The effect of hyperbaric oxygen therapy on gene expression: microarray analysis on wound healing

2020 ◽  
pp. 31-37
Author(s):  
Jakub Tlapák ◽  
◽  
Petr Chmátal ◽  
Boris Oniščenko ◽  
Vojtěch Pavlík ◽  
...  

Background: Hyperbaric oxygen (HBO2) therapy canhave a positive effect on wound healing, angiogenesis and blood flow. No prior study has described the effects of HBO2 therapy and gene expression of this process. The goal of our research was to show the effects of HBO2 and its impact at the molecular level on angiogenesis, proliferation, differentiation, oxidative stress, inflammation, and extracellular matrix formation. Live animal subjects were used for simulating the process of wound healing under standard conditions and under the influence of HBO2. Methods: Two experimental groups were created using injured rabbits (N=24), one group (N=12) treated with hyperbaric therapy twice a day and one (N=12) with standard wound care management. Wounds were surgical, uninfected, and in healthy animal test subjects. We compared the whole genomic analysis of the transcriptome with the use of microarray technology at three intervals during treatment. Results: The induction of the wounds in rabbit skin increased expression of hundreds of genes in both treatment groups. The numbers of elevated and decreased genes gradually reduced as the wound healed. Gene expression analysis showed elevated expression of several genes associated with inflammation in both groups of injured animals. Genes connected to the process of angiogenesis, proliferation, differentiation, oxidative stress and extracellular matrix formation were without statistically significant changes. Conclusion: The evidence did not support that HBO2 had any significant effect on gene expression during wound healing. Additionally, there was no evidence to support that there were changes in gene expression in either treatment group.

2009 ◽  
Vol 106 (3) ◽  
pp. 988-995 ◽  
Author(s):  
Stephen R. Thom

The goal of this review is to outline advances addressing the role that reactive species of oxygen and nitrogen play in therapeutic mechanisms of hyperbaric oxygen. The review will be organized around major categories of problems or processes where controlled clinical trials have demonstrated clinical efficacy for hyperbaric oxygen therapy. Reactive species are now recognized to play a major role in cell signal transduction cascades, and the discussion will focus on how hyperbaric oxygen acts through these pathways to mediate wound healing and ameliorate postischemic and inflammatory injuries.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3055-3055
Author(s):  
Thung S. Lai ◽  
Christopher Davies ◽  
Charles Greenberg

Abstract Abstract 3055 Poster Board II-1031 Fibrin deposition triggers an injury response that involves the migration of inflammatory cells, formation of new blood vessels and the synthesis of extracellular matrix (ECM). Tissue transglutaminase (TGM2) is a calcium dependent enzyme that covalently crosslinks a wide variety of ECM proteins producing a protease resistant matrix. TGM2 is secreted by inflammatory and endothelial cells, involved in activating transforming growth factor beta-1 (TGFbeta-1) and expressed during tissue injury. In this study, we investigated how TGM2 modulated fibrin-dependent wound healing and the associated angiogenic response. We used an animal model consisting of fibrin Z-chambers (F-ZC, dual porous plexiglass chambers containing fibrin) implanted into the subcutaneous tissue of rats and harvested subsequently for quantitative assessment of granulation tissue formation (wound healing) and microvessel density (angiogenesis). We found that local administration of recombinant TGM2 into F-ZC resulted in a dose-dependent, 2-fold increase in granulation tissue thickness by day 6 of wound healing (p<0.001), an effect similar in magnitude to 25 ng/ml of TGFbeta1 administered in the F-ZC. The pro-healing effect of TGM2 was associated with a 2-fold increase in microvessel density in granulation tissue at day 6 of wound healing response (p<0.001). As a negative control, inactive recombinant C277A/TGM2 mutant did not exhibit increased wound healing response or proangiogenic effect. The data suggested that TGM2 enhanced the transition from the inflammatory stage of wound healing to proliferation stage. The two areas where TGM2 enhanced wound healing were 1) angiogenesis and 2) deposition of ECM. To investigate TGM2-induced angiogenesis-related gene expression, total RNAs were isolated from control- and TGM2-treated F-ZCs (at Day 6). Biotin-labeled cDNA probes were synthesized, and hybridized to nylon membranes containing angiogenesis-related gene arrays (Superarray, MD). The signals were detected using streptavidin-peroxidase and quantitated. We identified increased expression of VEGF receptors Flk-1 (2-fold), Flt1 and neuropilin (1.4-fold), angiopoietin-1 (2-fold) and ephrin B2 (1.8-fold). There were decreased levels (5-fold) of matrix metalloproteinases (MMPs) and increased TGFbeta-1 receptors (1.5-fold) and connective tissue growth factor (CTGF)(1.4-fold) levels. The gene expression profile suggests that TGM2 promotes angiogenesis and enhances deposition of ECM. We then investigated whether Aspirin (Acetylsalicylic Acid, ASA) a potent anti-inflammatory agent would inhibit TGM2. ASA and another chemical acetylating agent, sulfosuccinimidyl acetate (SNA), were used to investigate whether acetylation would alter the crosslinking activity of TGM2. We found acetylation by either SNA or ASA resulted in a loss of >90% of crosslinking activity. The Lys residues that were critical for inhibition were identified by mass spectrometry as Lys468 and Lys663. Molecular modeling indicates that these Lys residues play an important role in the conformation change that occurs in TGM2 from a closed-to-open shape, i.e. inactive-to-active, transitions. In conclusion, we show that TGM2-fibrin crosslinking accelerates angiogenesis and promotes ECM deposition. This suggests that TGM2-fibrin interactions mediates outside-in signaling events that aides wound healing. Furthermore aspirin can acetylate and inhibit critical residues in TGM2 that regulate TGM-2 function. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 71 (20) ◽  
pp. 6340-6354
Author(s):  
Aakansha Kanojia ◽  
Saurabh Gupta ◽  
Maria Benina ◽  
Alisdair R Fernie ◽  
Bernd Mueller-Roeber ◽  
...  

Abstract Leaf senescence is the final stage of leaf development and is induced by the gradual occurrence of age-related changes (ARCs). The process of leaf senescence has been well described, but the cellular events leading to this process are still poorly understood. By analysis of progressively ageing, but not yet senescing, Arabidopsis thaliana rosette leaves, we aimed to better understand processes occurring prior to the onset of senescence. Using gene expression analysis, we found that as leaves mature, genes responding to oxidative stress and genes involved in stress hormone biosynthesis and signalling were up-regulated. A decrease in primary metabolites that provide protection against oxidative stress was a possible explanation for the increased stress signature. The gene expression and metabolomics changes occurred concomitantly to a decrease in drought, salinity, and dark stress tolerance of individual leaves. Importantly, stress-related genes showed elevated expression in the early ageing mutant old5 and decreased expression in the delayed ageing mutant ore9. We propose that the decreased stress tolerance with age results from the occurrence of senescence-inducing ARCs that is integrated into the leaf developmental programme, and that this ensures a timely and certain death.


2019 ◽  
pp. 75-79
Author(s):  
Bengusu Mirasoglu ◽  
Engin Egeren ◽  
Huseyin Karakaya ◽  
Samil Aktas ◽  

More blast injuries are encountered in the civilian setting in recent years as terrorist attacks have increased globally. A 17-year-old male patient with severe blast injury of the right lower extremity was admitted to our department on the fifth day after a terrorist bombing attack. Initially he had been admitted to an emergency department with segmental tibia fracture and arterial injury (Gustilo IIIC). An amputation had been foreseen due to ischemia that persisted even after orthopedic fixation and revascularization interventions, followed by fasciotomy incisions. After consultation with our department hyperbaric oxygen (HBO2) therapy was administered twice daily for the first week. Ischemia improved prominently after 10 HBO2 sessions. HBO2 therapy was continued together with antibiotherapy and wound care. The patient underwent a total of 40 HBO2 sessions and two reconstructive operations and healed without amputation. Vascular injuries with concomitant orthopedic trauma cause most of the delayed amputations in bombing attacks since ischemia can persist at the microvascular level even though adequate treatments are applied. HBO2 corrects hypoxia at tissue level and so provides oxygen for the critically ischemic cells in the injured area. HBO2 also enhances host defense and decreases the ischemia reperfusion injury. In this case, HBO2 was effective in survival and functional recovery (salvage) of the extremity together with regular wound care, antibiotherapy and surgical repair.


Author(s):  
Rajesh Kesavan ◽  
Changam Sheela Sasikumar ◽  
V.B. Narayanamurthy ◽  
Arvind Rajagopalan ◽  
Jeehee Kim

Chronic foot ulcers are the leading cause of prolonged hospitalization and loss of social participation in people with diabetes. Conventional management of diabetic foot ulcers (DFU) is associated with slow healing, high cost, and recurrent visits to the hospital. Currently, the application of autologous lipotransfer is more popular, as the regenerative and reparative effects of fat are well established. Herein we report the efficacy of minimally manipulated extracellular matrix (MA-ECM) prepared from autologous homologous adipose tissue by using 3D bioprinting in DFU (test group) in comparison to the standard wound care (control group). A total of 40 subjects were screened and randomly divided into test and control groups. In the test group, the customized MA-ECM was printed as a scaffold from the patient autologous fat using a 3D bioprinter device and applied to the wound directly. The control group received standard wound care and weekly follow-up was done for all the patients. We evaluated the efficacy of this novel technology by assessing the reduction in wound size and attainment of epithelialization. The patients in the test group (n = 17) showed complete wound closure with re-epithelialization approximately within a period of 4 weeks. On the other hand, most of the patients in the control group (n = 16) who received standard wound dressings care showed a delay in wound healing in comparison to the test group. This technique can be employed as a personalized therapeutic method to accelerate diabetic wound healing and may provide a promising potential alternative approach to protect against lower foot amputation a most common complication in diabetes.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ailyn Fadriquela ◽  
Ma Easter Joy Sajo ◽  
Johny Bajgai ◽  
Dong-Heui Kim ◽  
Cheol-Su Kim ◽  
...  

Strong acidic electrolyzed water (StAEW) is known to inactivate microorganisms but is not fully explored in the medical field. This study is aimed at exploring StAEW as a potential wound care agent and its mechanism. StAEW (pH: 2.65, ORP: 1159 mV, ACC: 32.1 ppm) was sprayed three times a day to the cutaneous wounds of hairless mice for seven days. Wound morphological and histological features and immune-redox markers were compared with saline- (Sal-) and alcohol- (Alc-) treated groups. Results showed that the StAEW group showed a significantly higher wound healing percentage than the Sal group on days 2, 4, 5, and 6 and the Alc group on day 4. The StAEW group also showed earlier mediation on proinflammatory cytokines such as tumor necrosis factor-α, interleukin- (IL-) 6, IL-1β, and keratinocyte chemoattractant. In addition, basic fibroblast growth factor and platelet-derived growth factor were found to be significantly changed in favor of the fibroblast synthesis and angiogenesis. In line, the StAEW group showed a controlled amount of ROS and significantly decreased compared to the Alc group. The StAEW group also favored oxidative stress balance through antioxidant responses. Additionally, matrix metalloproteinases (MMP) 9 and MMP1 were also modulated for keratinocyte and cell migration. Taken together, this study has proven the wound healing effect of StAEW and its earlier mediation through oxidative and inflammatory responses.


PLoS ONE ◽  
2016 ◽  
Vol 11 (11) ◽  
pp. e0166340 ◽  
Author(s):  
Marta Marzotto ◽  
Clara Bonafini ◽  
Debora Olioso ◽  
Anna Baruzzi ◽  
Laura Bettinetti ◽  
...  

2020 ◽  
Author(s):  
Timothy W. King ◽  
Sahil K. Kapur

This review presents normal wound healing as a complex process that is generally carried out in three overlapping stages: an inflammatory phase, a proliferative phrase (made up of fibroplasia, contraction, neovascularization, and granulation), and a remodeling phase. In addition, wound healing occurs under the influence of multiple cytokines, growth factors, and extracellular matrix signals. Figures show the layers of the skin and the cycles of wound healing.  This review contains 6 highly rendered figures, 8 tables, and 47 references Keywords: wound, wound care, healing, epithelialization, migration, granulation


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