Vitamin A resolves lineage plasticity to orchestrate stem cell lineage choices.

Lineage plasticity-a state of dual fate expression-is required to release stem cells from their niche constraints and redirect them to tissue compartments where they are most needed. In this work, we found that without resolving lineage plasticity, skin stem cells cannot effectively generate each lineage in vitro nor regrow hair and repair wounded epidermis in vivo. A small-molecule screen unearthed retinoic acid as a critical regulator. Combining high-throughput approaches, cell culture, and in vivo mouse genetics, we dissected its roles in tissue regeneration. We found that retinoic acid is made locally in hair follicle stem cell niches, where its levels determine identity and usage. Our findings have therapeutic implications for hair growth as well as chronic wounds and cancers, where lineage plasticity is unresolved.

Small Molecules Accelerate Skin Wound Healing: Shikonin Efficacy and Mechanism of Action in Mice / Las Moléculas Pequeñas Aceleran la Curación de Heridas en la Piel: Eficacia de Shikonin y Mecanismo de Acción en Ratones

SUMMARY: The objective of this study was to investigate the therapeutic wound healing potential and molecular mechanisms of shikonin as small molecules in vitro. A mouse burn model was used to explore the potential therapeutic effect of shikonin; we traced proliferating cells in vivo to locate the active area of skin cell proliferation. Through the results of conventional pathological staining, we found that shikonin has a good effect on the treatment of burned skin and promoted the normal distribution of skin keratin at the damaged site. At the same time, shikonin also promoted the proliferation of skin cells at the damaged site; importantly, we found a significant increase in the number of fibroblasts at the damaged site treated with shikonin. Most importantly, shikonin promotes fibroblasts to repair skin wounds by regulating the PI3K/AKT signaling pathway. This study shows that shikonin can effectively promote the proliferation of skin cell, and local injection of fibroblasts in burned skin can play a certain therapeutic role.

El objetivo de este trabajo fue investigar el potencial terapéutico de cicatrización de heridas y los mecanismos moleculares de la shikonina como moléculas pequeñas in vitro. Se utilizó un modelo de quemaduras en ratones para explorar el posible efecto terapéutico de la shikonina; Rastreamos las células en proliferación in vivo para localizar el área activa de proliferación de células de la piel. A través de los resultados de la tinción para patología convencional, encontramos que la shikonina tiene un buen efecto en el tratamiento de la piel quemada y promueve la distribución normal de la queratina de la piel en el sitio dañado. Al mismo tiempo, la shikonina también promovió la proliferación de células de la piel en el sitio dañado. Es importante destacar que encontramos un aumento significativo en la cantidad de fibroblastos en el sitio dañado tratado con shikonina. Lo más importante es que la shikonina promueve la función reparadora de fibroblastos en las heridas de la piel regulando la vía de señalización PI3K/ AKT. Este estudio muestra que la shikonina puede promover eficazmente la proliferación de células de la piel y que la inyección local de fibroblastos en la piel quemada puede desempeñar un cierto papel terapéutico.

The Neuropeptide α-Melanocyte-Stimulating Hormone Prevents Persistent Corneal Edema following Injury.

Corneal endothelial cells (CEnCs) regulate corneal hydration and maintain tissue transparency through their barrier and pump function. However, these cells exhibit limited regenerative capacity following injury. Currently, corneal transplantation is the only established therapy for restoring endothelial function, and there are no pharmacologic interventions available for restoring endothelial function. This study investigated the efficacy of the neuropeptide α-melanocyte-stimulating hormone (α-MSH) in promoting endothelial regeneration during the critical window between ocular injury and the onset of endothelial decompensation using an established murine model of injury using transcorneal freezing. Local administration of α-MSH following injury prevented corneal edema and opacity, reduced leukocyte infiltration, and limited CEnC apoptosis while promoting their proliferation. These results suggest that α-MSH has a proregenerative and cytoprotective function on CEnCs and shows promise as a therapy for the prevention and management of corneal endothelial dysfunction.

Propriedades Químicas e Farmacológicas do Gênero Copaifera no Tratamento de Lesões/feridas: Revisão Integrativa / Chemical and Pharmacological Properties of the Genus Copaifera in the Treatment of Injuries/wounds: Integrative Review / Propiedades Químicas y Farmacológicas del Género Copaifera en el Tratamiento de Lesiones/heridas: Revisión Integradora

Objetivo:Identificar propriedades químicas e farmacológicas do gênero Copaifera no tratamento de lesões e feridas. Método: Revisão integrativa da literatura realizada nas bases de dados LILACS, MEDLINE, PubMed, Taylor & Francis e Scopus, em janeiro de 2022, por meio da estratégia de busca: "Chemical Properties" AND "Copaifera" AND "Wounds and Injuries" e "Pharmacology" AND "Copaifera" AND "Wounds and Injuries". Foram incluídos artigos originais, de texto completo, identificados de acordo nível de evidência, redigidos em português, inglês ou espanhol. Resultados: Na busca primária foram encontrados 261 artigos. Após a seleção sistematizada, 12 estudos foram selecionados para análise qualitativa. Espécies do gênero Copaifera apresentam propriedades farmacológicas favoráveis ao tratamento de feridas: controle da dor inflamatória, diminuição da reação inflamatória, reepitelização e reparo tecidual, angiogênese, retração da ferida e remodelagem de cicatrizes. Dentre as propriedades químicas associadas ao tratamento de lesões, destacam-se presença de compostos bioativos: diterpenos, 3-hidroxi-copálico, sesquiterpenos, éster kolavic-15-metílico. Entre os diterpenos testados, o caurenoico e os ácidos copálicos mostraram atividades hemolíticas significativas. Apenas o ácido copálico e o ácido hardwíckiico inibiram a produção de óxido nítrico em macrófagos ativados por lipopolissacarídeos. Conclusão: As plantas do gênero Copaifera apresentam propriedades químicas e farmacológicas favoráveis ao tratamento de lesões e feridas

Objective:To identify chemical and pharmacological properties of Copaifera in the treatment of injuries and wounds. Method: Integrative literature review conducted in the LILACS, MEDLINE, PubMed, Taylor & Francis and Scopus databases in January 2022, using the search strategy: "Chemical Properties" AND "Copaifera" AND "Wounds and Injuries" and "Pharmacology" AND "Copaifera" AND "Wounds and Injuries." Original articles, full text, identified according to level of evidence, written in Portuguese, English or Spanish, were included. Results: In the primary search 261 articles were found. After systematized selection, 12 studies were selected for qualitative analysis. Species of the genus Copaifera have pharmacological properties favorable for wound treatment: control of inflammatory pain, reduction of inflammatory reaction, tissue reepithelialization and repair, angiogenesis, wound retraction and scar remodeling. Among the chemical properties associated with the treatment of injuries, the presence of bioactive compounds stand out: diterpenes, 3-hydroxy-copalic, sesquiterpenes, kolavic-15-methyl ester. Among the tested diterpenes, kaurenoic and copalic acids showed significant hemolytic activities. Only copalic acid and hardwickiic acid inhibited nitric oxide production in lipopolysaccharide-activated macrophages. Conclusion: Plants of the genus Copaifera have chemical and pharmacological properties favorable for the treatment of injuries and wounds.

Objetivo:Identificar las propiedades químicas y farmacológicas del género Copaifera en el tratamiento de lesiones y heridas. Método: Revisión integradora de la literatura realizada en las bases de datos LILACS, MEDLINE, PubMed, Taylor & Francis y Scopus, en enero de 2022, mediante la estrategia de búsqueda: "Chemical Properties" AND "Copaifera" AND "Wounds and Injuries" e "Pharmacology" AND "Copaifera" AND "Wounds and Injuries". Se incluyeron artículos originales, a texto completo, identificados según el nivel de evidencia, escritos en portugués, inglés o español. Resultados: En la búsqueda primaria se encontraron 261 artículos. Tras una selección sistematizada, se seleccionaron 12 estudios para el análisis cualitativo. Las especies del género Copaifera presentan propiedades farmacológicas favorables para el tratamiento de las enfermedades: control del dolor inflamatorio, disminución de la reacción inflamatoria, reepitelización y reparación tecidual, angiogénesis, retracción de la piel y remodelación de las cicatrices. Entre las propiedades químicas asociadas al tratamiento de las lesiones, destaca la presencia de compuestos bioactivos: diterpenos, 3-hidroxicopálico, sesquiterpenos, éster kolavico-15-metilo. Entre los diterpenos probados, los ácidos kaurenoico y copálico mostraron actividades hemolíticas significativas. Sólo el ácido copálico y el ácido hardwickiico inhibieron la producción de óxido nítrico en macrófagos activados por lipopolisacáridos. Conclusión: Las plantas del género Copaifera presentan propiedades químicas y farmacológicas favorables para el tratamiento de lesiones y heridas.

Highlighting the Benefits of AlpaWash in Wound Care: Case Reports in Small Animals.

Several studies have reported the potential of utilizing natural extracts in wound care, emphasizing those with anti-inflammatory and antimicrobial properties. In veterinary medicine, dermal-lesion treatment can be very challenging considering the patient's compliance and awareness of their condition. In this article, six veterinary case reports have been presented to elucidate the advantages of AlpaWash, a topical application utilized in combination with the prescribed medications of the patients, for the purpose of addressing the process of wound healing in three cats and three dogs. All animals were admitted to the veterinary clinic and treated under the supervision of a veterinarian. The cats and dogs were rescued from streets by people who lived in the neighborhood of Cão Bento´s Veterinary. They were admitted for the purpose of receiving medical care due to recent minor injuries or wounds due to a pet fight, preexisting condition, or accident. A veterinarian performed the anamnesis and monitored the animals during the period of treatment with AlpaWash. In each case report, the veterinarian observed significant improvement in the wound closures, and lesions healed within a couple of weeks to a couple of months depending on the case. The outcomes demonstrate the benefits of AlpaWash topical application and suggest that AlpaWash may be an alternative vehicle for compounded preparations in wound management.

Pterostilbene accelerates wound healing response in diabetic mice through Nrf2 regulation.

Pterostilbene (PTS), known for its diverse beneficial effects via Nuclear factor erythroid-2 related factor (Nrf2) activation, holds potential for Diabetic Foot Ulcer (DFU) treatment. However, PTS-mediated Nrf2 regulation in diabetic wounds has yet to be elucidated. We used IC21 macrophage-conditioned media to simulate complex events that can influence the fibroblast phenotype using L929 cells during the wound healing process under a hyperglycemic microenvironment. We found that PTS attenuated fibroblast migration and alpha-smooth muscle actin (α-SMA) levels and hypoxia-inducible factor- 1 alpha (HIF1α). Furthermore, we demonstrated that wounds in diabetic mice characterized by impaired wound closure in a heightened inflammatory milieu, such as the NOD-like receptor P3 (NLRP3) and intercellular adhesion molecule 1 (ICAM1), and deficient Nrf2 response accompanying lowered Akt signaling and heme oxygenase1 (HO1) expression along with the impaired macrophage M2 marker CD206 expression, was rescued by administration of PTS. Such an elicited response was also compared favorably with the standard treatment using Regranex, a commercially available topical formulation for treating DFUs. Our findings suggest that PTS regulates Nrf2 in diabetic wounds, triggering a pro-wound healing response mediated by macrophages. This insight holds the potential for developing targeted therapies to heal chronic wounds, including DFUs.

Triazolothiadiazine derivative positively modulates CXCR4 signaling and improves diabetic wound healing.

Development of specific therapies that target and accelerate diabetic wound repair is an urgent need to alleviate pain and suffering and the huge socioeconomic burden of this debilitating disease. C-X-C Motif Chemokine Ligand 12 (CXCL12) also know an stromal cell-derived factor 1α (SDF-1α) is a chemokine that binds the CXC chemokine receptor type 4 (CXCR4) and activates downstream signaling resulting in recruitment of hematopoietic cells to locations of tissue injury and promotes tissue repair. In diabetes, low expression of CXCL12 correlates with impaired wound healing. Activation of CXCR4 receptor signaling with agonists or positive allosteric modulators (PAMs) provides a potential for small molecule therapeutic discovery and development. We recently reported high throughput screening and identification of the CXCR4 partial agonist UCUF-728, characterization of in vitro activity and reduced wound closure time in diabetic mice at 100 µM as a proof-of-concept study. We report here, the discovery of a second chemical scaffold demonstrating increased agonist potency and represented by thiadiazine derivative, UCUF-965. UCUF-965 is a potent partial agonist of ß-arrestin recruitment in CXCR4 receptor overexpressing cell line. Furthermore, UCUF-965 potentiates the CXCL12 maximal response in cAMP signaling pathway, activates CXCL12 stimulated migration in lymphoblast cells and modulates the levels of specific microRNA involved in the complex wound repair process, specifically in mouse fibroblasts. Our results indicate that UCUF-965 acts as a PAM agonist of the CXCR4 receptor. Furthermore, UCUF-965 enhanced angiogenesis markers and reduced wound healing time by 36% at 10.0 µM in diabetic mice models compared to untreated control.

Accelerated Wound Healing with a Diminutive Scar through Cocrystal Engineered Curcumin.

Pharmaceutical cocrystals ( Regulatory Classification of Pharmaceutical Co-Crystals Guidance for Industry; Food and Drug Administration, 2018) are crystalline solids produced through supramolecular chemistry to modulate the physicochemical properties of active pharmaceutical ingredients (APIs). Despite their extensive development in interdisciplinary sciences, this is a pioneering study on the efficacy of pharmaceutical cocrystals in wound healing and scar reducing. Curcumin-pyrogallol cocrystal (CUR-PYR) was accordingly cherry-picked since its superior physicochemical properties adequately compensate for limitative drawbacks of curcumin (CUR). CUR-PYR has been synthesized by a liquid-assisted grinding (LAG) method and characterized via FT-IR, DSC, and PXRD analyses. In vitro antibacterial study indicated that CUR-PYR cocrystal, CUR+PYR physical mixture (PM), and PYR are more effective against both Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria in comparison with CUR. In vitro results also demonstrated that the viability of HDF and NIH-3T3 cells treated with CUR-PYR were improved more than those received CUR which is attributed to the effect of PYR in the form of cocrystal. The wound healing process has been monitored through a 15 day in vivo experiment on 75 male rats stratified into six groups: five groups treated by CUR-PYR+Vaseline (CUR-PYR.ung), CUR+PYR+Vaseline (CUR+PYR.ung), CUR+Vaseline (CUR.ung), PYR+Vaseline (PYR.ung), and Vaseline (VAS) ointments and a negative control group of 0.9% sodium chloride solution (NS). It was revealed that the wounds under CUR-PYR.ung treatment closed by day 12 postsurgery, while the wounds in other groups failed to reach the complete closure end point until the end of the experiment. Surprisingly, a diminutive scar (3.89 ± 0.97% of initial wound size) was observed in the CUR-PYR.ung treated wounds by day 15 after injury, followed by corresponding values for PYR.ung (12.08 ± 2.75%), CUR+PYR.ung (13.89 ± 5.02%), CUR.ung (16.24 ± 6.39%), VAS (18.97 ± 6.89%), and NS (20.33 ± 5.77%). Besides, investigating histopathological parameters including inflammation, granulation tissue, re-epithelialization, and collagen deposition signified outstandingly higher ability of CUR-PYR cocrystal in wound healing than either of its two constituents separately or their simple PM. It was concluded that desired solubility of the prepared cocrystal was essentially responsible for accelerating wound closure and promoting tissue regeneration which yielded minimal scarring. This prototype research suggests a promising application of pharmaceutical cocrystals for the purpose of wound healing.

rhFGF-21 accelerates corneal epithelial wound healing through the attenuation of oxidative stress and inflammatory mediators in diabetic mice.

Diabetic keratopathy, commonly associated with a hyperactive inflammatory response, is one of the most common eye complications of diabetes. The peptide hormone fibroblast growth factor-21 (FGF-21) has been demonstrated to have anti-inflammatory and antioxidant properties. However, whether administration of recombinant human (rh) FGF-21 can potentially regulate diabetic keratopathy is still unknown. Therefore, in this work, we investigated the role of rhFGF-21 in the modulation of corneal epithelial wound healing, the inflammation response, and oxidative stress using type 1 diabetic mice and high glucose-treated human corneal epithelial cells. Our experimental results indicated that the application of rhFGF-21 contributed to the enhancement of epithelial wound healing. This treatment also led to advancements in tear production and reduction in corneal edema. Moreover, there was a notable reduction in the levels of proinflammatory cytokines such as TNF-α, IL-6, IL-1ß, MCP-1, IFN-γ, MMP-2, and MMP-9 in both diabetic mouse corneal epithelium and human corneal epithelial cells treated with high glucose. Furthermore, we found rhFGF-21 treatment inhibited reactive oxygen species production and increased levels of anti-inflammatory molecules IL-10 and SOD-1, which suggests that FGF-21 has a protective role in diabetic corneal epithelial healing by increasing the antioxidant capacity and reducing the release of inflammatory mediators and matrix metalloproteinases. Therefore, we propose that administration of FGF-21 may represent a potential treatment for diabetic keratopathy.

Prophylactic antibiotics has no benefit for outcome in clean myringoplasty-A register-based cohort study from SwedEar.

OBJECTIVES: To investigate if prophylactic antibiotics (PA) in conjunction with myringoplasty of clean and uninfected ears entails a reduction of postoperative infections within 6 weeks after surgery, and whether it affects the healing rate of the tympanic membrane (TM) at follow-up, 6-24 months after surgery. DESIGN: A retrospective cohort study of prospectively collected data. SETTING: Data extracted from The Swedish Quality Register for Ear Surgery (SwedEar), the years 2013-2019. PARTICIPANTS: All patients in SwedEar with a registered clean conventional myringoplasty (tympanoplasty type I) including a follow-up visit. MAIN OUTCOME MEASURES: The effect of PA use on TM healing rate at follow-up and postoperative infection within 6 weeks of surgery. RESULTS: In the study group (n = 1665) 86.2% had a healed TM at follow-up. There was no significant difference between the groups that had PA administered (87.2%) or not (86.1%). A total of 8.0% had a postoperative infection within 6 weeks. Postoperative infection occurred in 10.2% of the group that received PA (n = 187) compared with 7.7% of the group that did not receive PA. However, this difference was not statistically significant. Postoperative infection within 6 weeks significantly lowered the frequency of healed TMs. CONCLUSION: PA administered during clean conventional myringoplasty does not improve the chance of having a healed TM at follow up, nor decrease the risk of having a postoperative infection within 6 weeks after surgery.

Corneal regeneration strategies: From stem cell therapy to tissue engineered stem cell scaffolds.

Corneal epithelial defects and excessive wound healing might lead to severe complications. As stem cells can self-renew infinitely, they are a promising solution for regenerating the corneal epithelium and treating severe corneal epithelial injury. The chemical and biophysical properties of biological scaffolds, such as the amniotic membrane, fibrin, and hydrogels, can provide the necessary signals for stem cell proliferation and differentiation. Multiple researchers have conducted investigations on these scaffolds and evaluated them as potential therapeutic interventions for corneal disorders. These studies have identified various inherent benefits and drawbacks associated with these scaffolds. In this study, we provided a comprehensive overview of the history and use of various stem cells in corneal repair. We mainly discussed biological scaffolds that are used in stem cell transplantation and innovative materials that are under investigation.

Sodium alginate/polycaprolactone co-axial wet-spun microfibers modified with N-carboxymethyl chitosan and the peptide AAPV for Staphylococcus aureus and human neutrophil elastase inhibition in potential chronic wound scenarios.

In chronic wound (CW) scenarios, Staphylococcus aureus-induced infections are very prevalent. This leads to abnormal inflammatory processes, in which proteolytic enzymes, such as human neutrophil elastase (HNE), become highly expressed. Alanine-Alanine-Proline-Valine (AAPV) is an antimicrobial tetrapeptide capable of suppressing the HNE activity, restoring its expression to standard rates. Here, we proposed the incorporation of the peptide AAPV within an innovative co-axial drug delivery system, in which the peptide liberation was controlled by N-carboxymethyl chitosan (NCMC) solubilization, a pH-sensitive antimicrobial polymer effective against Staphylococcus aureus. The microfibers' core was composed of polycaprolactone (PCL), a mechanically resilient polymer, and AAPV, while the shell was made of the highly hydrated and absorbent sodium alginate (SA) and NCMC, responsive to neutral-basic pH (characteristic of CW). NCMC was loaded at twice its minimum bactericidal concentration (6.144 mg/mL) against S. aureus, while AAPV was loaded at its maximum inhibitory concentration against HNE (50 µg/mL), and the production of fibers with a core-shell structure, in which all components could be detected (directly or indirectly), was confirmed. Core-shell fibers were characterized as flexible and mechanically resilient, and structurally stable after 28-days of immersion in physiological-like environments. Time-kill kinetics evaluations revealed the effective action of NCMC against S. aureus, while elastase inhibitory activity examinations proved the ability of AAPV to reduce HNE levels. Cell biology testing confirmed the safety of the engineered fiber system for human tissue contact, with fibroblast-like cells and human keratinocytes maintaining their morphology while in contact with the produced fibers. Data confirmed the engineered drug delivery platform as potentially effective for applications in CW care.

Efficacy of Antibiotic Cement in Preserving Endoplants After Infection With Plate Exposure.

Background: To study the feasibility and efficacy of antibiotic cement in preserving endoplants after infection in patients with early tibial plateau fracture on plate exposure. Patients and Methods: A retrospective analysis of 23 patients treated for post-operative infection with plate exposure after tibial plateau fracture between 2017 and 2021. They were divided into the observation group (10 patients) and the control group (13 patients). Total operation time, length of hospitalization, hospitalization cost, the number of surgeries, white blood cell (WBC) count, neutrophil (NEUT) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the post-operative evaluation index, and complications were observed during the follow-up period. Results: All patients were followed up for 6 to 12 months; wound healing was observed in both groups. The total operation time for patients in the control group was longer compared with the observation group. However, the length of hospitalization, hospitalization cost, and number of surgeries in the observation group were less compared with the control group. No difference in WBC, NEUT, ESR, and CRP levels was observed one day after surgery. Furthermore, WBC, NEUT, ESR, and CRP levels were higher in patients in the control group compared with the observation group 72 hours after surgery. There were no differences in the post-operative evaluation index and complications in both groups. Conclusions: The antibiotic cement coating used for treating early post-operative infection in patients with tibial plateau fracture could effectively control infection while retaining endoplant, thereby promoting wound healing. It could also reduce pain and the medical burden on patients.

Asymmetric tri-layer sponge-nanofiber wound dressing containing insulin-like growth factor-1 and multi-walled carbon nanotubes for acceleration of full-thickness wound healing.

To more closely resemble the structure of natural skin, multi-layered wound dressings have been developed. Herein, a tri-layer wound dressing was prepared containing a polyacrylamide (PAAm)-Aloe vera (Alo) sponge that had been incorporated with insulin-like growth factor-1 (IGF1) to provide a porous absorbent layer, which was able to promote angiogenesis. Alo nanofibers with multi-walled carbon nanotubes (MWCNT) were electrospun into the bottom layer to increase cell behavior, and a small film of stearic acid was put as a top layer to avoid germy penetration. In comparison to bilayer dressing, the tensile strength increased by 17.0 % (from 0.200 ± 0.010 MPa to 0.234 ± 0.022 MPa) and the elastic modulus by 45.6 % (from 0.217 ± 0.003 MPa to 0.316 ± 0.012 MPa) in the presence of Alo nanofibers containing 0.5 wt% of MWCNT at the bottom layer of Trilayer0.5 dressing. The release profile of IGF1, the antibacterial activity and the degradability of different wound dressings were investigated. Trilayer0.5 indicated the highest cell viability, cell adhesion and angiogenic potential among the prepared dressing materials. In-vivo rat model revealed that the Trilayer0.5 dressing treated group had the highest rate of wound closure and wound healing within 10 days compared to other groups.

Anti-ß7 integrin treatment impedes the recruitment on non-classical monocytes to the gut and delays macrophage-mediated intestinal wound healing.

BACKGROUND: Closing mucosal defects to reach mucosal healing is an important goal of therapy in inflammatory bowel disease (IBD). Among other cells, monocyte-derived macrophages are centrally involved in such intestinal wound healing. We had previously demonstrated that the anti-α4ß7 integrin antibody vedolizumab blocks the recruitment of non-classical monocytes as biased progenitors of wound healing macrophages to the gut and delays wound healing. However, although important for the interpretation of disappointing results in recent phase III trials in IBD, the effects of the anti-ß7 antibody etrolizumab on wound healing are unclear so far. METHODS: We analyzed the expression of etrolizumab targets on human and mouse monocyte subsets by flow cytometry and assessed their function in adhesion and homing assays. We explored wound-associated monocyte recruitment dynamics with multi-photon microscopy and compared the effects of etrolizumab and vedolizumab surrogate (-s) antibodies on experimental wound healing and wound-associated macrophage abundance. Finally, we investigated wound healing macrophage signatures in the large intestinal transcriptome of patients with Crohn's disease treated with etrolizumab. RESULTS: Human and mouse non-classical monocytes expressed more αEß7 integrin than classical monocytes and were a target of etrolizumab-s, which blocked non-classical monocyte adhesion to MAdCAM-1 and E-Cadherin as well as gut homing in vivo. Intestinal wound healing was delayed on treatment with etrolizumab-s along with a reduction of peri-lesional wound healing macrophages. Wound healing macrophage signatures in the colon of patients with Crohn's disease were substantially down-regulated on treatment with etrolizumab, but not with placebo. CONCLUSIONS: Combined blockade of αEß7 and α4ß7 with etrolizumab seems to exceed the effect of anti-α4ß7 treatment on intestinal wound healing, which might help to inform further investigations to understand the recent observations in the etrolizumab phase III trial program.

Evaluation of the therapeutic effect of dressing containing Silver (Ag coat) in the process of healing skin blisters caused by limb fractures: a clinical trial study.

BACKGROUND: The main activity of the skin is to create a protective barrier against damage. Loss of the skin due to injury or disease and failure to regenerate the affected area may result in disability, infection, or even death. We conducted a clinical trial to evaluate the therapeutic effect of dressing containing silver in process of healing skin blisters caused by limb fractures. METHOD: This is a pioneering randomized trial that compares the effectiveness of two dressings containing silver (Ag coat) and Gaz Vaseline among patients with skin blisters due to bone fractures who were randomly selected from patients referred to the Kashani Medical Training Center. There were two treatment groups containing 16 patients treated with Ag coat and 15 patients treated with Gaz Vaseline. Pictures were taken of blisters on days 0, 7, and 14 to evaluate the healing process. The amount of pain, duration of the visit (measured by minutes), and general condition of the wound were checked. The amount of pain, duration of visit (measured by minutes) and general condition of the wound was checked. All continuous and categorical data are presented as mean ± standard deviation (SD) and frequency (percentage), respectively. Paired sample T-test and repeated measure analysis of variance (ANOVA), Chi-squared test was used. All pictures were analyzed by Mosaic soft ward. RESULT: During this study, there was no significant difference between the mean of age and BMI and frequency of gender in the two study groups (P > 0.05). There was a significant difference in mean between the duration of the visit, number of dressings, and net cost of dressing [Formula: see text]. In the macroscopic study and analysis for evaluation and comparing wound area with the Mosaic soft ward, there was significant relation in time (p1 = 0.00). There is no significant difference between the groups (p2 = 0.84). There was a significant difference between time and group (p3 = 0.00). On day 14 the wound area between groups had a significant difference (p4 = 0.00) (Table 3). In the VAS score there was a significant difference in time, and group (p1,2 = 0.00), there was no significant relation between time and group (p3 = 0.62). On all days the wound area between groups had a significant difference (p4 = 0.00). CONCLUSION: In conclusion, Ag coat dressing, not only has a significant effect on wound healing but also, decreases pain, shorter visit time, and its more cost-effective.

Introducing aesthetic regenerative scaffolds: An immunological perspective.

BACKGROUND: Skin aging arises from immunological responses to tissue deterioration and damage. Tissue repair processes encompass the regeneration of original tissue and 'scarless' wound healing seen in foetuses, and the extreme fibrotic responses and scarring seen in adults. Anti-aging aesthetic medicine uses interventions like biomaterial-based fillers to influence these immunological responses and renew aged tissue structure and function. At filler injection sites, an inflammatory response occurs that causes a spectrum of outcomes, ranging from tissue regeneration to fibrosis and filler encapsulation. Importantly, the resulting inflammatory pathway can be predetermined by the biomaterial injected. AIMS: By understanding this immunological process, we can develop Aesthetic Regenerative Scaffolds (ARS) - aesthetic injectable biomaterials - to direct inflammatory wound healing away from chronic, fibrotic responses, and towards physiological tissue regeneration. MATERIALS AND METHODS: We identified and reviewed literature on the immunological and cellular responses to injected dermal fillers, whereby the wound healing response to the injection was moderated under the influence of an injected biomaterial. RESULTS: We described the mechanisms of dermal wound healing and the use of ARS to direct healing towards tissue regeneration instead of scarring. We also summarised studies on extracellular matrix remodeling by calcium hydroxylapatite. We found that Calcium hydroxylapatite fillers produce collagen as they gradually degrade and their spherical structures serve as a scaffold for tissue regeneration. Furthermore, CaHA improved fibroblast contractility, collagen type III and elastin production, proliferation and angiogenesis with less inflammation than hyaluronic acid fillers. DISCUSSION: Regneration pathways can be influenced at specific points between a facial filler biomaterial and the wound healingmechanisms at its site of implantaion. CONCLUSION: Physicians can select scaffolds that direct the immune response away from a fibrotic chronic inflammatory pathway and towards regeneration to enable true repair of the aging skin.

Flavonoids as Potential Wound-Healing Molecules: Emphasis on Pathways Perspective.

Wounds are considered to be a serious problem that affects the healthcare sector in many countries, primarily due to diabetes and obesity. Wounds become worse because of unhealthy lifestyles and habits. Wound healing is a complicated physiological process that is essential for restoring the epithelial barrier after an injury. Numerous studies have reported that flavonoids possess wound-healing properties due to their well-acclaimed anti-inflammatory, angiogenesis, re-epithelialization, and antioxidant effects. They have been shown to be able to act on the wound-healing process via expression of biomarkers respective to the pathways that mainly include Wnt/ß-catenin, Hippo, Transforming Growth Factor-beta (TGF-ß), Hedgehog, c-Jun N-Terminal Kinase (JNK), NF-E2-related factor 2/antioxidant responsive element (Nrf2/ARE), Nuclear Factor Kappa B (NF-κB), MAPK/ERK, Ras/Raf/MEK/ERK, phosphatidylinositol 3-kinase (PI3K)/Akt, Nitric oxide (NO) pathways, etc. Hence, we have compiled existing evidence on the manipulation of flavonoids towards achieving skin wound healing, together with current limitations and future perspectives in support of these polyphenolic compounds as safe wound-healing agents, in this review.

Skin mucus metabolomics provides insights into the interplay between diet and wound in gilthead seabream (Sparus aurata).

The molecular processes underlying skin wound healing in several fish species have been elucidated in the last years, however, metabolomic insights are scarce. Here we report the skin mucus metabolome of wounded and non-wounded gilthead seabream (Sparus aurata) fed with silk fibroin microparticles, a functional additive considered to accelerate the wound healing process. The three experimental diets (commercial diet enriched with 0 mg (control), 50 mg or 100 mg of silk fibroin microparticles Kg-1) were administered for 30 days and thereafter, a skin wound was inflicted. Skin mucus was collected on day 30 of feeding and 7 days post-wounding and subjected to metabolomic analysis by Ultra Performance Liquid Chromatography coupled with a high-resolution quadrupole-orbitrap mass spectrometry. The most enriched metabolite class was amino acids and derivatives, followed by nucleotides, nucleosides and analogues and carbohydrates and their derivatives. Metabolomic profiles revealed that the diet had a more profound effect than wounding in skin mucus. Metabolic pathway analysis of significantly affected metabolites revealed perturbations in the aminoacyl t-RNA biosynthesis in the skin. In particular, skin wound resulted in a decreased methionine level in mucus. Further, silk fibroin supplementation increased methionine level in skin mucus, which correlated with several wound morphometric parameters that characterized the epithelial healing capacity in seabream. The results provided new insight into the physiological consequences of skin wounds and how these processes could be influenced by dietary manipulation.

Multifaceted applications of ulvan polysaccharides: Insights on biopharmaceutical avenues.

Ulvans are water-soluble sulfated polysaccharides predominantly found in the cell wall of green algae. They hold unique characteristics that are attributed to their 3D conformation, functional groups along with the presence of saccharides and sulfate ions. Traditionally, ulvans are widely used as food supplements and probiotics owing to the high content of carbohydrates. Despite their widespread usage in food industry, an in-depth understanding is required for extrapolating their potential application as a nutraceutical and medicinal agent which could be beneficial in promoting human health and well-being. This review emphasizes novel therapeutic avenues where ulvan polysaccharides can be used beyond their nutritional applications. A collection of literature points towards multifarious applications of ulvan in various biomedical fields. Structural aspects along with extraction and purification methods have been discussed. The underlying molecular mechanisms associated with its biomedical potential in different therapeutic fields like oncology, infectious diseases, inflammation, neuroprotection and tissue engineering, etc. have been unravelled. Challenges associated with clinical translation and future perspectives have been deliberated.