11 results on '"Xu, Fangxi"'
Search Results
2. Electronic Cigarette Aerosol Modulates the Oral Microbiome and Increases Risk of Infection
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Pushalkar, Smruti, Paul, Bidisha, Li, Qianhao, Yang, Jian, Vasconcelos, Rebeca, Makwana, Shreya, González, Juan Muñoz, Shah, Shivm, Xie, Chengzhi, Janal, Malvin N., Queiroz, Erica, Bederoff, Maria, Leinwand, Joshua, Solarewicz, Julia, Xu, Fangxi, Aboseria, Eman, Guo, Yuqi, Aguallo, Deanna, Gomez, Claudia, Kamer, Angela, Shelley, Donna, Aphinyanaphongs, Yindalon, Barber, Cheryl, Gordon, Terry, Corby, Patricia, Li, Xin, and Saxena, Deepak
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- 2020
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3. A novel SUCNR1 inhibitor alleviates dysbiosis through inhibition of host responses without direct interaction with host microbiota.
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Thomas, Scott C., Guo, Yuqi, Xu, Fangxi, Saxena, Deepak, and Li, Xin
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Type 2 diabetes (T2D) is a chronic metabolic disorder in which insulin resistance and impaired insulin secretion result in altered metabolite balance, specifically elevated levels of circulating glucose and succinate, which increases the risk of many pathologies, including periodontitis. Succinate, a tricarboxylic acid (TCA) cycle intermediate, can be produced and metabolized by both host cells and host microbiota, where elevated levels serve as an inflammation and pathogen threat signal through activating the succinate G protein‐coupled receptor, SUCNR1. Modulating succinate‐induced SUCNR1 signaling remains a promising therapeutic approach for pathologies resulting in elevated levels of succinate, such as T2D and periodontitis. Here, we demonstrate hyperglycemia and elevated intracellular succinate in a T2D mouse model and determine gut microbiome composition. Drawing on previous work demonstrating the ability of a novel SUCNR1 antagonist, compound 7a, to block inflammation and alleviate dysbiosis in a mouse model, we examined if compound 7a has an impact on the growth and virulence gene expression of bacterial and fungal human microbiota in vitro, and if 7a could reduce bone loss in a periodontitis‐induced mouse model. T2D mice harbored a significantly different gut microbiome, suggesting the altered metabolite profile of T2D causes shifts in host‐microbial community structure, with enrichment in succinate producers and consumers and mucin‐degrading bacteria. Bacterial and fungal cultures showed that 7a did not influence growth or virulence gene expression, suggesting the therapeutic effects of 7a are a direct result of 7a interacting with host cells and that alterations in microbial community structure are driven by reduced host SUCNR1 signaling. This work further suggests that targeting SUCNR1 signaling is a promising therapeutic approach in metabolic, inflammatory, or immune disorders with elevated succinate levels. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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4. Intrahepatic microbes govern liver immunity by programming NKT cells
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Leinwand, Joshua C., Paul, Bidisha, Chen, Ruonan, Xu, Fangxi, Sierra, Maria A., Paluru, Madan M., Nanduri, Sumant, Alcantara, Carolina G., Shadaloey, Sorin A.A., Yang, Fan, Adam, Salma A., Li, Qianhao, Bandel, Michelle, Gakhal, Inderdeep, Appiah, Lara, Guo, Yuqi, Vardhan, Mridula, Flaminio, Zia, Grodman, Emilie R., Mermelstein, Ari, Wang, Wei, Diskin, Brian, Aykut, Berk, Khan, Mohammad, Werba, Gregor, Pushalkar, Smruti, McKinstry, Mia, Kluger, Zachary, Park, Jaimie J., Hsieh, Brandon, Dancel-Manning, Kristen, Liang, Feng-Xia, Park, James S., Saxena, Anjana, Li, Xin, Theise, Neil D., Saxena, Deepak, and Miller, George
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Microbiota (Symbiotic organisms) -- Health aspects -- Physiological aspects ,Host-bacteria relationships -- Research ,Immunity -- Research ,Killer cells -- Health aspects -- Physiological aspects ,Cellular control mechanisms -- Research ,Health care industry - Abstract
The gut microbiome shapes local and systemic immunity. The liver is presumed to be a protected sterile site. As such, a hepatic microbiome has not been examined. Here, we showed a liver microbiome in mice and humans that is distinct from that of the gut and is enriched in Proteobacteria. It undergoes dynamic alterations with age and is influenced by the environment and host physiology. Fecal microbial transfer experiments revealed that the liver microbiome is populated from the gut in a highly selective manner. Hepatic immunity is dependent on the microbiome, specifically the bacteroidetes species. Targeting bacteroidetes with oral antibiotics reduced hepatic immune cells by approximately 90%, prevented antigen-presenting cell (APC) maturation, and mitigated adaptive immunity. Mechanistically, our findings are consistent with presentation of bacteroidetes-derived glycosphingolipids to NKT cells promoting CCL5 signaling, which drives hepatic leukocyte expansion and activation, among other possible host-microbe interactions. Collectively, we reveal a microbial/glycosphingolipid/NKT/CCL5 axis that underlies hepatic immunity., Introduction Gut microbiota represent the most abundant and diverse collection of commensal organisms in the body (1). The intestinal microbiome plays a fundamental role in shaping the host immune system [...]
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- 2022
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5. Mouse model of NASH that replicates key features of the human disease and progresses to fibrosis stage 3.
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St. Rose, Kristy, Yan, Jun, Xu, Fangxi, Williams, Jasmine, Dweck, Virginia, Saxena, Deepak, Schwabe, Robert F., and Caviglia, Jorge Matias
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CLINICAL drug trials ,HEPATIC fibrosis ,NON-alcoholic fatty liver disease ,LABORATORY mice ,ANIMAL disease models - Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and the world; with no Food and Drug Administration–approved pharmacological treatment available, it remains an area of unmet medical need. In nonalcoholic steatohepatitis (NASH), the most important predictor of clinical outcome is the fibrosis stage. Moreover, the Food and Drug Administration recommends that clinical trials for drugs to treat this disease include patients with fibrosis stage 2 or greater. Therefore, when using animal models for investigating the pathophysiology of NAFLD and for the preclinical evaluation of new drugs, it is important that the animals develop substantial fibrosis. The aim of this study was to develop a mouse model of NAFLD that replicated the disease in humans, including obesity and progressive liver fibrosis. Agouti yellow mutant mice, which have hyperphagia, were fed a Western diet and water containing high‐fructose corn syrup for 16 weeks. Mice became obese and developed glucose intolerance. Their gut microbiota showed dysbiosis with changes that replicate some of the changes described in humans with NASH. They developed NASH with activity scores of 5–6 and fibrosis, which was stage 1 after 16 weeks, and stage 3 after 12 months. Changes in liver gene expression assessed by gene‐set enrichment analysis showed 90% similarity with changes in human patients with NASH. Conclusion: Ay mice, when fed a Western diet similar to that consumed by humans, develop obesity and NASH with liver histology, including fibrosis, and gene expression changes that are highly similar to the disease in humans. [ABSTRACT FROM AUTHOR]
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- 2022
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6. Electronic cigarette use enriches periodontal pathogens.
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Xu, Fangxi, Pushalkar, Smruti, Lin, Ziyan, Thomas, Scott C., Persaud, Julia Kishanie, Sierra, Maria A, Vardhan, Mridula, Vasconcelos, Rebeca, Akapo, Adenike, Guo, Yuqi, Gordon, Terry, Corby, Patricia M, Kamer, Angela R., Li, Xin, and Saxena, Deepak
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ELECTRONIC cigarettes , *PERIODONTAL disease , *GUT microbiome , *SALIVA , *PORPHYROMONAS gingivalis - Abstract
The effect of electronic cigarette (e‐cigarette) smoking, especially its long‐term impact on oral health, is poorly understood. Here, we conducted a longitudinal clinical study with two study visits, 6 months apart, to investigate the effect of e‐cigarette use on the bacterial community structure in the saliva of 101 periodontitis patients. Our data demonstrated that e‐cigarette use altered the oral microbiome in periodontitis patients, enriching members of the Filifactor, Treponema, and Fusobacterium taxa. For patients at the same periodontal disease stage, cigarette smokers and e‐cigarette smokers shared more similarities in their oral bacterial composition. E‐cigarette smoking may have a similar potential as cigarette smoking at altering the bacterial composition of saliva over time, leading to an increase in the relative abundance of periodontal disease‐associated pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum. The correlation analysis showed that certain genera, such as Dialister, Selenomonas, and Leptotrichia in the e‐cigarette smoking group, were positively correlated with the levels of proinflammatory cytokines, including IFN‐γ, IL‐1β, and TNF‐α. E‐cigarette use was also associated with elevated levels of proinflammatory cytokines such as IFN‐γ and TNF‐α, which contribute to oral microbiome dysbiosis and advanced disease state. [ABSTRACT FROM AUTHOR]
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- 2022
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7. The Gut Microbiome, Metformin, and Aging.
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Induri, Sri Nitya Reddy, Kansara, Payalben, Thomas, Scott C., Xu, Fangxi, Saxena, Deepak, and Li, Xin
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ACTIVE aging ,GUT microbiome ,TYPE 2 diabetes ,METFORMIN ,INFLAMMATORY mediators ,DRUG toxicity ,PHARMACODYNAMICS - Abstract
Metformin has been extensively used for the treatment of type 2 diabetes, and it may also promote healthy aging. Despite its widespread use and versatility, metformin's mechanisms of action remain elusive. The gut typically harbors thousands of bacterial species, and as the concentration of metformin is much higher in the gut as compared to plasma, it is plausible that microbiome-drug-host interactions may influence the functions of metformin. Detrimental perturbations in the aging gut microbiome lead to the activation of the innate immune response concomitant with chronic low-grade inflammation. With the effectiveness of metformin in diabetes and antiaging varying among individuals, there is reason to believe that the gut microbiome plays a role in the efficacy of metformin. Metformin has been implicated in the promotion and maintenance of a healthy gut microbiome and reduces many age-related degenerative pathologies. Mechanistic understanding of metformin in the promotion of a healthy gut microbiome and aging will require a systems-level approach. [ABSTRACT FROM AUTHOR]
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- 2022
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8. Microbial population shift and metabolic characterization of silver diamine fluoride treatment failure on dental caries.
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Paul, Bidisha, Sierra, Maria A., Xu, Fangxi, Crystal, Yasmi O., Li, Xin, Saxena, Deepak, and Ruff, Ryan Richard
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FLUORIDES ,DENTAL fluoride treatment ,DENTAL caries ,MICROORGANISM populations ,FISHER discriminant analysis ,MICROBIAL metabolites ,DENTAL care ,TREATMENT failure - Abstract
The objective of this pilot study was to describe the microbial profiles present in the plaque and saliva of children who continued to develop new carious lesions following treatment with silver diamine fluoride ("nonresponders") compared to caries active, caries-free, and children immediately receiving SDF treatment for untreated caries in order to identify potential microbial differences that may relate to a re-incidence of caries. Saliva and plaque samples from infected and contralateral sites were obtained from twenty children who were either caries free, had active carious lesions, were caries active and received SDF treatment immediately before sampling, or had previously received SDF treatment and developed new caries. In total, 8,057,899 Illumina-generated sequence reads from 60 samples were obtained. Reads were processed using the Quantitative Insights Into Microbial Ecology pipeline. Group differences were assessed using Analysis of Variance Models and Tukey Honest Significant Differences. To identify significant taxa between treatment groups, Linear discriminant analysis Effect Size (LefSe) and Analysis of Differential Abundance Taking Sample Variation Into Account were used. Differential abundant analysis indicated that members of the Lachnospiraceae family were significantly enriched in non-responders and the genus Tannerella and species Granulicatella adiances were also highly abundant in this group. LefSe analysis between non-responders and SDF-treated groups revealed that genera Leptotrichia and Granulicatella were enriched in non-responders. We observed the highest abundance of phosphotransferase system and lowest abundance of lipopolysaccharide synthesis in non-responders. The microbiome in dental biofilms is responsible for initiation and progression of dental caries. SDF has been shown to be effective in arresting the progression carious lesions, in part due to its antimicrobial properties. Findings suggest that the differential abundance of select microbiota and specific pathway functioning in individuals that present with recurrent decay after SDF treatment may contribute to a potential failure of silver diamine fluoride to arrest dental caries. However, the short duration of sample collection following SDF application and the small sample size emphasize the need for further data and additional analysis. [ABSTRACT FROM AUTHOR]
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- 2021
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9. Cross talk between drug‐resistant epilepsy and the gut microbiome.
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Holmes, Manisha, Flaminio, Zia, Vardhan, Mridula, Xu, Fangxi, Li, Xin, Devinsky, Orrin, and Saxena, Deepak
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GUT microbiome ,CROSSTALK ,EPILEPSY ,ANTICONVULSANTS ,BRAIN - Abstract
One‐third of epilepsy patients have drug‐resistant epilepsy (DRE), which is often complicated by polydrug toxicity and psychiatric and cognitive comorbidities. Advances in understanding the microbiome and gut‐brain‐axis are likely to shed light on epilepsy pathogenesis, anti‐seizure medication (ASM) resistance, and potential therapeutic targets. Gut dysbiosis is associated with inflammation, blood‐brain barrier disruption, and altered neuromodulators. High‐throughput and metagenomic sequencing has advanced the characterization of microbial species and functional pathways. DRE patients show altered gut microbiome composition compared to drug‐sensitive patients and healthy controls. The ketogenic and modified Atkins diets can reduce seizures in some patients with DRE. These low‐carbohydrate dietary therapies alter the taxonomic and functional composition of the gut microbiome, and composition varies between diet responders and nonresponders. Murine models suggest that specific phyla are necessary to confer efficacy from the diet, and antibiotic treatment may eliminate efficacy. The impact of diet might involve alterations in microbiota, promotion of select microbial interactions, and variance in brain neurotransmitter levels that then influence seizures. Understanding the mechanics of how diet manipulates seizures may suggest novel therapies. Most ASMs act on neuronal transmission via effects on ion channels and neurotransmitters. However, ASMs may also assert their effects via the gut microbiota. In animal models, the microbiota composition (eg, abundance of certain phyla) can vary with ASM active drug metabolites. Given the developing understanding of the gut microbiome in DRE, probiotics are another potential therapy. Probiotics alter the microbiota composition, and small studies suggest that these supplements can reduce seizures in some patients. DRE has enormous consequences to patients and society, and the gut microbiome holds promise as a potential therapeutic target. However, the exact mechanism and recognition of which patients are likely to be responders remain elusive. Further studies are warranted. [ABSTRACT FROM AUTHOR]
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- 2020
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10. Protective Measures against COVID-19: Dental Practice and Infection Control.
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Induri, Sri Nitya Reddy, Chun, Yunah Caroline, Chun, Joonmo Christopher, Fleisher, Kenneth E., Glickman, Robert S., Xu, Fangxi, Ioannidou, Efthimia, Li, Xin, and Saxena, Deepak
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COVID-19 ,INFECTION control ,PRACTICE of dentistry ,SARS-CoV-2 ,MEDICAL personnel ,VIRAL transmission - Abstract
The onset of the Coronavirus 2019 (COVID-19) pandemic has challenged the worldwide healthcare sector, including dentistry. The highly infectious nature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and risk of transmission through aerosol generating procedures has profoundly impacted the delivery of dental care services globally. As dental practices with renewed infection control strategies and preventive measures are re-opening in the "new normal" period, it is the responsibility of healthcare professionals to constantly analyze new data and limit the spread of COVID-19 in dental care settings. In the light of new variants of SARS-CoV-2 rapidly emerging in different geographic locations, there is an urgent need to comply more than ever with the rigorous public health measures to mitigate COVID-19 transmission. The aim of this article is to provide dental clinicians with essential information regarding the spread of SARS-CoV-2 virus and protective measures against COVID-19 transmission in dental facilities. We complied and provided guidance and standard protocols recommended by credible national and international organizations. This review will serve as an aid to navigating through this unprecedented time with ease. Here we reviewed the available literature recommended for the best current practices that must be taken for a dental office to function safely and successfully. [ABSTRACT FROM AUTHOR]
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- 2021
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11. Identification of Differentially Methylated Regions Associated with a Knockout of SUV39H1 in Prostate Cancer Cells.
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Yan, Wenbo, Guo, Yuqi, Xu, Fangxi, Saxena, Deepak, and Li, Xin
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PROSTATE cancer ,CANCER cells ,CELLULAR recognition ,HISTONE methylation ,DNA methylation - Abstract
Epigenetic alterations, such as histone methylations, affect the pathogenesis of tumors including prostate cancer (PCa). Previously, we reported that metformin reduced SUV39H1, a histone methyltransferase of H3 Lys9, to inhibit the migration of PCa cells. Since histone methylation is functionally linked to DNA methylation, we speculate that the knockout of the SUV39H1 gene will affect the genomic DNA methylation profile to regulate PCa cell migration and invasion. The genome-wide DNA methylation level is lower in SUV39H1 knockout (KO) cells than wild-type (WT) ones. However, the methylation levels in functional regions of CpG Islands (CGI), 5′ untranslated region (UTR5), and exon regions are higher in KO cells than WT cells. Analysis of differentially methylated regions (DMRs) identified 1241 DMR genes that have differential methylation on CG sites when comparing the KO and WT samples. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes Pathways analysis showed that knockout of SUV39H1 affects gene sets and pathways that are heavily involved in cell shapes, cell recognition, adhesion, motility, and migration. Our study suggests that SUV39H1 plays an important role in PCa migration via the epigenetic regulation of methylation on CG sites, and is a novel and legitimate target to inhibit PCa cell migration. [ABSTRACT FROM AUTHOR]
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- 2020
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