scholarly journals Age-severity matched cytokine profiling reveals specific signatures in Covid-19 patients

2020 ◽  
Author(s):  
Roberta Angioni ◽  
Ricardo Sanchez-Rodriguez ◽  
Fabio Munari ◽  
Nicole Bertoldi ◽  
Diletta Arcidiacono ◽  
...  
Keyword(s):  
Therapeutic Strategies ◽  
Severe Form ◽  
Host Immunity ◽  
Infected People ◽  
Immune Signature ◽  
Tnf Α ◽  
Age Dependent ◽  
Key Factor ◽  
Immune Profiling ◽  
Cytokine Profiling

A global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcome, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell exhaustion, and the increased levels of inflammatory mediators have been described in COVID-19 patients, in particular in severe cases1. Age represents a key factor in COVID-19 morbidity and mortality2. Understanding age-associated immune signatures of patients is therefore important to identify preventive and therapeutic strategies. In this study, we investigated the immune profile of COVID-19 hospitalized patients identifying a distinctive age-dependent immune signature associated with disease severity. Indeed, defined circulating factors - CXCL8, IL-10, IL-15, IL-27 and TNF-α - positively correlate with older age, longer hospitalization, and a more severe form of the disease and may thus represent the leading signature in critical COVID-19 patients.

scholarly journals Age-severity matched cytokine profiling reveals specific signatures in Covid-19 patients

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Roberta Angioni ◽  
Ricardo Sánchez-Rodríguez ◽  
Fabio Munari ◽  
Nicole Bertoldi ◽  
Diletta Arcidiacono ◽  
...  
Keyword(s):  
Therapeutic Strategies ◽  
Severe Form ◽  
Host Immunity ◽  
Infected People ◽  
Immune Signature ◽  
Tnf Α ◽  
Age Dependent ◽  
Key Factor ◽  
Immune Profiling ◽  
Cytokine Profiling

Abstract A global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcomes, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell exhaustion, and the increased levels of inflammatory mediators have been described in COVID-19 patients, in particular in severe cases1. Age represents a key factor in COVID-19 morbidity and mortality2. Understanding age-associated immune signatures of patients are therefore important to identify preventive and therapeutic strategies. In this study, we investigated the immune profile of COVID-19 hospitalized patients identifying a distinctive age-dependent immune signature associated with disease severity. Indeed, defined circulating factors - CXCL8, IL-10, IL-15, IL-27, and TNF-α - positively correlate with older age, longer hospitalization, and a more severe form of the disease and may thus represent the leading signature in critical COVID-19 patients.

Pentoxifylline and Oxypurinol: Potential Drugs to Prevent the “Cytokine Release (Storm) Syndrome” Caused by SARS-CoV-2?

2020 ◽  
Vol 26 (35) ◽  
pp. 4515-4521
Author(s):  
Francisco J. López-Iranzo ◽  
Ana M. López-Rodas ◽  
Luis Franco ◽  
Gerardo López-Rodas
Keyword(s):  
Lung Parenchyma ◽  
Interstitial Tissue ◽  
Cytokine Release ◽  
Phase I Clinical Trials ◽  
Infected People ◽  
Tnf Α ◽  
Transient Loss ◽  
Anti Inflammatory ◽  
And Control ◽  
Inflammatory Action

Background: COVID-19, caused by SARS-CoV-2, is a potentially lethal, rapidly-expanding pandemic and many efforts are being carried out worldwide to understand and control the disease. COVID-19 patients may display a cytokine release syndrome, which causes severe lung inflammation, leading, in many instances, to death. Objective: This paper is intended to explore the possibilities of controlling the COVID-19-associated hyperinflammation by using licensed drugs with anti-inflammatory effects. Hypothesis: We have previously described that pentoxifylline alone, or in combination with oxypurinol, reduces the systemic inflammation caused by experimentally-induced pancreatitis in rats. Pentoxifylline is an inhibitor of TNF-α production and oxypurinol inhibits xanthine oxidase. TNF-α, in turn, activates other inflammatory genes such as Nos2, Icam or IL-6, which regulate migration and infiltration of neutrophils into the pulmonary interstitial tissue, causing injury to the lung parenchyma. In acute pancreatitis, the anti-inflammatory action of pentoxifylline seems to be mediated by the prevention of the rapid and presumably transient loss of PP2A activity. This may also occur in the hyperinflammatory -cytokine releasing phase- of SARS-CoV-2 infection. Therefore, it may be hypothesized that early treatment of COVID-19 patients with pentoxifylline, alone or in combination with oxypurinol, would prevent the potentially lethal acute respiratory distress syndrome. Conclusion: Pentoxifylline and oxypurinol are licensed drugs used for diseases other than COVID-19 and, therefore, phase I clinical trials would not be necessary for the administration to SARS-CoV-2- infected people. It would be worth investigating their potential effects against the hyperinflammatory response to SARS-CoV-2 infection.

scholarly journals Metabolomics of aging in primary fibroblasts from small and large breed dogs

GeroScience ◽  
2021 ◽  
Author(s):  
Paul S. Brookes ◽  
Ana Gabriela Jimenez
Keyword(s):  
Aging Process ◽  
Tca Cycle ◽  
Therapeutic Strategies ◽  
Targeted Metabolomics ◽  
The Tca Cycle ◽  
Age Dependent ◽  
Primary Fibroblasts ◽  
Aging Rates ◽  
Underlying Mechanisms ◽  
Coenzyme A Biosynthesis

AbstractAmong several animal groups (eutherian mammals, birds, reptiles), lifespan positively correlates with body mass over several orders of magnitude. Contradicting this pattern are domesticated dogs, with small dog breeds exhibiting significantly longer lifespans than large dog breeds. The underlying mechanisms of differing aging rates across body masses are unclear, but it is generally agreed that metabolism is a significant regulator of the aging process. Herein, we performed a targeted metabolomics analysis on primary fibroblasts isolated from small and large breed young and old dogs. Regardless of size, older dogs exhibited lower glutathione and ATP, consistent with a role for oxidative stress and bioenergetic decline in aging. Furthermore, several size-specific metabolic patterns were observed with aging, including the following: (i) An apparent defect in the lower half of glycolysis in large old dogs at the level of pyruvate kinase. (ii) Increased glutamine anaplerosis into the TCA cycle in large old dogs. (iii) A potential defect in coenzyme A biosynthesis in large old dogs. (iv) Low nucleotide levels in small young dogs that corrected with age. (v) An age-dependent increase in carnitine in small dogs that was absent in large dogs. Overall, these data support the hypothesis that alterations in metabolism may underlie the different lifespans of small vs. large breed dogs, and further work in this area may afford potential therapeutic strategies to improve the lifespan of large dogs.

scholarly journals COVID-19 clinical implications: the significance of nanomedicine

Bioimpacts ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 137-138
Author(s):  
Jaleh Barar
Keyword(s):  
Quality Of Life ◽  
De Novo ◽  
Virus Entry ◽  
Therapeutic Strategies ◽  
Clinical Implications ◽  
Molecular Signaling ◽  
Key Factor ◽  
To Come

COVID-19 pandemic has profoundly affected the lives of humans worldwide. We no longer experience the same quality of life and need to come up with effective solutions to combat the clinical implications. The vast knowledge about the pathways that regulate the virus entry and molecular signaling of the pathogenesis of coronavirus are the key factor for the development of de novo diagnostic/therapeutic strategies. Meanwhile, the emergence of nanotechnology, could offer enormous help in the battle against coronavirus. In this editorial, the role of molecular elements in the pathobiology of the disease and the significance of nanoscaled pharmaceuticals is highlighted.

scholarly journals Novel Interventional Approaches for ALI/ARDS: Cell-Based Gene Therapy

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Ying-Gang Zhu ◽  
Jie-Ming Qu ◽  
Jing Zhang ◽  
Hong-Ni Jiang ◽  
Jin-Fu Xu
Keyword(s):  
Gene Therapy ◽  
Therapeutic Strategy ◽  
Distress Syndrome ◽  
Therapeutic Strategies ◽  
Severe Form ◽  
Pharmacological Treatments ◽  
Ventilator Support ◽  
Cell Lineages ◽  
Multiple Cell ◽  
Cell And Gene Therapy

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), continue to be a major cause of morbidity and mortality in critically ill patients. The present therapeutic strategies for ALI/ARDS including supportive care, pharmacological treatments, and ventilator support are still controversial. More scientists are focusing on therapies involving stem cells, which have self-renewing capabilities and differentiate into multiple cell lineages, and, genomics therapy which has the potential to upregulate expression of anti-inflammatory mediators. Recently, the combination of cell and gene therapy which has been demonstrated to provide additive benefit has opened up a new chapter in therapeutic strategy and provides a basis for the development of an innovative approach for the prevention and treatment of ALI/ARDS.

scholarly journals Age-Dependent Levels of Select Immunological Mediators in Sera of Healthy Children

1998 ◽  
Vol 5 (1) ◽  
pp. 28-32 ◽  
Author(s):  
Ulrich Sack ◽  
Ullrich Burkhardt ◽  
Michael Borte ◽  
Hiltrud Schädlich ◽  
Kerstin Berg ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Physical Growth ◽  
Intercellular Adhesion Molecule ◽  
Healthy Children ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Age Related ◽  
Tnf Α ◽  
Age Dependent ◽  
Ifn Γ

ABSTRACT Serum cytokine levels were measured in 275 healthy children of different ages (3 to 17 years). Interleukin-1 receptor antagonist (IL-1RA), soluble IL-2R (sIL-2R) (sCD25), IL-6, IL-8, tumor necrosis factor alpha (TNF-α), soluble TNF receptor type II (sTNF-RII) (sCD120b), gamma interferon (IFN-γ), soluble intercellular adhesion molecule 1 (sICAM-1) (sCD54), soluble E selectin (sE-selectin) (ELAM-1; sCD62E), sCD14, and neopterin were measured with commercial test kits. The mean levels of IL-1RA, sIL-2R, TNF-α, sICAM-1, sE-selectin, and sCD14 were higher than in healthy adults. In contrast, IFN-γ and IL-8 were hardly detectable in children and thereby significantly lower than in adults. In the case of TNF-α, sICAM-1, sE selectin, and sCD14, there was a high interindividual variability, apparently unrelated to disease. The profiles of some cytokines, i.e., IL-1RA, IL-6, and TNF-α, showed age-related increases that overlapped with known patterns of physical growth. Of note, sIL-2R and sE-selectin instead declined with time. Because of the remarkable age-dependent variability in healthy pediatric subjects, disease-related changes, as well as therapy-dependent alterations, should be considered with caution.

scholarly journals Immune Profiling To Predict Outcome of Clostridioides difficile Infection

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Mayuresh M. Abhyankar ◽  
Jennie Z. Ma ◽  
Kenneth W. Scully ◽  
Andrew J. Nafziger ◽  
Alyse L. Frisbee ◽  
...  
Keyword(s):  
Prediction Model ◽  
Risk Prediction ◽  
Mortality Risk ◽  
The United States ◽  
Host Bacterium ◽  
Clinical Parameters ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Tnf Α ◽  
Immune Profiling

ABSTRACT There is a pressing need for biomarker-based models to predict mortality from and recurrence of Clostridioides difficile infection (CDI). Risk stratification would enable targeted interventions such as fecal microbiota transplant, antitoxin antibodies, and colectomy for those at highest risk. Because severity of CDI is associated with the immune response, we immune profiled patients at the time of diagnosis. The levels of 17 cytokines in plasma were measured in 341 CDI inpatients. The primary outcome of interest was 90-day mortality. Increased tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand 5 (CCL-5), suppression of tumorigenicity 2 receptor (sST-2), IL-8, and IL-15 predicted mortality by univariate analysis. After adjusting for demographics and clinical characteristics, the mortality risk (as indicated by the hazard ratio [HR]) was higher for patients in the top 25th percentile for TNF-α (HR = 8.35, P = 0.005) and IL-8 (HR = 4.45, P = 0.01) and lower for CCL-5 (HR = 0.18, P ≤ 0.008). A logistic regression risk prediction model was developed and had an area under the receiver operating characteristic curve (AUC) of 0.91 for 90-day mortality and 0.77 for 90-day recurrence. While limited by being single site and retrospective, our work resulted in a model with a substantially greater predictive ability than white blood cell count. In conclusion, immune profiling demonstrated differences between patients in their response to CDI, offering the promise for precision medicine individualized treatment. IMPORTANCE Clostridioides difficile infection is the most common health care-associated infection in the United States with more than 20% patients experiencing symptomatic recurrence. The complex nature of host-bacterium interactions makes it difficult to predict the course of the disease based solely on clinical parameters. In the present study, we built a robust prediction model using representative plasma biomarkers and clinical parameters for 90-day all-cause mortality. Risk prediction based on immune biomarkers and clinical variables may contribute to treatment selection for patients as well as provide insight into the role of immune system in C. difficile pathogenesis.

The effect of nutrition on nematode faecal egg output in lactating, organically managed ewes

2003 ◽  
Vol 2003 ◽  
pp. 29-29 ◽  
Author(s):  
R. Keatinge ◽  
J.G.M. Houdijk ◽  
F. Jackson ◽  
I. Kyriazakis
Keyword(s):  
Dietary Protein ◽  
Animal Health ◽  
Late Pregnancy ◽  
Host Immunity ◽  
Early Lactation ◽  
Parasite Control ◽  
Commercial Practice ◽  
Key Factor ◽  
The Relationship ◽  
Organically Managed

Nematodes are a particular challenge to animal health and productivity in organic sheep systems, where the prophyllactic use of anthelmintic is prohibited. The peri-parturient rise in faecal egg output, a consequence of relaxation of host immunity in late pregnancy and early lactation, is potentially a key factor in the epidemiology of parasitic gastro-enteritis on organic sheep farms. Coop and Kyriazakis (1999) developed a hypothesis to explain the relationship between nutrition and periparturient breakdown of immunity to parasites, and there is now an increasing body of evidence for the involvement of dietary protein (Houdijk et al 2001). The objective of this study was to test this hypothesis in organically managed ewes carrying a mixed, naturally acquired infection, grazing on grass/clover in early lactation, and to examine the potential for a nutritional approach to parasite control in commercial practice.

scholarly journals Space-Dependent Glia–Neuron Interplay in the Hippocampus of Transgenic Models of β-Amyloid Deposition

2020 ◽  
Vol 21 (24) ◽  
pp. 9441
Author(s):  
Daniele Lana ◽  
Filippo Ugolini ◽  
Maria Grazia Giovannini
Keyword(s):  
Brain Regions ◽  
Therapeutic Strategies ◽  
Differential Sensitivity ◽  
Transgenic Models ◽  
Age Related ◽  
Neurodegenerative Pathology ◽  
Spatial Differences ◽  
Key Factor ◽  
Β Amyloid ◽  
The Brain

This review is focused on the description and discussion of the alterations of astrocytes and microglia interplay in models of Alzheimer’s disease (AD). AD is an age-related neurodegenerative pathology with a slowly progressive and irreversible decline of cognitive functions. One of AD’s histopathological hallmarks is the deposition of amyloid beta (Aβ) plaques in the brain. Long regarded as a non-specific, mere consequence of AD pathology, activation of microglia and astrocytes is now considered a key factor in both initiation and progression of the disease, and suppression of astrogliosis exacerbates neuropathology. Reactive astrocytes and microglia overexpress many cytokines, chemokines, and signaling molecules that activate or damage neighboring cells and their mutual interplay can result in virtuous/vicious cycles which differ in different brain regions. Heterogeneity of glia, either between or within a particular brain region, is likely to be relevant in healthy conditions and disease processes. Differential crosstalk between astrocytes and microglia in CA1 and CA3 areas of the hippocampus can be responsible for the differential sensitivity of the two areas to insults. Understanding the spatial differences and roles of glia will allow us to assess how these interactions can influence the state and progression of the disease, and will be critical for identifying therapeutic strategies.

Abstract 416: Hypertension During Pregnancy is Associated with Cerebral Damage in an Animal Model of severe preeclampsia

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Kedra Wallace ◽  
Sarah Tremble ◽  
Malikarjuna R Pabbidi ◽  
Rachael Morris ◽  
Shauna-Kay Spencer ◽  
...  
Keyword(s):  
Animal Model ◽  
Receptor Antagonist ◽  
Cerebral Edema ◽  
Severe Form ◽  
Myogenic Tone ◽  
Cerebral Damage ◽  
Pregnant Rats ◽  
Elevated Liver Enzymes ◽  
Tnf Α ◽  
Bbb Permeability

HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome is a severe form of preeclampsia that is accompanied by hypertension, headaches, visual disturbances and cerebral infarctions during pregnancy. HELLP is associated with hypertension and elevations in TNF-α and IL-6, both of which have been shown to activate the endothelin-1 system (ET-1). The objective of the current study was to determine if hypertension in an animal model of HELLP is associated with cerebral impairment. On gestational day (GD) 12 miniosmotic pumps infusing sEndoglin and sFlt-1 (7 and 4.7ug/kg/day) were implanted into normal pregnant (NP) rats to induce HELLP. On GD18 carotid catheters were inserted into HELLP and NP rats and mean arterial pressure (MAP) was recorded on GD19 followed by brain collection. Myogenic tone was calculated from the middle cerebral artery; brain water content was measured to determine cerebral edema. Blood brain barrier (BBB) permeability was determined by exposing cerebral vessels from non-pregnant rats intraluminally to plasma from NP or HELLP rats. MAP increased from 92±2.6mmHg in NP rats (n=10) to 120.6±3.6mmHg in HELLP rats (n=11; p<0.01). HELLP rats had significant cerebral edema compared to NP rats (p=0.04). Myogenic tone in HELLP rats was significantly impaired (p<0.05) at pressures greater than or equal to 80mmHg compared to NP rats (n=2/group). Plasma from HELLP rats (n=6) significantly increased BBB permeability at 100mmHg compared to plasma from NP rats (n=5). Administration of an endothelin A (ET A ) receptor antagonist (ABT-627, 5mg/kg on GD12-19), significantly decreased MAP in HELLP rats compared to untreated HELLP rats (97±5.3mmHg, n=5, p<0.01) and decreased cerebral edema to levels comparable to NP rats. Data from this study demonstrates that high MAP in HELLP rats is accompanied by cerebral edema, increased BBB permeability and impaired myogenic tone. Any of which could contribute to the neurologic complications that plague women with HELLP. Furthermore, as elevated ET-1 can damage the BBB and lead to cerebral damage we administered an ET A receptor antagonist which significantly decreased MAP and cerebral edema; future studies will determine if these changes are accompanied by improvement in myogenic tone and BBB permeability.

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