scholarly journals The Immunomodulatory Effects of Social Isolation in Mice are Linked to Temperature Control

2021 ◽  
Author(s):  
Alice Hamilton ◽  
Raffaella Rizzo ◽  
Samuel Brod ◽  
Masahiro Ono ◽  
Mauro Perretti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Social Isolation ◽  
Bacterial Sepsis ◽  
Immunomodulatory Effects ◽  
Artificial Nests ◽  
Blood Gene Expression ◽  
Physical Wellbeing ◽  
Societal Problem ◽  
Socially Isolated ◽  
Pro Inflammatory Cytokines

AbstractLiving in isolation is considered an emerging societal problem that negatively affects the physical wellbeing of its sufferers in ways that we are just starting to appreciate. This study investigates the immunomodulatory effects of social isolation in mice, utilising a two-week program of sole cage occupancy followed by the testing of immune-inflammatory resilience to bacterial sepsis. Our results revealed that mice housed in social isolation showed an increased ability to clear bacterial infection compared to control socially housed animals. These effects were associated with specific changes in whole blood gene expression profile and an increased production of classical pro-inflammatory cytokines. Interestingly, equipping socially isolated mice with artificial nests as a substitute for their natural huddling behaviour reversed the increased resistance to bacterial sepsis. These results further highlight the ability of the immune system to act as a sensor of our living conditions and to respond in a compensatory fashion to external challenges that might threaten the survival of the host.

A comparative study about the immunomodulatory effects of tramadol and metamizole in a murine model of postoperative ileus

2019 ◽  
Vol 53 (6) ◽  
pp. 610-618 ◽  
Author(s):  
Gun-Soo Hong ◽  
Kathy Stein ◽  
Mariola Lysson ◽  
Joerg Kalff ◽  
Sven Wehner
Keyword(s):  
Gene Expression ◽  
Inflammatory Response ◽  
Postoperative Ileus ◽  
Gastrointestinal Transit ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Immunomodulatory Effects ◽  
Muscularis Externa ◽  
Underlying Inflammation ◽  
Pro Inflammatory Cytokines

Postoperative ileus (POI) is a common complication after abdominal surgery characterized by motility disturbances leading to increased morbidity and mortality in surgical patients. Intestinal manipulation of the murine small bowel is an established animal model resulting in an increased postsurgical inflammation within the intestinal muscular externa and a delayed gastrointestinal transit. Some analgesics have been shown to affect inflammation. In this study, we compared the immunomodulatory effects of two different analgesics. Mice were treated with tramadol, metamizole or saline as a control in our established POI model. The postoperative inflammatory response was assessed by gene expression of pro-inflammatory cytokines at different time points and immunocytes extravasation into the muscularis externa. Functional motility analyses were performed by a gastrointestinal transit measurement. Metamizole application reduced the pro-inflammatory response after surgery and improved gastrointestinal motility, while tramadol showed no alteration in cytokine gene expression, influx of immunocytes and gastrointestinal transit compared with the controls. In conclusion. we suggest tramadol as analgesia in immunological studies on POI in mice as it does not affect the underlying inflammation of POI.

scholarly journals Prometastatic Molecular Profiles in Breast Tumors From Socially Isolated Women

2018 ◽  
Vol 2 (3) ◽  
Author(s):  
Julienne E Bower ◽  
Stephen L Shiao ◽  
Peggy Sullivan ◽  
Donald M Lamkin ◽  
Robert Atienza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Social Isolation ◽  
Cancer Progression ◽  
Standard Error ◽  
Lymphovascular Invasion ◽  
Breast Tumors ◽  
M2 Macrophage ◽  
Socially Isolated

Abstract Background Social isolation is associated with accelerated breast cancer progression and increased disease recurrence and mortality, but the underlying biological mechanisms remain poorly understood. In preclinical models, beta-adrenergic signaling from fight-or-flight stress responses can stimulate prometastatic processes in the tumor microenvironment including upregulation of M2 macrophages, epithelial–mesenchymal transition (EMT), and lymphovascular invasion. This study examines whether the same pathways are upregulated in breast tumors from socially isolated cancer patients. Methods EMT and M1/M2 macrophage gene expression programs were analyzed by genome-wide transcriptional profiling, and lymphatic and vascular density were assessed by immunohistochemistry in primary tumors from 56 early-stage breast cancer patients who were part of the UCLA RISE study. Social isolation was quantified by the Social Provisions Scale, and disease characteristics were assessed by medical record review. General linear models were used to quantify differential gene expression across risk factor groups. Linear regression models were used to examine associations between social isolation and lymphovascular invasion. Results Tumors from socially isolated patients showed upregulated expression of genes involved in EMT (average score difference = +0.080 log2 mRNA abundance ± 0.034 standard error) and M2 macrophage polarization (+0.033 ± 0.014) as well as increased density of lymphatic vessels (β= –.29) but no difference in blood vessel density. TELiS promoter–based bioinformatics analyses indicated activation of CREB family transcription factors that mediate the gene-regulatory effects of β-adrenergic signaling (log2 fold-difference in promoter binding site prevalence: mean ± standard error = +0.49 ± 0.19). Conclusions Primary breast tumors from socially isolated patients show multiple prometastatic molecular alterations, providing a plausible biological pathway through which poor social support may accelerate breast cancer progression and defining new targets for intervention.

scholarly journals Whole blood gene expression profiling of neonates with confirmed bacterial sepsis

Genomics Data ◽  
2015 ◽  
Vol 3 ◽  
pp. 41-48 ◽  
Author(s):  
Paul Dickinson ◽  
Claire L. Smith ◽  
Thorsten Forster ◽  
Marie Craigon ◽  
Alan J. Ross ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Whole Blood ◽  
Expression Profiling ◽  
Bacterial Sepsis ◽  
Blood Gene Expression

Addressing COVID-19 Worry and Social Isolation in Home-Based Primary Care

2020 ◽  
Author(s):  
Rachel Elizabeth Weiskittle ◽  
Michelle Mlinac ◽  
LICSW Nicole Downing
Keyword(s):  
Mental Health ◽  
Older Adults ◽  
Primary Care ◽  
Social Workers ◽  
Social Isolation ◽  
Mental Health Providers ◽  
Health Providers ◽  
Home Based Primary Care ◽  
Home Based ◽  
Socially Isolated

Social distancing measures following the outbreak of COVID-19 have led to a rapid shift to virtual and telephone care. Social workers and mental health providers in VA home-based primary care (HBPC) teams face challenges providing psychosocial support to their homebound, medically complex, socially isolated patient population who are high risk for poor health outcomes related to COVID-19. We developed and disseminated an 8-week telephone or virtual group intervention for front-line HBPC social workers and mental health providers to use with socially isolated, medically complex older adults. The intervention draws on skills from evidence-based psychotherapies for older adults including Acceptance and Commitment Therapy, Cognitive-Behavioral Therapy, and Problem-Solving Therapy. The manual was disseminated to VA HBPC clinicians and geriatrics providers across the United States in March 2020 for expeditious implementation. Eighteen HBPC teams and three VA Primary Care teams reported immediate delivery of a local virtual or telephone group using the manual. In this paper we describe the manual’s development and clinical recommendations for its application across geriatric care settings. Future evaluation will identify ways to meet longer-term social isolation and evolving mental health needs for this patient population as the pandemic continues.

scholarly journals A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents

Allergy ◽  
2020 ◽  
Vol 75 (12) ◽  
pp. 3248-3260 ◽  
Author(s):  
Nathanaël Lemonnier ◽  
Erik Melén ◽  
Yale Jiang ◽  
Stéphane Joly ◽  
Camille Ménard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Children And Adolescents ◽  
Whole Blood ◽  
Gene Expression Signature ◽  
Blood Gene Expression ◽  
Expression Signature

scholarly journals Epigenome-wide association study of whole blood gene expression in Framingham Heart Study participants provides molecular insight into the potential role of CHRNA5 in cigarette smoking-related lung diseases

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chen Yao ◽  
Roby Joehanes ◽  
Rory Wilson ◽  
Toshiko Tanaka ◽  
Luigi Ferrucci ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Dna Methylation ◽  
Cigarette Smoking ◽  
Association Study ◽  
Whole Blood ◽  
Lung Diseases ◽  
Epigenetic Modification ◽  
Blood Gene Expression ◽  
Increased Risk

Abstract Background DNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases. Results We performed an epigenome-wide association study of whole blood gene expression in ~ 6000 individuals from four cohorts. We discovered and replicated numerous CpGs associated with the expression of cis genes within 500 kb of each CpG, with 148 to 1,741 cis CpG-transcript pairs identified across cohorts. We found that the closer a CpG resided to a transcription start site, the larger its effect size, and that 36% of cis CpG-transcript pairs share the same causal genetic variant. Mendelian randomization analyses revealed that hypomethylation and lower expression of CHRNA5, which encodes a smoking-related nicotinic receptor, are causally linked to increased risk of COPD and lung cancer. This putatively causal relationship was further validated in lung tissue data. Conclusions Our results provide a large and comprehensive association study of whole blood DNA methylation with gene expression. Expression platform differences rather than population differences are critical to the replication of cis CpG-transcript pairs. The low reproducibility of trans CpG-transcript pairs suggests that DNA methylation regulates nearby rather than remote gene expression. The putatively causal roles of methylation and expression of CHRNA5 in relation to COPD and lung cancer provide evidence for a mechanistic link between patterns of smoking-related epigenetic variation and lung diseases, and highlight potential therapeutic targets for lung diseases and smoking cessation.

scholarly journals Whole blood gene expression within days after total-body irradiation predicts long term survival in Gottingen minipigs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sunita Chopra ◽  
Maria Moroni ◽  
Jaleal Sanjak ◽  
Laurel MacMillan ◽  
Bernadette Hritzo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Total Body Irradiation ◽  
Whole Blood ◽  
Radiation Effects ◽  
Expression Profiles ◽  
Mass Casualty ◽  
Machine Learning Algorithms ◽  
Term Survival ◽  
Blood Gene Expression ◽  
Total Body

AbstractGottingen minipigs mirror the physiological radiation response observed in humans and hence make an ideal candidate model for studying radiation biodosimetry for both limited-sized and mass casualty incidents. We examined the whole blood gene expression profiles starting one day after total-body irradiation with increasing doses of gamma-rays. The minipigs were monitored for up to 45 days or time to euthanasia necessitated by radiation effects. We successfully identified dose- and time-agnostic (over a 1–7 day period after radiation), survival-predictive gene expression signatures derived using machine-learning algorithms with high sensitivity and specificity. These survival-predictive signatures fare better than an optimally performing dose-differentiating signature or blood cellular profiles. These findings suggest that prediction of survival is a much more useful parameter for making triage, resource-utilization and treatment decisions in a resource-constrained environment compared to predictions of total dose received. It should hopefully be possible to build such classifiers for humans in the future.

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