scholarly journals Proteolysis-Induced Pathomechanisms in Acute Inflammation and Related Therapeutic Approaches

Author(s):  
M. Jochum ◽  
W. Machleidt ◽  
H. Fritz
2018 ◽  
Vol 29 (6) ◽  
pp. 645-660 ◽  
Author(s):  
Lan-yu Zhang ◽  
Ming-rui Jia ◽  
Tao Sun

Abstract The resolution of acute inflammation, once thought to be a passive process, is now recognized as an active one. The productions of endogenous special proresolving mediators (SPMs) are involved in this process. SPMs, including lipoxins, resolvins, protectins, and maresins, are endogenous lipid mediators generated from ω-6 arachidonic acid or ω-3 poly-unsaturated fatty acids during the resolution phase of acute inflammation. They have potent anti-inflammatory and proresolving actions in various inflammatory disorders. Due to the potent proresolving and anti-inflammatory effects, SPMs are also used for pain relief. This review focuses on the mechanisms by which SPMs act on their respective G-protein-coupled receptors in immune cells and nerve cells to normalize pain via regulating inflammatory mediators, transient receptor potential ion channels, and central sensitization. SPMs may offer novel therapeutic approaches for preventing and treating pain conditions associated with inflammation.


2011 ◽  
Vol 437 (2) ◽  
pp. 185-197 ◽  
Author(s):  
Gabrielle Fredman ◽  
Charles N. Serhan

Inflammation when unchecked is associated with many prevalent disorders such as the classic inflammatory diseases arthritis and periodontal disease, as well as the more recent additions that include diabetes and cardiovascular maladies. Hence mechanisms to curtail the inflammatory response and promote catabasis are of immense interest. In recent years, evidence has prompted a paradigm shift whereby the resolution of acute inflammation is a biochemically active process regulated in part by endogenous PUFA (polyunsaturated fatty acid)-derived autacoids. Among these are a novel genus of SPMs (specialized proresolving mediators) that comprise novel families of mediators including lipoxins, resolvins, protectins and maresins. SPMs have distinct structures and act via specific G-protein seven transmembrane receptors that signal intracellular events on selective cellular targets activating proresolving programmes while countering pro-inflammatory signals. An appreciation of these endogenous pathways and mediators that control timely resolution opened a new terrain for therapeutic approaches targeted at stimulating resolution of local inflammation. In the present review, we provide an overview of the biosynthesis and actions of resolvin E1, underscoring its protective role in vascular systems and regulating platelet responses. We also give an overview of newly described resolution circuitry whereby resolvins govern miRNAs (microRNAs), and transcription factors that counter-regulate pro-inflammatory chemokines, cytokines and lipid mediators.


2021 ◽  
Author(s):  
Gorana Jendrisek ◽  
Aleksandra Nikolic ◽  
Sandra Dragicevic

Abstract Purpose Montelukast, a leukotriene receptor antagonist, is the most prescribed non-steroidal anti-inflammatory drug used as add-on therapy at later stages of asthma to prevent disease progression. Besides its direct anti-inflammatory effect due to blocking leukotriene action, montelukast has been proposed to have secondary anti-inflammatory and anti-fibrotic properties. This study aimed to investigate the modulatory effect of montelukast on the expression of major genes involved in airway inflammation (TNF, IL6) and remodeling (MMP9, TGFB1) in response to lipopolysaccharide (LPS) in vitro. Methods Effect of montelukast on LPS-induced acute inflammation was analyzed in the immortalized cell line derived from human bronchial epithelium, BEAS-2B. The expression of selected genes was measured by quantitative real-time polymerase chain reaction 0h and 24h after LPS stimulation in cells pretreated with montelukast. Results Montelukast was found to significantly attenuate increased TNF and IL6 gene expression, has a mild effect on MMP9, and has no effect on TGFB1 expression upon stimulation with LPS. Conclusion The results of our study indicate that that patients already using montelukast therapy would have adequate response to acute microorganism-induced inflammation. Additional anti-inflammatory effects of montelukast could be better exploited in clinical practice and modes of montelukast use should be reconsidered to improve the therapeutic approaches in asthma.


2020 ◽  
Vol 4 (6) ◽  
pp. 645-675
Author(s):  
Parasuraman Padmanabhan ◽  
Mathangi Palanivel ◽  
Ajay Kumar ◽  
Domokos Máthé ◽  
George K. Radda ◽  
...  

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.


2011 ◽  
Vol 21 (1) ◽  
pp. 5-14
Author(s):  
Christy L. Ludlow

The premise of this article is that increased understanding of the brain bases for normal speech and voice behavior will provide a sound foundation for developing therapeutic approaches to establish or re-establish these functions. The neural substrates involved in speech/voice behaviors, the types of muscle patterning for speech and voice, the brain networks involved and their regulation, and how they can be externally modulated for improving function will be addressed.


2010 ◽  
Vol 20 (2) ◽  
pp. 29-36
Author(s):  
Erin M. Wilson ◽  
Ignatius S. B. Nip

Abstract Although certain speech development milestones are readily observable, the developmental course of speech motor control is largely unknown. However, recent advances in facial motion tracking systems have been used to investigate articulator movements in children and the findings from these studies are being used to further our understanding of the physiologic basis of typical and disordered speech development. Physiologic work has revealed that the emergence of speech is highly dependent on the lack of flexibility in the early oromotor system. It also has been determined that the progression of speech motor development is non-linear, a finding that has motivated researchers to investigate how variables such as oromotor control, cognition, and linguistic factors affect speech development in the form of catalysts and constraints. Physiologic data are also being used to determine if non-speech oromotor behaviors play a role in the development of speech. This improved understanding of the physiology underlying speech, as well as the factors influencing its progression, helps inform our understanding of speech motor control in children with disordered speech and provide a framework for theory-driven therapeutic approaches to treatment.


1958 ◽  
Vol 34 (3) ◽  
pp. 467-475 ◽  
Author(s):  
H.L. Bockus
Keyword(s):  

Author(s):  
Samira Salem ◽  
Essaid Leghouchi ◽  
Rachid Soulimani ◽  
Jaouad Bouayed

Abstract. Paw edema volume reduction is a useful marker in determining the anti-inflammatory effect of drugs and plant extracts in carrageenan-induced acute inflammation. In this study, the anti-inflammatory effect of Lobaria pulmonaria (LP) and Parmelia caperata (PC), two lichen species, was examined in carrageenan-induced mouse paw edema test. Compared to the controls in carrageenan-induced inflammation (n = 5/group), our results showed that pretreatment by single oral doses with PC extract (50–500 mg/kg) gives better results than LP extract (50–500 mg/kg) in terms of anti-edematous activity, as after 4 h of carrageenan subplantar injection, paw edema formation was inhibited at 82–99% by PC while at 35–49% by LP. The higher anti-inflammatory effect of PC, at all doses, was also observed on the time-course of carrageenan-induced paw edema, displaying profile closely similar to that obtained with diclofenac (25 mg/kg), an anti-inflammatory drug reference (all p < 0.001). Both LP and PC, at all doses, significantly ameliorated liver catalase (CAT) activity (all p < 0.05). However, superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity and glutathione (GSH) levels were found increased in liver of PC- compared to LP-carrageenan-injected mice. Our findings demonstrated on one hand higher preventive effects of PC compared to LP in a mouse carrageenan-induced inflammatory model and suggested, on the other hand, that anti-inflammatory effects elicited by the two lichens were closely associated with the amelioration in the endogenous antioxidant status of liver.


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