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Minerva Anestesiologica Jun 2020From the initial hypothesis considering 30 years ago the gut as the "motor" of multiple organ failure (MOF) related to an induced hyperpermeability leading to bacterial... (Review)
Review
From the initial hypothesis considering 30 years ago the gut as the "motor" of multiple organ failure (MOF) related to an induced hyperpermeability leading to bacterial translocation into the systemic circulation, the reality becomes significantly more complex. The gut contains three interplaying components - the epithelium, the microbiome, and the immune system - that have to cooperate to maintain two opposite function: adsorption of nutrients and maintenance of a barrier to prevent the crossing of intraluminal microbes or their products to avoid host response. Many critical illnesses are altering such a functional integrity that facilitate the growth of pathogens, their translocation toward blood or lymph, and the activation of the systemic inflammation with high risk of MOF. The gut becomes then the "hidden cause" of sepsis related to complex mechanisms. This review tries to give a comprehensive description of these mechanisms, focused on induced sepsis. Some new therapeutic strategies are discussed.
Topics: Bacterial Translocation; Critical Illness; Humans; Microbiota; Multiple Organ Failure; Sepsis
PubMed: 32013337
DOI: 10.23736/S0375-9393.20.14302-5 -
Experimental Cell Research Sep 2021Sepsis, an inflammation-related clinical syndrome, is characterized by disrupted immune homeostasis accompanied by infection and multiple organ dysfunction as determined... (Review)
Review
Sepsis, an inflammation-related clinical syndrome, is characterized by disrupted immune homeostasis accompanied by infection and multiple organ dysfunction as determined by the Sequential Organ Failure Assessment (SOFA). Substantial evidence has recently suggested that lncRNAs orchestrate various biological processes in diseases, and lncRNAs play special roles in the diagnosis and management of sepsis. To date, very few reviews have provided clear and comprehensive clues to demonstrate the roles of lncRNAs in the pathogenesis of sepsis. Based on previously published studies, in this review, we summarize the different functions of lncRNAs in sepsis-induced cellular disorders and sepsis-induced organ failure to show the potential roles of lncRNAs in the diagnosis and management of sepsis. We further depict the function of some lncRNAs known to be pivotal regulators in the pathogenesis of sepsis to discuss the underlying molecular events. Additionally, we list and discuss several hotspots in research on lncRNAs, which may be conducive to future lncRNA-targeted therapeutic approaches for sepsis treatment.
Topics: Animals; Humans; Inflammation; Multiple Organ Failure; RNA, Long Noncoding; Sepsis
PubMed: 34384779
DOI: 10.1016/j.yexcr.2021.112756 -
Der Anaesthesist Jan 2021The immune system is an effective defense against invading pathogens and is accompanied by recruitment of immune cells and initiation of an inflammatory reaction. This...
The immune system is an effective defense against invading pathogens and is accompanied by recruitment of immune cells and initiation of an inflammatory reaction. This can also be triggered by noninfectious stimuli, e.g. a large surgical intervention and cause severe tissue destruction and organ dysfunction. The organism cannot distinguish many stimuli that are released during a large surgical intervention from exogenous pathogens. Therefore, there is a high risk for the occurrence of systemic inflammatory reactions, particularly in large surgical interventions. This excessive immune response leads to release of proinflammatory cytokines, endothelial dysfunction, damage to the glycocalyx, activation of leukocytes as well as tissue and organ destruction. This article summarizes the molecular principles of the surgery-associated inflammatory reaction, the differentiation from other inflammatory complications and treatment options.
Topics: Humans; Inflammation; Multiple Organ Failure
PubMed: 33258991
DOI: 10.1007/s00101-020-00886-4 -
Journal of Cellular Physiology Nov 2021Signal transducer and activator of transcription 3 (STAT3) is a cellular signal transcription factor that has recently attracted a great deal of attention. It can... (Review)
Review
Signal transducer and activator of transcription 3 (STAT3) is a cellular signal transcription factor that has recently attracted a great deal of attention. It can trigger a variety of genes transcription in response to cytokines and growth factors stimulation, which plays an important role in many cellular biological processes involved in anti/proinflammatory responses. Sepsis is a life-threatening organ dysfunction resulting from dysregulated host responses to infection. As a converging point of multiple inflammatory responses pathways, accumulating studies have presented the elaborate network of STAT3 in sepsis pathophysiology; these results generally indicate a promising therapeutic application for targeting STAT3 in the treatment of sepsis. In the present review, we evaluated the published literature describing the use of STAT3 in the treatment of experimental and clinical sepsis. The information presented here may be useful for the design of future studies and may highlight the potential of STAT3 as a future biomarker and therapeutic target for sepsis.
Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Humans; Inflammation Mediators; Molecular Targeted Therapy; Multiple Organ Failure; Phosphorylation; STAT3 Transcription Factor; Sepsis; Signal Transduction
PubMed: 33885157
DOI: 10.1002/jcp.30394 -
Frontiers in Immunology 2023Sepsis represents a global health concern, and patients with severe sepsis are at risk of experiencing MODS (multiple organ dysfunction syndrome), which is associated... (Review)
Review
Sepsis represents a global health concern, and patients with severe sepsis are at risk of experiencing MODS (multiple organ dysfunction syndrome), which is associated with elevated mortality rates and a poorer prognosis. The development of sepsis involves hyperactive inflammation, immune disorder, and disrupted microcirculation. It is crucial to identify targets within these processes to develop therapeutic interventions. One such potential target is Panx1 (pannexin-1), a widely expressed transmembrane protein that facilitates the passage of molecules smaller than 1 KDa, such as ATP. Accumulating evidence has implicated the involvement of Panx1 in sepsis-associated MODS. It attracts immune cells via the purinergic signaling pathway, mediates immune responses via the Panx1-IL-33 axis, promotes immune cell apoptosis, regulates blood flow by modulating VSMCs' and vascular endothelial cells' tension, and disrupts microcirculation by elevating endothelial permeability and promoting microthrombosis. At the level of organs, Panx1 contributes to inflammatory injury in multiple organs. Panx1 primarily exacerbates injury and hinders recovery, making it a potential target for sepsis-induced MODS. While no drugs have been developed explicitly against Panx1, some compounds that inhibit Panx1 hemichannels have been used extensively in experiments. However, given that Panx1's role may vary during different phases of sepsis, more investigations are required before interventions against Panx1 can be applied in clinical. Overall, Panx1 may be a promising target for sepsis-induced MODS. Nevertheless, further research is needed to understand its complex role in different stages of sepsis fully and to develop suitable pharmaceutical interventions for clinical use.
Topics: Humans; Endothelial Cells; Multiple Organ Failure; Apoptosis; Inflammation; Membrane Proteins
PubMed: 37711629
DOI: 10.3389/fimmu.2023.1217366 -
Frontiers in Immunology 2022Dysfunctional complement activation and Toll-like receptor signaling immediately after trauma are associated with development of trauma-induced coagulopathy and multiple...
Dysfunctional complement activation and Toll-like receptor signaling immediately after trauma are associated with development of trauma-induced coagulopathy and multiple organ dysfunction syndrome. We assessed the efficacy of the combined inhibition therapy of complement factor C5 and the TLR co-receptor CD14 on thrombo-inflammation and organ damage in an exploratory 72-h polytrauma porcine model, conducted under standard surgical and intensive care management procedures. Twelve male pigs were subjected to polytrauma, followed by resuscitation (ATLS guidelines) and operation of the femur fracture (intramedullary nailing technique). The pigs were allocated to combined C5 and CD14 inhibition therapy group (n=4) and control group (n=8). The therapy group received intravenously C5 inhibitor (RA101295) and anti-CD14 antibody (rMil2) 30 min post-trauma. Controls received saline. Combined C5 and CD14 inhibition reduced the blood levels of the terminal complement complex (TCC) by 70% (p=0.004), CRP by 28% (p=0.004), and IL-6 by 52% (p=0.048). The inhibition therapy prevented the platelet consumption by 18% and TAT formation by 77% (p=0.008). Moreover, the norepinephrine requirements in the treated group were reduced by 88%. The inhibition therapy limited the organ damage, thereby reducing the blood lipase values by 50% (p=0.028), LDH by 30% (p=0.004), AST by 33%, and NGAL by 30%. Immunofluorescent analysis of the lung tissue revealed C5b-9 deposition on blood vessels in five from the untreated, and in none of the treated animals. In kidney and liver, the C5b-9 deposition was similarly detected mainly the untreated as compared to the treated animals. Combined C5 and CD14 inhibition limited the inflammatory response, the organ damage, and reduced the catecholamine requirements after experimental polytrauma and might be a promising therapeutic approach.
Topics: Animals; Complement C5; Complement Membrane Attack Complex; Inflammation; Male; Multiple Organ Failure; Multiple Trauma; Swine
PubMed: 36059503
DOI: 10.3389/fimmu.2022.952267 -
PloS One 2021Uricase-deficient rats could be one of the optimal model animals to study hyperuricemia. The present study aimed to find the biological differences between...
Uricase-deficient rats could be one of the optimal model animals to study hyperuricemia. The present study aimed to find the biological differences between uricase-deficient (Kunming-DY rats) and wild-type male rats. Uricase-deficient rats and wild-type rats were commonly bred. Their body weight, water and food consumption, 24-h urine and feces, uric acid in serum and organs, and serum indexes were recorded or assayed. Organs, including the heart, liver, spleen, lung, kidney, thymus, stomach, duodenum, and ileum, were examined using a routine hematoxylin-eosin staining assay. We found that the growth of male uricase-deficient rats was retarded. These rats excreted more urine than the wild-type rats. Their organ indexes (organ weight body weight ratio), of the heart, liver, kidney, and thymus significantly increased, while those of the stomach and small intestine significantly decreased. The uricase-deficient rats had a significantly higher level of serum uric acid and excreted more uric acid via urine at a higher concentration. Except for the liver, uric acid increased in organs and intestinal juice of uricase-deficient rats. Histological examination of the uricase-deficient rats showed mild injuries to the heart, liver, spleen, lung, kidney, thymus, stomach, duodenum, and ileum. Our results suggest that uricase-deficient rats have a different biological pattern from the wild-type rats. Uricase deficiency causes growth retardation of young male rats and the subsequent increase in serum uric acid results in mild organs injuries, especially in the kidney and liver.
Topics: Animals; Body Weight; Diet; Feces; Female; Intestines; Male; Multiple Organ Failure; Organ Specificity; Proteinuria; Rats, Sprague-Dawley; Urate Oxidase; Uric Acid; Rats
PubMed: 34437605
DOI: 10.1371/journal.pone.0256594 -
Nursing Jul 2020The prognosis for a patient with multiple organ dysfunction syndrome (MODS)-also known as organ dysfunction or organ failure-is grave, and mortality can be high when... (Review)
Review
The prognosis for a patient with multiple organ dysfunction syndrome (MODS)-also known as organ dysfunction or organ failure-is grave, and mortality can be high when three or more organ systems fail. This article reviews ongoing abnormalities of organ-specific parameters and a bedside clinical scoring assessment tool to identify the mortality of MODS, focusing on the management of MODS resulting from cardiogenic shock in ICU patients who require support of failing organs to survive.
Topics: Humans; Intensive Care Units; Multiple Organ Failure; Nursing Assessment; Nursing Diagnosis; Point-of-Care Testing; Shock, Cardiogenic
PubMed: 32558792
DOI: 10.1097/01.NURSE.0000580664.82974.cf -
Journal of Thrombosis and Haemostasis :... Aug 2019The aims of this review are to demonstrate that the changes in coagulation and fibrinolysis observed in cardiac arrest and resuscitation can be recognized as... (Review)
Review
The aims of this review are to demonstrate that the changes in coagulation and fibrinolysis observed in cardiac arrest and resuscitation can be recognized as disseminated intravascular coagulation (DIC), and to discuss the probability of DIC being a therapeutic target. The appearance of triggers of DIC, such as damage-associated molecular patterns, inflammatory cytokines, and adrenaline, is associated with platelet activation, marked thrombin generation and fibrin formation, insufficient anticoagulation pathways, and increased fibrinolysis by tissue-type plasminogen activator, followed by the suppression of fibrinolysis by plasminogen activator inhibitor-1, in patients with cardiac arrest and resuscitation. Simultaneous neutrophil activation and endothelial injury associated with glycocalyx perturbation have been observed in these patients. The degree of these changes is more severe in patients with prolonged precardiac arrest hypoxia and long no-flow and low-flow times, patients without return of spontaneous circulation, and non-survivors. Animal and clinical studies have confirmed decreased cerebral blood flow and microvascular fibrin thrombosis in vital organs, including the brain. The clinical diagnosis of DIC in patients with cardiac arrest and resuscitation is associated with multiple organ dysfunction, as assessed with the sequential organ failure assessment score, and increased mortality. This review confirms that the coagulofibrinolytic changes in cardiac arrest and resuscitation meet the definition of DIC proposed by the ISTH, and that DIC is associated with organ dysfunction and poor patient outcomes. This evidence implies that established DIC should be considered to be one of the main therapeutic targets in post-cardiac arrest syndrome.
Topics: Animals; Blood Coagulation; Disseminated Intravascular Coagulation; Fibrinolysis; Heart Arrest; Humans; Multiple Organ Failure; Resuscitation; Risk Factors; Treatment Outcome
PubMed: 31102491
DOI: 10.1111/jth.14480 -
Pediatric Annals Oct 2022Sepsis is a clinical syndrome manifested by a dysregulation of the immune system triggered by an infection. The severity of illness is variable, which can include mild...
Sepsis is a clinical syndrome manifested by a dysregulation of the immune system triggered by an infection. The severity of illness is variable, which can include mild symptoms with no organ dysfunction to severe symptoms and multiorgan failure, eventually leading to death. Advances in bioinformatics have elucidated distinct sepsis endotypes and have allowed for a better understanding of the pathophysiologic mechanisms. As we learn more about these sepsis endotypes, more precise therapies will emerge for use as adjuncts to antibiotics. .
Topics: Anti-Bacterial Agents; Child; Genomics; Humans; Multiple Organ Failure; Sepsis
PubMed: 36215090
DOI: 10.3928/19382359-20220803-04