Wound Healing Markers Research Articles

1-Tetracosanol isolated from the leaves of Eupatorium glandulosum, accelerates wound healing by expressing inflammatory cytokines and matrix metalloproteinase

Ethnopharmacological relevanceThe leave paste of the plant, Eupatorium glandulosum H. B & K, has been traditionally used to treat cuts and wounds by the tribal community of the Nilgiris district of Tamilnadu, India. Aim of the studyThe present study was carried out to investigate the wound healing potential of this plant extract and the compound, 1-Tetracosanol, isolated from the ethyl acetate fraction. Materials and methodsAn in vitro study was designed to compare the viability, migration and apoptosis of the fresh methanolic extract fractions and 1-Tetracosanol using mouse fibroblast NIH3T3 cell lines and human keratinocytes HaCaT cell lines, respectively. 1-Tetracosanol was evaluated for its viability, migration, qPCR analysis, in silico, in vitro and in vivo. Results1-Tetracosanol at the concentration of 800, 1600, 3200 μM has significant wound closure of 99% at 24 h. The compound when screened in silico against various wound healing markers, TNF-α, IL-12, IL-18, GM-CSF and MMP-9, revealed high binding energy of −5, 4.9 and −6.4 kcal/mol for TNF-α, IL-18 and MMP-9, respectively. Gene expression and the release of cytokines increased at an early stage of the wound repair. 1-Tetracosanol, at 2% gel showed 97.35 ± 2.06% wound closure at 21st day. Conclusion1-Tetracosanol is a good lead for drug development targeted towards wound healing activity and work in this direction is in progress.

Vitamin C influences antioxidative, anti-inflammatory and wound healing markers in smokers’ gingival fibroblasts in vitro

BackgroundSaudi Arabia has an overall smoking rate of 15.9%. The link between smoking and periodontal disease has been studied extensively. It is possible for human gingival fibroblasts to accumulate nicotine intracellularly over a period of four hours. Additionally, unmetabolized nicotine is released into the environment. Tobacco presence can impair tissue inflammation, wound healing, and organ development. To counterbalance tobacco toxins, vitamin C has been added to a variety of products. AimThis study aims to analyze the RNA expression of antioxidant, anti-inflammatory, and wound healing proteins in human gingival fibroblasts from smokers and nonsmokers using polymerase chain reaction. Materials and MethodshGFs were extracted from clinically healthy periodontium sites of adult male subjects. Both heavy cigarette smokers and never-smokers participated as subjects. Cells were cultured and subcultured in supplemented growth medium. Vitamin C was inducted in the medium at the experimental 6th passage. RNA expression analysis (qRT-PCR) was performed to analyze adhesion, proliferation, and extracellular matrix expression. ResultsThe results revealed marked expression of a wound healing gene (VEGF-A) in never-smokers (p value = 0.016). GPX3 and SOD3 represent antioxidants that are highly expressed in treated never-smoker cells. SOD2 significantly increased (p value = 0.016) in smokers after vitamin C exposure. The anti-inflammatory markers IL-6 and IL-8 were lower among smokers than among nonsmokers (p < 0.0001). ConclusionTobacco smoking suppressed gingival fibroblasts' abilities to regenerate, heal, combat inflammation, and resist free radicals. Vitamin C at cellular levels was beneficial and should be considered in the treatment component of smokers in the dental clinic.

Bilayer scaffold from PLGA/fibrin electrospun membrane and fibrin hydrogel layer supports wound healing in vivo

Hybrid scaffolds from natural and synthetic polymers have been widely used due to the complementary nature of their physical and biological properties. The aim of the present study, therefore, has been to analyze in vivo a bilayer scaffold of poly(lactide-co-glycolide)/fibrin electrospun membrane and fibrin hydrogel layer on a rat skin model. Fibroblasts were cultivated in the fibrin hydrogel layer and keratinocytes on the electrospun membrane to generate a skin substitute. The scaffolds without and with cells were tested in a full-thickness wound model in Wistar Kyoto rats. The histological results demonstrated that the scaffolds induced granulation tissue growth, collagen deposition and epithelial tissue remodeling. The wound-healing markers showed no difference in scaffolds when compared with the positive control. Activities of antioxidant enzymes were decreased concerning the positive and negative control. The findings suggest that the scaffolds contributed to the granulation tissue formation and the early collagen deposition, maintaining an anti-inflammatory microenvironment.

Effects of Flaxseed Oil and Olive Oil on Markers of Inflammation and Wound Healing in Burn Patients: A Randomized Clinical Trial.

To study the anti-inflammatory and antioxidant effects of flaxseed oil and olive oil on inflammatory markers for facilitating wound healing. One hundred and twelve patients were randomly selected to four groups with a total burn surface area (TBSA) of 20-50%. The four groups includes olive oil (OO), flaxseed oil (FO), mixture of olive oil and flaxseed oil (OF), and control group and received 30g of oils for three weeks. Serum high-sensitivity C-reactive protein (hs-CRP), ferritin and albumin level as inflammatory markers, as well as cholesterol, triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) as the lipid profile were explored. Wound healing was assessed by photographing on days 2, 8, 15, and 22 (during three weeks of intervention) and were analyzed in imageJ software. The greatest reduction in the level of hs-CRP and ferritin was observed in the OF (-21.38±44.41) (-132.79±165.36), while the lowest reduction was reported in the control group (-36.36±79.03) (141.08±262.36). Compared to control group, OO significantly increased albumin (0.88±0.65). Reduction of wound healing at the end of the first week of intervention was not significant in the study groups. However, the stereology examination showed significant improvement in wound healing at the end of the second and third weeks in the OF. Based on the findings, combination of herbal oils reduce inflammation and improve wound healing and showed positive effects on the size of wounds in burn patients.

Modern aspects of burn injury immunopathogenesis and immuno-biochemical markers of wound healing (review of literature).

Burns are one of the most common traumatic injuries in the world, representing a global public health problem. Major burns (severe burn injury or burn disease) are one of the most life-threatening injuries. There is a great need to identify and monitor the development of complications (sepsis and septic shock, coagulopathy and DIC) in burned patients. The basis of the pathogenesis of burn injury, as well as any general pathological process, is an inflammatory reaction, ultimately aimed at restoring the structure and function of the damaged tissue. A feature of the inflammatory reaction in burn injury is the scale of alteration of the skin and mucous membranes. The review presents the main aspects of the burn injuries immunopathogenesis and the features of post-burn immune dysfunction, manifested by disorders in the innate and adaptive immunity systems. Attention is focused on the role in the immunopathogenesis of developing systemic and local disorders in burn injury. Also the role are discussed of a minor subpopulations of lymphocytes (Treg-, Th-17-, γδT-cells) in the immunopathogenesis and in the bacterial infection protection. The characteristics of the main immuno-biochemical markers of burn injury (cytokines and growth factors, nitric oxide, matrix metalloproteases, bacteria concentration levels) are present. The prognostic role of these biomarkers in assessing of the severity degree of patients with burn injury and wound healing processes is shown. The review has been compiled using references from major databases such as RSCI, Web of Science, PubMed, Scopus and Google Scholar (up to march 2022). After obtaining all reports from database, the papers were carefully analyzed in order to find data related to the topic of this review (60 references).

Bacteriophage therapy as an alternative technique for treatment of multidrug-resistant bacteria causing diabetic foot infection

Diabetic foot ulcer (DFU) represented the most feared diabetic complication that caused the hospitalization of the diabetic patient. DFU was usually characterized with delayed healing as the diabetic neuropathy, angiopathy, and ulcer concomitant infections, among them, are multidrug-resistant (MDR) bacteria that emphasized the clinical importance for developing new therapeutic strategy with safe and effective alternatives for the antibiotics to overcome DFU-MDR bacterial infection. Bacteriophage therapy was considered a novel approach to eradicate the MDR, but its role in the polymicrobial infection of the DFU remains elusive. Thus, the current work was designed to investigate the effect of the topical application of the phage cocktail on the healing of the diabetic wound infected with clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella variicola, Escherichia coli, and Proteus mirabilis. Bacterial isolation was performed from clinical hospitalized and non-hospitalized cases of DFU, identified morphologically, biochemically, molecularly via 16 s rRNA sequencing, and typed for the antibiotic resistance pattern. Moreover, phages were isolated from the aforementioned clinical isolates and identified with electron microscope. Forty-five adult male Sprague–Dawley rats were assigned in 3 groups (15 rats each), namely, the diabetic infected wound group, diabetic infected wound ceftriaxone-treated group, and the diabetic infected wound phage cocktail-treated group. The results revealed that phage cocktail had a superior effect over the ceftriaxone in wound healing parameters (wound size, wound index, wound bacterial load, and mRNA expression); wound healing markers (Cola1a, Fn1, MMP9, PCNA, and TGF-β); inflammatory markers (TNF-α, NF-κβ, IL-1β, IL-8, and MCP-1); anti-inflammatory markers (IL-10 and IL-4); and diabetic wound collagen deposition; and also the histomorphic picture of the diabetic infected wound. Based on the current findings, it could be speculated that phage therapy could be considered a novel antibiotic substitute in the DFU with MDR-polymicrobial infection therapeutic strategies.

Platelet distribution width associated with short-term prognosis and cost in paediatrics with partial-thickness thermal burns: A retrospective comparative study.

Platelets exert important roles in burn wound healing and involving in inflammatory regulation and tissue repair. Platelet distribution width (PDW) is an indicator representing platelet morphology and activation. In this study, we try to evaluate the value of PDW in predicting short-term prognosis and cost of paediatrics with partial-thickness thermal burns. This retrospective study enrolled 73 children with partial-thickness thermal burns. The Ability of PDW to predict wound healing was evaluated by receiver operating characteristic (ROC) curve. All 73 patients were assigned into high and low PDW group according to optimal cut-off value from ROC curve. Associations between PDW and 2-weeks healing rate, time to wound healing, in-hospital cost and length of stay were evaluated. Furthermore, Univariate and multivariate logistic regression analysis were used to furtherly evaluate the significance of PDW in wound healing. We found that all baseline characteristics between groups were comparable (all P > .05). High PDW group had a significant higher 2-weeks wound healing rate than those with a low PDW (66.7% versus 32.6%, P < .01). Moreover, the mean time to wound healing of high PDW was obviously shorter than that of low PDW group (15.4 ± 10.1 vs 20.7 ± 10.9, P=.04). Univariate (OR: 0.24, 95%CI: 0.09-0.65, P < .01) and multivariate (OR: 0.15, 95CI%:0.05-0.52, P < .01) analysis confirmed PDW as an independent marker for wound healing. Patients in high PDW group had a significant lower medical burden than low PDW group, including in-hospital cost (13.7 ± 10.6 vs 21.9 ± 16.7, ×103RMB, P=.02) and length of stay (12.2 ± 8.8 vs 19.0 ± 10.8 days, P < .01). In conclusion, PDW can sever as a potential indictor to predict the short-term prognosis of paediatrics with partial thickness thermal burns.

Supplemental Protein and a Multinutrient Beverage Speed Wound Healing after Acute Sleep Restriction in Healthy Adults

BackgroundPhysiologic and psychologic stress slow healing from experimental wounds by impairing immune function. ObjectivesWe aimed to determine whether supplemental protein and multinutrient supplementation improved wound healing markers after acute stress induced by acute sleep restriction. MethodsIn this single-blind, crossover study in generally healthy young adults (18 males/2 females; mean ± SD age: 19.7 ± 2.30 y), experimental wounds were created by removing the top layer of forearm blisters induced via suction after 48 h of 72-h sleep restriction (2-h nightly sleep), a protocol previously shown to delay wound healing. Skin barrier restoration (measured by transepidermal water loss) assessed wound healing ≤10 d postblistering, and local immune responses were evaluated by serial measurement of cytokine concentrations in fluid collected at wound sites for 48 h postblistering. Participants consumed controlled, isocaloric diets with either 0.900 g · kg−1 · d−1 protein plus placebo (PLA) or 1.50 g · kg−1 · d−1 protein plus multinutrient beverage [l-arginine: 20.0 g/d; l-glutamine: 30.0 g/d; omega-3 (n–3) fatty acids: 1.00 g/d; zinc sulfate: 24.0 mg/d; cholecalciferol: 800 IU/d; and vitamin C: 400 mg/d] (NUT) during sleep restriction and for 4 d afterwards. ResultsSkin barrier restoration (primary outcome) was shorter for NUT (median: 3.98 d; IQR: 1.17 d) than for PLA (median: 5.25 d; IQR: 1.05 d) (P = 0.001). Cytokines from wound fluid (secondary outcome) increased over time (main effect of time P ≤ 0.001), except IL-13 (P = 0.07); however, no effects of treatment were observed. ConclusionsSupplemental nutrition may promote wound healing after sleep restriction in healthy adults including military personnel, the latter of which also have a high incidence of wounds and infection.This trial was registered at clinicaltrials.gov as NCT03525184.

The Healing Capability of Clove Flower Extract (CFE) in Streptozotocin-Induced (STZ-Induced) Diabetic Rat Wounds Infected with Multidrug Resistant Bacteria.

Treatment of diabetic foot ulcer (DFU) is of great challenge as it is shown to be infected by multidrug resistant bacteria (MDR bacteria). Sixty four bacterial isolates were isolated from DFU cases; antibiotic susceptibility tests were carried out for all of them. One bacterial isolate (number 11) was shown to resist the action of 8 out of 12 antibiotics used and was identified by both a Vitek-2 system and 16S rRNA fingerprints as belonging to Proteus mirabilis, and was designated Proteus mirabilis LC587231 (P. mirabilis). Clove flower extract (CFE) inhibited distinctively the P. mirabilis bacterium obtained. GC-MS spectroscopy showed that this CFE contained nine bioactive compounds. The effect of CFE on wound healing of Type 1 diabetic albino rats (Rattus norvegicus) was studied. The results indicated that topical application of CFE hydrogel improved wound size, wound index, mRNA expression of the wound healing markers (Coli1, MMP9, Fibronectin, PCNA, and TGFβ), growth factor signaling pathways (PPAR-α, PGC1-α, GLP-1, GLPr-1, EGF-β, EGF-βr, VEGF-β, and FGF-β), inflammatory cytokine expression (IL8, TNFα, NFKβ, IL1β, and MCP1), as well as anti-inflammatory cytokines (IL4 & IL10), pro-apoptotic markers (FAS, FAS-L, BAX, BAX/BCL-2, Caspase-3, P53, P38), as well as an antiapoptotic one (BCL2). Furthermore, it improved the wound oxidative state and reduced the wound microbial load, as the cefepime therapy improved the wound healing parameters. Based on the previous notions, it could be concluded that CFE represents a valid antibiotics alternative for DFU therapy since it improves diabetic wound healing and exerts antibacterial activity either in vitro or in vivo.

Ceramide kinase regulates acute wound healing by suppressing 5-oxo-ETE biosynthesis and signaling via its receptor OXER1

The sphingolipid, ceramide-1-phosphate (C1P), has been shown to promote the inflammatory phase and inhibit the proliferation and remodeling stages of wound repair via direct interaction with group IVA cytosolic phospholipase A2, a regulator of eicosanoid biosynthesis that fine-tunes the behaviors of various cell types during wound healing. However, the anabolic enzyme responsible for the production of C1P that suppresses wound healing as well as bioactive eicosanoids and target receptors that drive enhanced wound remodeling have not been characterized. Herein, we determined that decreasing C1P activity via inhibitors or genetic ablation of the anabolic enzyme ceramide kinase (CERK) significantly enhanced wound healing phenotypes. Importantly, postwounding inhibition of CERK enhanced the closure rate of acute wounds, improved the quality of healing, and increased fibroblast migration via a “class switch” in the eicosanoid profile. This switch reduced pro-inflammatory prostaglandins (e.g., prostaglandin E2) and increased levels of 5-hydroxyeicosatetraenoic acid and the downstream metabolite 5-oxo-eicosatetraenoic acid (5-oxo-ETE). Moreover, dermal fibroblasts from mice with genetically ablated CERK showed enhanced wound healing markers, while blockage of the murine 5-oxo-ETE receptor (oxoeicosanoid receptor 1) inhibited the enhanced migration phenotype of these cell models. Together, these studies reinforce the vital roles eicosanoids play in the wound healing process and demonstrate a novel role for CERK-derived C1P as a negative regulator of 5-oxo-ETE biosynthesis and the activation of oxoeicosanoid receptor 1 in wound healing. These findings provide foundational preclinical results for the use of CERK inhibitors to shift the balance from inflammation to resolution and increase the wound healing rate.

Clinical and Laboratory Factors Associated With Wound Healing in Patients With Pyoderma Gangrenosum: A Retrospective Study

Pyoderma gangrenosum (PG) is a rare, chronic, inflammatory, and ulcerative condition that often affects the lower extremities. Laboratory markers such as neutrophil-to-lymphocyte ratio, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level may have prognostic utility in the management of ulcerative or inflammatory conditions. This exploratory analysis investigated the relationship between readily available clinical factors and target ulcer healing within 6 months from the first visit. Two logistic regression models were fit-one focused on ESR as a primary predictor adjusted for age and hemoglobin level, and the other focused on CRP level adjusted for body mass index (BMI) and smoking history. The odds of wound healing at 6 months for patients with abnormal CRP was 0.19 times the odds of healing (95% CI, 0.03-0.77) for those with normal CRP (<10 mg/L), after accounting for BMI and smoking. Similarly, after accounting for age and hemoglobin, those with high ESR experienced 2.81 times the odds of healing (95% CI, 0.69-14.58) at 6 months compared with patients with normal ESR. After adjustment, an increased CRP level was associated with lower odds of healing; however, further research is warranted to investigate its prognostic utility. The relationship between ESR and odds of healing should be interpreted with caution because the wide 95% CI for the adjusted odds ratio reflects marked uncertainty in the estimate. This research brief may inform investigations into inflammatory markers as possible prognostic markers for wound healing in patients with PG.

Autologous Stem Cell Therapy for Chronic Lower Extremity Wounds: A Meta-Analysis of Randomized Controlled Trials.

Lower extremity chronic wounds (LECWs) commonly occur in patients with diabetes mellitus (DM) and peripheral arterial disease (PAD). Autologous stem cell therapy (ASCT) has emerged as a promising alternative treatment for those who suffered from LECWs. The purpose of this study was to assess the effects of ASCT on LECWs. Two authors searched three core databases, and independently identified evidence according to predefined criteria. They also individually assessed the quality of the included randomized controlled trials (RCTs), and extracted data on complete healing rate, amputation rate, and outcomes regarding peripheral circulation. The extracted data were pooled using a random-effects model due to clinical heterogeneity among the included RCTs. A subgroup analysis was further performed according to etiology, source of stem cells, follow-up time, and cell markers. A total of 28 RCTs (n = 1096) were eligible for this study. The pooled results showed that patients receiving ASCT had significantly higher complete healing rates (risk ratio (RR) = 1.67, 95% confidence interval (CI) 1.28–2.19) as compared with those without ASCT. In the CD34+ subgroup, ASCT significantly led to a higher complete healing rate (RR = 2.70, 95% CI 1.50–4.86), but there was no significant difference in the CD34− subgroup. ASCT through intramuscular injection can significantly improve wound healing in patients with LECWs caused by either DM or critical limb ischemia. Lastly, CD34+ is an important cell marker for potential wound healing. However, more extensive scale and well-designed studies are necessary to explore the details of ASCT and chronic wound healing.

Extracellular matrix-based combination scaffold for guided regeneration of large-area full-thickness rabbit burn wounds upon a single application.

Regeneration of large acute and chronic wounds is a concern worldwide. The present study evaluates wound healing competence of a completely human-origin, extracellular matrix (ECM)-based skin substitute/graft. It comprises cell-less amniotic membrane (AM), clinical-grade fibrin (FIB), and hyaluronic acid (HA) termed as AMFIBHA. The use of large-area third-degree rabbit burn wounds evaluated the product efficiency. The AMFIBHA induces hemostasis and permits suture-less positioning on the wound bed. In wet wounds, the AMFIBHA degrades and release biologically active molecules and guide cell migration, proliferation, and regeneration. The study demonstrated the effectiveness of this wound care product in terms of epithelial-dermal regeneration with angiogenesis. The study assessed injury-associated inflammation and different wound healing markers after 28 days of experiment and compared with both positive and negative controls-treated wounds. The regeneration of mature epidermis and dermis with rete pegs and hair follicle-like structure was evident upon a single application. The active involvement of host cells resulted in supple tissue formation. The ECM organization of AMFIBHA-treated tissue resulted in re-gain of mechanical properties comparable to native skin after 56 days. These guided regenerative outcomes reveal a promising translational value of the novel AMFIBHA skin substitute as an off-the-shelf product for clinical use.

The Protective Effect of Snail Secretion Filtrate in an Experimental Model of Excisional Wounds in Mice.

Wound healing is a physiological process comprising several coordinated phases, such as inflammation, proliferation, and remodeling. For centuries, Helix aspersa Muller mucus has been known to have biological properties that are useful for treating skin disorders. In this study, we used a full-thickness excisional wound model in mice to test the hypothesis that Snail Secretion Filtrate (SSF) can improve the wound healing process. The mucus from Helix aspersa Muller was obtained mechanically by manually stimulating snails with a sterile cotton swab tip, and then the mucus was subjected to a series of filtrations to obtain SSF. After wounding, the mice were treated topically with SSF for 14 days. Our macroscopic results show that the SSF treatment significantly improved the speed and percentage of wound area closure. Furthermore, SSF improved several markers of proper wound healing, such as collagen deposition (Masson, COL3A1, matrix metalloproteinases (MMPs)) and the tissue remodeling process (α-sma, vascular-endothelial growth factor (VEGF)). SSF was also able to counteract the inflammatory process in injured wound tissue (myeloperoxidase (MPO) IL-1β, IL-6, TNF-α). In conclusion, our results show that SSF is able to enhance the speed and efficiency of wound healing and positively regulate several aspects of the wound healing process, such as the proliferative and remodeling phases.

Calcineurin (PPP3CB) regulates angiotensin II‐dependent vascular remodelling by potentiating EGFR signalling in mice

This study investigates the role of calcineurin for angiotensin II (AngII)-induced vascular remodelling with the help of a mouse model lacking the catalytic beta subunit of calcineurin (PPP3CB KO). Wildtype (WT) and PPP3CB KO mice were treated for 4weeks with AngII followed by assessment of blood pressure, histological evaluation of aortas and mRNA analysis of aortic genes PPP3CB-dependently regulated by AngII. Primary murine vascular smooth muscle cells (VSMCs) were used for qPCR, ELISA and Western Blot experiments as well as wound healing and cell proliferation assays. Upon AngII treatment, PPP3CB KO mice showed less aortic media thickening, lumen dilation and systolic blood pressure compared to WT mice. Next-generation sequencing data of aortic tissue indicated an increase in extracellular matrix components (EMCs), cell migration and cell proliferation. A PPP3CB-dependent increase in EMC was confirmed by qPCR in aorta and VSMCs. PPP3CB-dependent stimulation of VSMC migration could be verified by wound healing assays but markers of enhanced cell proliferation were only detectable in aortic tissue of WT mice but not in isolated WT or KO VSMCs. We could demonstrate in VSMCs with pharmacological inhibitors that PPP3CB leads to enhanced heparin-binding EGF-like growth factor (HB-EGF) secretion, epidermal growth factor receptor (EGFR) activation and consecutive stimulation of transforming growth factor β(TGFβ) and connective tissue growth factor (CTGF) signalling that enhances collagen expression. AngII-induced vascular remodelling involves PPP3CB, which leads to enhanced EMC production, VSMC migration and sustained increase in systolic blood pressure via HBEGF/EGFR-TGFβ-CTGF signalling.

An unsupervised method for physical cell interaction profiling of complex tissues.

Cellular identity in complex multicellular organisms is determined in part by the physical organization of cells. However, large-scale investigation of the cellular interactome remains technically challenging. Here we develop cell interaction by multiplet sequencing (CIM-seq), an unsupervised and high-throughput method to analyze direct physical cell-cell interactions between cell types present in a tissue. CIM-seq is based on RNA sequencing of incompletely dissociated cells, followed by computational deconvolution into constituent cell types. CIM-seq estimates parameters such as number of cells and cell types in each multiplet directly from sequencing data, making it compatible with high-throughput droplet-based methods. When applied to gut epithelium or whole dissociated lung and spleen, CIM-seq correctly identifies known interactions, including those between different cell lineages and immune cells. In the colon, CIM-seq identifies a previously unrecognized goblet cell subtype expressing the wound-healing marker Plet1, which is directly adjacent to colonic stem cells. Our results demonstrate that CIM-seq is broadly applicable to unsupervised profiling of cell-type interactions in different tissue types.

O44: WOUND HEALING INFLAMMATORY MARKERS PREDICT PROGNOSIS AND SURVIVAL IN EARLY BREAST CANCER

Abstract Introduction Cancer is likened to a non-healing wound. There is limited evidence on the expression of wound healing tissue inflammatory markers, CD68(pan-macrophage marker), HO-1(tumour cell marker) and FAP(cancer-associated fibroblast marker) in human breast cancer. Method In 201 invasive breast cancer and 58 DCIS patients, CD68+TAM expression, tumour HO-1 and fibroblast FAP expression, quantified by immunohistochemistry(dichotomised: high/present vs low/absent), was correlated with tumour factors (grade, proliferation(Ki67), ER, HER2); demographic factors, behavioural factors (smoking, alcohol) and survival status(DFS, OS) Result High CD68+macrophage expression was increased in invasive breast cancer, compared to DCIS, and normal tissue distant from the tumour(59%,41%and 6% respectively; p&amp;lt;0.001).In invasive cancer,CD68+TAM expression increased with increasing tumour grade(Grade 1:42%, Grade 2:58%, Grade 3:72%; p=0.006), high Ki67(71%vs.47%; p=0.004), ER negativity(79.4%vs.55.4%; p=0.01) and HER2(HER2 positive 81.8% vs. HER2 negative 56.3%; p=0.03). CD68+TAM expression was higher in high compared to low/intermediate grade DCIS(44% % vs. 31% p=0.52). CD68+TAM expression was increased in patients who self-reported alcohol intake(non-drinker 43% vs. drinker 62%; p=0.01). HO-1 was associated with shorter DFS(HR:3.22,p=0.027) and OS(HR:2.86,p=0.029).FAP fibroblast expression correlated with longer DFS (HR:0.296,p=0.029) and OS (HR:0.271,p=0.008). Conclusion Tumour inflammation as assessed by CD68+TAM expression shows utility in identifying aggressive breast cancer sub-types. The association reported between CD68+TAM density and alcohol intake suggests a possible mechanism for alcohol as a risk factor for breast cancer. The prognostic value of HO-1 and FAP expression demonstrated here suggests a functional role of these wound healing markers in breast cancer. HO-1:Heme-oxygenase-1; FAP:Fibroblast activation protein; TAM:Tumour associated macrophage; DCIS: Ductal carcinoma in situ Take-home message Wound healing pathways of inflammation may be implicated in early breast cancer development

The effect of platelet-rich plasma-fibrin glue dressing in combination with oral vitamin E and C for treatment of non-healing diabetic foot ulcers: a randomized, double-blind, parallel-group, clinical trial

ABSTRACT Objective The current study assesses the effects of platelet-rich plasma-fibrin glue (PRP-FG) dressing along with oral vitamin E and C on wound healing and biochemical markers in patients with non-healing diabetic foot ulcers (non-healing DFU). Methods This randomized controlled trial was performed on 25 patients with non-healing DFU. Patients were treated with PRP-FG dressing plus oral vitamin E and C (intervention group) or PRP-FG dressing plus placebo (control group) for 8 weeks. Results Eight weeks after treatment, six wounds in the intervention group and two wounds in the control group were completely closed, and also wound size significantly reduced in both intervention and control groups (p < 0.05). This reduction in wound size was significantly greater in the intervention group compared to the control group (p = 0.019). Also, a significant decrease in prooxidant–antioxidant balance (PAB) , ESR, and hs-CRP was observed in the intervention group compared to the control group (p < 0.05). Conclusion Our results showed that PRP-FG dressing along with oral vitamin E and C could be used to increase wound healing in patients with non-healing DFU by enhancing the wound healing process and reducing oxidative stress. Trial Registration This trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04315909).

Potential Effect of Djambal Catfish (Pangasius djambal) Gelatin as Biomaterial Product on Healing Socket after Tooth Extraction in Rats

Purpose: Adequate wound healing after a tooth extraction is significant because the oral cavity has amasticatory function and plays a role in nutrient intake. Various scientific studies have been conducted tofind the ideal biomaterial to support wound healing. This study aims to determine the wound healing activityusing Djambal Catfish (Pangasius djambal) gelatin after tooth extraction.Method: Gelatin was obtained from Djambal Catfish (Pangasius djambal). The sample was selected byrandom sampling, divided into 6 groups, namely the control group on the 3rd day (n=6), the control groupon the 5th day (n=6), the control group on the 7th day (n=6), the treatment group on the 3rd day (n=6), thetreatment group on the 5th day (n=6), and the treatment on the 7th day (n=6). Wound healing was examinedby evaluating wound healing marker such as macrophages, fibroblasts, epithelialization, angiogenesis, andcollagen. Data were processed using statistical analysis.Results: The treatments had a positive result in wound healing as compared with the control groups.Histological assessment showed a remarkable sign of an increased number of macrophage, fibroblast,epithelialization, and collagen deposition.Conclusion: Gelatin derived from Djambal Catfish (Pangasius djambal) can accelerate the wound healingprocess thus could be a component therapeutic potential product that may be beneficial in wound healing inthe future.

Monocyte phenotype as a predictive marker for wound healing in diabetes-related foot ulcers.

Delayed healing of diabetes-related foot ulcers (DRFUs) is associated with increased macrophage and matrix metalloproteinases (MMPs) at the wound site. Whether circulating monocyte phenotype and/or MMPs are altered in association with wound healing outcome is unknown, and was investigated in this study. Blood was obtained from 21 participants with DRFU, at initial visit (V1), week-4 (V2), and week-8 (V3) for measurement of monocyte number (CD14+), phenotype (CD16, CD163) and chemokine receptors (CCRs) by flow cytometry, and circulating MMPs and TIMP-1 by ELISA. Six wounds healed during the study. At V1, non-classical CD16++ monocytes and MMP-3 were higher in healed vs unhealed (both p < 0.05). At V3, the increased %CD16++ persisted and %CCR2+ was decreased in healed, but no other monocyte markers nor MMP/TIMP differed between groups. Increased wound closure rate (WCR) at V3 correlated with increased %CD16++ monocytes and decreased MMP-2 at V1 or V1 + V2. Receiver operating characteristic (ROC) curves yielded an area-under-the-curve of %CD16++ at V1 of 0.78 to predict ulcer healing at V3. These results indicate that circulating monocyte phenotype and MMPs alter as DRFUs heal. The relationship of %CD16++ monocytes with WCR and ROC curve suggest a predictive role of %CD16++ monocytes for ulcer healing.