scholarly journals Quantifying the role of different surface coatings in experimental models of wound healing

2019 ◽  
Author(s):  
Wang Jin ◽  
Kai-Yin Lo ◽  
Yung-Shin Sun ◽  
Ya-Han Ting ◽  
Matthew J Simpson
Keyword(s):  
Experimental Data ◽  
Wound Healing ◽  
Experimental Models ◽  
Surface Coatings ◽  
Parameter Estimates ◽  
Increase Cell Motility ◽  
Gap Width

In vitro surface coatings are widely used to mimic the role of extracellular matrix in the in vivo environment. Different effects are reported for different surface coatings, however, some of these results are inconsistent across the literature. To explore the role of different surface coatings, we use a new modified stopper-based wound-healing assay, called a stopper assay, with two commonly used surface coatings: gelatin and poly-L-lysine (PLL). Our experimental data show the gap width decreases faster with the gelatin and PLL coatings. Similarly, the number of cells in certain subregions increases faster with these coatings. Unfortunately, neither of these observations provides definitive mechanistic insight into the role of the coatings. To provide such insight we calibrate the solution of the Fisher-Kolmogorov model to match the experimental data. Our parameter estimates indicate that both coatings significantly increase cell motility without affecting cell proliferation.

scholarly journals Arginase Activity in Eisenia andrei Coelomocytes: Function in the Earthworm Innate Response

2021 ◽  
Vol 22 (7) ◽  
pp. 3687
Author(s):  
Joanna Homa ◽  
Alina Klosowska ◽  
Magdalena Chadzinska
Keyword(s):  
Immune Response ◽  
Wound Healing ◽  
Arginase Activity ◽  
Eisenia Andrei ◽  
Heavy Metals Ions ◽  
First Time ◽  
Important Marker

Arginase is the manganese metalloenzyme catalyzing the conversion of l-arginine to l-ornithine and urea. In vertebrates, arginase is involved in the immune response, tissue regeneration, and wound healing and is an important marker of alternative anti-inflammatory polarization of macrophages. In invertebrates, data concerning the role of arginase in these processes are very limited. Therefore, in the present study, we focused on the changes in arginase activity in the coelomocytes of Eisenia andrei. We studied the effects of lipopolysaccharide (LPS), hydrogen peroxide (H2O2), heavy metals ions (e.g., Mn2+), parasite infection, wound healing, and short-term fasting (5 days) on arginase activity. For the first time in earthworms, we described arginase activity in the coelomocytes and found that it can be up-regulated upon in vitro stimulation with LPS and H2O2 and in the presence of Mn2+ ions. Moreover, arginase activity was also up-regulated in animals in vivo infected with nematodes or experiencing segment amputation, but not in fasting earthworms. Furthermore, we confirmed that the activity of coelomocyte arginase can be suppressed by l-norvaline. Our studies strongly suggest that similarly to the vertebrates, also in the earthworms, coelomocyte arginase is an important element of the immune response and wound healing processes.

scholarly journals Role of the C5a-C5a receptor axis in the inflammatory responses of the lungs after experimental polytrauma and hemorrhagic shock

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shinjini Chakraborty ◽  
Veronika Eva Winkelmann ◽  
Sonja Braumüller ◽  
Annette Palmer ◽  
Anke Schultze ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Inflammatory Responses ◽  
Experimental Models ◽  
Lung Damage ◽  
C5a Receptor ◽  
Cytokine Levels ◽  
Vitro Model

AbstractSingular blockade of C5a in experimental models of sepsis is known to confer protection by rescuing lethality and decreasing pro-inflammatory responses. However, the role of inhibiting C5a has not been evaluated in the context of sterile systemic inflammatory responses, like polytrauma and hemorrhagic shock (PT + HS). In our presented study, a novel and highly specific C5a L-aptamer, NoxD21, was used to block C5a activity in an experimental murine model of PT + HS. The aim of the study was to assess early modulation of inflammatory responses and lung damage 4 h after PT + HS induction. NoxD21-treated PT + HS mice displayed greater polymorphonuclear cell recruitment in the lung, increased pro-inflammatory cytokine levels in the bronchoalveolar lavage fluids (BALF) and reduced myeloperoxidase levels within the lung tissue. An in vitro model of the alveolar-capillary barrier was established to confirm these in vivo observations. Treatment with a polytrauma cocktail induced barrier damage only after 16 h, and NoxD21 treatment in vitro did not rescue this effect. Furthermore, to test the exact role of both the cognate receptors of C5a (C5aR1 and C5aR2), experimental PT + HS was induced in C5aR1 knockout (C5aR1 KO) and C5aR2 KO mice. Following 4 h of PT + HS, C5aR2 KO mice had significantly reduced IL-6 and IL-17 levels in the BALF without significant lung damage, and both, C5aR1 KO and C5aR2 KO PT + HS animals displayed reduced MPO levels within the lungs. In conclusion, the C5aR2 could be a putative driver of early local inflammatory responses in the lung after PT + HS.

scholarly journals Role of Berry Anthocyanins and Phenolic Acids on Cell Migration and Angiogenesis: An Updated Overview

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1075 ◽  
Author(s):  
Panagiotis Tsakiroglou ◽  
Natalie E. VandenAkker ◽  
Cristian Del Bo’ ◽  
Patrizia Riso ◽  
Dorothy Klimis-Zacas
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Phenolic Acids ◽  
Rho Gtpase ◽  
Small Gtpases ◽  
Endothelial Cell Migration ◽  
Berry Extracts

Cell migration is a critical process that is highly involved with normal and pathological conditions such as angiogenesis and wound healing. Important members of the RHO GTPase family are capable of controlling cytoskeleton conformation and altering motility characteristics of cells. There is a well-known relationship between small GTPases and the PI3K/AKT pathway. Endothelial cell migration can lead to angiogenesis, which is highly linked to wound healing processes. Phenolics, flavonoids, and anthocyanins are major groups of phytochemicals and are abundant in many natural products. Their antioxidant, antimicrobial, anti-inflammatory, antidiabetic, angiogenenic, neuroprotective, hepatoprotective, and cardioprotective properties have been extensively documented. This comprehensive review focuses on the in vitro and in vivo role of berry extracts and single anthocyanin and phenolic acid compounds on cell migration and angiogenesis. We aim to summarize the most recent published studies focusing on the experimental model, type of berry extract, source, dose/concentration and overall effect(s) of berry extracts, anthocyanins, and phenolic acids on the above processes.

scholarly journals Modeling Amantadine Treatment of Inuenza A Virus In Vitro

2021 ◽  
Author(s):  
Catherine A. A. Beauchemin ◽  
James J. McSharry ◽  
George L. Drusano ◽  
Jack T. Nguyen ◽  
Gregory T. Went ◽  
...  
Keyword(s):  
Experimental Data ◽  
Viral Infection ◽  
Mathematical Models ◽  
Influenza A ◽  
Mdck Cells ◽  
Rapid Development ◽  
Human Model ◽  
Parameter Estimates

We analyzed the dynamics of an influenza A/Albany/1/98 (H3N2) viral infection, using a set of mathematical models highlighting the differences between in vivo and in vitro infection. For example, we found that including virion loss due to cell entry was critical for the in vitro model but not for the in vivo model. Experiments were performed on influenza virus-infected MDCK cells in vitro inside a hollow-fiber (HF) system, which was used to continuously deliver the drug amantadine. The HF system captures the dynamics of an influenza infection, and is a controlled environment for producing experimental data which lend themselves well to mathematical modeling. The parameter estimates obtained from fitting our mathematical models to the HF experimental data are consistent with those obtained earlier for a primary infection in a human model. We found that influenza A/Albany/1/98 (H3N2) virions under normal experimental conditions at 37°C rapidly lose infectivity with a half-life of ~ 6.6 ± 0.2 h, and that the lifespan of productively infected MDCK cells is ~ 13 h. Finally, using our models we estimated that the maximum efficacy of amantadine in blocking viral infection is ~ 74%, and showed that this low maximum efficacy is likely due to the rapid development of drug resistance.

scholarly journals Five-Decade Update on Chemopreventive and Other Pharmacological Potential of Kurarinone: a Natural Flavanone

2021 ◽  
Vol 12 ◽  
Author(s):  
Shashank Kumar ◽  
Kumari Sunita Prajapati ◽  
Mohd Shuaib ◽  
Prem Prakash Kushwaha ◽  
Hardeep Singh Tuli ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Therapeutic Potential ◽  
Experimental Models ◽  
Xenograft Models ◽  
Inhibitory Potential ◽  
Pharmacological Potential

In the present article we present an update on the role of chemoprevention and other pharmacological activities reported on kurarinone, a natural flavanone (from 1970 to 2021). To the best of our knowledge this is the first and exhaustive review of kurarinone. The literature was obtained from different search engine platforms including PubMed. Kurarinone possesses anticancer potential against cervical, lung (non-small and small), hepatic, esophageal, breast, gastric, cervical, and prostate cancer cells. In vivo anticancer potential of kurarinone has been extensively studied in lungs (non-small and small) using experimental xenograft models. In in vitro anticancer studies, kurarinone showed IC50 in the range of 2–62 µM while in vivo efficacy was studied in the range of 20–500 mg/kg body weight of the experimental organism. The phytochemical showed higher selectivity toward cancer cells in comparison to respective normal cells. kurarinone inhibits cell cycle progression in G2/M and Sub-G1 phase in a cancer-specific context. It induces apoptosis in cancer cells by modulating molecular players involved in apoptosis/anti-apoptotic processes such as NF-κB, caspase 3/8/9/12, Bcl2, Bcl-XL, etc. The phytochemical inhibits metastasis in cancer cells by modulating the protein expression of Vimentin, N-cadherin, E-cadherin, MMP2, MMP3, and MMP9. It produces a cytostatic effect by modulating p21, p27, Cyclin D1, and Cyclin A proteins in cancer cells. Kurarinone possesses stress-mediated anticancer activity and modulates STAT3 and Akt pathways. Besides, the literature showed that kurarinone possesses anti-inflammatory, anti-drug resistance, anti-microbial (fungal, yeast, bacteria, and Coronavirus), channel and transporter modulation, neuroprotection, and estrogenic activities as well as tyrosinase/diacylglycerol acyltransferase/glucosidase/aldose reductase/human carboxylesterases 2 inhibitory potential. Kurarinone also showed therapeutic potential in the clinical study. Further, we also discussed the isolation, bioavailability, metabolism, and toxicity of Kurarinone in experimental models.

scholarly journals Locus Coeruleus Modulates Neuroinflammation in Parkinsonism and Dementia

2020 ◽  
Vol 21 (22) ◽  
pp. 8630
Author(s):  
Filippo Sean Giorgi ◽  
Francesca Biagioni ◽  
Alessandro Galgani ◽  
Nicola Pavese ◽  
Gloria Lazzeri ◽  
...  
Keyword(s):  
Experimental Data ◽  
Locus Coeruleus ◽  
Clinical Symptoms ◽  
Experimental Studies ◽  
Anatomy And Physiology ◽  
The Central Nervous System ◽  
Near Future

Locus Coeruleus (LC) is the main noradrenergic nucleus of the central nervous system, and its neurons widely innervate the whole brain. LC is severely degenerated both in Alzheimer’s disease (AD) and in Parkinson’s disease (PD), years before the onset of clinical symptoms, through mechanisms that differ among the two disorders. Several experimental studies have shown that noradrenaline modulates neuroinflammation, mainly by acting on microglia/astrocytes function. In the present review, after a brief introduction on the anatomy and physiology of LC, we provide an overview of experimental data supporting a pathogenetic role of LC degeneration in AD and PD. Then, we describe in detail experimental data, obtained in vitro and in vivo in animal models, which support a potential role of neuroinflammation in such a link, and the specific molecules (i.e., released cytokines, glial receptors, including pattern recognition receptors and others) whose expression is altered by LC degeneration and might play a key role in AD/PD pathogenesis. New imaging and biochemical tools have recently been developed in humans to estimate in vivo the integrity of LC, the degree of neuroinflammation, and pathology AD/PD biomarkers; it is auspicable that these will allow in the near future to test the existence of a link between LC-neuroinflammation and neurodegeneration directly in patients.

Challenges with Wound Infection Models in Drug Development

2020 ◽  
Vol 21 (13) ◽  
pp. 1301-1312 ◽  
Author(s):  
Sandeep K. Shukla ◽  
Ajay K. Sharma ◽  
Vanya Gupta ◽  
Aman Kalonia ◽  
Priyanka Shaw
Keyword(s):  
Wound Healing ◽  
Wound Infection ◽  
Chronic Wound ◽  
Wound Care ◽  
Infection Model ◽  
In Vivo Models ◽  
Infection Models

: Wound research is an evolving science trying to unfold the complex untold mechanisms behind the wound healing cascade. In particular, interest is growing regarding the role of microorganisms in both acute and chronic wound healing. Microbial burden plays an important role in the persistence of chronic wounds, ultimately resulting in delayed wound healing. It is therefore important for clinicians to understand the evolution of infection science and its various etiologies. Therefore, to understand the role of bacterial biofilm in chronic wound pathogenesis, various in vitro and in vivo models are required to investigate biofilms in wound-like settings. Infection models should be refined comprising an important signet of biofilms. These models are eminent for translational research to obtain data for designing an improved wound care formulation. However, all the existing models possess limitations and do not fit properly in the model frame for developing wound care agents. Among various impediments, one of the major drawbacks of such models is that the wound they possess does not mimic the wound a human develops. Therefore, a novel wound infection model is required which can imitate the human wounds. : This review article mainly discusses various in vitro and in vivo models showing microbial colonization, their advantages and challenges. Apart from these models, there are also present ex vivo wound infection models, but this review mainly focused on various in vitro and in vivo models available for studying wound infection in controlled conditions. This information might be useful in designing an ideal wound infection model for developing an effective wound healing formulation.

scholarly journals Crucial role of vinexin for keratinocyte migration in vitro and epidermal wound healing in vivo

2010 ◽  
Vol 316 (10) ◽  
pp. 1728-1738 ◽  
Author(s):  
Noriyuki Kioka ◽  
Takuya Ito ◽  
Hiroshi Yamashita ◽  
Natsuko Uekawa ◽  
Tsutomu Umemoto ◽  
...  
Keyword(s):  
Wound Healing ◽  
Crucial Role ◽  
Keratinocyte Migration

scholarly journals Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hamza Atcha ◽  
Amit Jairaman ◽  
Jesse R. Holt ◽  
Vijaykumar S. Meli ◽  
Raji R. Nagalla ◽  
...  
Keyword(s):  
Wound Healing ◽  
Immune Responses ◽  
Positive Feedback ◽  
Macrophage Activation ◽  
Molecular Mechanisms ◽  
Macrophage Polarization ◽  
Subcutaneous Implantation

AbstractMacrophages perform diverse functions within tissues during immune responses to pathogens and injury, but molecular mechanisms by which physical properties of the tissue regulate macrophage behavior are less well understood. Here, we examine the role of the mechanically activated cation channel Piezo1 in macrophage polarization and sensing of microenvironmental stiffness. We show that macrophages lacking Piezo1 exhibit reduced inflammation and enhanced wound healing responses. Additionally, macrophages expressing the transgenic Ca2+ reporter, Salsa6f, reveal that Ca2+ influx is dependent on Piezo1, modulated by soluble signals, and enhanced on stiff substrates. Furthermore, stiffness-dependent changes in macrophage function, both in vitro and in response to subcutaneous implantation of biomaterials in vivo, require Piezo1. Finally, we show that positive feedback between Piezo1 and actin drives macrophage activation. Together, our studies reveal that Piezo1 is a mechanosensor of stiffness in macrophages, and that its activity modulates polarization responses.

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