scholarly journals SLAMF7 Regulates Inflammatory Response In Macrophage During Polymicrobial Sepsis

2021 ◽  
Author(s):  
Yongjian Wu ◽  
Juanfeng Lao ◽  
Miao Li ◽  
Minhao Wu ◽  
Siqi Ming ◽  
...  
Keyword(s):  
Lymphocyte Activation ◽  
Multiple Organ ◽  
Polymicrobial Sepsis ◽  
Organ Injury ◽  
Cytokine Storm ◽  
Phosphatase Domain ◽  
Lethal Sepsis ◽  
Monocytes And Macrophages ◽  
Src Homology ◽  
Signaling Activation

Abstract Uncontrolled microbe-triggered inflammation results in multiple organ injury and shock in sepsis. However, the regulatory mechanisms that restrict cytokine storm are still elusive. Using gene screening, we identified an immunoglobulin-like receptor called Signaling Lymphocyte Activation Molecular Family-7 (SLAMF7), as a key regulator of inflammation during sepsis. We found that the expression of SLAMF7 on monocytes and macrophages was significantly elevated in sepsis subjects and septic mice. SLAMF7 attenuated TLR dependent MAPKs and NF-κB signaling activation by co-operating with Src homology 2-containing inositol‑5'‑phosphatase1 (SHIP1). Furthermore, SLAMF7 interacted with SHIP1 and TNF receptor associated factor 6 (TRAF6) to inhibite K63 ubiquitination of TRAF6. In addition, we found that intracellular domain tyrosine phosphorylation sites of SLAMF7 and phosphatase domain of SHIP1 were indispensable for the interaction of SLAMF7/SHIP1/TRAF6 and the modulation of cytokines production. Finally, recombinant murine SLAMF7 peptide agonist or genetic knockout of SLAMF7 in mice demonstrated that SLAMF7 confered protection against lethal sepsis and endotoxemia by suppressing inflammatory cytokines. Taken together, our findings reveal a critical negative regulatory role of SLAMF7 on cytokine storm in macrophages during polymicrobial sepsis, and therefore provide new sights into a novel diagnostic marker and therapeutic target for sepsis.

Effects of Carvacrol on Survival, Mesenteric Blood Flow, Aortic Function and Multiple Organ Injury in a Murine Model of Polymicrobial Sepsis

Inflammation ◽  
2017 ◽  
Vol 40 (5) ◽  
pp. 1654-1663 ◽  
Author(s):  
Erdem Kamil Ozer ◽  
Mustafa Tugrul Goktas ◽  
Aysun Toker ◽  
Hulagu Bariskaner ◽  
Ceyhan Ugurluoglu ◽  
...  
Keyword(s):  
Blood Flow ◽  
Murine Model ◽  
Multiple Organ ◽  
Polymicrobial Sepsis ◽  
Organ Injury ◽  
Mesenteric Blood Flow ◽  
Multiple Organ Injury

scholarly journals Attenuation of COVID-19-induced cytokine storm in a young male patient with severe respiratory and neurological symptoms

2021 ◽  
Author(s):  
Christian Muschitz ◽  
Anita Trummert ◽  
Theresa Berent ◽  
Norbert Laimer ◽  
Lukas Knoblich ◽  
...  
Keyword(s):  
Decision Making ◽  
Male Patient ◽  
Young Male ◽  
Standard Of Care ◽  
Multiple Organ ◽  
Cytokine Storm ◽  
Invasive Ventilation ◽  
Organ Systems ◽  
The Central Nervous System

SummarySevere acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), produces protean manifestations and causes indiscriminate havoc in multiple organ systems. This rapid and vast production of proinflammatory cytokines contributes to a condition termed cytokine storm. A 35-year-old, otherwise healthy, employed, male patient was tested positive for COVID-19. He was admitted to the hospital on disease day 10 due to retarded verbal reactions and progressive delirium. On account of these conditions and the need for noninvasive/invasive ventilation, a combination treatment with baricitinib and remdesivir in conjunction with standard of care was initiated. The cytokine storm was rapidly blocked, leading to a vast pulmonary recovery with retarded recovery of the central nervous system. We conclude that the rapid blockade of the COVID-19-induced cytokine storm should be considered of avail as a principle of careful decision-making for effective recovery.

scholarly journals Pathogenesis and Management of COVID-19

2021 ◽  
Vol 11 (2) ◽  
pp. 77-93
Author(s):  
Khalid O. Alfarouk ◽  
Sari T. S. AlHoufie ◽  
Samrein B. M. Ahmed ◽  
Mona Shabana ◽  
Ahmed Ahmed ◽  
...  
Keyword(s):  
Multiple Organ Failure ◽  
Human Body ◽  
Inflammatory Mediators ◽  
Expression Patterns ◽  
Multiple Organ ◽  
Cytokine Storm ◽  
Chain Reaction ◽  
Road Map ◽  
A Chain ◽  
Global War

COVID-19, occurring due to SARS-COV-2 infection, is the most recent pandemic disease that has led to three million deaths at the time of writing. A great deal of effort has been directed towards altering the virus trajectory and/or managing the interactions of the virus with its subsequent targets in the human body; these interactions can lead to a chain reaction-like state manifested by a cytokine storm and progress to multiple organ failure. During cytokine storms the ratio of pro-inflammatory to anti-inflammatory mediators is generally increased, which contributes to the instigation of hyper-inflammation and confers advantages to the virus. Because cytokine expression patterns fluctuate from one person to another and even within the same person from one time to another, we suggest a road map of COVID-19 management using an individual approach instead of focusing on the blockbuster process (one treatment for most people, if not all). Here, we highlight the biology of the virus, study the interaction between the virus and humans, and present potential pharmacological and non-pharmacological modulators that might contribute to the global war against SARS-COV-2. We suggest an algorithmic roadmap to manage COVID-19.

The selective guanylate cyclase inhibitor ODQ reduces multiple organ injury in rodent models of Gram-positive and Gram-negative shock

2001 ◽  
Vol 29 (8) ◽  
pp. 1599-1608 ◽  
Author(s):  
Kai Zacharowski ◽  
Reinhard Berkels ◽  
Antje Olbrich ◽  
Prabal K. Chatterjee ◽  
Salvatore Cuzzocrea ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Multiple Organ ◽  
Organ Injury ◽  
Rodent Models ◽  
Gram Positive ◽  
Gram Negative ◽  
Multiple Organ Injury ◽  
Negative Shock

scholarly journals Ubiquitin-Specific Protease 25 Aggravates Acute Pancreatitis and Acute Pancreatitis-Related Multiple Organ Injury by Destroying Tight Junctions Through Activation of The STAT3 Pathway

2022 ◽  
Vol 9 ◽  
Author(s):  
Zhengru Liu ◽  
Mingming Qi ◽  
Shan Tian ◽  
Qian Yang ◽  
Jian Liu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Tight Junctions ◽  
Multiple Organ ◽  
Organ Injury ◽  
Pancreatic Acinar Cells ◽  
Stat3 Pathway ◽  
Specific Protease ◽  
Ubiquitin Specific Protease ◽  
Multiple Organ Injury

Ubiquitin-specific protease 25 (USP25) plays an important role in inflammation and immunity. However, the role of USP25 in acute pancreatitis (AP) is still unclear. To evaluate the role of USP25 in AP, we conducted research on clinical AP patients, USP25wild-type(WT)/USP25 knockout (USP25−/−) mice, and pancreatic acinar cells. Our results showed that serum USP25 concentration was higher in AP patients than in healthy controls and was positively correlated with disease severity. AP patients’ serum USP25 levels after treatment were significantly lower than that at the onset of AP. Moreover, USP25 expression was upregulated in cerulein-induced AP in mice, while USP25 deficiency attenuates AP and AP-related multiple organ injury. In vivo and in vitro studies showed that USP25 exacerbates AP by promoting the release of pro-inflammatory factors and destroying tight junctions of the pancreas. We showed that USP25 aggravates AP and AP-related multiple organ injury by activating the signal transducer and activator of transcription 3 (STAT3) pathway. Targeting the action of USP25 may present a potential therapeutic option for treating AP.

scholarly journals Repurposing Anti-Malaria Phytomedicine Artemisinin as a COVID-19 Drug

2021 ◽  
Vol 12 ◽  
Author(s):  
Fatih M. Uckun ◽  
Saran Saund ◽  
Hitesh Windlass ◽  
Vuong Trieu
Keyword(s):  
High Risk ◽  
Health Condition ◽  
Infection Process ◽  
Spike Protein ◽  
Organ Injury ◽  
Cytokine Storm ◽  
Infection Cycle ◽  
Chinese Scientist ◽  
Anti Inflammatory ◽  
Post Entry

Artemisinin is an anti-inflammatory phytomedicine with broad-spectrum antiviral activity. Artemisinin and its antimalarial properties were discovered by the Chinese scientist Tu Youyu, who became one of the laureates of the 2015 Nobel Prize in Physiology or Medicine for this breakthrough in tropical medicine. It is a commonly used anti-malaria drug. Artemisinin has recently been repurposed as a potential COVID-19 drug. Its documented anti-SARS-CoV-2 activity has been attributed to its ability to inhibit spike-protein mediated and TGF-β-dependent early steps in the infection process as well as its ability to disrupt the post-entry intracellular events of the SARS-CoV-2 infection cycle required for viral replication. In addition, Artemisinin has anti-inflammatory activity and reduces the systemic levels of inflammatory cytokines that contribute to cytokine storm and inflammatory organ injury in high-risk COVID-19 patients. We postulate that Artemisinin may prevent the worsening of the health condition of patients with mild-moderate COVID-19 when administered early in the course of their disease.

scholarly journals Laboratory Markers in the Management of Pediatric Polytrauma: Current Role and Areas of Future Research

2021 ◽  
Vol 9 ◽  
Author(s):  
Birte Weber ◽  
Ina Lackner ◽  
Christian Karl Braun ◽  
Miriam Kalbitz ◽  
Markus Huber-Lang ◽  
...  
Keyword(s):  
Imaging Techniques ◽  
Lactate Concentration ◽  
Organ Damage ◽  
Severe Trauma ◽  
Multiple Organ ◽  
Organ Injury ◽  
Future Research ◽  
Acid Base Balance ◽  
Early Assessment ◽  
Laboratory Markers

Severe trauma is the most common cause of mortality in children and is associated with a high socioeconomic burden. The most frequently injured organs in children are the head and thorax, followed by the extremities and by abdominal injuries. The efficient and early assessment and management of these injuries is essential to improve patients' outcome. Physical examination as well as imaging techniques like ultrasound, X-ray and computer tomography are crucial for a valid early diagnosis. Furthermore, laboratory analyses constitute additional helpful tools for the detection and monitoring of pediatric injuries. Specific inflammatory markers correlate with post-traumatic complications, including the development of multiple organ failure. Other laboratory parameters, including lactate concentration, coagulation parameters and markers of organ injury, represent further clinical tools to identify trauma-induced disorders. In this review, we outline and evaluate specific biomarkers for inflammation, acid-base balance, blood coagulation and organ damage following pediatric polytrauma. The early use of relevant laboratory markers may assist decision making on imaging tools, thus contributing to minimize radiation-induced long-term consequences, while improving the outcome of children with multiple trauma.

scholarly journals Azolo[1,5-a]pyrimidines and Their Condensed Analogs with Anticoagulant Activity

Molecules ◽  
2022 ◽  
Vol 27 (1) ◽  
pp. 274
Author(s):  
Konstantin V. Savateev ◽  
Victor V. Fedotov ◽  
Vladimir L. Rusinov ◽  
Svetlana K. Kotovskaya ◽  
Alexandr A. Spasov ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Anticoagulant Activity ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Antiviral Agents ◽  
Multiple Organ ◽  
Thrombin Time ◽  
Cytokine Storm ◽  
Reference Drug

Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. Anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time, it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of most active compounds was confirmed using lipopolysaccharide (LPS)-treated blood to mimic the conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5–15.2 times as compared to LPS-treated blood.

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