International immunopharmacology
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Int. Immunopharmacol. · Dec 2020
ReviewToll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets.
Cytokine storm generates during various systemic acute infections, including sepsis and current pandemic called COVID-19 (severe) causing devastating inflammatory conditions, which include multi-organ failure or multi-organ dysfunction syndrome (MODS) and death of the patient. Toll-like receptors (TLRs) are one of the major pattern recognition receptors (PRRs) expressed by immune cells as well as non-immune cells, including neurons, which play a crucial role in generating cytokine storm. They recognize microbial-associated molecular patterns (MAMPs, expressed by pathogens) and damage or death-associate molecular patterns (DAMPs; released and/expressed by damaged/killed host cells). ⋯ This state-of-the-art review describes the importance of TLR signaling in the onset of the sepsis-associated cytokine storm and discusses various host-derived endogenous negative regulators of TLR signaling pathways. The subject is very important as there is a vast array of genes and processes implicated in these negative feedback mechanisms. These molecules and mechanisms can be targeted for developing novel therapeutic drugs for cytokine storm-associated diseases, including sepsis, severe COVID-19, and other inflammatory diseases, where TLR-signaling plays a significant role.
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Int. Immunopharmacol. · Dec 2020
Novel serological biomarkers for inflammation in predicting disease severity in patients with COVID-19.
Patients with severe coronavirus disease 2019 (COVID-19) develop acute respiratory distress and multi-system organ failure and are associated with poor prognosis and high mortality. Thus, there is an urgent need to identify early diagnostic and prognostic biomarkers to determine the risk of developing serious illness. ⋯ Taken together, PNI, HsCAR, and HsCPAR may serve as accurate biomarkers for the prediction of disease severity in patients with COVID-19 upon admission/hospitalization.
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Int. Immunopharmacol. · Dec 2020
Antidepressant-like effects of Schisandrin on lipopolysaccharide-induced mice : Gut microbiota, short chain fatty acid and TLR4/NF-κB signaling pathway.
Growing evidence shows that gut microbiota and neuroinflammatory responses play a critical role in the pathogenesis of depression. Our previous study demonstrated that schisandrin (SCH) could reduce proinflammatory factors of depressive mice. Therefore, our present study is to research the potential connection between gut microbial and anti-inflammatory effects of SCH on a depressive mouse model induced by lipopolysaccharide (LPS). ⋯ And the results of 16S rRNA demonstrated that SCH pre-administration attenuated the dysbiosis of gut microbiota of depressive mice, along with altered fecal short-chain fatty acids (SCFAs). Furthermore, SCH reduced the levels of proinflammatory factors of depressive mice and the expression of TLR4/NF-κB signaling pathway in the hippocampus. Overall, our study indicated that SCH might recover the gut microbial disorder of depressive mice through suppressing the expression of TLR4/NF-κB signaling pathway.
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Int. Immunopharmacol. · Dec 2020
Multicenter Study Clinical TrialSubcutaneous tocilizumab in adults with severe and critical COVID-19: A prospective open-label uncontrolled multicenter trial.
Potential therapeutic approaches in coronavirus disease 2019 (COVID-19) comprise antiviral and immunomodulatory agents; however, no immunomodulator drug has been approved. This multicenter, prospective, open-label, uncontrolled study aimed to assess the use of subcutaneous tocilizumab in adult patients with severe and critical COVID-19. Tocilizumab was added to the standard care of therapy at a dose of 324 mg (<100 kg bodyweight) or 486 mg (≥100 kg bodyweight). ⋯ Significant improvement in the required level of oxygenation was reported in severe patients seven days after tocilizumab administration. No tocilizumab-related serious adverse event occurred in this study. Subcutaneous tocilizumab might improve some clinical parameters and reduce the risk of death in COVID-19 patients, particularly if used in the early stages of respiratory failure.
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Int. Immunopharmacol. · Dec 2020
ReviewTocilizumab for treatment patients with COVID-19: Recommended medication for novel disease.
The coronavirus disease 2019 (COVID-19) virus has spread all over the world. Scientists are trying to discover drugs as effective treatment for patients with COVID-19. So far about 30 drugs have been introduced that one of them is Tocilizumab. ⋯ Although Tocilizumab has been accepted by China Health Commission to treat infected patients, its positive effects still cannot be predicted in all patients. Based on evidence of the Tocilizumab's effect on the SARS COV 2, researchers hope this drug will make effective and promising treatment to improve lung tissue inflammation in patients with the fatal COVID-19 virus. The present study provides an overview of respiratory inflammation with COVID-19 and probable effect of Tocilizumab on SARS-COV 2.