scholarly journals SARS-CoV-2 infection in the mouse olfactory system

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Qing Ye ◽  
Jia Zhou ◽  
Qi He ◽  
Rui-Ting Li ◽  
Guan Yang ◽  
...  
Keyword(s):  
Immune Cell ◽  
Inflammatory Responses ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Underlying Mechanism ◽  
Olfactory Dysfunction ◽  
Target Cells ◽  
Physiological Basis ◽  
Sustentacular Cells ◽  
Massive Cell Death

AbstractSARS-CoV-2 infection causes a wide spectrum of clinical manifestations in humans, and olfactory dysfunction is one of the most predictive and common symptoms in COVID-19 patients. However, the underlying mechanism by which SARS-CoV-2 infection leads to olfactory disorders remains elusive. Herein, we demonstrate that intranasal inoculation with SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), not the olfactory bulb (OB), resulting in transient olfactory dysfunction in humanized ACE2 (hACE2) mice. The sustentacular cells and Bowman’s gland cells in the OE were identified as the major target cells of SARS-CoV-2 before invasion into olfactory sensory neurons (OSNs). Remarkably, SARS-CoV-2 infection triggers massive cell death and immune cell infiltration and directly impairs the uniformity of the OE structure. Combined transcriptomic and quantitative proteomic analyses revealed the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptor (OR) genes in the OE from the infected animals. Overall, our mouse model recapitulates olfactory dysfunction in COVID-19 patients and provides critical clues for understanding the physiological basis for extrapulmonary manifestations of COVID-19.

SARS-CoV-2 infection causes transient olfactory dysfunction in mice

2020 ◽  
Author(s):  
Qing Ye ◽  
Jia Zhou ◽  
Guan Yang ◽  
Rui-Ting Li ◽  
Qi He ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Olfactory Receptors ◽  
Causal Link ◽  
Olfactory Dysfunction ◽  
Immune Cell Infiltration ◽  
Physiological Basis ◽  
Intranasal Inoculation ◽  
Sustentacular Cells

AbstractOlfactory dysfunction caused by SARS-CoV-2 infection represents as one of the most predictive and common symptoms in COVID-19 patients. However, the causal link between SARS-CoV-2 infection and olfactory disorders remains lacking. Herein we demonstrate intranasal inoculation of SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), resulting in transient olfactory dysfunction in humanized ACE2 mice. The sustentacular cells and Bowman’s gland cells in OE were identified as the major targets of SARS-CoV-2 before the invasion into olfactory sensory neurons. Remarkably, SARS-CoV-2 infection triggers cell death and immune cell infiltration, and impairs the uniformity of OE structure. Combined transcriptomic and proteomic analyses reveal the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptors in OE from the infected animals. Overall, our mouse model recapitulates the olfactory dysfunction in COVID-19 patients, and provides critical clues to understand the physiological basis for extrapulmonary manifestations of COVID-19.

scholarly journals NF-κB Pathway as a Potential Target for Treatment of Critical Stage COVID-19 Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Ralf Kircheis ◽  
Emanuel Haasbach ◽  
Daniel Lueftenegger ◽  
Willm T. Heyken ◽  
Matthias Ocker ◽  
...  
Keyword(s):  
Immune Cell ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Synergistic Effects ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Published Data ◽  
Critical Stage ◽  
Cytokines And Chemokines ◽  
Simultaneous Inhibition

Patients infected with SARS-CoV-2 show a wide spectrum of clinical manifestations ranging from mild febrile illness and cough up to acute respiratory distress syndrome, multiple organ failure, and death. Data from patients with severe clinical manifestations compared to patients with mild symptoms indicate that highly dysregulated exuberant inflammatory responses correlate with severity of disease and lethality. Epithelial-immune cell interactions and elevated cytokine and chemokine levels, i.e. cytokine storm, seem to play a central role in severity and lethality in COVID-19. The present perspective places a central cellular pro-inflammatory signal pathway, NF-κB, in the context of recently published data for COVID-19 and provides a hypothesis for a therapeutic approach aiming at the simultaneous inhibition of whole cascades of pro-inflammatory cytokines and chemokines. The simultaneous inhibition of multiple cytokines/chemokines is expected to have much higher therapeutic potential as compared to single target approaches to prevent cascade (i.e. redundant, triggering, amplifying, and synergistic) effects of multiple induced cytokines and chemokines in critical stage COVID-19 patients.

scholarly journals NF-kappaB pathway as a potential target for treatment of critical stage COVID-19 patients

2020 ◽  
Author(s):  
Ralf Kircheis ◽  
Emanuel Haasbach ◽  
Daniel Lueftenegger ◽  
Will T. Heyken ◽  
Matthias Ocker ◽  
...  
Keyword(s):  
Immune Cell ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Published Data ◽  
Critical Stage ◽  
Cytokines And Chemokines ◽  
Simultaneous Inhibition ◽  
Nf Kappab

Abstract Patients infected with SARS-CoV-2 show a wide spectrum of clinical manifestations ranging from mild febrile illness and cough up to acute respiratory distress syndrome, multiple organ failure and death. Data from patients with severe clinical manifestations compared to patients with mild symptoms indicate that highly dysregulated exuberant inflammatory responses correlate with severity of disease and lethality. Epithelial-immune cell interactions and elevated cytokine and chemokine levels, i.e. cytokine storm, seem to play a central role in severity and lethality in COVID-19. The present perspective places a central cellular pro-inflammatory signal pathway, NF-kappaB, in the context of recently published data for COVID-19 and provides a hypothesis for a therapeutic approach aiming at the simultaneous inhibition of whole cascades of pro-inflammatory cytokines and chemokines. The simultaneous inhibition of multiple cytokines/chemokines is expected to have much higher therapeutic potential as compared to single target approaches to prevent cascade (i.e. triggering, synergistic, and redundant) effects of multiple induced cytokines and chemokines in critical stage COVID-19 patients.

scholarly journals Sustained Cellular Immune Dysregulation in Individuals Recovering from SARS-CoV-2 Infection

2020 ◽  
Author(s):  
Jacob K Files ◽  
Sushma Boppana ◽  
Mildred D Perez ◽  
Sanghita Sarkar ◽  
Kelsey E Lowman ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Immune Cell ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Immune Dysregulation ◽  
Hospitalized Patients ◽  
Activation Markers ◽  
Cellular Immune

SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and non-hospitalized individuals. In hospitalized patients, many adaptive and innate immune cells were decreased in frequency compared to healthy and convalescent individuals, with the exception of B lymphocytes which increased. Our findings show increased frequencies of T-cell activation markers (CD69, Ox40, HLA-DR and CD154) in hospitalized patients, with other T-cell activation/exhaustion markers (CD25, PD-L1 and TIGIT) remaining elevated in hospitalized and non-hospitalized individuals. B cells had a similar pattern of activation/exhaustion, with increased frequency of CD69 and CD95 during hospitalization, followed by an increase in PD1 frequencies in non-hospitalized individuals. Interestingly, many of these changes were found to increase over time in non-hospitalized longitudinal samples, suggesting a prolonged period of immune dysregulation following SARS-CoV-2 infection. Changes in T-cell activation/exhaustion in non-hospitalized patients were found to positively correlate with age. Severely infected individuals had increased expression of activation and exhaustion markers. These data suggest a prolonged period of immune dysregulation following SARS-CoV-2 infection highlighting the need for additional studies investigating immune dysregulation in convalescent individuals.

scholarly journals The Potential Roles of Exosomes in Chronic Obstructive Pulmonary Disease

2021 ◽  
Vol 7 ◽  
Author(s):  
Nan Wang ◽  
Qin Wang ◽  
Tiantian Du ◽  
Abakundana Nsenga Ariston Gabriel ◽  
Xue Wang ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Biological Properties ◽  
Chronic Obstructive ◽  
Target Cells ◽  
Obstructive Pulmonary Disease ◽  
Complex Interactions ◽  
Chronic Lung Diseases

Currently, chronic obstructive pulmonary disease (COPD) is one of the most common chronic lung diseases. Chronic obstructive pulmonary disease is characterized by progressive loss of lung function due to chronic inflammatory responses in the lungs caused by repeated exposure to harmful environmental stimuli. Chronic obstructive pulmonary disease is a persistent disease, with an estimated 384 million people worldwide living with COPD. It is listed as the third leading cause of death. Exosomes contain various components, such as lipids, microRNAs (miRNAs), long non-coding RNAs(lncRNAs), and proteins. They are essential mediators of intercellular communication and can regulate the biological properties of target cells. With the deepening of exosome research, it is found that exosomes are strictly related to the occurrence and development of COPD. Therefore, this review aims to highlight the unique role of immune-cell-derived exosomes in disease through complex interactions and their potentials as potential biomarkers new types of COPD.

Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint

Lupus ◽  
2021 ◽  
pp. 096120332110142
Author(s):  
Tamer A Gheita ◽  
Rasha Abdel Noor ◽  
Esam Abualfadl ◽  
Osama S Abousehly ◽  
Iman I El-Gazzar ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Age Of Onset ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Population Based ◽  
Systemic Lupus ◽  
Cross Sectional

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). Conclusion SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

scholarly journals Transcriptomic Data Analysis Reveals a Down-Expression of Galectin-8 in Schizophrenia Hippocampus

2021 ◽  
Vol 11 (8) ◽  
pp. 973
Author(s):  
Maria Cristina Petralia ◽  
Rosella Ciurleo ◽  
Alessia Bramanti ◽  
Placido Bramanti ◽  
Andrea Saraceno ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Clinical Manifestations ◽  
Antipsychotic Agents ◽  
Standards Of Care ◽  
Specific Gene ◽  
Contributing Factors ◽  
Healthy Donors ◽  
Dorsolateral Prefrontal ◽  
Inflammatory Processes ◽  
Disease Specific

Schizophrenia (SCZ) is a severe psychiatric disorder with several clinical manifestations that include cognitive dysfunction, decline in motivation, and psychosis. Current standards of care treatment with antipsychotic agents are often ineffective in controlling the disease, as only one-third of SCZ patients respond to medications. The mechanisms underlying the pathogenesis of SCZ remain elusive. It is believed that inflammatory processes may play a role as contributing factors to the etiology of SCZ. Galectins are a family of β-galactoside-binding lectins that contribute to the regulation of immune and inflammatory responses, and previous reports have shown their role in the maintenance of central nervous system (CNS) homeostasis and neuroinflammation. In the current study, we evaluated the expression levels of the galectin gene family in post-mortem samples of the hippocampus, associative striatum, and dorsolateral prefrontal cortex from SCZ patients. We found a significant downregulation of LGALS8 (Galectin-8) in the hippocampus of SCZ patients as compared to otherwise healthy donors. Interestingly, the reduction of LGALS8 was disease-specific, as no modulation was observed in the hippocampus from bipolar nor major depressive disorder (MDD) patients. Prediction analysis identified TBL1XR1, BRF2, and TAF7 as potential transcription factors controlling LGALS8 expression. In addition, MIR3681HG and MIR4296 were negatively correlated with LGALS8 expression, suggesting a role for epigenetics in the regulation of LGALS8 levels. On the other hand, no differences in the methylation levels of LGALS8 were observed between SCZ and matched control hippocampus. Finally, ontology analysis of the genes negatively correlated with LGALS8 expression identified an enrichment of the NGF-stimulated transcription pathway and of the oligodendrocyte differentiation pathway. Our study identified LGALS8 as a disease-specific gene, characterizing SCZ patients, that may in the future be exploited as a potential therapeutic target.

scholarly journals Administration route governs the therapeutic efficacy, biodistribution and macrophage targeting of anti-inflammatory nanoparticles in the lung

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lu Wang ◽  
Yafei Rao ◽  
Xiali Liu ◽  
Liya Sun ◽  
Jiameng Gong ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Lung Inflammation ◽  
Respiratory Diseases ◽  
Inflammatory Responses ◽  
The Other ◽  
Target Cells ◽  
Administration Route ◽  
Toll Like Receptor ◽  
Administration Routes ◽  
Anti Inflammatory

Abstract Background Uncontrolled inflammation is a central problem for many respiratory diseases. The development of potent, targeted anti-inflammatory therapies to reduce lung inflammation and re-establish the homeostasis in the respiratory tract is still a challenge. Previously, we developed a unique anti-inflammatory nanodrug, P12 (made of hexapeptides and gold nanoparticles), which can attenuate Toll-like receptor-mediated inflammatory responses in macrophages. However, the effect of the administration route on its therapeutic efficacy and tissue distribution remained to be defined. Results In this study, we systematically compared the effects of three different administration routes [the intratracheal (i.t.), intravenous (i.v.) and intraperitoneal (i.p.)] on the therapeutic activity, biodistribution and pulmonary cell targeting features of P12. Using the LPS-induced ALI mouse model, we found that the local administration route via i.t. instillation was superior in reducing lung inflammation than the other two routes even treated with a lower concentration of P12. Further studies on nanoparticle biodistribution showed that the i.t. administration led to more accumulation of P12 in the lungs but less in the liver and other organs; however, the i.v. and i.p. administration resulted in more nanoparticle accumulation in the liver and lymph nodes, respectively, but less in the lungs. Such a lung favorable distribution was also determined by the unique surface chemistry of P12. Furthermore, the inflammatory condition in the lung could decrease the accumulation of nanoparticles in the lung and liver, while increasing their distribution in the spleen and heart. Interestingly, the i.t. administration route helped the nanoparticles specifically target the lung macrophages, whereas the other two administration routes did not. Conclusion The i.t. administration is better for treating ALI using nanodevices as it enhances the bioavailability and efficacy of the nanodrugs in the target cells of the lung and reduces the potential systematic side effects.

scholarly journals Mild Clinical Presentation of Joubert Syndrome in a Male Adult Carrying Biallelic MKS1 Truncating Variants

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1218
Author(s):  
Raffaella Brunetti-Pierri ◽  
Marianthi Karali ◽  
Francesco Testa ◽  
Gerarda Cappuccio ◽  
Maria Elena Onore ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Brain Magnetic Resonance Imaging ◽  
Joubert Syndrome ◽  
Male Adult ◽  
Full Field ◽  
Pathogenic Variants ◽  
Disease Spectrum ◽  
Male Individual ◽  
The Central Nervous System

Pathogenic variants in the MKS1 gene are responsible for a ciliopathy with a wide spectrum of clinical manifestations ranging from Meckel and Joubert syndrome (JBTS) to Bardet-Biedl syndrome, and involving the central nervous system, liver, kidney, skeleton, and retina. We report a 39-year-old male individual presenting with isolated Retinitis Pigmentosa (RP), as assessed by full ophthalmological evaluation including Best-Corrected Visual Acuity measurements, fundus examination, Goldmann Visual Field test, and full-field Electroretinography. A clinical exome identified biallelic nonsense variants in MKS1 that prompted post-genotyping investigations for systemic abnormalities of ciliopathy. Brain magnetic resonance imaging revealed malformations of the posterior cranial fossa with the ‘molar tooth sign’ and cerebellar folia dysplasia, which are both distinctive features of JBTS. No other organ or skeletal abnormalities were detected. This case illustrates the power of clinical exome for the identification of the mildest forms of a disease spectrum, such as a mild JBTS with RP in the presented case of an individual carrying biallelic truncating variants in MKS1.

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