Inorganic fraction of oil sands process-affected water induces mammalian macrophage stress gene expression and acutely modulates immune cell functional markers at both the gene and protein levels

2020 ◽  
Vol 66 ◽  
pp. 104875
Author(s):  
Nicole A.I. Phillips ◽  
Dustin M.E. Lillico ◽  
Rui Qin ◽  
Mark McAllister ◽  
Mohamed Gamal El-Din ◽  
...  
Keyword(s):  
Gene Expression ◽  
Oil Sands ◽  
Immune Cell ◽  
Functional Markers ◽  
Protein Levels ◽  
Stress Gene ◽  
Inorganic Fraction

scholarly journals Stroke increases the expression of ACE2, the SARS-CoV-2 binding receptor, in murine lungs

2020 ◽  
Author(s):  
Vikramjeet Singh ◽  
Alexander Beer ◽  
Andreas Kraus ◽  
Xiaoni Zhang ◽  
Jinhua Xue ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Injury ◽  
Systemic Inflammation ◽  
Immune Cell ◽  
Risk Group ◽  
Tissue Injury ◽  
Lung Epithelial Cells ◽  
Experimental Stroke ◽  
Virus Surface ◽  
Protein Levels

AbstractBackgroundThe newly emerged severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused a worldwide pandemic of human respiratory disease. Angiotensin-converting enzyme (ACE) 2 is the key receptor on lung epithelial cells to facilitate initial binding and infection of SARS-CoV-2. The binding to ACE2 is mediated via the spike glycoprotein present on the virus surface. Recent clinical data have demonstrated that patients suffering from stroke are particularly susceptible to severe courses of SARS-CoV-2 infection, thus forming a defined risk group. However, a mechanistic explanation for this finding is lacking. Sterile tissue injuries including stroke induce lymphocytopenia and systemic inflammation that might modulate the expression levels of surface proteins in distant organs. Whether systemic inflammation following stroke can specifically modulate ACE2 expression in the lung has not been investigated.MethodsMice were subjected to transient middle cerebral artery occlusion (MCAO) for 45 min and sacrificed after 24 h and 72 h for analysis of brain and lung tissues. Gene expression and protein levels of ACE2, ACE, IL-6 and IL1β were measured by quantitative PCR and Western blot, respectively. Immune cell populations in lymphoid organs were analyzed by flow cytometry.ResultsStrikingly, 24 h after stroke, we observed a substantial increase in the expression of ACE2 both on the transcriptional and protein levels in the lungs of MCAO mice compared to sham-operated mice. This increased expression persisted until day 3 after stroke. In addition, MCAO increased the expression of inflammatory cytokines IL-6 and IL-1β in the lungs. Higher gene expression of cytokines IL-6 and IL-1β was found in ischemic brain hemispheres and a reduced number of T-lymphocytes were present in the blood and spleen as an indicator of sterile tissue injury-induced immunosuppression.ConclusionsWe demonstrate significantly augmented ACE2 levels and inflammation in murine lungs after experimental stroke. These pre-clinical findings might explain the clinical observation that patients with pre-existing stroke represent a high-risk group for the development of severe SARS-CoV-2 infections. Our studies call for further investigations into the underlying signaling mechanisms and possible therapeutic interventions.HighlightsBrain tissue injury increases ACE2 levels in the lungsBrain injury induces pro-inflammatory cytokine expression in the lungsBrain injury causes parenchymal inflammation and systemic lymphopenia

scholarly journals Comprehensive Analysis of the Expression, Prognostic Value and Immune Microenvironment of CMTM Family Members in Ovarian Cancer

2021 ◽  
Author(s):  
Mengjun Zhang ◽  
Yue Yin ◽  
Zhenxing Sun ◽  
Yuan Liu ◽  
Yiru Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Prognostic Value ◽  
Immune Cell ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
High Expression ◽  
Immune Checkpoints ◽  
Immune Microenvironment ◽  
Protein Levels

Abstract Background: Ovarian cancer (OV) is one of the most common gynecological malignancies worldwide, and its immunotherapy has considerable prospects. Multiple members of the CMTM family were aberrantly expressed in human cancers and controled key malignant biological processes and immune regulation in cancer development. However, little is known about the function of this gene family in ovarian cancer, especially in terms of immunity.Methods: GEPIA, Oncomine, HPA, Kaplan-Meier plotter, cBioPortal, GeneMANIA and TIMER were used to analyze the differential gene expression, prognostic value, genetic alterations and alterations in the immune microenvironment of the CMTM family in patients with ovarian cancer. Importantly, RT-qPCR was used to verify the gene expression of the CMTM family.Results: CMTM1/3/4/6/7/8 showed abnormally high expression at the mRNA and protein levels in OV tissues based on the GEPIA and HPA databases. RT-qPCR showed that CMTM1/6/8 was highly expressed in ovarian cancer cell lines. Survival analysis showed that high expression of CMTM1/2/3/5/8 can lead to a significant reduction in overall survival and progression-free survival. There were many types of genetic alterations in the CMTM family. And CMTM1/2/3/6 had a certain correlation with the changes of immune microenvironment such as immune cell infiltration and immune checkpoint expression, which may be the potential mechanism of the CMTM family in ovarian cancer.Conclusion: This study confirmed that the CMTM family has abnormal expression in ovarian cancer and can be used as a biomarker for prognostic evaluation. And the CMTM family may be used as a potential target for immunotherapy based on the suppression of immune checkpoints.

scholarly journals Comprehensive Analysis of the Expression, Prognostic Value and Immune Microenvironment of Family Members in Ovarian Cancer

2021 ◽  
Author(s):  
Mengjun Zhang ◽  
Yue Yin ◽  
Zhenxing Sun ◽  
Yuan Liu ◽  
Yiru Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Prognostic Value ◽  
Immune Cell ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
High Expression ◽  
Immune Checkpoints ◽  
Immune Microenvironment ◽  
Protein Levels

Abstract Background: Ovarian cancer (OV) is one of the most common gynecological malignancies worldwide, and its immunotherapy has considerable prospects. Multiple members of the CMTM family were aberrantly expressed in human cancers and controled key malignant biological processes and immune regulation in cancer development. However, little is known about the function of this gene family in ovarian cancer, especially in terms of immunity.Methods: GEPIA, Oncomine, HPA, Kaplan-Meier plotter, cBioPortal, GeneMANIA and TIMER were used to analyze the differential gene expression, prognostic value, genetic alterations and alterations in the immune microenvironment of the CMTM family in patients with ovarian cancer. Importantly, RT-qPCR was used to verify the gene expression of the CMTM family.Results: CMTM1/3/4/6/7/8 showed abnormally high expression at the mRNA and protein levels in OV tissues based on the GEPIA and HPA databases. RT-qPCR showed that CMTM1/6/8 was highly expressed in ovarian cancer cell lines. Survival analysis showed that high expression of CMTM1/2/3/5/8 can lead to a significant reduction in overall survival and progression-free survival. There were many types of genetic alterations in the CMTM family. And CMTM1/2/3/6 had a certain correlation with the changes of immune microenvironment such as immune cell infiltration and immune checkpoint expression, which may be the potential mechanism of the CMTM family in ovarian cancer.Conclusion: This study confirmed that the CMTM family has abnormal expression in ovarian cancer and can be used as a biomarker for prognostic evaluation. And the CMTM family may be used as a potential target for immunotherapy based on the suppression of immune checkpoints.

scholarly journals Inflamm-Aging Is Associated with Lower Plasma PTX3 Concentrations and an Impaired Capacity of PBMCs to Express hTERT following LPS Stimulation

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Aaron L. Slusher ◽  
Tiffany M. Zúñiga ◽  
Edmund O. Acevedo
Keyword(s):  
Gene Expression ◽  
Young Adults ◽  
Telomere Length ◽  
Immune Cell ◽  
Ex Vivo ◽  
Middle Aged ◽  
Human Telomerase Reverse Transcriptase ◽  
Negatively Associated ◽  
Htert Gene ◽  
Age Related

Age-related elevations in proinflammatory cytokines, known as inflamm-aging, are associated with shorter immune cell telomere lengths. Purpose. This study examined the relationship of plasma PTX3 concentrations, a biomarker of appropriate immune function, with telomere length in 15 middle-aged (40-64 years) and 15 young adults (20-31 years). In addition, PBMCs were isolated from middle-aged and young adults to examine their capacity to express a key mechanistic component of telomere length maintenance, human telomerase reverse transcriptase (hTERT), following ex vivo cellular stimulation. Methods. Plasma PTX3 and inflammatory cytokines (i.e., IL-6, IL-10, TGF-β, and TNF-α), PBMC telomere lengths, and PBMC hTERT gene expression and inflammatory protein secretion following exposure to LPS, PTX3, and PTX3+LPS were measured. Results. Aging was accompanied by the accumulation of centrally located visceral adipose tissue, without changes in body weight and BMI, and alterations in the systemic inflammatory milieu (decreased plasma PTX3 and TGF-β; increased TNF-α (p≤0.050)). In addition, shorter telomere lengths in middle-aged compared to young adults (p=0.011) were negatively associated with age, body fat percentages, and plasma TNF-α (r=−0.404, p=0.027; r=−0.427, p=0.019; and r=−0.323, p=0.041, respectively). Finally, the capacity of PBMCs to increase hTERT gene expression following ex vivo stimulation was impaired in middle-aged compared to young adults (p=0.033) and negatively associated with telomere lengths (r=0.353, p=0.028). Conclusions. Proinflammation and the impaired hTERT gene expression capacity of PBMCs may contribute to age-related telomere attrition and disease.

scholarly journals Evaluation of potential tumor markers that may predict neoadjuvant treatment efficiency in rectal cancer

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Fatma Demet Arslan ◽  
Ayse Kocak ◽  
Cengiz Aydın ◽  
Emel Ebru Pala ◽  
Dilek Oncel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rectal Cancer ◽  
Tumor Markers ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Beclin 1 ◽  
Tumor Regression Grade ◽  
Protein Levels ◽  
Study Gene Expression ◽  
Regression Grade

AbstractObjectivesThe recurrence of rectal cancer or its resistance to neoadjuvant treatment develops due to the adaptation to hypoxia, apoptosis or autophagy. Survivin, one of the inhibitors of apoptosis; Beclin 1, which is a positive regulator in the autophagy pathway; and hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase-9 (CA9), which are associated with tumor tissue hypoxia, may be related to resistance to treatment. Our aim was to evaluate the potential tumor markers that may help to monitor the response to neoadjuvant treatment in locally advanced rectal cancer (RC).MethodsTwenty-five patients with locally advanced RC were included in the study. Gene expression and protein levels of Beclin 1, Survivin, HIF-1α, and CA9 were analyzed in fresh tissue specimens and blood samples. The relationships of these markers to tumor staging and regression grade were evaluated.ResultsHigher blood CA9 gene expression levels and lower blood HIF-1α protein levels were found in the response group according to tumor regression grade. After neoadjuvant treatment, tissue Beclin 1 and blood Survivin gene expressions and tissue CA9, blood Beclin 1 and blood HIF-1α protein levels decreased significantly.ConclusionBeclin 1, Survivin, HIF-1α ve CA9 may help to predict the effects of the applied treatment approach.

scholarly journals Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ashley A. Krull ◽  
Deborah O. Setter ◽  
Tania F. Gendron ◽  
Sybil C. L. Hrstka ◽  
Michael J. Polzin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebrospinal Fluid ◽  
Growth Factors ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Large Scale ◽  
Therapeutic Benefit ◽  
Protein Levels ◽  
Genes Encoding ◽  
Intrathecal Space

Abstract Background Mesenchymal stromal cells (MSCs) have been studied with increasing intensity as clinicians and researchers strive to understand the ability of MSCs to modulate disease progression and promote tissue regeneration. As MSCs are used for diverse applications, it is important to appreciate how specific physiological environments may stimulate changes that alter the phenotype of the cells. One need for neuroregenerative applications is to characterize the spectrum of MSC responses to the cerebrospinal fluid (CSF) environment after their injection into the intrathecal space. Mechanistic understanding of cellular biology in response to the CSF environment may predict the ability of MSCs to promote injury repair or provide neuroprotection in neurodegenerative diseases. Methods In this study, we characterized changes in morphology, metabolism, and gene expression occurring in human adipose-derived MSCs cultured in human (hCSF) or artificial CSF (aCSF) as well as examined relevant protein levels in the CSF of subjects treated with MSCs for amyotrophic lateral sclerosis (ALS). Results Our results demonstrated that, under intrathecal-like conditions, MSCs retained their morphology, though they became quiescent. Large-scale transcriptomic analysis of MSCs revealed a distinct gene expression profile for cells cultured in aCSF. The aCSF culture environment induced expression of genes related to angiogenesis and immunomodulation. In addition, MSCs in aCSF expressed genes encoding nutritional growth factors to expression levels at or above those of control cells. Furthermore, we observed a dose-dependent increase in growth factors and immunomodulatory cytokines in CSF from subjects with ALS treated intrathecally with autologous MSCs. Conclusions Overall, our results suggest that MSCs injected into the intrathecal space in ongoing clinical trials remain viable and may provide a therapeutic benefit to patients.

scholarly journals Bioinformatics analysis of DNMT1 expression and its role in head and neck squamous cell carcinoma prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jili Cui ◽  
Lian Zheng ◽  
Yuanyuan Zhang ◽  
Miaomiao Xue
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Hub Genes ◽  
Significant Difference ◽  
Dnmt1 Expression

AbstractHead and neck squamous cell carcinoma (HNSCC) is the sixth most common type of malignancy in the world. DNA cytosine-5-methyltransferase 1 (DNMT1) play key roles in carcinogenesis and regulation of the immune micro-environment, but the gene expression and the role of DNMT1 in HNSCC is unknown. In this study, we utilized online tools and databases for pan-cancer and HNSCC analysis of DNMT1 expression and its association with clinical cancer characteristics. We also identified genes that positively and negatively correlated with DNMT1 expression and identified eight hub genes based on protein–protein interaction (PPI) network analysis. Enrichment analyses were performed to explore the biological functions related with of DNMT1. The Tumor Immune Estimation Resource (TIMER) database was performed to explore the relationship between DNMT1 expression and immune-cell infiltration. We demonstrated that DNMT1 gene expression was upregulated in HNSCC and associated with poor prognosis. Based on analysis of the eight hub genes, we determined that DNMT1 may be involved in cell cycle, proliferation and metabolic related pathways. We also found that significant difference of B cells infiltration based on TP 53 mutation. These findings suggest that DNMT1 related epigenetic alterations have close relationship with HNSCC progression, and DNMT1 could be a novel diagnostic biomarker and a promising therapeutic target for HNSCC.

scholarly journals A Polyphenol Enriched Variety of Apple Alters Circulating Immune Cell Gene Expression and Faecal Microbiota Composition in Healthy Adults: A Randomized Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1092
Author(s):  
Matthew P. G. Barnett ◽  
Wayne Young ◽  
Kelly Armstrong ◽  
Diane Brewster ◽  
Janine M. Cooney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Cell ◽  
Controlled Trial ◽  
Composition Analysis ◽  
Cell Mediated Immunity ◽  
Anthocyanin Content ◽  
Microbiota Composition ◽  
Faecal Microbiota ◽  
Apple Variety ◽  
Relative Abundances

Polyphenols within fruits and vegetables may contribute to health benefits due to their consumption, with the anthocyanin sub-set also adding colour. The Lemonade™ apple variety has green skin and white flesh, with low anthocyanin content, while some apple varieties have high anthocyanin content in both the skin and flesh. Effects of red compared with white-fleshed apples were studied in healthy human subjects in a randomized, placebo-controlled, cross-over intervention trial. Twenty-five healthy subjects consumed dried daily portions of the red-fleshed or placebo (white-fleshed) apple for two weeks, followed by one-week washout and further two-week crossover period. During the study, volunteers provided faecal samples for microbiota composition analysis and blood samples for peripheral blood mononuclear cell (PBMC) gene expression analysis. Subtle differences were observed in the faecal microbiota of subjects that were fed the different apples, with significant (p < 0.05) reductions in relative abundances of Streptococcus, Ruminococcus, Blautia, and Roseburia, and increased relative abundances of Sutterella, Butyricicoccus, and Lactobacillus in subjects after consuming the red apple. Changes in PBMC gene expression showed 18 mRNA transcripts were differentially expressed between the two groups, of which 16 were immunoglobulin related genes. Pathway analysis showed that these genes had roles in pathways such as immunoglobulin production, B cell-mediated immunity, complement activation, and phagocytosis. In conclusion, this study shows that anthocyanin-rich apples may influence immune function compared to control apples, with changes potentially associated with differences in the faecal microbiota.

scholarly journals Predicting Host Immune Cell Dynamics and Key Disease-Associated Genes Using Tissue Transcriptional Profiles

Processes ◽  
2019 ◽  
Vol 7 (5) ◽  
pp. 301
Author(s):  
Muying Wang ◽  
Satoshi Fukuyama ◽  
Yoshihiro Kawaoka ◽  
Jason E. Shoemaker
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Immune Cell ◽  
Mean Squared Error ◽  
Expression Profiles ◽  
Statistical Tests ◽  
Critical Factor ◽  
Expression Data ◽  
Cell Dynamics ◽  
Cell Counts

Motivation: Immune cell dynamics is a critical factor of disease-associated pathology (immunopathology) that also impacts the levels of mRNAs in diseased tissue. Deconvolution algorithms attempt to infer cell quantities in a tissue/organ sample based on gene expression profiles and are often evaluated using artificial, non-complex samples. Their accuracy on estimating cell counts given temporal tissue gene expression data remains not well characterized and has never been characterized when using diseased lung. Further, how to remove the effects of cell migration on transcript counts to improve discovery of disease factors is an open question. Results: Four cell count inference (i.e., deconvolution) tools are evaluated using microarray data from influenza-infected lung sampled at several time points post-infection. The analysis finds that inferred cell quantities are accurate only for select cell types and there is a tendency for algorithms to have a good relative fit (R 2 ) but a poor absolute fit (normalized mean squared error; NMSE), which suggests systemic biases exist. Nonetheless, using cell fraction estimates to adjust gene expression data, we show that genes associated with influenza virus replication and increased infection pathology are more likely to be identified as significant than when applying traditional statistical tests.

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