Mechanical Stress Changes the Complex Interplay Between HO-1, Inflammation and Fibrosis, During Excisional Wound Repair

Mechanical stress following surgery or injury can promote pathological wound healing and fibrosis, and lead to functional loss and esthetic problems. Splinted excisional wounds can be used as model for inducing mechanical stress. The cytoprotective enzyme heme oxygenase-1 (HO-1) is thought to orchestrate the defense against inflammatory and oxidative insults that drive fibrosis. Here, we investigated the activation of the HO-1 system in a splinted and non-splinted full thickness excisional wound model using HO-1-luc transgenic mice. Effects of splinting on wound closure, HO-1 promoter activity, and markers of inflammation and fibrosis were assessed. After seven days, splinted wounds were more than 3 times larger than non-splinted wounds, demonstrating a delay in wound closure. HO-1 promoter activity rapidly decreased following removal of the (epi)dermis, but was induced in both splinted and non-splinted wounds during skin repair. Splinting induced more HO-1 gene expression in 7-day wounds; however, HO-1 protein expression remained lower in the epidermis, likely due to lower number of keratinocytes in the re-epithelialization tissue. Higher numbers of F4/80-positive macrophages, αSMA-positive myofibroblasts, and increased levels of the inflammatory genes IL-1β, TNF-α, and COX-2 were present in 7-day splinted wounds. Surprisingly, mRNA expression of newly-formed collagen (type III) was lower in 7-day wounds after splinting; whereas, VEGF and MMP-9 were increased. Summarizing, these data demonstrate that splinting delays cutaneous wound closure and HO-1 protein induction. The pro-inflammatory environment following splinting, may facilitate higher myofibroblast numbers and increases the risk of fibrosis and scar formation. Therefore, inducing HO-1 activity against mechanical stress-induced inflammation and fibrosis may be an interesting strategy to prevent negative effects of surgery on growth and function in patients with orofacial clefts or in burns patients

Sweet Relief:Determining the Antimicrobial Activity of Medical Grade Honey Against Vaginal Isolates of Candida albicans

Contains fulltext : 215323.pdf (publisher's version ) (Open Access)Recurrent vulvovaginal candidiasis (RVVC) is predicted to increase to almost 158 million cases annually by 2030. Extensive self-diagnosis and easily accessible over-the-counter (OTC) fungistatic drugs contribute to antifungal-resistance, illustrating the need for novel therapies. Honey possesses multiple antimicrobial mechanisms, and there is no antimicrobial resistance towards honey reported. We evaluated the susceptibility of five clinical isolates of Candida albicans and a control strain to regular honey and a medical grade honey (MGH) gel formulation (L-Mesitran, containing 40% honey and vitamins C and E) using an adapted version of the EUCAST protocol at pH 5.2, 4.6, and 4.0. 40% regular honey did not kill or inhibit C. albicans. In contrast, the minimal inhibitory concentration (MIC) of L-Mesitran was 25%-50%, while fungicidal effects occurred at a 50% concentration (MBC) of the MGH formulation, except for one strain which was not killed at pH 4.0. Overall, pH had little effect on antimicrobial activity. MGH formulation L-Mesitran has antimicrobial activity against C. albicans over a relevant pH range. The vitamin supplements or other components of L-Mesitran may enhance the antifungal activity of the honey. This study supports performing clinical trials for conditions, such as RVVC, to find an alternative to available OTC fungistatic drugs

Medical grade honey : hope for wounded white rhinos

South Africa is home to some of the world’s most endangered wildlife, with the White rhinoceros (Cerathotherium simum) among its most threatened species due to its highly sought-after horn. Since the reproduction number is below the mortality rate, there is a decrease in rhinos year over year, urgently requiring changes and saving the survivors. In this study, the efficacy of medical grade honey (MGH) for wound care in rhinos was investigated. We presented a case series of seven rhinos with wounds of different etiologies, including gunshots and poaching. Four wounds were around the horns and three on the limbs. It was a challenge to take care and followup the wounds of these wild animals in their natural habitat. A well-balanced decision between the need of treatment and risk of immobilization is constantly evaluated. In the presented cases, MGH proved a novel tool with minimal intervention and maximal effectiveness. With the severity of the wounds taken into consideration, there was a rapid healing in all cases, while infection resolved when present. MGH creates a moist and antiinflammatory wound environment, while promoting almost all aspects in the wound healing processes, such as autolytic debridement, angiogenesis and re-epithelialization. The efficacy of MGH has constantly been confirmed in other cases and literature as well. MGH forms a potent therapy for treating wounded rhinos, independent of the severity of the wound. The strong antimicrobial and healing properties make it an easy and versatile product that can be used in all kinds of wounds.https://www.elsevier.com/locate/vaspm2022Companion Animal Clinical Studie

Revolutionizing non-conventional wound healing using honey by simultaneously targeting multiple molecular mechanisms

Hospital-acquired infections and treatment-related wound complications constitute a tremendous burden for the health care system, particularly given the serious increase in multidrug resistant pathogens. Imagine that a large part of nosocomial infections can be prevented using a simple treatment. In this respect, honey is used mainly in topical cutaneous wound care because of its potent broad-spectrum antibacterial and wound healing activities. However, therapeutic use outside this scope has been limited. The current review provides an in-depth view of studies using honey outside the conventional wound care indications. Non-conventional routes of honey appli-cation include subcutaneous, intra-socket, abdominal, and oral administration in novel indications, such as post colon surgery, mucositis, and tooth extraction. Honey consistently demonstrates beneficial therapeutic activities in these novel applications, orchestrating antimicrobial and prophylactic activity, reducing inflammation and wound dehiscence, and inducing healing, epithelialization, and analgesic activity. Several molecular mechanisms are responsible for these beneficial clinical effects of honey during the course of wound healing. Pro-inflammatory effects of honey, such as induction of iNOS, IL-1??, and COX-2, are mediated by TLR4 signaling. In contrast, honey???s anti-inflammatory actions and flavonoids induce anti-inflammatory and antioxidant path-ways by inducing NRF2 target genes, including HO-1 and PRDX1. The molecular and biochemical pathways activated by honey during the different phases of wound healing are also discussed in more detail in this review. Variation between different honey origins exists, and therefore standardized medical-grade honey may offer an optimized and safe treatment. Honey is a valuable alternative to conventional antimicrobial and anti-inflammatory therapies that can strongly reduce nosocomial infections

Efficacy of a medical grade honey formulation (L-Mesitran) in comparison with fluconazole in the treatment of women with recurrent vulvovaginal candidiasis:protocol for a randomised controlled trial (HONEY STUDY)

Introduction Recurrent vulvovaginal candidiasis (RVVC) affects up to 9% of women worldwide. This amount is expected to increase due to lifestyle changes, increased fungal resistance and biofilm formation. Treatment options are limited and in 57% of the cases, relapses occur within 12 months after starting fluconazole therapy (golden standard). The pathogenesis of RVVC is multifactorial and includes fungal biology, the vaginal microenvironment and the immune system. Fluconazole is antimicrobial and effective in inducing short-term remission but a long-term cure is hard to achieve. Medical grade honey (MGH) has antimicrobial, protective, antioxidative and immunomodulatory activity and may therefore be a good alternative treatment. This study aims to investigate the clinical cure rate and long-term efficacy of MGH compared with fluconazole in patients with RVVC.Methods and analysis This study is a multicentre, randomised controlled trial (Maastricht University Medical Centre+ and Zuyderland Medical Centre). A total of 252 eligible women will be randomly assigned to the fluconazole group (control) or the MGH group (L-Mesitran, treatment). The primary objective is to investigate the mycological cure rate after 1 month assessed through a vaginal culture. Secondary objectives are the clinical cure rate regarding symptoms, the prophylactic activity after 6 months of maintenance therapy and the number of relapses within 12 months. Moreover, information about side effects, discomfort and quality of life will be collected with the use of questionnaires.Ethics and dissemination Ethical approval from the Medical Ethics Review Committee of the academic hospital Maastricht/University Maastricht has been obtained (NL 73974.068.21, V.7 on 8 February 2022). Additional approval was obtained from the Ethics Committee of the Zuyderland Medical Centre Heerlen (Z2021141 on 4 March 2022). The first patient was randomised on 22 August 2022. Results will be made available to researchers and healthcare professionals via conferences, meetings and peer-reviewed international publications.Trial registration number NCT05367089