Wound Healing Research Articles

Design of an Innovative Method for Measuring the Contractile Behavior of Engineered Tissues.

Hypertrophic scarring is a common complication in severely burned patients who undergo autologous skin grafting. Meshed skin grafts tend to contract during wound healing, increasing the risk of pathological scarring. Although various technologies have been used to study cellular contraction, current methods for measuring contractile forces at the tissue level are limited and do not replicate the complexity of native tissues. Self-assembled skin substitutes (SASSs) were developed at the "Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX" and are used as permanent full-thickness skin grafts. The autologous skin substitutes are produced using the self-assembly method, allowing the cultured cells to produce their extracellular matrix leading to a tissue-engineered substitute resembling the native skin. The level of contraction of the SASSs during the fabrication process is patient-dependent. Thus, because of its architecture and composition, SASS is an interesting model to study skin contraction in vitro. Unfortunately, standard measurement methods are unsuited for SASS contraction assessment, mainly due to incompatibilities between the SASS manufacturing process and the current contraction force measurement methods. Here, we present an innovative contraction measurement method specifically designed to quantify the contractile behavior of tissue-engineered substitutes, without disrupting the protocol of production. The method uses C-shape anchoring frames that close at different speeds and magnitudes according to the tissue contractile behavior. A finite element analysis model is then used to associate the frame deformation to a contractile force amplitude. This article shows that the method can be used to measure the contraction force of tissues produced with cells displaying different contractile properties, such as primary skin fibroblasts and myofibroblasts. It can also be used to study the effects of cell culture conditions on tissue contraction, such as serum concentration. This protocol can be easily and affordably applied and tuned to many regenerative medicine applications or contraction-related pathological studies. Impact Statement The protocol presented in this article is a new and simple method to quantify contraction forces present in tissue-engineered substitutes. Using finite element analysis, it allows for the measurement of a contraction force rather than a surface reduction as usually provided by other tissue contraction measurement methods. The results shown are in correlation with the current literature relevant to tissue contraction. It can be easily implemented, and hence, this method will open up new avenues to study tissue contraction of living substitutes engineered with various cell types and to optimize culture conditions.

A Prospective Observational Study to Evaluate the Effectiveness of Platelet-Rich Plasma Therapy for Complex Wounds: Influential Clinical Variables on Wound Healing Outcomes.

Objective: Autologous platelet-rich plasma (PRP) has shown promising outcomes in treating wounds, but the profile of patients benefiting most from this therapy is not known. This study aimed to identify influential variables in the success of this therapy, analyzing its personalized therapeutic potential for complex wounds. Approach: A prospective observational study was conducted in elderly patients with complex wounds receiving autologous PRP. Patient's data about sociodemographic parameters, comorbidities, frailty (FI-VIG score), complete blood count including albumin, wound depth, location, chronicity, and etiology were collected at the beginning of the study. The wound area was monitored weekly. The data were analyzed using descriptive and inferential statistics, longitudinal data analysis, and survival analysis. Results: Ninety-seven elderly patients were included. The FI-VIG, baseline wound area, depth, and etiology were significantly correlated with wound outcome. Strong differences in wound area variation from treatment initiation were observed in healed wounds (13% reduction/week) compared with stagnant and complicated wounds (1 and 2% reduction/week, respectively). The healing time analysis showed that nearly 80% of patients required at least 15 weeks for complete healing. In addition, patients with smaller wound sizes, younger age, or lower FI-VIG scores had shorter healing times. Innovation: This is the first study that identifies prognostic indicators for wound outcomes to guide clinician decision-making for using autologous PRP. It also highlights the relevance of patient health baseline and wound features and evolution for the success of this therapy. Conclusion: This study demonstrates that personalizing autologous PRP therapy to treat complex wounds in elderly patients is possible.

Treatment of local purulent postoperative soft tissue complications in patients of older age groups with fractures of the proximal femur

BACKGROUND: Surgical treatment of fractures of the proximal femur in elderly patients makes it possible to put patients on their feet early and improve their quality of life. Local purulent complications in the postoperative period after hip fractures surgical treatment occur in 5–10% of cases. AIM: To improve the treatment outcomes of patients with local postoperative purulent complications of soft tissues by a comparative analysis of treatment methods with various antibacterial, antiseptic hydrogels and physical methods of wound treatment. MATERIALS AND METHODS: The article presents the nature of local purulent complications, their clinical picture, and diagnostic features. All the patients are divided into 2 groups. The main group included 53 patients, and the control group included 48. The patients of the main group underwent comprehensive treatment of local purulent complications using modern technologies (plasma scalpel) and dressings with hydrogel Argacol. The control group was treated with traditional bandages with dioxomethyltetrahydropyrimidine and chloramphenicol. RESULTS: The use of surgical wound treatment using a plasma scalpel and dressings with multifunctional hydrogel allows to accelerate the wound healing process by 2–3 weeks compared with the use of traditional techniques. CONCLUSIONS: The application of the proposed tactics of providing specialized care to elderly patients with a fracture of the proximal femur allows for a significant (p 0.05) improvement in treatment results.

Post-operative Wound Healing Efficacy of Eucalyptus Camaldulensis Phenolic-rich Extracts Incorporated Hydrogel With Enhanced Antioxidant, Antibacterial, and Anti-inflammatory Activities

Post-operative Wound Healing Efficacy of Eucalyptus Camaldulensis Phenolic-rich Extracts Incorporated Hydrogel With Enhanced Antioxidant, Antibacterial, and Anti-inflammatory Activities

A guide to removing sutures.

This article provides an overview of the wound healing process, outlining the four distinct phases of the healing cascade: haemostasis, inflammation, proliferation, and maturation. The different types of closure method are described and, specifically, the various types of surgical suture that can be used for wound closure, as well as the strengths and limitations of each. The article explains aspects of patient care that need to be considered such as obtaining informed consent, and the importance of nurses maintaining appropriate clinical skills. It concludes with a step-by-step outline of best practice on how to remove sutures.

A functional dual responsive CMC/OHA/SA/TOB hydrogel as wound dressing to enhance wound healing.

Within the clinical realm, the complexities of wound healing have consistently presented formidable challenges. Recent advancements, notably in hydrogel technologies, have broadened the therapeutic spectrum. This study focuses on investigating a novel dual responsive composite hydrogel for wound healing. This hydrogel is ingeniously designed to maintain an optimal moist environment, expedite healing, and combat bacterial infection during wound recovery. This study combining carboxymethyl chitosan (CMC), oxidized hyaluronic acid (OHA), and sodium alginate (SA), in addition, tobramycin (TOB) was incorporated to create a CMC/OHA/SA/TOB hydrogel. Hydrogel cross-linking was verified by infrared spectroscopy, and the microstructure was examined with scanning electron microscopy. We explored its swelling and degradation behaviors in different pH environments. The drug release profile and biocompatibility was evaluated via cytotoxicity and hemolysis assays. The antibacterial efficacy of hydrogel was tested in both solid and liquid media. Additionally, the wound models in Sprague-Dawley (SD) rat was employed to investigate the hydrogel's wound healing capabilities in vivo. Results showed that CMCOHA/SA/TOB hydrogel was effectively cross-linked with a network structure. The hydrogel exhibited pronounced responsiveness in its swelling and degradation characteristics, which was significantly influenced by different levels of pH. In vitro results demonstrated that the CMC/OHA/SA/TOB hydrogel exhibits limited cytotoxicity and hemolysis, coupled with a drug release profile of dual responsive characteristics. Antibacterial activity of the hydrogel against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was confirmed. Furthermore, in vivo experiments underscored the hydrogel's proficiency in promoting wound healing, highlighting its potential for clinical applications. The CMC/OHA/SA/TOB hydrogel not only fosters a moist environment essential for wound healing and enhances structural stability, but it also exhibits functional dual responsive capabilities in swelling and degradation. These distinctive abilities enable the precise release of TOB, thereby optimizing wound healing.

Autologous platelet-rich fibrin enhances skin wound healing in a feline trauma model.

Trauma is a common cause of cutaneous surgical disease with an increased risk of secondary infection in cat clinics. Platelet-rich fibrin (PRF), a platelet and leukocyte concentrate containing multiple cytokines and growth factors, is known to accelerate the healing of wounds. However, how PRF affects wound healing in the cat trauma model has not been fully investigated. The study aimed to examine the impact of PRF on skin wound healing in the cat trauma model. In this study, PRF from cats was successfully produced for our investigation. The models of feline trauma were effectively established. A total of 18 cats were randomly divided into 3 groups (n = 6): (1) Control group (CON); (2) PRF group; (3) Manuka honey group (MAN, as a positive control). Experiments were performed separately on days 7, 14, 21, and 28. Our results showed that PRF was a safe and efficient method of wound healing that did not influence the cat's body temperature, respiration rate, and heart rate (HR). PRF accelerated skin wound healing in the cat trauma model based on the rate and histological observation of wound healing. In addition, PRF promoted the production of growth factors and suppressed inflammation during wound healing. PRF accelerated wound healing by increasing the formation of collagen fibers, as shown by Masson-trichrome staining. The outcomes of the PRF and MAN groups were comparable. In conclusion, PRF improves the healing of skin wounds in cats by boosting the synthesis of growth factors, reducing inflammation, and enhancing the synthesis of collagen fibers.

Impact of Chronic Moderate Psychological Stress on Skin Aging: Exploratory Clinical Study and Cellular Functioning.

Skin is continuously exposed to environmental external and internal factors, including psychological stress (PS). PS has been reported to trigger different dermatoses such as psoriasis, atopic dermatitis, vitiligo, alopecia areata, and acne through the release of cortisol and epinephrine. To clinically explore PS-induced measurable skin aging signs in subjects with moderate versus mild chronic PS, and to investigate the effect of chronic PS on DNA damage at cellular level. In vitro stress tests with cortisol and epinephrine, and with cortisol only on extracellular matrix (ECM) synthesis, as well as on normal human skin fibroblast and keratinocyte functioning, including skin barrier and wound healing were performed. Moderately stressed subjects in the context of the clinical study had a significantly decreased antioxidant potential and impacted skin barrier integrity, as well as significantly increased signs of microrelief alterations (skin texture and fine lines) reaching an increased severity of about 32.9%. At a cellular level, DNA integrity, ECM synthesis, wound healing, and skin barrier parameters were impacted by increased stress hormone levels. The clinical exploratory studies presented herewith, as well as the study of cell functioning under stress, have provided evidence that chronic PS significantly affects skin homeostasis and triggers skin aging.

Topical Reconstituted High-Density Lipoproteins Elicit Anti-Inflammatory Effects in Diabetic Wounds.

Objective: Reconstituted high-density lipoproteins (rHDL) improve wound healing in diabetes. We aimed to determine if rHDL elicit anti-inflammatory effects in diabetic wounds, as a mechanism to explain their wound healing benefits. Approach: Diabetes was induced using streptozotocin in C57Bl6/J mice. Two full-thickness wounds were placed on the subflanks of diabetic and nondiabetic (ND) mice. Phosphate-buffered saline (PBS) or rHDL (50 µg/wound/day) were applied topically. Wound closure was assessed daily. Inflammatory gene transcripts were measured by qPCR and proteins by Western blotting and enzyme-linked immunosorbent assay in wounds collected at baseline, 24 h, and 3 days postwounding. Wound macrophages were assessed by flow cytometry 7 days postwounding. The fate of fluorescent 3,3-dioctadecyloxacarbocyanine, perchlorate (DiO)-labeled rHDL was tracked by flow cytometry, fluorescent imaging, and microscopy. Results: In diabetic mice, rHDL increased wound closure rates at days 6 (+288%, p < 0.01) and 7 (+639%, p < 0.0001) postwounding, compared with PBS controls. After 3 days, rHDL-treated diabetic wounds had lower Rela (-65%) and C-C motif chemokine ligand 2 (Ccl2) (-59%) mRNA levels and CCL2 protein (29%) than PBS controls, p < 0.05 for all. Wound macrophage content was higher in diabetic than ND wounds, but rHDL did not change macrophage content or polarity. DiO-rHDL were taken up by key wound cells including fibroblasts, macrophages, keratinocytes and endothelial cells, and retained in wounds for at least 48 h. Innovation: rHDL exerts anti-inflammatory effects in diabetic wounds early postwounding, which may contribute to its wound healing properties. Conclusion: The anti-inflammatory properties of rHDL in diabetic wounds present topical rHDL as a novel treatment option for improving healing in patients with diabetic foot ulcers.

The impact of electronic cigarettes on the outcomes of total joint arthroplasty.

Cigarette smoking is known to result in poorer outcomes for patients undergoing total joint arthroplasty. Smoking tobacco cigarettes in the perioperative period is associated with higher analgesia usage, increased mortality, poorer healing, and an increased risk of medical complications. As such, many surgeons advise their patients not to smoke in the perioperative period. Electronic cigarettes are emerging as a popular alternative for usage by patients who would otherwise continue to smoke traditional cigarettes. Importantly, there has been limited investigation into the impact of electronic cigarette usage on the outcomes of total joint arthroplasty. This review investigates the potential detrimental effects caused by the usage of electronic cigarettes on the outcomes of total joint arthroplasty. A systematic review was carried out in accordance with the PRISMA Guidelines. We have drawn from studies that investigated the impact of the constituents of E-cigarette vapour on bone health, wound healing, the immune system and the direct impact of electronic cigarette usage on surgical outcomes. Electronic cigarettes release nicotine in an inconsistent manner, resulting in many negative consequences for bone health. Furthermore, they depress the immune system, impair wound healing and may result in longer hospital stays. Electronic cigarette usage should be monitored in the perioperative period to reduce the risk of complication. There is a pressing need for more comprehensive research in this area to fully understand the implications of EC usage on the outcomes of total joint arthroplasty.

The effect of cold atmospheric plasma on viability of osteoblasts and expression of RANKL and OPG genes in medium with bisphosphonates.

Medication-related osteonecrosis of the jaw is a rare but severe complication with challenging treatment protocols. Cold atmospheric plasma (CAP) has shown promising effects in wound healing, cell proliferation and viability. This study investigated the effect of CAP on osteoblasts in a culture medium containing bisphosphonates. Pilot study was designed to determine the optimal setting of CAP. MG-63 cells were exposed to zoledronic acid at a concentration of 10 micromolar for 72h. Study groups with the best MTT assay results, were chosen for assessing OPG and RANKL genes by RT-PCR. Cell viability was significantly higher in groups 9kV.1mm.90s, 10kV.1mm.60s, and 12kV.1mm.60s (P < 0.05). Expression of RANKL in these groups was significantly lower than the positive control group (medium culture without zoledronic and plasma treatment) and higher than the BP group (culture with zoledronic without plasma treatment), except for the 12kV.1mm.60s group, which did not differ significantly from the positive control group (P > 0.05). OPG decreased in all test groups compared to BP (p < 0.05), except for the 12kV.1mm.60s group, which did not significantly differ from BP (P > 0.05). RANKL/OPG ratio in groups 9kV.1mm.90s and 12kV.1mm.60s significantly increased compared to BP (P < 0.05).CAP treatment may enhance the viability of osteoblasts exposed to bisphosphonates, increase their activity levels, enhance osteoclast activity, and improve bone turnover rates.

Deciphering transcriptome patterns in porcine mesenchymal stem cells promoting phenotypic maintenance and differentiation by key driver genes

Mesenchymal stem cells (MSC) are fibroblast-like non-hematopoietic cells with self-renewal and differentiation capacity, and thereby great potential in regeneration and wound healing. MSC populations are heterogeneous not only inherently, but also among different model species. In particular, porcine MSC serve as a frequently used resource for translational research, due to pigs’ distinctive closeness to human anatomy and physiology. However, information on gene expression profiles from porcine MSC and its dynamics during differentiation is sparse, especially with regard to cell surface and inner cell markers. In this study, we investigated the transcriptome of bone marrow-derived MSC and its differentiated cell types in a minipig breed for experimental research, known as Mini-LEWE, using bulk mRNA sequencing. Our data highlighted Rap1 signaling and downstream pathways PI3K-Akt and MAPK signaling as potential players for the maintenance of stemness of BM-MSC. In addition, we were able to link the process of differentiation to changes in the regulation of actin cytoskeleton. A total of 18 “BM-MSC differentiation driver markers” were identified, potentially promoting the process of differentiation into adipocytes, chondrocytes as well as osteocytes. Our results offer a new perspective on the molecular phenotype of porcine BM-MSC and the transcriptional responses in new differentiated progeny.

Refrigerated amniotic membrane maintains its therapeutic qualities for 48 hours

During wound healing, the migration of keratinocytes is critical for wound closure. The application of amniotic membrane (AM) on wounds with challenging contexts (e.g., chronification and diabetic foot ulcer) has proven very successful. However, the use of AM for clinical practice has several restraints when applied to patients; the most important restriction is preserving AM’s therapeutic properties between its thawing and application onto the patient’s wound. Moreover, AM collection and processing requires a cleanroom, together with specialized staff and equipment, and facilities that are not usually available in many hospitals and healthcare units. In this publication, we kept previously cryopreserved AM at different temperatures (37°C, 20°C, and 4°C) in different media (DMEM high glucose and saline solution with or without human albumin) and for long incubation time periods after thawing (24 h and 48 h). HaCaT keratinocytes and TGF-β1-chronified HaCaT keratinocytes were used to measure several parameters related to wound healing: migration, cell cycle arrest rescue, and the expression of key genes and migration-related proteins. Our findings indicate that AM kept in physiological saline solution at 4°C for 24 h or 48 h performed excellently in promoting HaCaT cell migration compared to AM that had been immediately thawed (0 h). Indeed, key proteins, extracellular signal-regulated kinase (ERK) and c-Jun, were induced by AM at 4°C in saline solution. Similarly, cell proliferation and different genes related to survival, inflammation, and senescence had, in all cases, the same response as to standard AM. These data suggest that the handling method in saline solution at 4°C does not interfere with AM’s therapeutic properties.

REVIEW: PHYTOCHEMICAL CONSTITUENTS AND PHARMACOLOGICAL ACTIVITY OF Strobilanthes crispus

Strobilanthes crispus (S. crispus), called keji beling leaves, is a plant belonging to the genus Strobilanthes and family Acanthaceae. Keji beling (S.crispus) has been applied by Indonesians to cure some diseases like diabetes and dissolve kidney stones. The aim of this review article is to compile an update on the phytochemical studies and pharmacological activity of S. crispus. A literature review was carried out by searching for articles in the Scopus, PubMed, and Google Scholar data bases between 2014-2024. Studies have shown that the leaves of S. crispus contain flavonoids, phenolics, alkaloids, tannins, terpenoids, phytosterols, and fatty acids. Current pharmacological studies have revealed that the extracts, fractions, or secondary metabolites of S. crispus possess antimicrobial, antioxidant, antidiabetic, anti-urothelial, immunomodulatory, wound healing, cytotoxic, and anti-cancer activities. Although previous studies have provided information about S. crispus, pharmacological and phytochemical data are still limited. Further studies are still necessary to explore the bioactive compounds, toxicity, safety and future development of S.crispus as herbal medicine Keywords: keji beling, Strobilanthes crispus, phytochemical constituent, pharmacological activity

Mechanisms of microRNA Regulation of the Epithelial–Mesenchymal Transition (EMT) in Lung Cancer

Lung cancer remains the cancer with the highest mortality worldwide, largely due to a limited understanding of the precise molecular mechanisms that drive its progression. microRNAs (miRNAs) have emerged as crucial regulators of lung cancer progression by influencing key cellular processes, notably the epithelial–mesenchymal transition (EMT). EMT is a complex and potentially reversible process where epithelial cells lose their polarity and adhesion, reorganize their cytoskeleton, and transition to a mesenchymal phenotype, enhancing their migratory and invasive capacities. While EMT plays an essential role in normal physiological contexts such as tissue development and wound healing, it is also a critical mechanism underlying the progression and metastasis of lung cancer. This review aims to summarize the latest research findings on the role of endogenous and exosome-derived microRNAs in regulating EMT in lung cancer, focusing on studies conducted over the past five years. It also provides an overview of EMT’s essential molecular mechanisms to better understand how miRNAs regulate EMT in lung cancer.

PTPN20 promotes metastasis through activating NF-κB signaling in triple-negative breast cancer.

Cancer metastasis remains a major challenge in the clinical management of triple-negative breast cancer (TNBC). The NF-κB signaling pathway has been implicated as a crucial factor in the development of metastases, but the underlying molecular mechanisms remain largely unclear. PTPN20 expression was evaluated using data from the Sweden Cancerome Analysis Network-Breast and The Cancer Genome Atlas database, as well as by western blotting and immunohistochemistry in 88 TNBC patients. The ability of PTPN20 to activate NF-κB was assessed by luciferase reporter assays. The effects of PTPN20 overexpression and knockdown via short hairpin RNA were examined in TNBC cell lines by wound healing and transwell matrix penetration assays. Additionally, we analyzed the growth and metastasis abilitiy of 4T1 xenograft tumors in nude mice. PTPN20 levels were elevated in TNBC cell lines and patient samples compared to controls, and higher protein levels correlated with metastasis-free survival. Overexpression of PTPN20 enhanced migration and invasion in vitro, and promoted lung metastasis in vivo. Our finding revealed that PTPN20 activates NF-κB signaling by dephosphorylating p65 at Ser468, preventing its binding to COMMD1, thereby protecting p65 from degradation. Downregulation of PTPN20 effectively inhibit, while p65 S468A mutant restored the migratory and invasive abilities of TNBC cells. Collectively, our results demonstrate that PTPN20 plays a critical role in TNBC metastasis through the activation of NF-κB signaling. We propose that PTPN20 may serve as a novel prognostic marker and potential therapeutic target for the treatment of TNBC.

Postbiotic Metabolite Derived from Lactiplantibacillus plantarum PD18 Maintains the Integrity of Cell Barriers and Affects Biomarkers Associated with Periodontal Disease

Background/Objectives: Periodontal disease is caused by oral infections, biofilms, persistent inflammation, and degeneration of cell barrier integrity, allowing pathogens to invade host cells. Probiotics have been extensively studied for the treatment of periodontal disease. However, research on the involvement of beneficial substances produced by probiotics, called “postbiotics,” in periodontal diseases remains in its early stages. The present study aimed to evaluate the effect of a postbiotic metabolite (PM) from Lactiplantibacillus plantarum PD18 on immunomodulation and maintenance of cell barrier integrity related to periodontal disease. Method: The main substance in PM PD18 was analyzed by GC-MS. The cytotoxic effect of PM PD18 was performed using the MTT assay, wound healing through the scratch assay, cell permeability through TEER value, modulation of inflammatory cytokines through ELISA, and gene expression of inflammatory cytokines and tight junction protein was determined using qRT-PCR. Results: The main substance found in PM PD18 is 2,3,5,6-tetramethylpyrazine. PM PD18 did not exhibit cytotoxic effects on RAW 264.7 cells but promoted wound healing and had an antiadhesion effect on Porphyromonas gingivalis concerning SF-TY cells. This postbiotic could maintain cell barrier integrity by balancing transepithelial electrical resistance (TEER) and alkaline phosphatase (ALP) activity. In addition, the gene and protein expression levels of zonula occludens-1 (ZO-1) increased. PM PD18 was found to have immunomodulatory properties, as demonstrated by regulated anti- and pro-inflammatory cytokines. Interleukin-10 (IL-10) increased, while IL-6 and IL-8 were reduced. Conclusions: This study demonstrated that PM PD18 is efficient as a natural treatment for maintaining cell barrier integrity and balancing inflammatory responses associated with periodontal disease.

RNF19A inhibits bladder cancer progression by regulating ILK ubiquitination and inactivating the AKT/mTOR signalling pathway.

The role of the RING finger protein superfamily in carcinogenesis has been widely studied, but one member of this family, RNF19A, has not yet been thoroughly explored in bladder cancer (BCa). The expression levels of RNF19A in BCa samples and cell lines were analysed through data mining of public resources and further experiments. BCa cells in which RNF19A was stably overexpressed or knocked down were generated through lentivirus infection. The effects of RNF19A on cell proliferation, migration, and invasion were explored by performing a series of in vitro experiments, including CCK-8, colony formation, wound healing, and Transwell invasion assays. Using bioinformatics methods and multiple experiments, including western blot, qRT‒PCR, immunoprecipitation, cycloheximide, ubiquitination, and rescue assays, the mechanism underlying the effect of RNF19A on the progression of BCa was investigated. Here, we found that RNF19A expression was reduced in BCa samples and cell lines and that lower RNF19A expression predicted shorter overall survival of BCa patients. Functionally, forced expression of RNF19A suppressed BCa cell proliferation, migration, and invasion by inactivating the AKT/mTOR signalling pathway, whereas silencing RNF19A had the opposite effects. Mechanistically, RNF19A could directly interact with ILK and promote its ubiquitination and degradation. Rescue experiments revealed that forced ILK expression partially rescued the decreased phosphorylation of AKT, mTOR, and S6K1 caused by RNF19A overexpression and that the increased levels of the p-AKT, p-mTOR, and p-S6K1 proteins induced by RNF19A knockdown were eliminated after silencing ILK. Similarly, the effects of RNF19A overexpression or knockdown on the phenotypes of cell proliferation, migration, and invasion could also be restored by forced or decreased ILK expression. RNF19A suppressed the proliferation, migration, and invasion abilities of BCa cells by regulating ILK ubiquitination and inactivating the AKT/mTOR signalling pathway. RNF19A might be a potential prognostic biomarker and promising therapeutic target for BCa.

Dental Pulp Stem Cell Lysate-Based Hydrogel Improves Diabetic Wound Healing via the Regulation of Anti-Inflammatory Macrophages and Keratinocytes.

The prolonged existence of chronic wounds heightens the risk of patients experiencing chronic pain, necrosis, and amputation. Dental pulp stem cells (DPSCs) have garnered attention due to their potential immunomodulatory and tissue repair regenerative effects in the management of chronic wounds. However, stem-cell-based therapy faces challenges such as malignant differentiation, immune rejection, and long-term effectiveness. To overcome these challenges, we proposed a chronic wound therapy using a hydrogel derived from human-originated dental pulp stem cell lysate (DPSCL). Our data indicate that, with the degradation of the dental pulp stem cell lysate-based hydrogel (DPSCLH), the slowly released cell lysates recruit anti-inflammatory M2 macrophages and promote the proliferation, migration, and keratinization of HacaT cells. In addition, in vivo studies revealed that DPSCLH avoids immune rejection reactions and induces a long-term accumulation of endogenous M2 macrophages. In a mouse model of diabetic wounds, DPSCLH effectively modulates the inflammatory microenvironment around diabetic wounds, promotes the formation of the stratum corneum, and facilitates the healing of wounds, thus holding tremendous potential for the treatment of diabetic wounds.

A Novel Look at Mechanisms and Applications of Xanthohumol (XN) in Dermatology and Cosmetology

Xanthohumol (XN), representing the group of chalcones, is a hydroxyl and superoxide free radical scavenger. It also has antimicrobial properties, showing antibacterial activity against Staphylococcus aureus, Staphylococcus pyogenes, Staphylococcus epidermidis and Propionibacterium acnes. XN exerts an inhibitory effect on tyrosinase (it hinders the oxidation of l-tyrosine and l-DOPA). However, it also affects the transport of pigment (through a reduction in the number and length of dendrites) and its degradation (through damage to melanosomes). Additionally, it has been shown to inhibit the different activation pathways of the premeditated response in macrophages and reduce the secretion of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. Xanthohumol also improves skin elasticity by reducing the activity of elastase and MMP 1, 2 and 9, and it increases the expression of type I, III and V collagen, as well as elastin and fibrillins in skin fibroblasts. It acts against the main factors contributing to the pathogenesis of acne by inhibiting pro-inflammatory mediators (e.g., COX-2, PGE2, IL-1β and TNF-α). Moreover, it shows antibacterial activity against P. acnes and S. aureus, as well as seboregulatory and antioxidant properties. It has also been recognized that XN intake could affect diabetic wound healing. XN shows antitumoral activity, e.g., in the case of skin melanoma, which is associated with the antioxidant, pro-apoptotic, anti-angiogenic and immunostimulating effects of this compound.