Immune Fitness, Migraine, and Headache Complaints in Individuals with Self-Reported Impaired Wound Healing.

Background: Having chronic wounds and impaired wound healing are associated with psychological distress. The current study aims to evaluate migraine and headache complaints in young adults with self-reported impaired wound healing. Methods: A survey was conducted among N=1935 young adults (83.6% women), 18-30 years old, living in the Netherlands. Wound healing status was verified, immune fitness was assessed using a single-item rating scale, and ID Migraine was completed. In addition, several questions were answered on past year's headache experiences (including frequency, quantity, type, location, and severity). Results: In both the control group (p < 0.001) and the IWH group (p = 0.002) immune fitness was significantly lower among those that reported headaches compared to those that reported no headaches. Individuals with self-reported impaired wound healing (IWH) scored significantly higher on the ID Migraine scale, and individuals of the IWH group scored significantly more often positive for migraine (ie, an ID Migraine score ≥2). They reported a younger age of onset of experiencing headaches, and significantly more often reported having a beating or pounding headache than the control group. Compared to the control group, the IWH group reported being significantly more limited in their daily activities compared to the control group. Conclusion: Headaches and migraines are more frequently reported by individuals with self-reported impaired wound healing, and their reported immune fitness is significantly poorer compared to healthy controls. These headache and migraine complaints significantly limit them in their daily activities.

The Impact of COVID-19 Lockdowns in Germany on Mood, Attention Control, Immune Fitness, and Quality of Life of Young Adults with Self-Reported Impaired Wound Healing.

BACKGROUND: Previous studies in Dutch young adults revealed that individuals with self-reported impaired wound healing reported poorer mood, increased inattention and impulsivity, poorer quality of life, and poorer immune fitness compared to healthy controls. Another study revealed that the negative impact of lockdowns during the 2019 coronavirus disease (COVID-19) pandemic was significantly more profound among the impaired wound healing group than the control group. The purpose of the current study was to replicate and extend these findings among young adults living in Germany. METHODS: A retrospective, cross-sectional survey was conducted among N = 317 young adults living in Germany, 18-35 years old. They were allocated to the IWH group (N = 66) or the control group (N-251). Participants completed the Attention Control Scale, and mood, quality of life, and immune fitness were assessed with single-item ratings. All assessments were made for (1) the period before the COVID-19 pandemic, (2) the first lockdown period, March-May 2020, (3) the first no-lockdown period, summer 2020, (4) the second lockdown, November 2020 to May 2021, and (5) the second no-lockdown period, summer 2021. RESULTS: The impaired wound healing group reported significantly poorer mood, quality of life, and immune fitness. The effects were evident before the pandemic. The impaired wound healing group scored significantly poorer on attention focusing, but no significant differences between the groups were found for attention shifting. During the pandemic, negative lockdown effects (i.e., further aggravation of mood and immune fitness and lower quality of life) were evident in both groups but significantly more profound in the impaired wound healing group. No differences between the groups were found for the no-lockdown periods. CONCLUSION: Individuals with self-reported impaired wound healing have significantly poorer mood, attention focusing, and immune fitness and report a poorer quality of life than healthy controls. The impact of COVID-19 lockdowns was significantly more profound in the impaired wound-healing group.

Liver insulin-like growth factor-1 mediates effects of low-intensity vibration on wound healing in diabetic mice.

Chronic wounds in diabetic patients are associated with significant morbidity and mortality; however, few therapies are available to improve healing of diabetic wounds. Our group previously reported that low-intensity vibration (LIV) could improve angiogenesis and wound healing in diabetic mice. The purpose of this study was to begin to elucidate the mechanisms underlying LIV-enhanced healing. We first demonstrate that LIV-enhanced wound healing in db/db mice is associated with increased IGF1 protein levels in liver, blood, and wounds. The increase in insulin-like growth factor (IGF) 1 protein in wounds is associated with increased Igf1 mRNA expression both in liver and wounds, but the increase in protein levels preceded the increase in mRNA expression in wounds. Since our previous study demonstrated that liver was a primary source of IGF1 in skin wounds, we used inducible ablation of IGF1 in the liver of high-fat diet (HFD)-fed mice to determine whether liver IGF1 mediated the effects of LIV on wound healing. We demonstrate that knockdown of IGF1 in liver blunts LIV-induced improvements in wound healing in HFD-fed mice, particularly increased angiogenesis and granulation tissue formation, and inhibits the resolution of inflammation. This and our previous studies indicate that LIV may promote skin wound healing at least in part via crosstalk between the liver and wound. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Impaired wound healing in diabetes.

Impaired wound healing for patients with diabetes is due to a constellation of structural, biochemical, cellular and microbial factors. Hyperglycaemia and its associated inflammation contribute to immune dysfunction, vascular damage, neuropathy, cellular senescence, impaired transition beyond the inflammatory stage, microbiome disruptions, failed extracellular matrix formation, growth factor and cytokine imbalance, limited re-epithelialisation, and alterations in fibroblast migration and proliferation. Optimising glycaemic control remains the primary intervention to prevent continual dysfunction and comorbid disease progression.

Advances in non-invasive biosensing measures to monitor wound healing progression.

Impaired wound healing is a significant financial and medical burden. The synthesis and deposition of extracellular matrix (ECM) in a new wound is a dynamic process that is constantly changing and adapting to the biochemical and biomechanical signaling from the extracellular microenvironments of the wound. This drives either a regenerative or fibrotic and scar-forming healing outcome. Disruptions in ECM deposition, structure, and composition lead to impaired healing in diseased states, such as in diabetes. Valid measures of the principal determinants of successful ECM deposition and wound healing include lack of bacterial contamination, good tissue perfusion, and reduced mechanical injury and strain. These measures are used by wound-care providers to intervene upon the healing wound to steer healing toward a more functional phenotype with improved structural integrity and healing outcomes and to prevent adverse wound developments. In this review, we discuss bioengineering advances in 1) non-invasive detection of biologic and physiologic factors of the healing wound, 2) visualizing and modeling the ECM, and 3) computational tools that efficiently evaluate the complex data acquired from the wounds based on basic science, preclinical, translational and clinical studies, that would allow us to prognosticate healing outcomes and intervene effectively. We focus on bioelectronics and biologic interfaces of the sensors and actuators for real time biosensing and actuation of the tissues. We also discuss high-resolution, advanced imaging techniques, which go beyond traditional confocal and fluorescence microscopy to visualize microscopic details of the composition of the wound matrix, linearity of collagen, and live tracking of components within the wound microenvironment. Computational modeling of the wound matrix, including partial differential equation datasets as well as machine learning models that can serve as powerful tools for physicians to guide their decision-making process are discussed.

Advanced oxidation protein products mediate human keratinocytes apoptosis by inducing cell autophagy through the mTOR-Beclin-1 pathway.

Excessive keratinocyte apoptosis leads to impaired wound healing. Recently, advanced oxidation protein products (AOPP) have been recognized as a marker of oxidative stress and a potent inducer of apoptosis. Previously, we have demonstrated that extracellular AOPP accumulation induced keratinocyte apoptosis, and we discovered that autophagy was involved. To further elucidate the role and mechanism of autophagy in AOPP-induced-apoptosis of keratinocytes, we treated HaCaT cells with increasing concentrations of AOPP-human serum albumin or with AOPP-human serum albumin for increasing durations. Cyto-ID solution staining was used to assess cell autophagy using confocal laser scanning microscopy. Autophagy-related protein interactions were investigated using western blot analysis. Exposure of HaCaT cells to AOPP decreased the expression of mammalian target of rapamycin (mTOR) and increased the expression of autophagy-related proteins Beclin-l and LC3, and eventually led to autophagy. Furthermore, an autophagy agonist significantly decreased the expression of apoptosis-related proteins. Taken together, we showed that accumulation of extracellular AOPP induced autophagy in HaCaT cells via a reactive oxygen species-dependent, mTOR-Beclin-1-mediated pathway, and that excessive autophagy-mediated apoptosis, which resulted in delayed wound healing.

An optimized mouse model of Staphylococcus aureus infected diabetic ulcers.

OBJECTIVE: Diabetic foot infection (DFI) represents a major healthcare burden, for which treatment is challenging owing to the pathophysiological alterations intrinsic to diabetes and the alarming increase of antimicrobial resistance. Novel therapies targeting DFI are therefore a pressing research need for which proper models of disease are required. RESULTS: Here, we present an optimized diabetic mouse model of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds, that resemble key features of DFI, such as pathogen invasion through wound bed and surrounding tissue, necrosis, persistent inflammation and impaired wound healing. Thus, in a time-efficient manner and using simple techniques, this model represents a suitable approach for studying emerging therapies targeting DFI caused by MRSA.

Inattention, Impulsivity, and Hyperactivity among Individuals with Self-Reported Impaired Wound Healing.

BACKGROUND: Inattention and impulsivity are common causes of accidents and injury. The aim of the current study was to examine the level of attention deficit (AD), hyperactivity, and impulsivity (HI) in individuals with and without self-reported impaired wound healing (IWH). METHODS: A survey was conducted among N = 773 Dutch young adults, 18-30 years old. N = 198 were allocated to the IWH group and N = 575 to the control group. All participants completed the Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale. RESULTS: The analysis revealed that the IWH group has significantly higher scores on AD and HI, compared to the control group. Among the IWH group, 12.8% screened positive for AD (compared to 5.8% of the control group) and 14.0% screened positive for HI (compared to 7.4% of the control group). CONCLUSION: Clinically relevant increased inattention, impulsivity, and hyperactivity were observed among individuals with self-reported impaired wound healing.

Assessment of the concentration of selected metalloproteinases (MMP-2, MMP-3, MMP-9 and MMP-13) in patients with ulcers as a complication of type 2 diabetes.

Introduction: Impaired chronic wound healing is a great challenge for modern medicine. This process causes ulceration especially in the course of diseases such as type II diabetes mellitus. Aim: This study assesses the concentration of selected matrix metalloproteinases in the example of metalloproteinase 2, 3, 9, 13 in patients with impaired healing of chronic wounds as a complication of type 2 diabetes. Material and methods: Nineteen people took part in the assessment of wound healing in patients with type 2 diabetes. The control group consisted of 21 healthy people. In the blood serum the concentration of MMP-2, MMP-3, MMP-9 and MMP-13 was determined. Results: The concentrations of MMP-2 and MMP-3 in the group of patients with ulcers were significantly higher (61% and 84% accordingly) compared to those in the control group without chronic wounds. No statistically significant differences in MMP-9 and MMP-13 concentrations were observed between the study and control groups. Conclusions: The increase in MMP-2 concentration, which is particularly active in the degradation of type IV collagen, which is the main component of the basal membranes, in patients with type 2 diabetes may impede and delay the healing of chronic wounds and thus contribute to the intensification of vascular complications. In turn, the increase in MMP-3 concentration, which plays a significant role in vascular diseases, in patients with type 2 diabetes may lead to intensification of atherosclerotic changes involving the arteries of the lower extremities and ulceration.

Mental Resilience, Mood, and Quality of Life in Young Adults with Self-Reported Impaired Wound Healing.

The purpose of this study was to evaluate the impact of self-reported impaired wound healing on quality of life, wellbeing, and mood. It was hypothesized that individuals with impaired wound healing report significantly poorer mood compared to healthy controls. An online survey was conducted among 2173 Dutch young adults (18-30 years old) to investigate mood, neuroticism, and mental resilience. Participants were allocated to a healthy control group (N = 1728) or impaired wound healing groups comprising a wound infection group (WI, N = 76), a slow-healing wounds group (SHW, N = 272), and a group that experienced both WI and SHW (the COMBI group, N = 97). The Kruskal-Wallis test was used to compare outcomes the groups. Compared to the healthy control group, the SHW and COMBI groups, but not the WI group, reported significantly poorer mood, increased neuroticism, reduced mental resilience, and reduced quality of life. An analysis evaluating sex differences found that negative effects on stress, mental resilience, and neuroticism were significantly more pronounced among women than among men. In conclusion, self-reported impaired wound healing is associated with poorer mood and reduced quality of life. To improve future wound care, these findings advocate for an interdisciplinary approach taking into account mood effects accompanying having impaired wound healing.

Clinically relevant experimental rodent models of diabetic foot ulcer.

Chronic wounds are a substantial clinical problem in diabetes and nearly 6% of diabetics suffer from foot disease including ulceration, infection, and tissue necrosis. Wound healing in diabetes is impaired and delayed and is augmented by diabetic complications. Wound healing involves complex cellular, molecular, and biochemical processes and animal models are the most suitable prototype to investigate and understand the underlying pathological changes in the process of wound healing. Animal models are also useful in evaluating the safety and efficacy of newer therapeutic agents and improving the clinical approaches for human patients with chronic ulcers. The wound healing strategies get more complicated in the presence of diabetes and its associated complication. Despite the advancement in methods of wound healing, the healing of the chronic diabetic foot ulcer (DFU) remains an important clinical problem resulting in costly and prolonged treatment and poses a risk for major amputation. Saying that it is important to elucidate the newer therapeutic targets and strategies via an in-depth understanding of the complicated cascade of the chronic DFU. A major challenge in translating lab findings to clinics is the lack of an optimal preclinical model capable of properly recapitulating human wounds. Both small and large animal models of wound healing involving rodents, rabbits, and pigs have been discussed. Mouse and rats as small animal models and pig as large animal models have been discussed in association with the diabetic wound but there are advantages and limitations for each model. In this review, we critically reviewed the pros and cons of experimental models of diabetic wound healing with a focus on type II diabetes rodent models.

Verbascoside Protects Gingival Cells against High Glucose-Induced Oxidative Stress via PKC/HMGB1/RAGE/NFκB Pathway.

Impaired wound healing often occurs in patients with diabetes and causes great inconvenience to them. Aside from the presence of prolonged inflammation, the accumulation of oxidative stress is also implicated in the delayed wound healing. In the present study, we tested the effect of verbascoside, a caffeoyl phenylethanoid glycoside, on the improvement of cell viability and wound healing capacity of gingival epithelial cells under high glucose condition. We showed that verbascoside attenuated the high glucose-induced cytotoxicity and impaired healing, which may be associated with the downregulation of oxidative stress. Our results demonstrated that verbascoside increased the activity of the antioxidant enzyme SOD and reduced the oxidative stress indicator, 8-OHdG, as well as apoptosis. Moreover, verbascoside upregulated the PGC1-α and NRF1 expression and promoted mitochondrial biogenesis, which was mediated by suppression of PKC/HMGB1/RAGE/NFκB signaling. Likewise, we showed the inhibitory effect of verbascoside on oxidative stress was via repression of PKC/HMGB1/RAGE/NFκB activation. Also, our data suggested that the PKC-mediated oxidative stress may lead to the elevated production of inflammatory cytokines, IL-6 and IL-1ß. Collectively, we demonstrated that verbascoside may be beneficial to ameliorate impaired oral wound healing for diabetic patients.

Development of stabilized dual growth factor-loaded hyaluronate collagen dressing matrix.

Patients with diabetes experience impaired growth factor production such as epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), and they are reportedly involved in wound healing processes. Here, we report dual growth factor-loaded hyaluronate collagen dressing (Dual-HCD) matrix, using different ratios of the concentration of stabilized growth factors-stabilized-EGF (S-EGF) and stabilized-bFGF (S-bFGF). At first, the optimal concentration ratio of S-EGF to S-bFGF in the Dual-HCD matrix is determined to be 1:2 in type I diabetic mice. This Dual-HCD matrix does not cause cytotoxicity and can be used in vivo. The wound-healing effect of this matrix is confirmed in type II diabetic mice. Dual HCD enhances angiogenesis which promotes wound healing and thus, it shows a significantly greater synergistic effect than the HCD matrix loaded with a single growth factor. Overall, we conclude that the Dual-HCD matrix represents an effective therapeutic agent for impaired diabetic wound healing.

Effects of Vitamin and Amino Acid-Enriched Hyaluronic Acid Gel on the Healing of Oral Mucosa: In Vivo and In Vitro Study.

Background and Objectives: Wound healing is a dynamic process that can be compromised in patients with chronic and metabolic conditions or unhealthy lifestyles. Numerous medical substances designed for topical use, charged with compounds that promote the healing process, have been developed to improve wound healing, especially in compromised subjects. The present study aimed to extend our understanding of the in vivo effects of a hyaluronic acid gel charged with amino acids (HAplus gel, Aminogam gel® Errekappa Euroterapici spa, Milan, Italy) and study the in vitro effects of the same gel charged with additional substances in an attempt to optimize its formulation. Materials and Methods: In a randomized controlled split-mouth clinical and histological trial, HAplus gel was tested on the gingival tissue of the lower third molar post-extraction socket. The gingiva was collected at the time of extraction (T0) and ten days after the extraction (T1) to be histologically analyzed. During the second stage of the study, culture media with HAplus gel and vitamin C and E at different concentrations (TEST) were tested on human gingival fibroblasts and compared to the HAplus-enriched medium (HA-Control). Results: Histological and immunohistochemical analysis of collected gingiva showed higher microvascular density and collagen fibers organized in closely packed and well-oriented bundles in sites treated with HAplus gel. In the in vitro study, all TEST groups showed an increased viability from 24 h to 48 h. After 24 h, the viability percentage in all experimental groups was below 100% of the HA-Control, demonstrating a mild toxicity. After 48 h from seeding, the TEST groups' viability grew significantly compared to HA-Control. Conclusions: These encouraging preliminary results suggest that the use of HAplus gel enriched with vitamins C and E may be beneficial in patients with conditions that impair soft tissue healing.

Safety and clinical efficacy of the secretome of stressed peripheral blood mononuclear cells in patients with diabetic foot ulcer-study protocol of the randomized, placebo-controlled, double-blind, multicenter, international phase II clinical trial MARSYAS II.

BACKGROUND: Diabetes and its sequelae such as diabetic foot ulcer are rising health hazards not only in western countries but all over the world. Effective, yet safe treatments are desperately sought for by physicians, healthcare providers, and of course patients. METHODS/DESIGN: APOSEC, a novel, innovative drug, is tested in the phase I/II study MARSYAS II, where its efficacy to promote healing of diabetic foot ulcers will be determined. To this end, the cell-free secretome of peripheral blood mononuclear cells (APOSEC) blended with a hydrogel will be applied topically three times weekly for 4 weeks. APOSEC is predominantly effective in hypoxia-induced tissue damages by modulating the immune system and enhancing angiogenesis, whereby its anti-microbial ability and neuro-regenerative capacity will exert further positive effects. In total, 132 patients will be enrolled in the multicenter, randomized, double-blind, placebo-controlled, parallel group, dose-ranging phase I/II study and treated with APOSEC at three dose levels or placebo for 4 weeks, followed by an 8-week follow-up period to evaluate safety and efficacy of the drug. Wound area reduction after 4 weeks of treatment will serve as the primary endpoint. CONCLUSION: We consider our study protocol to be suitable to test topically administered APOSEC in patients suffering from diabetic foot ulcers in a clinical phase I/II trial. TRIAL REGISTRATION: EudraCT 2018-001653-27 . Registered on 30 July 2019. ClinicalTrials.gov NCT04277598 . Registered on 20 February 2020. TITLE: "A randomized, placebo-controlled, double-blind study to evaluate safety and dose-dependent clinical efficacy of APO-2 at three different doses in patients with diabetic foot ulcer (MARSYAS II)".

Preoperative skin antisepsis using chlorhexidine may reduce surgical wound infections in lower limb trauma surgery when compared to povidone-iodine - a prospective randomized trial.

BACKGROUND: For the prevention of surgical wound infections (SSIs), local microorganism counts can be lowered by skin antisepsis prior to surgical incisions. Until now, it has been unclear which antiseptic is the most effective. METHODS: This prospective randomized trial analyzed the efficacy of 2 frequently used agents in the reduction of postoperative wound complication rates after aseptic trauma surgery on the lower leg and foot. In the study, 279 consecutive participants were randomized; 112 received surgical skin preparations using chlorhexidine (CHX) (ChloraPrep; Becton Dickinson, Franklin Lakes, NJ) and 167 received preparations with povidone-iodine (PVP-I) (Braunoderm; B. Braun Melsungen AG, Melsungen, Germany). Primary clinical endpoints were SSIs and wound healing disorders (WHDs) within 6 months after surgery. Secondary outcome variables included demographic and perioperative risk factors for SSIs. RESULTS: Rates of WHDs and SSIs were significantly higher in the PVP-I treatment group, which experienced 9 SSIs and 12 WHDs (n = 21; 12.6%), compared to the CHX treatment group, which had 2 SSIs and 3 WHDs (n = 5; 4.5%) (P = .022). Perioperative risk factors for WHDs were obesity and longer surgery time, whereas SSIs were increased in participants with cardiovascular diseases and suction drainage. Logistic regression analysis showed that the odds of complications of wound healing were 3.5 times higher for PVP-I than for CHX (odds ratio = 3.5; 95% confidence interval, 1.1-11.2; P = .032). CONCLUSIONS: Preoperative skin antisepsis for trauma surgery of the lower leg and foot using CHX led to significantly fewer complications of wound healing when compared to PVP-I.

The Dynamics of the Skin's Immune System.

The skin is a complex organ that has devised numerous strategies, such as physical, chemical, and microbiological barriers, to protect the host from external insults. In addition, the skin contains an intricate network of immune cells resident to the tissue, crucial for host defense as well as tissue homeostasis. In the event of an insult, the skin-resident immune cells are crucial not only for prevention of infection but also for tissue reconstruction. Deregulation of immune responses often leads to impaired healing and poor tissue restoration and function. In this review, we will discuss the defensive components of the skin and focus on the function of skin-resident immune cells in homeostasis and their role in wound healing.

"Dry mouth" and "Flammer" syndromes-neglected risks in adolescents and new concepts by predictive, preventive and personalised approach.

BACKGROUND: "Dry mouth" syndrome (chronic hyposalivation) can be caused by a number of pathophysiological conditions such as acute and chronic stress exposure, abnormal body weight (both too high and too low ones), eating disorders (such as anorexia nervosa), metabolic syndrome(s), Sjögren's and Sicca syndromes, drugs and head/neck radiotherapy application. In turn, the chronic hyposalivation as a suboptimal health condition significantly reduces quality of life, may indicate a systemic dehydration, provokes and contributes to a number of pathologies such as a strongly compromised protection of the oral cavity, chronic infections and inflammatory processes, periodontitis, voice and digestive disorders. Consequently, "dry mouth" syndrome might be extremely useful as an indicator for an in-depth diagnostics of both-co-existing and snowballing health-threating conditions. However, predictive diagnostics, targeted prevention and personalisation of treatments are evidently underdeveloped for individuals at high risk suffering from the "dry mouth" syndrome. WORKING HYPOTHESIS AND METHODOLOGY: In the current study, we have hypothesised that individuals demonstrating "Flammer syndrome" (FS) phenotype may suffer from the "dry mouth" syndrome more frequently, due to disturbed microcirculation, psychological factors (obsessional personality/perfectionism), and diminished feeling of thirst with consequently insufficient daily liquid intake potentially resulting in the systemic dehydration with individually pronounced level of severity. If confirmed, FS phenotyping linked to the chronic hyposalivation might be predictive for individuals at risk identified by innovative screening programmes. To verify the working hypothesis, healthy individuals (negative control group) versus individuals with evident hyposalivation as well as patients diagnosed with periodontitis (positive control group) observed and treated at the dental clinic were investigated. The degree to which an individual is affected by hyposalivation was determined by the Bother xerostomia Index utilising a questionnaire of 10 issue-specific items and monitoring of a typically matt roof of the mouth in dental practice. An extent to which individuals included in the study are the carriers of the FS phenotype was estimated by the specialised 15-item questionnaire. RESULTS AND CONCLUSIONS: For both-the target group (hyposalivation) and positive control group (periodontitis)-FS phenotype was demonstrated to be more specific compared to the disease-free (negative control) group. Moreover, self-reports provided by interviewed adolescents of the target group frequently recorded remarkable discomfort related to "dry mouth" syndrome, acute and chronic otorhinolaryngological infections and even delayed wound healing. Further, interviewed adolescents do worry about the symptoms which might be indicative for potential diseases; they are also amazed that too little attention is currently paid to the issue by caregivers. In conclusion, FS questionnaire linked to the "dry mouth" syndrome is strongly recommended for application in primary healthcare. Consequently, targeted preventive measures can be triggered early in life. For example, traditional, complementary and alternative medicine demonstrates positive therapeutic effects in individuals suffering from xerostomia. For in-depth diagnostics, epi/genetic regulations involved into pathophysiologic mechanisms of hyposalivation in FS-affected individuals should be thoroughly investigated at molecular level. Identified biomarker panels might be of great clinical utility for predictive diagnostics and patient stratification that, further, would sufficiently improve personalised care to the patient.

Vitamin D ameliorates impaired wound healing in streptozotocin-induced diabetic mice by suppressing NF-κB-mediated inflammatory genes.

Diabetic wounds are characterized by delayed wound healing due to persistent inflammation and excessive production of reactive oxygen species. Vitamin D, which is well acknowledged to enhance intestinal calcium absorption and increase in plasma calcium level, has recently been shown to display beneficial effects in various vascular diseases by promoting angiogenesis and inhibiting inflammatory responses. However, the role of Vitamin D in diabetic wound healing is still unclear. In the present study, we investigated the role of Vitamin D in cutaneous wound healing in streptozotocin (STZ)-induced diabetic mice. Four weeks after injection of STZ, a full thickness excisional wound was created with a 6-mm diameter sterile biopsy punch on the dorsum of the mice. Vitamin D was given consecutively for 14 days by intraperitoneal injection. Vitamin D supplementation significantly accelerated wound healing in diabetic mice and improved the healing quality as assessed by measuring the wound closure rate and histomorphometric analyses. By monitoring the level of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL) 6 (IL-6), IL-1ß) in the wounds, reduced inflammatory response was found in VD treatment group. Furthermore, nuclear factor κB (NF-κB) pathway was found to be involved in the process of diabetic wound healing by assessing the relative proteins in diabetic wounds. Vitamin D supplementation obviously suppressed NF-κB pathway activation. These results demonstrated that Vitamin D improves impaired wound healing in STZ-induced diabetic mice through suppressing NF-κB-mediated inflammatory gene expression.