scholarly journals Lack of Atorvastatin Effect on Monocyte Gene Expression and Inflammatory Markers in HIV-1- infected ART-suppressed Individuals at Risk of non-AIDS Comorbidities

2021 ◽  
Vol 6 (2) ◽  
pp. 1-26
Author(s):  
Anjana Yadav ◽  
Andrew Kossenkov ◽  
Louise Showe ◽  
Sarah Ratcliffe ◽  
Grace Choi ◽  
...  
Keyword(s):  
Gene Expression ◽  
At Risk ◽  
Inflammatory Markers ◽  
Inflammatory Marker ◽  
Expression Patterns ◽  
People Living With Hiv ◽  
Surface Markers ◽  
Monocyte Activation ◽  
Double Blind ◽  
Atorvastatin Treatment

Background: Many people living with HIV have persistent monocyte activation despite viral suppression by antiretroviral therapy (ART), which contributes to non-AIDS complications including neurocognitive and other disorders. Statins have immunomodulatory properties that might be beneficial by reducing monocyte activation.  Methods: We previously characterized monocyte gene expression and inflammatory markers in 11 HIV-positive individuals on long-term ART (HIV/ART) at risk for non-AIDS complications because of low nadir CD4+ counts (median 129 cells/uL) and elevated hsCRP. Here, these individuals participated in a double-blind, randomized, placebo-controlled crossover study of 12 weeks of atorvastatin treatment. Monocyte surface markers were assessed by flow cytometry, plasma mediators by ELISA and Luminex, and monocyte gene expression by microarray analysis.  Results: Among primary outcome measures, 12 weeks of atorvastatin treatment led to an unexpected increase in CCR2+ monocytes (P=0.04), but did not affect CD16+ or CD163+ monocytes, nor levels in plasma of CCL2/MCP-1 or sCD14. Among secondary outcomes, atorvastatin treatment was associated with decreased plasma hsCRP (P=0.035) and IL-2R (P=0.012). Treatment was also associated with increased total CD14+ monocytes (P=0.015), and increased plasma CXCL9 (P=0.003) and IL-12 (P<0.001). Comparable results were seen in a subgroup that had inflammatory marker elevations at baseline. Atorvastatin treatment did not significantly alter monocyte gene expression or normalize aberrant baseline transcriptional patterns. Conclusions: In this study of aviremic HIV+ individuals at high risk of non-AIDS events, 12 weeks of atorvastatin did not normalize monocyte gene expression patterns nor lead to significant changes in monocyte surface markers or plasma mediators linked to non-AIDS comorbidities. 

scholarly journals An 8-week freeze-dried blueberry supplement impacts immune-related pathways: a randomized, double-blind placebo-controlled trial

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Michèle Rousseau ◽  
Justine Horne ◽  
Frédéric Guénard ◽  
Juan de Toro-Martín ◽  
Véronique Garneau ◽  
...  
Keyword(s):  
Gene Expression ◽  
At Risk ◽  
Treatment Time ◽  
Expression Profiles ◽  
Controlled Trial ◽  
Cardiometabolic Health ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Double Blind Placebo ◽  
Freeze Dried

Abstract Background Blueberries contain high levels of polyphenolic compounds with high in vitro antioxidant capacities. Their consumption has been associated with improved vascular and metabolic health. Purpose The objective was to examine the effects of blueberry supplement consumption on metabolic syndrome (MetS) parameters and potential underlying mechanisms of action. Methods A randomized double-blind placebo-controlled intervention trial was conducted in adults at risk of developing MetS. Participants consumed 50 g daily of either a freeze-dried highbush blueberry powder (BBP) or a placebo powder for 8 weeks (n = 49). MetS phenotypes were assessed at weeks 0, 4 and 8. Fasting blood gene expression profiles and plasma metabolomic profiles were examined at baseline and week 8 to assess metabolic changes occurring in response to the BBP. A per-protocol analysis was used. Results A significant treatment effect was observed for plasma triglyceride levels that was no longer significant after further adjustments for age, sex, BMI and baseline values. In addition, the treatment*time interactions were non-significant therefore suggesting that compared with the placebo, BBP had no statistically significant effect on body weight, blood pressure, fasting plasma lipid, insulin and glucose levels, insulin resistance (or sensitivity) or glycated hemoglobin concentrations. There were significant changes in the expression of 49 genes and in the abundance of 35 metabolites following BBP consumption. Differentially regulated genes were clustered in immune-related pathways. Conclusion An 8-week BBP intervention did not significantly improve traditional markers of cardiometabolic health in adults at risk of developing MetS. However, changes in gene expression and metabolite abundance suggest that clinically significant cardiometabolic changes could take longer than 8 weeks to present and/or could result from whole blueberry consumption or a higher dosage. BBP may also have an effect on factors such as immunity even within a shorter 8-week timeframe. Clinical trial registration clinicaltrials.gov, NCT03266055, 2017

scholarly journals An 8-Week Freeze-Dried Blueberry Supplement Impacts Immune-Related Pathways: A Randomized, Double-Blind Placebo-Controlled Trial

2020 ◽  
Author(s):  
Michèle Rousseau ◽  
Justine Horne ◽  
Frédéric Guénard ◽  
Juan de Toro-Martín ◽  
Véronique Garneau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
At Risk ◽  
Placebo Group ◽  
Expression Profiles ◽  
Controlled Trial ◽  
Cardiometabolic Health ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Freeze Dried

Abstract Background: Blueberries contain high level of polyphenolic compounds with high in vitro antioxidant capacities. Their consumption has been associated with improved vascular and metabolic health.Purpose: The objective was to examine the effects of blueberry supplement consumption on metabolic syndrome (MetS) parameters and potential underlying mechanisms of action. Methods: A randomized double-blind placebo-controlled intervention trial was conducted in adults at risk of developing MetS. Participants consumed 50g daily of either a freeze-dried highbush blueberry powder (BBP) or a placebo powder for 8 weeks (n=49). MetS phenotypes were assessed at week 0, 4 and 8. Fasting blood gene expression profiles and plasma metabolomic profiles were examined at baseline and week 8 to assess metabolic changes occurring in response to the BBP. A per-protocol analysis was used. Results: Interaction effects were non-significant demonstrating that compared to the placebo, BBP had no statistically significant effect on body weight, blood pressure, fasting plasma lipid, insulin and glucose levels, insulin resistance (or sensitivity) and on glycated hemoglobin concentrations. However, there were significant within- and between-group differences including increased insulin resistance in the placebo group only, greater TG at week 4 in the BBP compared to placebo group and increased fasting insulin from week 4 to 8 in both groups. Moreover, there were significant changes in the expression of 49 genes and 35 metabolites following BBP consumption. Differentially regulated genes were clustered in immune-related pathways.Conclusion: An 8-week BBP intervention did not significantly improve traditional markers of cardiometabolic health in adults at risk of developing MetS. However, metabolically relevant changes in gene expression and metabolites suggest that clinically significant cardiometabolic changes could take longer than 8 weeks to present and/or could result from whole blueberry consumption or a higher dosage. BBP may also have an effect on factors such as immunity even within a shorter 8-week timeframe. Clinical trial registration: clinicaltrials.gov, NCT03266055, 2017, https://clinicaltrials.gov/ct2/show/NCT03266055?term=blueberry+vohl&draw=2&rank=1

scholarly journals Gene‐Expression Patterns in Whole Blood Identify Subjects at Risk for Recurrent Tuberculosis

2007 ◽  
Vol 195 (3) ◽  
pp. 357-365 ◽  
Author(s):  
Rohit Mistry ◽  
Jacqueline M. Cliff ◽  
Christopher L. Clayton ◽  
Nulda Beyers ◽  
Yasmin S. Mohamed ◽  
...  
Keyword(s):  
Gene Expression ◽  
At Risk ◽  
Whole Blood ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Recurrent Tuberculosis

scholarly journals Insights into the Gene Expression Profiles of Active and Restricted Red/Green-HIV+ Human Astrocytes: Implications for Shock or Lock Therapies in the Brain

2020 ◽  
Vol 94 (6) ◽  
Author(s):  
Venkata Viswanadh Edara ◽  
Anuja Ghorpade ◽  
Kathleen Borgmann
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Neurocognitive Disorders ◽  
Antiretroviral Drugs ◽  
Gene Expression Patterns ◽  
People Living With Hiv ◽  
Human Astrocytes ◽  
Living With Hiv ◽  
Hiv 1

ABSTRACT A significant number of people living with human immunodeficiency virus type 1 (HIV-1) suffer from HIV-associated neurocognitive disorders (HAND). Many previous studies investigating HIV in astrocytes as a heterogenous population have established the relevance of astrocytes to HIV-associated neuropathogenesis. However, these studies were unable to differentiate the state of infection, i.e., active or latent, or to evaluate how this affects astrocyte biology. In this study, the pseudotyped doubly labeled fluorescent reporter red/green (R/G)-HIV-1 was used to identify and enrich restricted and active populations of HIV+ astrocytes based on the viral promoter activity. Here, we report that the majority of human astrocytes restricted R/G-HIV-1 gene expression early during infection and were resistant to reactivation by vorinostat and interleukin 1β. However, actively infected astrocytes were inducible, leading to increased expression of viral proteins upon reactivation. R/G-HIV-1 infection also significantly decreased the cell proliferation and glutamate clearance ability of astrocytes, which may contribute to excitotoxicity. Moreover, transcriptome analyses to compare gene expression patterns of astrocyte harboring active versus restricted long terminal repeats (LTRs) revealed that the gene expression patterns were similar and that the active population demonstrated more widespread and robust changes. Our data suggest that harboring the HIV genome profoundly alters astrocyte biology and that strategies that keep the virus latent (e.g., block and lock) or those that reactivate the latent virus (e.g., shock and kill) would be detrimental to astrocyte function and possibly augment their contributions to HAND. IMPORTANCE More than 36 million people are living with HIV-1 worldwide, and despite antiretroviral therapy, 30 to 50% of the people living with HIV-1 suffer from mild to moderate neurocognitive disorders. HIV-1 reservoirs in the central nervous system (CNS) are challenging to address due to low penetration of antiretroviral drugs, lack of resident T cells, and permanent integration of provirus into neural cells such as microglia and astrocytes. Several studies have shown astrocyte dysfunction during HIV-1 infection. However, little is known about how HIV-1 latency affects their function. The significance of our research is in identifying that the majority of HIV+ astrocytes restrict HIV expression and were resistant to reactivation. Further, simply harboring the HIV genome profoundly altered astrocyte biology, resulting in a proinflammatory phenotype and functional changes. In this context, therapeutic strategies to reactivate or silence astrocyte HIV reservoirs, without excising proviral DNA, will likely lead to detrimental neuropathological outcomes during HIV CNS infection.

Gene expression patterns in blood predict future severe endpoints in community acquired pneumonia

Pneumologie ◽  
2018 ◽  
Vol 72 (S 01) ◽  
pp. S8-S9
Author(s):  
M Bauer ◽  
H Kirsten ◽  
E Grunow ◽  
P Ahnert ◽  
M Kiehntopf ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Community Acquired Pneumonia ◽  
Gene Expression Patterns

Identification of Differentially Expressed Genes Using cDNA-AFLP During Six Days In Vitro Tuberization of Potato

Zuriat ◽  
2015 ◽  
Vol 14 (1) ◽  
Author(s):  
Nono Carsono ◽  
Christian Bachem
Keyword(s):  
Gene Expression ◽  
Developmental Process ◽  
Expression Patterns ◽  
Induction Medium ◽  
In Vitro Tuberization ◽  
Storage Organ ◽  
Developmentally Regulated ◽  
Study Gene Expression ◽  
Differential Pattern

Tuberization in potato is a complex developmental process resulting in the differentiation of stolon into the storage organ, tuber. During tuberization, change in gene expression has been known to occur. To study gene expression during tuberization over the time, in vitro tuberization system provides a suitable tool, due to its synchronous in tuber formation. An early six days axillary bud growing on tuber induction medium is a crucial development since a large number of genes change in their expression patterns during this period. In order to identify, isolate and sequencing the genes which displaying differential pattern between tuberizing and non-tuberizing potato explants during six days in vitro tuberization, cDNA-AFLP fingerprint, method for the visualization of gene expression using cDNA as template which is amplified to generate an RNA-fingerprinting, was used in this experiment. Seventeen primer combinations were chosen based on their expression profile from cDNA-AFLP fingerprint. Forty five TDFs (transcript derived fragment), which displayed differential expressions, were obtained. Tuberizing explants had much more TDFs, which developmentally regulated, than those from non tuberizing explants. Seven TDFs were isolated, cloned and then sequenced. One TDF did not find similarity in the current databases. The nucleotide sequence of TDF F showed best similarity to invertase ezymes from the databases. The homology of six TDFs with known sequences is discussed in this paper.

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