scholarly journals Pathomechanisms of Posttraumatic Osteoarthritis: Chondrocyte Behavior and Fate in a Precarious Environment

2020 ◽  
Vol 21 (5) ◽  
pp. 1560 ◽  
Author(s):  
Jana Riegger ◽  
Rolf E. Brenner
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Strategies ◽  
Traumatic Injuries ◽  
Posttraumatic Osteoarthritis ◽  
Catabolic Enzymes ◽  
Regulated Cell Death ◽  
Chondrocyte Metabolism ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Novel Therapeutic

Traumatic injuries of the knee joint result in a wide variety of pathomechanisms, which contribute to the development of so-called posttraumatic osteoarthritis (PTOA). These pathogenetic processes include oxidative stress, excessive expression of catabolic enzymes, release of damage-associated molecular patterns (DAMPs), and synovial inflammation. The present review focuses on the underlying pathomechanisms of PTOA and in particular the behavior and fate of the surviving chondrocytes, comprising chondrocyte metabolism, regulated cell death, and phenotypical changes comprising hypertrophy and senescence. Moreover, possible therapeutic strategies, such as chondroanabolic stimulation, anti-oxidative and anti-inflammatory treatment, as well as novel therapeutic targets are discussed.

scholarly journals Roles of PRR-Mediated Signaling Pathways in the Regulation of Oxidative Stress and Inflammatory Diseases

2021 ◽  
Vol 22 (14) ◽  
pp. 7688
Author(s):  
Pengwei Li ◽  
Mingxian Chang
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Inflammatory Diseases ◽  
Therapeutic Strategies ◽  
Signaling Cascades ◽  
Oxygen Species ◽  
Inflammatory Signaling ◽  
Future Studies ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Oxidative stress is a major contributor to the pathogenesis of various inflammatory diseases. Accumulating evidence has shown that oxidative stress is characterized by the overproduction of reactive oxygen species (ROS). Previous reviews have highlighted inflammatory signaling pathways, biomarkers, molecular targets, and pathogenetic functions mediated by oxidative stress in various diseases. The inflammatory signaling cascades are initiated through the recognition of host cell-derived damage associated molecular patterns (DAMPs) and microorganism-derived pathogen associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). In this review, the effects of PRRs from the Toll-like (TLRs), the retinoic acid-induced gene I (RIG-I)-like receptors (RLRs) and the NOD-like (NLRs) families, and the activation of these signaling pathways in regulating the production of ROS and/or oxidative stress are summarized. Furthermore, important directions for future studies, especially for pathogen-induced signaling pathways through oxidative stress are also reviewed. The present review will highlight potential therapeutic strategies relevant to inflammatory diseases based on the correlations between ROS regulation and PRRs-mediated signaling pathways.

scholarly journals Biomarkers of Radiotherapy-Induced Immunogenic Cell Death

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 930
Author(s):  
Rianne D. W. Vaes ◽  
Lizza E. L. Hendriks ◽  
Marc Vooijs ◽  
Dirk De Ruysscher
Keyword(s):  
Cell Death ◽  
Immune Responses ◽  
Tumor Cells ◽  
Immunogenic Cell Death ◽  
Type I ◽  
Future Studies ◽  
Regulated Cell Death ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Potential Biomarkers

Radiation therapy (RT) can induce an immunogenic variant of regulated cell death that can initiate clinically relevant tumor-targeting immune responses. Immunogenic cell death (ICD) is accompanied by the exposure and release of damage-associated molecular patterns (DAMPs), chemokine release, and stimulation of type I interferon (IFN-I) responses. In recent years, intensive research has unraveled major mechanistic aspects of RT-induced ICD and has resulted in the identification of immunogenic factors that are released by irradiated tumor cells. However, so far, only a limited number of studies have searched for potential biomarkers that can be used to predict if irradiated tumor cells undergo ICD that can elicit an effective immunogenic anti-tumor response. In this article, we summarize the available literature on potential biomarkers of RT-induced ICD that have been evaluated in cancer patients. Additionally, we discuss the clinical relevance of these findings and important aspects that should be considered in future studies.

scholarly journals Necroptosis in Cholangiocarcinoma

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 982
Author(s):  
Samantha Sarcognato ◽  
Iris E. M. de Jong ◽  
Luca Fabris ◽  
Massimiliano Cadamuro ◽  
Maria Guido
Keyword(s):  
Cell Death ◽  
Current Knowledge ◽  
Kinase Domain ◽  
Alternative Mode ◽  
Interacting Protein ◽  
Regulated Cell Death ◽  
Anti Cancer ◽  
Regulatory Complex ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Necroptosis is a type of regulated cell death that is increasingly being recognized as a relevant pathway in different pathological conditions. Necroptosis can occur in response to multiple stimuli, is triggered by the activation of death receptors, and is regulated by receptor-interacting protein kinases 1 and 3 and mixed-lineage kinase domain-like, which form a regulatory complex called the necrosome. Accumulating evidence suggests that necroptosis plays a complex role in cancer, which is likely context-dependent and can vary among different types of neoplasms. Necroptosis serves as an alternative mode of programmed cell death overcoming apoptosis and, as a pro-inflammatory death type, it may inhibit tumor progression by releasing damage-associated molecular patterns to elicit robust cross-priming of anti-tumor CD8+ T cells. The development of therapeutic strategies triggering necroptosis shows great potential for anti-cancer therapy. In this review, we summarize the current knowledge on necroptosis and its role in liver biliary neoplasms, underlying the potential of targeting necroptosis components for cancer treatment.

scholarly journals Ferroptosis in Different Pathological Contexts Seen through the Eyes of Mitochondria

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
V. Otasevic ◽  
M. Vucetic ◽  
I. Grigorov ◽  
V. Martinovic ◽  
A. Stancic
Keyword(s):  
Therapeutic Strategies ◽  
Ultrastructural Changes ◽  
Future Research ◽  
Intracellular Iron ◽  
Antioxidant Defence ◽  
Regulated Cell Death ◽  
Liver And Kidney ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic ◽  
Morphological Phenotype

Ferroptosis is a recently described form of regulated cell death characterized by intracellular iron accumulation and severe lipid peroxidation due to an impaired cysteine-glutathione-glutathione peroxidase 4 antioxidant defence axis. One of the hallmarks of ferroptosis is a specific morphological phenotype characterized by extensive ultrastructural changes of mitochondria. Increasing evidence suggests that mitochondria play a significant role in the induction and execution of ferroptosis. The present review summarizes existing knowledge about the mitochondrial impact on ferroptosis in different pathological states, primarily cancer, cardiovascular diseases, and neurodegenerative diseases. Additionally, we highlight pathologies in which the ferroptosis/mitochondria relation remains to be investigated, where the process of ferroptosis has been confirmed (such as liver- and kidney-related pathologies) and those in which ferroptosis has not been studied yet, such as diabetes. We will bring attention to avenues that could be followed in future research, based on the use of mitochondria-targeted approaches as anti- and proferroptotic strategies and directed to the improvement of existing and the development of novel therapeutic strategies.

scholarly journals Neuronal Mitochondrial Dysfunction and Bioenergetic Failure in Inflammation-Associated Depression

2021 ◽  
Vol 15 ◽  
Author(s):  
Angela Maria Casaril ◽  
Robert Dantzer ◽  
Carlos Bas-Orth
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Brain Function ◽  
Vicious Cycle ◽  
Wide Range ◽  
Stress Energy ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Depressive Episodes ◽  
Insufficient Knowledge

Depression is a leading cause of disability and affects more than 4% of the population worldwide. Even though its pathophysiology remains elusive, it is now well accepted that peripheral inflammation might increase the risk of depressive episodes in a subgroup of patients. However, there is still insufficient knowledge about the mechanisms by which inflammation induces alterations in brain function. In neurodegenerative and neuroinflammatory diseases, extensive studies have reported that inflammation negatively impacts mitochondrial health, contributing to excitotoxicity, oxidative stress, energy deficits, and eventually neuronal death. In addition, damaged mitochondria can release a wide range of damage-associated molecular patterns that are potent activators of the inflammatory response, creating a feed-forward cycle between oxidative stress, mitochondrial impairment, inflammation, and neuronal dysfunction. Surprisingly, the possible involvement of this vicious cycle in the pathophysiology of inflammation-associated depression remains understudied. In this mini-review we summarize the research supporting the association between neuroinflammation, mitochondrial dysfunction, and bioenergetic failure in inflammation-associated depression to highlight the relevance of further studies addressing this crosstalk.

scholarly journals Targeting Innate Immunity to Combat Cutaneous Stress: The Vitiligo Perspective

2021 ◽  
Vol 12 ◽  
Author(s):  
Katia Boniface ◽  
Thierry Passeron ◽  
Julien Seneschal ◽  
Meri K. Tulic
Keyword(s):  
Immune Response ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Innate Immune ◽  
Danger Signals ◽  
Multiple Factors ◽  
Autoimmune Condition ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Multiple factors are involved in the process leading to melanocyte loss in vitiligo including environmental triggers, genetic polymorphisms, metabolic alterations, and autoimmunity. This review aims to highlight current knowledge on how danger signals released by stressed epidermal cells in a predisposed patient can trigger the innate immune system and initiate a cascade of events leading to an autoreactive immune response, ultimately contributing to melanocyte disappearance in vitiligo. We will explore the genetic data available, the specific role of damage-associated-molecular patterns, and pattern-recognition receptors, as well as the cellular players involved in the innate immune response. Finally, the relevance of therapeutic strategies targeting this pathway to improve this inflammatory and autoimmune condition is also discussed.

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