scholarly journals Metabolic Reprogramming and Host Tolerance: A Novel Concept to Understand Sepsis-Associated AKI

2021 ◽  
Vol 10 (18) ◽  
pp. 4184
Author(s):  
Juan Toro ◽  
Carlos L. Manrique-Caballero ◽  
Hernando Gómez
Keyword(s):  
Defense Mechanisms ◽  
Cellular Response ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Metabolic Reprogramming ◽  
Tolerance Mechanism ◽  
Risk Of Progression ◽  
Novel Concept ◽  
Host Tolerance

Acute kidney injury (AKI) is a frequent complication of sepsis that increases mortality and the risk of progression to chronic kidney disease. However, the mechanisms leading to sepsis-associated AKI are still poorly understood. The recognition that sepsis induces organ dysfunction in the absence of overt necrosis or apoptosis has led to the consideration that tubular epithelial cells (TEC) may deploy defense mechanisms to survive the insult. This concept dovetails well with the notion that the defense against infection does not only depend on the capacity of the immune system to limit the microbial load (known as resistance), but also on the capacity of cells and tissues to limit tissue injury (known as tolerance). In this review, we discuss the importance of TEC metabolic reprogramming as a defense strategy during sepsis, and how this cellular response is likely to operate through a tolerance mechanism. We discuss the fundamental role of specific regulatory nodes and of mitochondria in orchestrating this response, and how this opens avenues for the exploration of targeted therapeutic strategies to prevent or treat sepsis-associated AKI.

scholarly journals The Role of Nrf2 in the Antioxidant Cellular Response to Medical Ozone Exposure

2019 ◽  
Vol 20 (16) ◽  
pp. 4009 ◽  
Author(s):  
Mirco Galiè ◽  
Viviana Covi ◽  
Gabriele Tabaracci ◽  
Manuela Malatesta
Keyword(s):  
Cellular Response ◽  
Tissue Injury ◽  
Scientific Evidence ◽  
Antioxidant Response ◽  
Ozone Exposure ◽  
Related Factor ◽  
Cellular Mechanisms ◽  
Medical Ozone ◽  
Living Organisms

Ozone (O3) is a natural, highly unstable atmospheric gas that rapidly decomposes to oxygen. Although not being a radical molecule, O3 is a very strong oxidant and therefore it is potentially toxic for living organisms. However, scientific evidence proved that the effects of O3 exposure are dose-dependent: high dosages stimulate severe oxidative stress resulting in inflammatory response and tissue injury, whereas low O3 concentrations induce a moderate oxidative eustress activating antioxidant pathways. These properties make O3 a powerful medical tool, which can be used as either a disinfectant or an adjuvant agent in the therapy of numerous diseases. In this paper, the cellular mechanisms involved in the antioxidant response to O3 exposure will be reviewed with special reference to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its role in the efficacy of ozone therapy.

scholarly journals Metabolic profiling during malaria reveals the role of the aryl hydrocarbon receptor in regulating kidney injury

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Michelle M Lissner ◽  
Katherine Cumnock ◽  
Nicole M Davis ◽  
José G Vilches-Moure ◽  
Priyanka Basak ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Metabolic Response ◽  
Acute Infection ◽  
Critical Role ◽  
Kidney Injury ◽  
High Plasma ◽  
Metabolic Reprogramming ◽  
Aryl Hydrocarbon ◽  
Specific Effects

Systemic metabolic reprogramming induced by infection exerts profound, pathogen-specific effects on infection outcome. Here, we detail the host immune and metabolic response during sickness and recovery in a mouse model of malaria. We describe extensive alterations in metabolism during acute infection, and identify increases in host-derived metabolites that signal through the aryl hydrocarbon receptor (AHR), a transcription factor with immunomodulatory functions. We find that Ahr-/- mice are more susceptible to malaria and develop high plasma heme and acute kidney injury. This phenotype is dependent on AHR in Tek-expressing radioresistant cells. Our findings identify a role for AHR in limiting tissue damage during malaria. Furthermore, this work demonstrates the critical role of host metabolism in surviving infection.

scholarly journals Stress Response Protein BolA Influences Fitness and PromotesSalmonella entericaSerovar Typhimurium Virulence

2018 ◽  
Vol 84 (8) ◽  
pp. e02850-17 ◽  
Author(s):  
Dalila Mil-Homens ◽  
Susana Barahona ◽  
Ricardo N. Moreira ◽  
Inês J. Silva ◽  
Sandra N. Pinto ◽  
...  
Keyword(s):  
Host Defense ◽  
Defense Mechanisms ◽  
Cellular Response ◽  
Critical Role ◽  
Bacterial Virulence ◽  
Public Health Care ◽  
Infection Model ◽  
Content Type ◽  
Determining Factor

ABSTRACTThe intracellular pathogenSalmonella entericaserovar Typhimurium has emerged as a major cause of foodborne illness, representing a severe clinical and economic concern worldwide. The capacity of this pathogen to efficiently infect and survive inside the host depends on its ability to synchronize a complex network of virulence mechanisms. Therefore, the identification of new virulence determinants has become of paramount importance in the search of new targets for drug development. BolA-like proteins are widely conserved in all kingdoms of life. InEscherichia coli, this transcription factor has a critical regulatory role in several mechanisms that are tightly related to bacterial virulence. Therefore, in the present work we used the well-established infection modelGalleria mellonellato evaluate the role of BolA protein inS. Typhimurium virulence. We have shown that BolA is an important player inS. Typhimurium pathogenesis. Specifically, the absence of BolA leads to a defective virulence capacity that is most likely related to the remarkable effect of this protein onS. Typhimurium evasion of the cellular response. Furthermore, it was demonstrated that BolA has a critical role in bacterial survival under harsh conditions since BolA conferred protection against acidic and oxidative stress. Hence, we provide evidence that BolA is a determining factor in the ability ofSalmonellato survive and overcome host defense mechanisms, and this is an important step in progress to an understanding of the pathways underlying bacterial virulence.IMPORTANCEBolA has been described as an important protein for survival in the late stages of bacterial growth and under harsh environmental conditions. High levels of BolA in stationary phase and under stresses have been connected with a plethora of phenotypes, strongly suggesting its important role as a master regulator. Here, we show that BolA is a determining factor in the ability ofSalmonellato survive and overcome host defense mechanisms, and this is an important step in progress to an understanding of the pathways underlying bacterial virulence. This work constitutes a relevant step toward an understanding of the role of BolA protein and may have an important impact on future studies in other organisms. Therefore, this study is of utmost importance for understanding the genetic and molecular bases involved in the regulation ofSalmonellavirulence and may contribute to future industrial and public health care applications.

scholarly journals RAS Equilibrium Involves in Mesenteric Lymph Return-Mediated Acute Kidney Injury in Mice Underwent Acute Hemorrhage

2020 ◽  
Author(s):  
Yu-Jie Jin ◽  
Kun Su ◽  
Hong Zhang ◽  
Jin Xie ◽  
Hong Sun ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Hemorrhagic Shock ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Organ Injury ◽  
Ang Ii ◽  
Acute Hemorrhage ◽  
Mesenteric Lymph ◽  
Duct Ligation

Abstract Background: Previous studies demonstrated renin-angiotensin system (RAS) played vital roles in shock-induced organ injury, and mesenteric lymph return was involved in hemorrhagic shock-induced acute kidney injury (AKI). Nevertheless, whether RAS is involved in PHSML-mediated AKI remains unclear. Therefore, this study investigated the role of RAS in post-hemorrhagic shock mesenteric lymph (PHSML)-induced AKI. Methods: After acute hemorrhage and fluid resuscitation, the mice were treated with mesenteric lymph duct ligation (MLDL) and administrations of angiotensin converting enzyme (ACE) inhibitor enalapril, angiotensin (1-7) (Ang (1-7)), angiotensin II (Ang II) type 1 receptor (AT1R) inhibitor losartan, respectively. In addition, the parts of mice with hemorrhage plus MLDL were treated with Ang II, Mas receptor (MasR) inhibitor A-779, respectively. Meanwhile, the ACE2-/- mice received hemorrhage plus MLDL. At 4 h after resuscitation, the kidneys were harvested for the observation of histomorphology and measurement of ACE, ACE2, AT1R, MasR expressions and Ang II and Ang (1-7) levels.Results: Hemorrhagic shock induced renal tissue injury, increased the ACE and AT1R expressions, decreased the ACE2 and MasR expressions in kidney, accompanied by elevated Ang II and depressed Ang (1-7) in kidney. These adverse effects were partially reversed by MLDL or administrations of enalapril, Ang-(1-7), and losartan, respectively. In addition, the beneficial role of MLDL was reversed by ACE2 deficiency and Ang II or A-779 administrations. Conclusion: MLDL alleviates hemorrhagic shock-induced AKI in mice is related to the equilibrium ACE-AngII-AT1R and ACE2-Ang (1-7)-MasR axis.

scholarly journals Contemporary views on inflammatory pain mechanisms: TRPing over innate and microglial pathways

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2425 ◽  
Author(s):  
Zhonghui Guan ◽  
Judith Hellman ◽  
Mark Schumacher
Keyword(s):  
Cellular Response ◽  
Transient Receptor Potential ◽  
Tissue Injury ◽  
Trauma Surgery ◽  
Receptor Potential ◽  
Cell Types ◽  
Metabolic Dysfunction ◽  
Pain Mechanisms ◽  
Transient Receptor

Tissue injury, whether by trauma, surgical intervention, metabolic dysfunction, ischemia, or infection, evokes a complex cellular response (inflammation) that is associated with painful hyperalgesic states. Although in the acute stages it is necessary for protective reflexes and wound healing, inflammation may persist well beyond the need for tissue repair or survival. Prolonged inflammation may well represent the greatest challenge mammalian organisms face, as it can lead to chronic painful conditions, organ dysfunction, morbidity, and death. The complexity of the inflammatory response reflects not only the inciting event (infection, trauma, surgery, cancer, or autoimmune) but also the involvement of heterogeneous cell types including neuronal (primary afferents, sensory ganglion, and spinal cord), non-neuronal (endothelial, keratinocytes, epithelial, and fibroblasts), and immune cells. In this commentary, we will examine 1.) the expression and regulation of two members of the transient receptor potential family in primary afferent nociceptors and their activation/regulation by products of inflammation, 2.) the role of innate immune pathways that drive inflammation, and 3.) the central nervous system’s response to injury with a focus on the activation of spinal microglia driving painful hyperalgesic states.

Neuromyelitis optica spectrum: novel concept of pathogenesis, diagnosis and treatment of Devic’s disease

2009 ◽  
Vol 150 (46) ◽  
pp. 2101-2109 ◽  
Author(s):  
Péter Csécsei ◽  
Anita Trauninger ◽  
Sámuel Komoly ◽  
Zsolt Illés
Keyword(s):  
Neuromyelitis Optica ◽  
Water Channel ◽  
Diagnostic Procedures ◽  
Diagnosis And Treatment ◽  
Clinical Settings ◽  
Permanent Disability ◽  
Therapeutic Decisions ◽  
Novel Concept ◽  
The Brain

The identification of autoantibodies generated against the brain isoform water channel aquaporin4 in the sera of patients, changed the current diagnostic guidelines and concept of neuromyelitis optica (NMO). In a number of cases, clinical manifestation is spatially limited to myelitis or relapsing optic neuritis creating a diverse. NMO spectrum. Since prevention of relapses provides the only possibility to reduce permanent disability, early diagnosis and treatment is mandatory. In the present study, we discuss the potential role of neuroimaging and laboratory tests in differentiating the NMO spectrum from other diseases, as well as the diagnostic procedures and therapeutic options. We also present clinical cases, to provide examples of different clinical settings, diagnostic procedures and therapeutic decisions.

Protective Role of Mitophagy Associated Metabolic Reprogramming of Peripheral Macrophages During Tuberculosis

2020 ◽  
Author(s):  
Ranjeet Singh Mahla ◽  
Akhilesh Kumar ◽  
Helena Tutil ◽  
Sreevidhya Tarakkad Krishnaji ◽  
Bharathwaj Sathyamoorthy ◽  
...  
Keyword(s):  
Protective Role ◽  
Metabolic Reprogramming

Semi-Quantitative Ultrasonographic Evaluation of NAFLD

2020 ◽  
Vol 26 (32) ◽  
pp. 3915-3927 ◽  
Author(s):  
Stefano Ballestri ◽  
Claudio Tana ◽  
Maria Di Girolamo ◽  
Maria Cristina Fontana ◽  
Mariano Capitelli ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Imaging Techniques ◽  
Metabolic Complications ◽  
Nonalcoholic Fatty Liver ◽  
Non Invasive ◽  
Increased Risk ◽  
Risk Of Progression ◽  
Progressive Liver Disease

: Nonalcoholic fatty liver disease (NAFLD) embraces histopathological entities ranging from the relatively benign simple steatosis to the progressive form nonalcoholic steatohepatitis (NASH), which is associated with fibrosis and an increased risk of progression to cirrhosis and hepatocellular carcinoma. NAFLD is the most common liver disease and is associated with extrahepatic comorbidities including a major cardiovascular disease burden. : The non-invasive diagnosis of NAFLD and the identification of subjects at risk of progressive liver disease and cardio-metabolic complications are key in implementing personalized treatment schedules and follow-up strategies. : In this review, we highlight the potential role of ultrasound semiquantitative scores for detecting and assessing steatosis severity, progression of NAFLD, and cardio-metabolic risk. : Ultrasonographic scores of fatty liver severity act as sensors of cardio-metabolic health and may assist in selecting patients to submit to second-line non-invasive imaging techniques and/or liver biopsy.

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