Apoptotic cell: linkage of inflammation and wound healing

Wu, Yu‐Sheng; Chen, Shiu-Nan

doi:10.3389/fphar.2014.00001

Cited by 208 publications

(252 citation statements)

References 67 publications

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“…Thus, apoptotic cleavage of kindlin-3 might contribute to inactivation of integrins and thereby accelerate apoptosis during resolution of inflammation. Because apoptosis of immune cells is thought to play a pivotal role in wound progression (87), a general increase in abundance of caspasegenerated neo-N termini in wound fluids (Fig. 6B) might be indicative for normal healing.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Assessment of Protease Dynamics in Cutaneous Wound Healing by Degradomics Analysis of Porcine Wound Exudates

Sabino

Hermes

Egli

et al. 2015

Molecular & Cellular Proteomics

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Proteases control complex tissue responses by modulating inflammation, cell proliferation and migration, and matrix remodeling. All these processes are orchestrated in cutaneous wound healing to restore the skin's barrier function upon injury. Altered protease activity has been implicated in the pathogenesis of healing impairments, and proteases are important targets in diagnosis and therapy of this pathology. Global assessment of proteolysis at critical turning points after injury will define crucial events in acute healing that might be disturbed in healing disorders. As optimal biospecimens, wound exudates contain an ideal proteome to detect extracellular proteolytic events, are noninvasively accessible, and can be collected at multiple time points along the healing process from the same wound in the clinics. In this study, we applied multiplexed Terminal Amine Isotopic Labeling of Substrates (TAILS) to globally assess proteolysis in early phases of cutaneous wound healing. By quantitative analysis of proteins and protein N termini in wound fluids from a clinically relevant pig wound model, we identified more than 650 proteins and discerned major healing phases through distinctive abundance clustering of markers of inflammation, granulation tissue formation, and re-epithelialization. TAILS revealed a high degree of proteolysis at all time points after injury by detecting almost 1300 N-terminal peptides in ϳ450 proteins. Quantitative positional proteomics mapped pivotal interdependent processing events in the blood coagulation and complement cascades, temporally discerned clotting and fibrinolysis during the healing process, and detected processing of complement C3 at distinct time points after wounding and by different proteases. Exploiting data on primary cleavage specificities, we related candidate proteases to cleavage events and revealed processing of the integrin adapter protein kindlin-3 by caspase-3, generating new hypotheses for protease-substrate relations in the healing skin wound in vivo.

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Section: Discussionmentioning

confidence: 99%

In Vivo Assessment of Protease Dynamics in Cutaneous Wound Healing by Degradomics Analysis of Porcine Wound Exudates

Sabino

Hermes

Egli

et al. 2015

Molecular & Cellular Proteomics

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“…43 Wound healing is the result of the proliferation and differentiation of broblasts, new blood vessel formation and extracellular matrix brosis, as well as epithelial cell proliferation and covering of the wound surfaces. 44 Our study established a BALB/c mouse infected wound model to evaluate the anti-infection ability and repair capacity of the CTS-SF Ag0.5/SA dressing. H&E staining on the 8th day (Fig.…”

Section: Histological Analysismentioning

confidence: 99%

An asymmetric wettable chitosan–silk fibroin composite dressing with fixed silver nanoparticles for infected wound repair: in vitro and in vivo evaluation

et al. 2017

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The treatment of large-area infected wounds remains a significant challenge, as there is no effective wound dressing for infected wound healing applicable to clinical applications. In this study, chitosan-silk fibroin composite scaffolds containing silver nanoparticles (AgNP) that underwent asymmetric modification were fabricated for tissue engineering dressings. The scaffolds were prepared from a solution containing a chitosan-silk-fibroin emulsion with added AgNPs using a lyophilization approach and with an asymmetric coating on the surface of one side. Transmission electron microscopy images and laser particle size analysis showed the AgNP distribution, scanning electron microscopy images showed the surface morphology of the dressings, and inductively coupled plasma mass spectrometry showed the silver content. The asymmetric wettability of the dressings was measured using a contact angle meter.High porosity, good moisture retention capability and appropriate tensile strength were observed by measuring the physical and mechanical properties. Good antimicrobial properties towards various bacteria were observed via in vitro antibacterial effect analysis. Controlled AgNP release by the dressings and their resistance to the infiltration of microorganisms were also observed in our experiments. A highly biocompatible dressing was observed by the MTT assay experiment and subcutaneous sensitization test.Moreover, the effects of the dressings on infected wound healing were measured in mice infected wound models. Analysis of the wound healing rate, bacterial cultures of the exudate, blood samples and histological examination all provided satisfactory results. These results demonstrate that the dressings we prepared offer the potential for infected wound tissue repair and regeneration.

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“…Of course, it is a challenge to apply such multidrug remedies for AD treatment with clinical rationale. Thus, new approaches such as quantitative system pharmacology with computational system polypharmacology algorithms [157,158] and chemogenomics knowledgebases [159,160] will open up a broad and promising avenue to advance the discovery and development of new-generation drugs for AD in the future.…”

Section: Conclusion and Future Perspectivementioning

confidence: 99%

Advances in Recent Patent and Clinical Trial Drug Development for Alzheimer’s Disease

et al. 2014

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease, involving a large number of genes, proteins and their complex interactions. Currently, no effective therapeutic agents are available to either stop or reverse the progression of this disease, likely due to its polygenic nature. The complicated pathophysiology of AD remains unresolved. Although it has been hypothesized that the amyloid β cascade and the hyper-phosphorylated tau protein may be primarily involved, other mechanisms, such as oxidative stress, deficiency of central cholinergic neurotransmitter, mitochondrial dysfunction and inflammation have also been implicated. The main focus of this review is to document current therapeutic agents in clinical trials and patented candidate compounds under development based on their main mechanisms of action. It also discusses the relationship between the recent understanding of key targets and the development of potential therapeutic agents for the treatment of AD.

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Apoptotic cell: linkage of inflammation and wound healing

Cited by 208 publications

References 67 publications

In Vivo Assessment of Protease Dynamics in Cutaneous Wound Healing by Degradomics Analysis of Porcine Wound Exudates

In Vivo Assessment of Protease Dynamics in Cutaneous Wound Healing by Degradomics Analysis of Porcine Wound Exudates

An asymmetric wettable chitosan–silk fibroin composite dressing with fixed silver nanoparticles for infected wound repair: in vitro and in vivo evaluation

Advances in Recent Patent and Clinical Trial Drug Development for Alzheimer’s Disease

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