Biology subjects

Fang, Z.

Publications and source records attributed to Fang, Z..

114 records · Page 7Linked to original sources

bioRxiv2019

Structural changes in the gut microbiome of short-term and long-term medical workers compared to normal controls

ObjectiveHospital environment has been implicated in enrichment and exchange of pathogens and antibiotic resistances, but its potential in shaping the symbiotic microbial community of the hospital staff is unclear. This study was designed to evaluate the alteration of gut microbiome in medical workers compared to non-medical controls.\n\nDesignProspective cross-sectional cohort study.\n\nSettingIntensive care unit (ICU) and other departments from a center in northeast China.\n\nSubjects175 healthy medical workers (1-3 months short-term workers, n = 80; >1 year long-term workers, n = 95) and 80 healthy normal controls.\n\nInterventionsNone.\n\nMeasurements and Main ResultsFecal samples of all subjects were analyzed using the 16S rRNA gene sequencing. Medical workers exhibited remarkable deviation in gut microbial within-sample diversity and enterotypes stratification, and shift in overall microbial structure. Short-term workers were significantly more abundant in taxa including Lactobacillus, Butyrivibrio, Clostridiaceae_Clostridium, Ruminococcus, Dialister, Bifidobacterium, Odoribacter and Desulfovibrio, and with lower abundances of Bacteroides and Blautia compared with the controls. While long-term workers were enriched in taxa including Dialister, Veillonella, Clostridiaceae_Clostridium, Bilophila, Desulfovibrio, Pseudomonas and Akkermansia, with lower abundances of Bacteroides and Coprococcus compared with the controls. In addition, medical workers working years (short-term vs. long-term), hospital department (resident doctor vs. nursing staff) and work position (ICU vs. not-ICU) revealed considerable effects on their gut microbiome. Moreover, by analyzing the environmental samples (n = 9) around the inpatient wards and the hospital, we showed that the gut microbiota of medical workers was closer to environmental microbiota than that of the normal controls, probably in correlation to lasting exposure to the pathogenic taxa (e.g. Pseudomonas) in health workers.\n\nConclusionsOur findings demonstrated structural changes in the gut microbial community of the medical workers. Further studies are proposed for investigating the potentially physiological influence of the altered gut microbiome in medical participants.\n\nIMPORTANCEIn this study, we for the first time focused on the influence of hospital environmental factors on gut microbiota of medical workers. The significance of our study is not limited to revealing the remodeling effect of the hospital environment on the gut microbiota of medical workers. Based on these, we also propose targeted and operational recommendations that can promote the health of hospital staff.

microbiology↗

bioRxiv2019

Remodeling gut microbiota by Streptococcus thermophilus 19 attenuates inflammation in septic mice

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is the leading cause of death in burn patients. Streptococcus thermophilus 19 is a highly effective probiotic, with well-studied health benefits, but its role in protecting viscera against injury caused by sepsis and the underlying mechanism is poorly understood. The goal of this study was to evaluate protection potency of S. thermophilus against inflammation in mice and evaluate the influence of sepsis and S. thermophilus on microbial community. We tested the utility of S. thermophilus 19 in attenuating inflammation in vitro and vivo of LPS-induced sepsis mouse model. We also evaluated the influence of sepsis and S. thermophilus on microbial community. In vitro, S. thermophilus 19 decrease the expression of inflammatory factors. Additionally, in a lipopolysaccharide-induced septic mouse model, mice administered the probiotic 19 was highly resistant to Lps and exhibited decreased expression of inflammatory factors compared to Lps-treated control mice. A MiSeq-based sequence analysis revealed that gut microbiota alterations in mice intraperitoneally injected with 1 mg/ml LPS were mitigated by the administration of oral probiotics 19. Together these findings indicate that S. thermophilus 19 may be a new avenue for interventions against inflammation caused by sepsis and other systemic inflammatory diseases. In an analysis of the gut microbiota of the all group mice, we found that sepsis is associated with gut microbiota and probiotics attenuate the inflammation through remodeling gut microbiota. ImportanceSepsis is life-threatening organ dysfunction which is the leading cause of death in burn patients. Although our understanding of sepsis has increased substantially in recent years, its still reported to be the leading cause of death in seriously ill patients. Evidences showed that gut microbiota play an important role in sepsis. Moreover, probiotics have been used to prevent numbers of gut health disorders and alleviate inflammation associated with some human diseases by promoting changes in the gut microbiota composition. Hence, to investigate the mechanism of probiotics in the treatment of sepsis has emerged. The significance of our research is in identifying the role of gut microbiota in sepsis and found an effective probiotic that reduces inflammation, S. thermophilus 19, and investigating the therapeutic effect and mechanism of S. thermophilus 19 on sepsis, which might be a new avenue for interventions against inflammation caused by sepsis and other systemic inflammatory diseases.

microbiology↗

bioRxiv2018

Comparative Pathway Integrator: a framework of meta-analytic integration of multiple transcriptomic studies for consensual and differential pathway analysis

MotivationPathway analysis provides a knowledge-driven approach to interpret differentially expressed genes associated with disease status. Many tools have been developed to analyze a single study. When multiple studies of different conditions are jointly analyzed, novel integrative tools are needed. In addition, pathway redundancy issue introduced by combining public pathway databases hinders knowledge discovery.\n\nMethods and ResultsWe present a meta-analytic integration tool, Comparative Pathway Integrator (CPI), to address these issues using adaptively weighted Fishers method to discover consensual and differential enrichment patterns, consensus clustering to reduce pathway redundancy, and a novel text mining algorithm to assist interpretation of the pathway clusters. We applied CPI to jointly analyze six psychiatric disorder transcriptomic studies to demonstrate its effectiveness, and found functions confirmed by previous biological studies as well novel enrichment patterns.\n\nAvailabilityCPI is accessible online: http://tsenglab.biostat.pitt.edu/software.htm.\n\nContactxiangruz@andrew.cmu.edu

bioinformatics↗

bioRxiv2017

SPIN1 promotes tumorigenesis by blocking the uL18-MDM2-p53 pathway

Ribosomal proteins (RPs) play important roles in modulating the MDM2-p53 pathway. However, less is known about the upstream regulators of the RPs. Here we identify SPIN1 (Spindlin 1) as a novel binding partner of human RPL5/uL18 that is important for this pathway. SPIN1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of cancer cells by sequestering uL18 in the nucleolus, preventing it from interacting with MDM2, and thereby alleviating uL18-mediated inhibition of MDM2 ubiquitin ligase activity towards p53. SPIN1 deficiency increases ribosome-free uL18 and uL5 (human RPL11), which are required for SPIN1 depletion-induced p53 activation. Analysis of cancer genomic databases suggests that SPIN1 is highly expressed in several human cancers, and its overexpression is positively correlated with poor prognosis in cancer patients. Altogether, our findings reveal that the oncogenic property of SPIN1 is highly attributed to its negative regulation of uL18, leading to p53 inactivation.

cancer biology↗

bioRxiv2017

Neural Correlates of human cognitive abilities during sleep

Inter-individual differences in sleep spindles are highly correlated with \"Reasoning\" abilities (problem solving skills; i.e., the ability to employ logic, identify complex patterns), but not Short Term Memory or Verbal abilities. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) have revealed brain activations time-locked to spindles (e.g., thalamic, paralimbic, and motor cortical areas)-yet the functional significance of inter-individual differences in spindle-related brain activation remains to be investigated. Using EEG-fMRI during sleep, we identified, for the first time, the neural activation patterns time-locked to spindles that are correlated with cognitive abilities. Similar to previous studies, activations time-locked to spindles were observed in thalamocortical circuitry and basal ganglia regions. Importantly, spindle-related activation in a subset of these regions were specifically related to inter-individual differences in Reasoning, but not STM or Verbal abilities. These results may help elucidate the physiological mechanisms which support the function of sleep for the capacity for reasoning.

neuroscience↗

bioRxiv2017

Exome-Capture RNA-Sequencing Of Decade-Old Breast Cancers And Matched Decalcified Bone Metastases Identifies Clinically Actionable Targets

Bone metastases (BoM) are a significant cause of morbidity in patients with Estrogen-receptor (ER)-positive breast cancer, yet characterizations of human specimens are limited. In this study, exome-capture RNA-sequencing (ecRNA-seq) on aged (8-12 years), formalin-fixed paraffin-embedded (FFPE) and decalcified cancer specimens was first evaluated. Gene expression values and RNA-seq quality metrics from FFPE or decalcified tumor RNA showed minimal differences when compared to matched flash-frozen or non-decalcified tumors. ecRNA-seq was then applied on a longitudinal collection of 11 primary breast cancers and patient-matched de novo or recurrent BoM. BoMs harbored shifts to more Her2 and LumB PAM50 intrinsic subtypes, temporally influenced expression evolution, recurrently dysregulated prognostic gene sets and altered expression of clinically actionable genes, particularly in the CDK-Rb-E2F and FGFR-signaling pathways. Taken together, this study demonstrates the use of ecRNA-seq on decade-old and decalcified specimens and defines expression-based tumor evolution in long-term, estrogen-deprived metastases that may have immediate clinical implications.\n\nGrant SupportResearch funding for this project was provided in part by a Susan G. Komen Scholar award to AVL and to SO, the Breast Cancer Research Foundation (AVL and SO), the Fashion Footwear Association of New York, the Magee-Womens Research Institute and Foundation, and through a Postdoctoral Fellowship awarded to RJW from the Department of Defense (BC123242). NP was supported by a training grant from the NIH/NIGMS (2T32GM008424-21) and an individual fellowship from the NIH/NCI (5F30CA203095).\n\nConflicts of Interest DisclosureNo relevant conflicts of interest disclosed for this study.\n\nAuthor ContributionsStudy concept and design (NP, RJW, SO, AVL); acquisition, analysis, or interpretation of data (all authors); drafting of the manuscript (NP, RJW, SO, AVL); critical revision of the manuscript for important intellectual content (all authors); administrative, technical, or material support (PCL, AB, RB, KRW, WH, JK, MR, ZF, AMB).

cancer biology↗