life Sciences ,Magnetic resonance imaging ,030229 sport sciences ,Patellar tendon ,Biological Tissue ,Age Groups ,Body Limbs ,People and Places ,Animal Studies ,Population Groupings ,human activities - Abstract
Prior studies have analyzed growth of musculoskeletal tissues between species or across body segments; however, little research has assessed the differences in similar tissues within a single joint. Here we studied changes in the length and cross-sectional area of four ligaments and tendons, (anterior cruciate ligament, patellar tendon, medial collateral ligament, lateral collateral ligament) in the tibiofemoral joint of female Yorkshire pigs through high-field magnetic resonance imaging throughout growth. Tissue lengths increased by 4-to 5-fold from birth to late adolescence across the tissues while tissue cross-sectional area increased by 10-20-fold. The anterior cruciate ligament and lateral collateral ligament showed allometric growth favoring change in length over change in cross-sectional area while the patellar tendon and medial collateral ligament grow in an isometric manner. Additionally, changes in the length and cross-sectional area of the anterior cruciate ligament did not increase as much as in the other ligaments and tendon of interest. Overall, these findings suggest that musculoskeletal soft tissue morphometry can vary within tissues of similar structure and within a single joint during post-natal growth.
- Published
- 2019
24. Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions
- Author
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Xiaoming Bian, Bei Gao, Liang Chi, Kun Lu, Pengcheng Tu, and Hongyu Ru
- Subjects
0301 basic medicine ,Male ,Metabolite ,Inflammation ,Biology ,Gut flora ,Toxicology ,digestive system ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Metabolomics ,Saccharin ,medicine ,Animals ,Humans ,Gastrointestinal tract ,Tumor Necrosis Factor-alpha ,Liver Diseases ,Gastrointestinal Microbiome ,digestive, oral, and skin physiology ,General Medicine ,biology.organism_classification ,Gastrointestinal Tract ,Mice, Inbred C57BL ,030104 developmental biology ,chemistry ,Liver ,030220 oncology & carcinogenesis ,Sweetening Agents ,Immunology ,Tumor necrosis factor alpha ,medicine.symptom ,psychological phenomena and processes ,Food Science - Abstract
Maintaining the balance of the gut microbiota and its metabolic functions is vital for human health, however, this balance can be disrupted by various external factors including food additives. A range of food and beverages are sweetened by saccharin, which is generally considered to be safe despite controversial debates. However, recent studies indicated that saccharin perturbed the gut microbiota. Inflammation is frequently associated with disruptions of the gut microbiota. The aim of this study is to investigate the relationship between host inflammation and perturbed gut microbiome by saccharin. C57BL/6J male mice were treated with saccharin in drinking water for six months. Q-PCR was used to detect inflammatory markers in mouse liver, while 16S rRNA gene sequencing and metabolomics were used to reveal changes of the gut microbiota and its metabolomic profiles. Elevated expression of pro-inflammatory iNOS and TNF-α in liver indicated that saccharin induced inflammation in mice. The altered gut bacterial genera, enriched orthologs of pathogen-associated molecular patterns, such as LPS and bacterial toxins, in concert with increased pro-inflammatory metabolites suggested that the saccharin-induced liver inflammation could be associated with the perturbation of the gut microbiota and its metabolic functions.
- Published
- 2017
25. Manganese-induced sex-specific gut microbiome perturbations in C57BL/6 mice
- Author
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Xiaoming Bian, Liang Chi, Bei Gao, Hongyu Ru, Pengcheng Tu, and Kun Lu
- Subjects
0301 basic medicine ,Male ,Gut–brain axis ,Biology ,Toxicology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Metabolomics ,Immune system ,Metabolome ,medicine ,Animals ,Pharmacology ,Gastrointestinal tract ,Manganese ,Sex Characteristics ,Neurotoxicity ,medicine.disease ,Cell biology ,Gastrointestinal Microbiome ,Gastrointestinal Tract ,Mice, Inbred C57BL ,Quorum sensing ,030104 developmental biology ,chemistry ,Biochemistry ,Female ,Xenobiotic - Abstract
Overexposure to manganese (Mn) leads to toxic effects, such as promoting the development of Parkinson's-like neurological disorders. The gut microbiome is deeply involved in immune development, host metabolism, and xenobiotics biotransformation, and significantly influences central nervous system (CNS) via the gut-brain axis, i.e. the biochemical signaling between the gastrointestinal tract and the CNS. However, it remains unclear whether Mn can affect the gut microbiome and its metabolic functions, particularly those linked to neurotoxicity. In addition, sex-specific effects of Mn have been reported, with no mechanism being identified yet. Recently, we have shown that the gut microbiome is largely different between males and females, raising the possibility that differential gut microbiome responses may contribute to sex-selective toxicity of Mn. Here, we applied high-throughput sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics to explore how Mn2+ exposure affects the gut microbiome and its metabolism in C57BL/6 mice. Mn2+ exposure perturbed the gut bacterial compositions, functional genes and fecal metabolomes in a highly sex-specific manner. In particular, bacterial genes and/or key metabolites of neurotransmitter synthesis and pro-inflammatory mediators are significantly altered by Mn2+ exposure, which can potentially affect chemical signaling of gut-brain interactions. Likewise, functional genes involved in iron homeostasis, flagellar motility, quorum sensing, and Mn transportation/oxidation are also widely changed by Mn2+ exposure. Taken together, this study has demonstrated that Mn2+ exposure perturbs the gut microbiome and its metabolic functions, which highlights the potential role of the gut microbiome in Mn2+ toxicity, particularly its sex-specific toxic effects.
- Published
- 2017
- Full Text
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26. Gut Microbiome Phenotypes Driven by Host Genetics Affect Arsenic Metabolism
- Author
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James A. Swenberg, Wanda Bodnar, Ridwan Mahbub, Steven R. Tannenbaum, Nicola Parry, James G. Fox, Kun Lu, Hongyu Ru, John S. Wishnok, Miroslav Styblo, and Peter Hans Cable
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inorganic chemicals ,chemistry.chemical_element ,Context (language use) ,010501 environmental sciences ,Biology ,Toxicology ,01 natural sciences ,Mass Spectrometry ,Arsenic ,03 medical and health sciences ,Mice ,RNA, Ribosomal, 16S ,Animals ,Gene knockout ,Biotransformation ,Chromatography, High Pressure Liquid ,030304 developmental biology ,0105 earth and related environmental sciences ,Genetics ,Mice, Knockout ,0303 health sciences ,integumentary system ,Rapid Report ,Host (biology) ,Microbiota ,General Medicine ,Metabolism ,Integrated approach ,Phenotype ,Gut microbiome ,3. Good health ,Interleukin-10 ,Gastrointestinal Tract ,chemistry ,Environmental Pollutants - Abstract
Large individual differences in susceptibility to arsenic-induced diseases are well-documented and frequently associated with different patterns of arsenic metabolism. In this context, the role of the gut microbiome in directly metabolizing arsenic and triggering systemic responses in diverse organs raises the possibility that gut microbiome phenotypes affect the spectrum of metabolized arsenic species. However, it remains unclear how host genetics and the gut microbiome interact to affect the biotransformation of arsenic. Using an integrated approach combining 16S rRNA gene sequencing and HPLC-ICP-MS arsenic speciation, we demonstrate that IL-10 gene knockout leads to a significant taxonomic change of the gut microbiome, which in turn substantially affects arsenic metabolism.
- Published
- 2014
27. Lipid and Cholesterol Homeostasis after Arsenic Exposure and Antibiotic Treatment in Mice: Potential Role of the Microbiota.
- Author
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Liang Chi, Yunjia Lai, Pengcheng Tu, Chih-Wei Liu, Jingchuan Xue, Hongyu Ru, and Kun Lu
- Subjects
ANTIBIOTICS ,LIPID metabolism ,CHOLESTEROL metabolism ,ANIMAL experimentation ,ANIMALS ,ARSENIC poisoning ,CELLULAR signal transduction ,GENE expression ,HOMEOSTASIS ,LIGANDS (Biochemistry) ,MICE ,PROTEINS ,RESEARCH funding ,RETINOIDS ,ENVIRONMENTAL exposure ,GUT microbiome - Abstract
BACKGROUND: Arsenic-induced liver X receptor/retinoid X receptor (LXR/RXR) signaling inhibition is a potential mechanism underlying the cardiovascular effects caused by arsenic. The gut microbiota can influence arsenic toxic effects. OBJECTIVE: We aimed to explore whether gut microbiota play a role in arsenic-induced LXR/RXR signaling inhibition and the subsequent lipid and cholesterol dysbiosis. METHODS: Conventional and antibiotic-treated mice (AB-treated mice) were exposed to 0:25 ppm and 1 ppm arsenic for 2 wk. Hepatic mRNAs were extracted and sequenced. The expression levels of genes associated with LXR/RXR signaling were quantified by quantitative real-time polymerase chain reaction (qPCR), and serum and hepatic cholesterol levels were measured. Liquid chromatography-mass spectrometry (LC-MS)-based lipidomics were used to examine serum and hepatic lipids. RESULTS: Pathway analysis indicated that arsenic exposure differentially influenced the hepatic signaling pathways in conventional and AB-treated mice. The expression of sterol regulatory element-binding protein 1 (Srebp1c), 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), and cytochrome P450 family 7 subfamily A member 1 (Cyp7a1), as well as cholesterol efflux genes, including ATP binding cassette subfamily G member 5/8 (Abcg5/8) and cluster of differentiation 36 (Cd36), was lower in arsenic-exposed conventional mice but not in AB-treated mice. Similarly, under arsenic exposure, the hepatic expression of scavenger receptor class B member 1 (Scarb1), which is involved in reverse cholesterol transport (RCT), was lower in conventional mice, but was higher in AB-treated animals compared with controls. Correspondingly, arsenic exposure exerted opposite effects on the serum cholesterol levels in conventional and AB-treated mice, i.e., higher serum cholesterol levels in conventional mice but lower levels in AB-treated mice than in respective controls. Serum lipid levels, especially triglyceride (TG) levels, were higher in conventional mice exposed to 1 ppm arsenic, while arsenic exposure did not significantly affect the serum lipids in AB-treated mice. Liver lipid patterns were also differentially perturbed in a microbiota-dependent manner. CONCLUSIONS: Our results suggest that in mice, the gut microbiota may be a critical factor regulating arsenic-induced LXR/RXR signaling perturbation, suggesting that modulation of the gut microbiota might be an intervention strategy to reduce the toxic effects of arsenic on lipid and cholesterol homeostasis. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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- View/download PDF
28. Stifle joint osteoarthritis at the time of diagnosis of cranial cruciate ligament injury is higher in Boxers and in dogs weighing more than 35 kilograms.
- Author
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Gilbert, Samuel, Langenbach, Anke, Marcellin-Little, Denis J., Pease, Anthony P., and Hongyu Ru
- Abstract
Osteoarthritis is a ubiquitous disease in dogs. The purpose of this retrospective studywas to characterize the severity and distribution of osteoarthritis (OA) within the joint and to identify differences among dog breeds in the severity ofOAin the cranial cruciate ligament (CCL)-deficient stifle joint. Radiographs of 240 stifles from 51 Boxers, 66 German Shepherds, 100 Labrador Retrievers, and 23 Siberian Huskies with confirmed CCL rupture were included. Radiographs of the stifle joint were evaluated and OA severity was graded at 33 sites within and around the joint, and patella alta was graded as present or absent for a potential total stifle OA score of 100. Osteophyte size was correlated to OA severity score. Total OA scores were calculated and compared within and between breeds globally as well as at each joint site. Dogs weighing >35 kg had a higher total OA score than those weighing <35 kg. Osteoarthritis scores were highest at the apical patella, proximolateral tibia, and sesamoid bones, corresponding to the proximal, lateral, and caudal aspects of the joint, respectively. No statistically significant differences were found among the mean OA scores of various stifle joint regions. Boxer dogs had a higher total OA score than other breeds. We concluded that dogs have a consistent distribution pattern of OA within the stifle joint after CCL injury. Radiographic OA is more severe in the proximal, lateral, and caudal aspects of the joint. Boxers had more severeOA than the other breeds evaluated in the study. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
29. Arsenic Exposure from Drinking Water and Urinary Metabolomics: Associations and Long-Term Reproducibility in Bangladesh Adults.
- Author
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Fen Wu, Liang Chi, Hongyu Ru, Parvez, Faruque, Slavkovich, Vesna, Eunus, Mahbub, Ahmed, Alauddin, Islam, Tariqul, Rakibuz-Zaman, Muhammad, Hasan, Rabiul, Sarwar, Golam, Graziano, Joseph H., Ahsan, Habibul, Kun Lu, and Yu Chen
- Subjects
PHYSIOLOGICAL effects of arsenic ,METABOLOMICS ,ENVIRONMENTAL exposure ,ARSENIC content of drinking water ,ENVIRONMENTALLY induced cancer ,BIOLOGICAL tags ,CHRONIC diseases ,URINALYSIS ,ARSENIC metabolism ,STATISTICAL correlation ,GAS chromatography ,LONGITUDINAL method ,MASS spectrometry ,REGRESSION analysis ,RESEARCH evaluation ,WATER supply - Abstract
BACKGROUND: Chronic exposure to inorganic arsenic from drinking water has been associated with a host of cancer and noncancer diseases. The application of metabolomics in epidemiologic studies may allow researchers to identify biomarkers associated with arsenic exposure and its health effects. OBJECTIVE: Our goal was to evaluate the long-term reproducibility of urinary metabolites and associations between reproducible metabolites and arsenic exposure. METHODS: We studied samples and data from 112 nonsmoking participants (58 men and 54 women) who were free of any major chronic diseases and who were enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS), a large prospective cohort study in Bangladesh. Using a global gas chromatography-mass spectrometry platform, we measured metabolites in their urine samples, which were collected at baseline and again 2 y apart, and estimated intraclass correlation coefficients (ICCs). Linear regression was used to assess the association between arsenic exposure at baseline and metabolite levels in baseline urine samples. RESULTS: We identified 2,519 molecular features that were present in all 224 urine samples from the 112 participants, of which 301 had an ICC of ≥0:60. Of the 301 molecular features, water arsenic was significantly related to 31 molecular features and urinary arsenic was significantly related to 74 molecular features after adjusting for multiple comparisons. Six metabolites with a confirmed identity were identified from the 82 molecular features that were significantly associated with either water arsenic or urinary arsenic after adjustment for multiple comparisons. CONCLUSIONS: Our study identified urinary metabolites with long-term reproducibility that were associated with arsenic exposure. The data established the feasibility of using metabolomics in future larger studies. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
30. Nicotine Alters the Gut Microbiome and Metabolites of Gut-Brain Interactions in a Sex-Specific Manner.
- Author
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Liang Chi, Mahbub, Ridwan, Bei Gao, Xiaoming Bian, Pengcheng Tu, Hongyu Ru, and Kun Lu
- Published
- 2017
- Full Text
- View/download PDF
31. The Effects of an Environmentally Relevant Level of Arsenic on the Gut Microbiome and Its Functional Metagenome.
- Author
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Liang Chi, Xiaoming Bian, Bei Gao, Pengcheng Tu, Hongyu Ru, and Kun Lu
- Subjects
ARSENIC ,GUT microbiome ,RIBOSOMAL RNA ,RNA sequencing ,METAGENOMICS ,CARBOHYDRATE metabolism ,DNA repair - Abstract
Multiple environmental factors induce dysbiosis in the gut microbiome and cause a variety of human diseases. Previously, we have first demonstrated that arsenic alters the composition of the gut microbiome. However, the functional impact of arsenic on the gut microbiome has not been adequately assessed, particularly at environmentally relevant concentrations. In this study, we used 16S rRNA sequencing and metagenomics sequencing to investigate how exposure to 100 ppb arsenic for 13 weeks alters the composition and functional capacity of the gut microbiome in mice. Arsenic exposure altered the alpha and beta diversities as well as the composition profile of the gut microbiota. Metagenomics data revealed that the abundances of genes involved in carbohydrate metabolism, especially pyruvate fermentation, short-chain fatty acid synthesis, and starch utilization, and were significantly changed. Moreover, lipopolysaccharide biosynthesis genes, multiple stress response genes, and DNA repair genes were significantly increased in the gut microbiome of arsenicexposed mice. The genes involved in the production or processing of multiple vitamins, including folic acid and vitamins B6, B12, and K2, were also enriched in arsenic-treated mice. In, addition, genes involved in multidrug resistance and conjugative transposon proteins were highly increased after treatment with arsenic. In conclusion, we demonstrate that arsenic exposure, at an environmentally relevant dose, not only perturbed the communal composition of the gut microbiome but also profoundly altered a variety of important bacterial functional pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
32. The epigenetic reader PHF21B modulates murine social memory and synaptic plasticity–related genes
- Author
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Eunice W.M. Chin, Qi Ma, Hongyu Ruan, Camille Chin, Aditya Somasundaram, Chunling Zhang, Chunyu Liu, Martin D. Lewis, Melissa White, Tracey L. Smith, Malcolm Battersby, Wei-Dong Yao, Xin-Yun Lu, Wadih Arap, Julio Licinio, and Ma-Li Wong
- Subjects
Neuroscience ,Medicine - Abstract
Synaptic dysfunction is a manifestation of several neurobehavioral and neurological disorders. A major therapeutic challenge lies in uncovering the upstream regulatory factors controlling synaptic processes. Plant homeodomain (PHD) finger proteins are epigenetic readers whose dysfunctions are implicated in neurological disorders. However, the molecular mechanisms linking PHD protein deficits to disease remain unclear. Here, we generated a PHD finger protein 21B–depleted (Phf21b-depleted) mutant CRISPR mouse model (hereafter called Phf21bΔ4/Δ4) to examine Phf21b’s roles in the brain. Phf21bΔ4/Δ4 animals exhibited impaired social memory. In addition, reduced expression of synaptic proteins and impaired long-term potentiation were observed in the Phf21bΔ4/Δ4 hippocampi. Transcriptome profiling revealed differential expression of genes involved in synaptic plasticity processes. Furthermore, we characterized a potentially novel interaction of PHF21B with histone H3 trimethylated lysine 36 (H3K36me3), a histone modification associated with transcriptional activation, and the transcriptional factor CREB. These results establish PHF21B as an important upstream regulator of synaptic plasticity–related genes and a candidate therapeutic target for neurobehavioral dysfunction in mice, with potential applications in human neurological and psychiatric disorders.
- Published
- 2022
- Full Text
- View/download PDF
33. Organophosphate Diazinon Altered Quorum Sensing, Cell Motility, Stress Response, and Carbohydrate Metabolism of Gut Microbiome.
- Author
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Bei Gao, Xiaoming Bian, Liang Chi, Pengcheng Tu, Hongyu Ru, and Kun Lu
- Subjects
DIAZINON ,CHOLINESTERASE-inhibiting insecticides ,CELL motility ,CARBOHYDRATE metabolism ,CARBOHYDRATES ,GUT microbiome - Abstract
The gut microbiome plays a key role in energy production, immune system development, and host resistance against invading pathogens, etc. Disruption of gut bacterial homeostasis is associated with a number of human diseases. Several environmental chemicals have been reported to induce alterations of the gut microbiome. Diazinon, one of important organophosphate insecticides, has been widely used in agriculture. Diazinon and its metabolites are readily detected in different environmental settings and human urine. The toxicity of organophosphates has been a long-standing public health concern. We recently demonstrated that organophosphate insecticide diazinon perturbed the gut microbiome composition of mice. However, the functional impact of exposure on the gut microbiome has not been adequately assessed yet. In particular, the molecular mechanism responsible for exposure-induced microbial profile and community structure changes has not been identified. Therefore, in this study, we used metatranscriptomics to examine the effects of diazinon exposure on the gut metatranscriptome in C57BL/6 mice. Herein, we demonstrated for the first time that organophosphate diazinon modulated quorum sensing, which may serve as a key mechanism to regulate bacterial population, composition, and more importantly, their functional genes. In addition, we also found that diazinon exposure activated diverse stress response pathways and profoundly impaired energy metabolismof gut bacteria. These findings provide new understandings of the functional interplay between the gut microbiome and environmental chemicals, such as organophosphates. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
34. Multi-Omics Reveals that Lead Exposure Disturbs Gut Microbiome Development, Key Metabolites, and Metabolic Pathways.
- Author
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Gao, Bei, Liang Chi, Mahbub, Ridwan, Xiaoming Bian, Pengcheng Tu, Hongyu Ru, and Kun Lu
- Published
- 2017
- Full Text
- View/download PDF
35. Distribution of DNA Adducts Caused by Inhaled Formaldehyde Is Consistent with Induction of Nasal Carcinoma but Not Leukemia.
- Author
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Kun Lu, Collins, Leonard B., Hongyu Ru, Bermudez, Edilberto, and Swenberg, James A.
- Subjects
FORMALDEHYDE ,DNA adducts ,LEUKEMIA ,NOSE cancer ,CARCINOGENS ,CARCINOGENESIS - Abstract
Inhaled formaldehyde is classified as a known human and animal carcinogen, causing nasopharyngeal cancer. Additionally, limited epidemiological evidence for leukemia in humans is available; however, this is inconsistent across studies. Both genotoxicity and cytotoxicity are key events in formaldehyde nasal carcinogenicity in rats, but mechanistic data for leukemia are not well established. Formation of DNA adducts is a key event in initiating carcinogenesis. Formaldehyde can induce DNA monoadducts, DNA-DNA cross-links, and DNA protein cross-links. In this study, highly sensitive liquid chromatography-tandem mass spectrometry-selected reaction monitoringmethods were developed and [13CD2]-formaldehyde exposures utilized, allowing differentiation of DNA adducts and DNA-DNA cross-links originating from endogenous and inhalation-derived formaldehyde exposure. The results show that exogenous formaldehyde induced N2-hydroxymethyl-dG monoadducts and dG-dG cross-links in DNA from rat respiratory nasal mucosa but did not form [13CD2]-adducts in sites remote to the portal of entry, even when five times more DNA was analyzed. Furthermore, no N6-HO13CD2-dA adducts were detected in nasal DNA. In contrast, high amounts of endogenous formaldehyde dG and dA monoadducts were present in all tissues examined. The number of exogenous N2-HO13CD2-dG in 1- and 5-day nasal DNA samples from rats exposed to 10-ppm [13CD2]-formaldehyde was 1.28 ± 0.49 and 2.43 ± 0.78 adducts/107 dG, respectively, while 2.63 ± 0.73 and 2.84 ± 1.13 N2-HOCH2-dG adducts/107 dG and 3.95 ± 0.26 and 3.61 ± 0.95 N6-HOCH2-dA endogenous adducts/107 dA were present. This study provides strong evidence supporting a genotoxic and cytotoxic mode of action for the carcinogenesis of inhaled formaldehyde in respiratory nasal epithelium but does not support the biological plausibility that inhaled formaldehyde also causes leukemia. [ABSTRACT FROM PUBLISHER]
- Published
- 2010
- Full Text
- View/download PDF
36. Sex-Specific Effects of Arsenic Exposure on the Trajectory and Function of the Gut Microbiome.
- Author
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Liang Chi, Xiaoming Bian, Bei Gao, Hongyu Ru, Pengcheng Tu, and Kun Lu
- Published
- 2016
- Full Text
- View/download PDF
37. Three-dimensional assessment of the influence of juvenile pubic symphysiodesis on the pelvic geometry of dogs.
- Author
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Dunlap, Anna E., Mathews, Kyle G., Walters, Bethany L., Bruner, Kent A., Hongyu Ru, and Marcellin-Little, Denis J.
- Subjects
- *
PELVIC anatomy , *COMPUTED tomography , *VETERINARY health risk assessment , *VETERINARY therapeutics , *LABRADOR retriever , *GOLDEN retriever ,DOG anatomy - Abstract
OBJECTIVE To evaluate the 3-D geometry of canine pelves and to characterize the longte rm effects of juvenile pubic symphysiodesis (JPS) on pelvic geometry by comparing the pelvic configuration between littermates that did and did not undergo the procedure. ANIMALS 24 Labrador Retriever, Golden Retriever, or Labrador R etriever-Golden Retriever crossbred service dogs from 13 litters. PROCEDURES At 16 weeks old, puppies with a hip joint distraction index > 0.5 were randomly assigned to undergo thermal JPS (n = 9), mechanical JPS (7), or a sham (control) surgical procedure (8). Ten years later, each dog underwent a CT scan of the pelvic region. Modeling software was used to create 3-D reconstructions from the CT scans, and various pelvic measurements were made and compared among the 3 treatments. RESULTS Compared with the control treatment, thermal and mechanical JPS increased the hemipelvis acetabular angle by 4°, the acetabular angle of lateral opening by 5°, and the orientation of the medial acetabular wall in a transverse plane by 6°, which indicated that JPS increased dorsal femoral head coverage by the acetabulum. Both JPS procedures decreased the pelvic canal area by approximately 20% and acetabular inclination by 6° but did not alter acetabular retroversion. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that thermal and mechanical JPS were equally effective in altering the 3-D pelvic geometry of dogs. These findings may help guide future studies of alternatives for optimizing canine pelvic anatomy to minimize the risk of hip dysplasia and associated osteoarthritis. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
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