The study looked at changes in gene expression profiles in subjects with Pulmonary Arterial Hypertension and Scleroderma (PAH-SSc) before and after treatment with Tadalafil. A total of ten subjects were enrolled and various clinical assessments including 6-minute walk tes, cardiac MRI and right heart catheterization were done in addition to gene expression study.
Changes in gene expression profiles in patients with pulmonary arterial hypertension associated with scleroderma treated with tadalafil.
Specimen part, Subject, Time
View SamplesWe used microarrays to identify transcripts regulated by dexamethasone in omental (Om) and abdominal subcutaneous (Abdsc) adipose tissues of severely obese females obtained during elective surgeries.
Depot Dependent Effects of Dexamethasone on Gene Expression in Human Omental and Abdominal Subcutaneous Adipose Tissues from Obese Women.
Specimen part, Disease stage, Treatment
View SamplesThe emergence of fully antimicrobial resistant Neisseria gonorrhoeae has led global public health agencies to identify a critical need for next generation anti-gonococcal pharmaceuticals. The development and success of these compounds will rely upon valid pre-clinical models of gonorrhoeae infection. We recently developed and reported the first model of upper genital tract gonococcal infection. During initial characterization, we observed significant reproductive cycle-based variation in infection outcome. When uterine infection occurred in the diestrus phase, there was significantly greater pathology than during estrus phase. The aim of this study was to evaluate transcriptional profiles of infected uterine tissue from mice in either estrus or diestrus phase in order to elucidate possible mechanisms for these differences. Genes and biological pathways with phase-independent induction during infection showed a chemokine dominant cytokine response to Neisseria gonorrhoeae. Despite general induction being phase-independent, this common anti-gonococcal response demonstrated greater induction during diestrus phase infection. Greater activity of granulocyte adhesion and diapedesis regulators during diestrus infection, particularly in chemokines and diapedesis regulators, was also shown. In addition to a greater induction of the common anti-gonococcal response, Gene Set Enrichment Analysis (GSEA) identified a diestrus-specific induction of type-1 interferon signaling pathways. This transcriptional analysis of murine uterine gonococcal infection during distinct points in the natural reproductive cycle provided evidence for a common anti-gonococcal response characterized by significant induction of granulocyte chemokine expression and high proinflammatory mediators. The basic biology of this host response to N. gonorrhoeae in estrus and diestrus is similar at the pathway level, but varies drastically in magnitude. Overlaying this, we observed type-1 interferon induction specifically in diestrus infection where greater pathology is observed. This supports recent work suggesting this pathway has a significant, possibly host-detrimental, function in gonococcal infection. Together these findings lay the groundwork for further examination of the role of interferons in gonococcal infection. Additionally, this work enables the implementation of the diestrus uterine infection model using the newly characterized host response as a marker of pathology and its prevention as a correlate of candidate vaccine efficacy and ability to protect against the devastating consequences of N. gonorrhoeae-associated sequelae.
Murine host response to Neisseria gonorrhoeae upper genital tract infection reveals a common transcriptional signature, plus distinct inflammatory responses that vary between reproductive cycle phases.
Specimen part, Treatment
View SamplesPhosphate is essential for healthy bone growth and plays an essential role in fracture repair. Although phosphate deficiency has been shown to impair fracture healing, the mechanisms involved in impaired healing are unknown. More recently, studies have shown that the effect of phosphate deficiency on the repair process varied based on the genetic strain of mice, which is not characterized.
Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm.
Sex, Specimen part, Time
View SamplesThe long noncoding RNA NKX2-1-AS1 is highly expressed in primary lung adenocarcinomas compared to squamous carcinomas, similar to its adjacent protein-coding gene NKX2-1, but its contribution to lung tumorigenesis is not well understood. In this study we knockdown NKX2-1-AS1 by siRNA transfection and analyze the effect on gene expression in the lung carcinoma H441 cell line.
NKX2-1-AS1 negatively regulates CD274/PD-L1, cell-cell interaction genes, and limits human lung carcinoma cell migration.
No sample metadata fields
View SamplesRecent research has shown that peripheral treatment with amylin reduces Alzheimers disease (AD) pathology in the brain and improves learning and memory in AD mouse models. To understand the mechanism underlying this novel treatment for AD, we interrogated the transcriptome for changes in cortical gene expression in amyloid precursor protein (APP) transgenic mice treated with amylin compared to a vehicle treated group and wild type (WT) mice. Using weighted gene co-expression network analysis, we discovered that amylin treatment influenced two gene modules linked to AD pathology: 1) a module related to proinflammation and transport/vesicle process that included a hub gene of Cd68, and 2) a module related to mitochondria function that included a hub gene of Atp5b. Amylin treatment restored the expression of most genes in the APP cortex toward levels observed in the WT cortex including 23 key hub genes in these two modules. In cultured activated microglia cell line BV-2, we validated that Cd68 expression was attenuated by amylin through binding to the amylin receptor. Using publically-available transcriptomic human data, we found that the expression levels of the orthologues of these hub genes, including Cd68 and Atp5b, strongly correlated with the neurofibrillary tangle burden in the AD brain and with Mini-Mental Status Exam scores. Our study is the first to show the transcriptome-wide targets of amylin treatment, and further supports the potential use of amylin-type peptides to treat AD.
Amylin Treatment Reduces Neuroinflammation and Ameliorates Abnormal Patterns of Gene Expression in the Cerebral Cortex of an Alzheimer's Disease Mouse Model.
Specimen part
View SamplesBasal-like breast cancer (BLBC) cells share phenotypic similarities with cancer stem cells (CSCs) but the underlying molecular basis for this connection remains elusive. We hypothesized that BLBC cells are able to establish a niche permissive to the maintenance of CSCs and found that tumor cell-derived periostin (POSTN), a component of the extracellular matrix, as well as a corresponding cognate receptor, integrin v3, are highly expressed in a subset of BLBC cell lines as well as in cancer stem cell-enriched populations. Furthermore, we demonstrated that an intact periostin-integrin 3 signaling axis is required for the maintenance of breast CSCs. POSTN activates the ERK signaling pathway and regulates NF-B-mediated transcription of key cytokines, namely IL6 and IL8, which in turn mediate downstream activation of STAT3. In summary, these findings suggest that BLBC cells have an innate ability to establish a microenvironmental niche supportive of CSCs.
Tumor Cell-Derived Periostin Regulates Cytokines That Maintain Breast Cancer Stem Cells.
Cell line
View SamplesAlveolar macrophages orchestrate pulmonary innate immunity and are essential for early immune surveillance and clearance of microorganisms in the airways. Inflammatory signaling must be sufficiently robust to promote host defense but limited enough to prevent excessive tissue injury. Macrophages in the lungs utilize multiple transcriptional and post-transcriptional mechanisms of inflammatory gene expression to delicately balance the elaboration of immune mediators. RNA terminal uridyltransferases (TUTs), including the closely homologous family members Zcchc6 (TUT7) and Zcchc11 (TUT4), have been implicated in the post-transcriptional regulation of inflammation from studies conducted in vitro. In vivo, we observed that Zcchc6 is expressed in mouse and human primary macrophages. Zcchc6-deficient mice are viable and born in Mendelian ratios and do not exhibit an observable spontaneous phenotype under basal conditions. Following an intratracheal challenge with S. pneumoniae, Zcchc6 deficiency led to a modest but significant increase in the expression of select cytokines including IL-6, CXCL1, and CXCL5. These findings were recapitulated in vitro whereby Zcchc6-deficient macrophages exhibited similar increases in cytokine expression due to bacterial stimulation. Although loss of Zcchc6 also led to increased neutrophil emigration to the airways during pneumonia, these responses were not sufficient to impact host defense against infection.
The RNA uridyltransferase Zcchc6 is expressed in macrophages and impacts innate immune responses.
No sample metadata fields
View SamplesThe goal of this study was to define gene expression profiles in aortic tissue in response to three pro-atherogenic stimuli at two time points. We identified gene expression profiles induced by oral P.gingivalis (Pg), intranasal C. pneumoniae (Cp), and Western diet (WD) at acute (1 day after last infection, Pg, Cp, and control groups) and chronic (9 weeks after last infection, Pg, Cp, and control groups; WD for 9 weeks) time points in aortas of Apolipoprotein E (Apoe-/-) mice. 3 replicates per group were analyzed. RNA was analyzed using Mouse Gene 1.0 ST Array (Affymetrix, Santa Clara, CA).
Distinct gene signatures in aortic tissue from ApoE-/- mice exposed to pathogens or Western diet.
Specimen part, Treatment, Time
View SamplesA growing body of evidence suggests that epithelial cells have special roles during pneumonia. The purpose of this study was to elucidate epithelial-specific responses during lung infection.
Epithelial Cell-Derived Secreted and Transmembrane 1a Signals to Activated Neutrophils during Pneumococcal Pneumonia.
Specimen part
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