scholarly journals Transcriptional Response in a Sepsis Mouse Model Reflects Transcriptional Response in Sepsis Patients

2022 ◽  
Vol 23 (2) ◽  
pp. 821
Author(s):  
Florian Rosier ◽  
Nicolas Fernandez Nuñez ◽  
Magali Torres ◽  
Béatrice Loriod ◽  
Pascal Rihet ◽  
...  
Keyword(s):  
Septic Shock ◽  
Mouse Model ◽  
Transcriptional Response ◽  
Human Cells ◽  
Molecular Signature ◽  
Inflammatory Disorder ◽  
Cellular Mechanisms ◽  
Human Sepsis ◽  
Risk Of Death

Mortality due to sepsis remains unacceptably high, especially for septic shock patients. Murine models have been used to better understand pathophysiology mechanisms. However, the mouse model is still under debate. Herein we investigated the transcriptional response of mice injected with lipopolysaccharide (LPS) and compared it to either human cells stimulated in vitro with LPS or to the blood cells of septic patients. We identified a molecular signature composed of 2331 genes with an FDR median of 0%. This molecular signature is highly enriched in regulated genes in peritoneal macrophages stimulated with LPS. There is significant enrichment in several inflammatory signaling pathways, and in disease terms, such as pneumonia, sepsis, systemic inflammatory response syndrome, severe sepsis, an inflammatory disorder, immune suppression, and septic shock. A significant overlap between the genes upregulated in mouse and human cells stimulated with LPS has been demonstrated. Finally, genes upregulated in mouse cells stimulated with LPS are enriched in genes upregulated in human cells stimulated in vitro and in septic patients, who are at high risk of death. Our results support the hypothesis of common molecular and cellular mechanisms between mouse and human sepsis.

scholarly journals Transcriptional response in a sepsis mouse model reflects transcriptional response in sepsis patients

2021 ◽  
Author(s):  
Florian Rosier ◽  
Nicolas Nunez Fernandez ◽  
Magali Torres ◽  
Beatrice Loriod ◽  
Pascal Rihet ◽  
...  
Keyword(s):  
Septic Shock ◽  
Mouse Model ◽  
Transcriptional Response ◽  
Human Cells ◽  
Molecular Signature ◽  
Inflammatory Disorder ◽  
Cellular Mechanisms ◽  
Human Sepsis ◽  
Risk Of Death

Mortality due to sepsis remains unacceptably high, especially for septic shock patients. Murine models have been used to better understand pathophysiology mechanisms. However, the mouse model is still under de-bate. Here we investigated the transcriptional response of mice injected with lipopolysaccharide (LPS) and compared it to either human cells stimulated in vitro with LPS or to blood cells of septic patients. We identified a molecular signature composed of 2331 genes with an FDR median of 0%. This molecular signature is highly enriched in regulated genes in peritoneal macrophages stimulated with LPS. There is a significant enrichment in several inflammatory signaling pathways, and in disease terms, such as pneumonia, sepsis, systemic inflammatory response syndrome, severe sepsis, an inflammatory disorder, immune suppression, and septic shock. A significant overlap between the genes up-regulated in mouse and human cells stimulated with LPS has been demonstrated. Finally, genes up-regulated in mouse cells stimulated with LPS are enriched in genes up-regulated in human cells stimulated in vitro and in septic patients, who are at high risk of death. Our results support the hypothesis of common molecular and cellular mechanisms between mouse and human sepsis.

scholarly journals Kv4.3 channel downregulation mediates chronic post-lesional pacemaker acceleration in surviving dopamine substantia nigra neurons

2021 ◽  
Author(s):  
Lora Kovacheva ◽  
Josef Shin ◽  
Navid Farassat ◽  
Jochen Roeper
Keyword(s):  
Substantia Nigra ◽  
Mouse Model ◽  
Homeostatic Plasticity ◽  
Cellular Mechanisms ◽  
Differential Vulnerability ◽  
Autonomous Adaptation ◽  
Partial Lesion ◽  
Firing Properties

Substantia nigra dopamine (SN DA) neurons are progressively lost in Parkinson disease (PD). While the molecular and cellular mechanisms of their differential vulnerability and degeneration have been extensively studied, we still know very little about potential functional adaptations of those SN DA neurons that at least for some time manage to survive during earlier stages of PD. We utilized a partial lesion 6-OHDA mouse model to characterize initial electrophysiological impairments and chronic adaptations of surviving identified SN DA neurons, both in vivo and in vitro. Early after lesion (3 weeks), we detected a selective loss of in vivo burst firing in surviving SN DA neurons, which was accompanied by in vitro pacemaker instability. In contrast, late after lesion (>2 months), in vivo firing properties of surviving SN DA neurons had recovered in the presence of 2-fold accelerated pacemaking in vitro. Finally, we show that this chronic cell-autonomous adaptation in surviving SN DA neurons was mediated by Kv4.3 channel downregulation. Our study demonstrates substantial homeostatic plasticity of surviving SN DA neurons after a single-hit non-progressive lesion, which might contribute to the phenotype of initially surviving SN DA neurons in PD.

Epigenetic biomarkers for human sepsis and septic shock: insights from immunosuppression

Epigenomics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 617-646 ◽  
Author(s):  
Jesús Beltrán-García ◽  
Rebeca Osca-Verdegal ◽  
Carlos Romá-Mateo ◽  
Nieves Carbonell ◽  
José Ferreres ◽  
...  
Keyword(s):  
Septic Shock ◽  
The Body ◽  
Sepsis Management ◽  
Human Sepsis ◽  
Risk Of Death ◽  
Epigenetic Biomarkers ◽  
Life Threatening ◽  
Sepsis Survivors ◽  
New Biomarkers ◽  
Sepsis And Septic Shock

Sepsis is a life-threatening condition that occurs when the body responds to an infection damaging its own tissues. Sepsis survivors sometimes suffer from immunosuppression increasing the risk of death. To our best knowledge, there is no ‘gold standard’ for defining immunosuppression except for a composite clinical end point. As the immune system is exposed to epigenetic changes during and after sepsis, research that focuses on identifying new biomarkers to detect septic patients with immunoparalysis could offer new epigenetic-based strategies to predict short- and long-term pathological events related to this life-threatening state. This review describes the most relevant epigenetic mechanisms underlying alterations in the innate and adaptive immune responses described in sepsis and septic shock, and their consequences for immunosuppression states, providing several candidates to become epigenetic biomarkers that could improve sepsis management and help predict immunosuppression in postseptic patients.

Cytotoxicity and cellular mechanisms of toxicity of CuO NPs in mussel cells in vitro and comparative sensitivity with human cells

2018 ◽  
Vol 48 ◽  
pp. 146-158 ◽  
Author(s):  
Alberto Katsumiti ◽  
Andrew J. Thorley ◽  
Inmaculada Arostegui ◽  
Paul Reip ◽  
Eugenia Valsami-Jones ◽  
...  
Keyword(s):  
Human Cells ◽  
Cellular Mechanisms ◽  
Mechanisms Of Toxicity ◽  
Comparative Sensitivity ◽  
Cuo Nps

scholarly journals BATF2 and FOXJ1 are differentially expressed in coronavirus infections.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Transcription Factors ◽  
Viral Infections ◽  
Transcriptional Response ◽  
Human Cells ◽  
Differentially Expressed ◽  
In Vivo Models ◽  
Microarray Datasets ◽  
Coronavirus Infections

Unraveling the host transcriptional response to viral infections is important for understanding host-pathogen interactions. We mined published microarray datasets (1-5) to identify conserved and specific differentially expressed genes in in vitro and in vivo models of coronavirus infections. We found significant transcriptional induction of the transcription factors BATF2 and FOXJ1 in Middle East Respiratory Syndrome (MERS) coronavirus infection in human cells in vitro; BATF2 was also differentially expressed in the lungs of mice infected with the Severe Acute Respiratory Syndrome (SARS) coronavirus 1 (SARS-CoV-1) but not in human cells infected with the human coronavirus HCoV-229E. These data highlight specific host induction of transcription factors by different members of the coronavirus family.

scholarly journals The disruption of central CO2 chemosensitivity in a mouse model of Rett syndrome

2011 ◽  
Vol 301 (3) ◽  
pp. C729-C738 ◽  
Author(s):  
Xiaoli Zhang ◽  
Junda Su ◽  
Ningren Cui ◽  
Hongyu Gai ◽  
Zhongying Wu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Rett Syndrome ◽  
Expression System ◽  
Brain Slices ◽  
Cellular Mechanisms ◽  
Stem Respiration ◽  
High Incidence ◽  
Abnormal Brain

People with Rett syndrome (RTT) have breathing instability in addition to other neuropathological manifestations. The breathing disturbances contribute to the high incidence of unexplained death and abnormal brain development. However, the cellular mechanisms underlying the breathing abnormalities remain unclear. To test the hypothesis that the central CO2 chemoreception in these people is disrupted, we studied the CO2 chemosensitivity in a mouse model of RTT. The Mecp2-null mice showed a selective loss of their respiratory response to 1–3% CO2 (mild hypercapnia), whereas they displayed more regular breathing in response to 6–9% CO2 (severe hypercapnia). The defect was alleviated with the NE uptake blocker desipramine (10 mg·kg−1·day−1 ip, for 5–7 days). Consistent with the in vivo observations, in vitro studies in brain slices indicated that CO2 chemosensitivity of locus coeruleus (LC) neurons was impaired in Mecp2-null mice. Two major neuronal pH-sensitive Kir currents that resembled homomeric Kir4.1 and heteromeric Ki4.1/Kir5.1 channels were identified in the LC neurons. The screening of Kir channels with real-time PCR indicated the overexpression of Kir4.1 in the LC region of Mecp2-null mice. In a heterologous expression system, an overexpression of Kir4.1 resulted in a reduction in the pH sensitivity of the heteromeric Kir4.1-Kir5.1 channels. Given that Kir4.1 and Kir5.1 subunits are also expressed in brain stem respiration-related areas, the Kir4.1 overexpression may not allow CO2 to be detected until hypercapnia becomes severe, leading to periodical hyper- and hypoventilation in Mecp2-null mice and, perhaps, in people with RTT as well.

scholarly journals An investigation of the molecular and cellular mechanisms of in vitro phage therapy in human cells

2019 ◽  
Vol 1 (1A) ◽  
Author(s):  
Christian Møller-Olsen ◽  
Siu Ho ◽  
Toby Ross ◽  
Antonia Sagona
Keyword(s):  
Phage Therapy ◽  
Human Cells ◽  
Cellular Mechanisms
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