Wound Healing Research Articles

Updates on some medicinal and ornamental plants- Ayurvedic medicines

This literature review paper highlights morphology, distribution, medicinal properties of commercially important tree species, Thespesia populnea, Terminalia arjuna, Butea monosperma (Palas), Silver oak (Grevillea robusta), Mangifera indica, Madhuca longifolia,Melia azadirachta, Michelia champaca, Moringa oleifera, Peltophorum pterocarpum, and Aegle marmelos. These plants have been used for centuries by local communities and traditional healers for their therapeutic and medicinal properties. Medicinal plants play a crucial role in the Western Ghats, both ecologically and culturally. The use of herbal medicines for the treatment of diseases is safe and traditional. Therefore, medicinal plants have been receiving great attention because of their safety. The Western Ghats harbors more than 7,500 flowering plant species, of which nearly 1,500 are recognized for their medicinal values by local communities and traditional healers. The Western Ghats population traditional medical practices frequently center on using plant-based treatments. These medicinal plants are carefully chosen, and preparation techniques have been perfected through many years of practice. Studies indicated that Mangifera indica possesses antidiabetic, anti-oxidant, anti-viral, cardiotonic, hypotensive, and anti-inflammatory properties. Mango contains Mangiferin, a polyphenolic antioxidant and a glucosyl xanthone, has strong antioxidant, anti lipid peroxidation, immunomodulation, cardiotonic, hypotensive, wound healing, antidegenerative and antidiabetic activities.

Treatment of Fournier's gangrene with "firebreak" drainage based on skin preservation

Objective: To observe the clinical efficacy of a new type of "firebreak" drainage with skin preservation in the treatment of Fournier's gangrene. Methods: This technique is suitable for patients with perianal necrotizing fasciitis who can tolerate surgery without large area of skin blackness and necrosis. Procedure and key points: (1) The dividing line between inflammatory tissue and normal tissue was determined according to imaging examination and intraoperative exploration; (2) The abscess cavity was cut along the most obvious part of the abscess fluctuation, with a long diameter of 3~4 cm and a short diameter of 1~2 cm; (3) Necrotic tissue was discreetly separated and removed from the main incision to the outer edge of the infection. A fusiform incision was made every 3 to 5 cm, with a long diameter of 2 to 3 cm and a short diameter of 1 cm, and discreetly separated until the normal tissue, and a hose was hung between the adjacent incisions for drainage. (4) Each adjacent edge cut between the stealth separation and hanging hose drainage, forming a "firebreak"; (5) Rinse the wound repeatedly; (6) If the infection invades the rectum, colostomy is performed as required. The case data of 11 patients with perianal necrotizing fasciitis admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from July 2019 to February 2023 were retrospectively analyzed. All patients were treated with emergency surgical debridement by "firebreak" drainage with skin preservation. Results: All 11 cases were cured with 100%. One case underwent multiple operations. The hospitalization time was 11-46 days, with an average of 22 days. The wound healing time was 28-75 days, with an average of 43 days. Except for 1 patient with trauma, all the other patients had no significant anal function injury after surgery. All the 11 patients recovered and were discharged from hospital with a median follow-up of 136 (115-413) days. Conclusions: The "firebreak" drainage based on skin preservation has the advantages of less trauma and faster recovery, and do not cause obvious anal function damage.

Black Phosphorus Nanosheets-Based Hydrogel for Efficient Bacterial Inhibition and Accelerating Wound Healing.

With the swift evolution of multidrug-resistant bacteria resulting from the intense and inappropriate use of antibiotics, there is a pressing need for innovative solutions. In this study, a thermosensitive hydrogel was developed for efficient bacterial inhibition and promotion of wound healing. The antibacterial chitosan (CS) thermosensitive hydrogel, cross-linked with two-dimensional photothermal nanomaterial black phosphorus (BP) nanosheets through electrostatic interactions, effectively encapsulates and sustains the release of angiogenic drug deferoxamine mesylate (DFO). This facilitates the acceleration of re-epithelialization and neovascularization by enhancing cell migration and proliferation. Following near-infrared (NIR) treatment, this hydrogel demonstrates rapid eradication of the most common multidrug-resistant bacteria encountered in clinical settings, achieved through physical disruption of bacterial membranes and photothermal therapies. Noteworthy is the significant upregulation of IL-19 expression via STAT3 signaling pathways by the BP/CS-DFO hydrogel in a full-thickness wound model. This results in the polarization of the anti-inflammatory M2 macrophage phenotype, altering the microenvironment to a pro-healing state and enhancing extracellular matrix deposition and blood vessel formation. In conclusion, the BP/CS-DFO hydrogel shows immense promise as a potential clinical candidate for wound healing and antimicrobial therapy. Its innovative design and multifunctional capabilities position it as a valuable asset in combating antibiotic resistance and enhancing efficiency in wound healing.

Mid-term outcomes of sartorius flap reconstruction in groin infection following vascular procedures or intravenous drug injections.

In this study, the early and mid-term outcomes of sartorius flap reconstruction after the development of a prior groin infection were investigated. From January 2017 until June 2023, 44 patients from 2 centers in Italy underwent sartorius flap reconstruction after the development of a prior groin infection. Thirty-day outcome measures including major morbidity, amputation-free survival, and mortality were assessed. At 2-year follow-up, estimated outcomes of freedom from hemorrhagic complications, freedom from recurrent infection, freedom from reintervention, and amputation-free survival were analyzed using Kaplan-Meier curves. In 35 cases (79.5%) a previous vascular procedure was performed, whilst in the remaining 9 cases (20.5%) the patient was an intravenous drug abuser. Thirty-day mortality and major amputation rates were 4.5%, and 2.3%, respectively. Overall 30-day wound healing rate was 56.8% (25 cases). The overall median duration of follow-up was 12 months (IQR 4-24). Complete wound healing was obtained in 36 cases (81.8%) after a median period of 1 month (IQR 1-3). The 2-year Kaplan-Meier estimates of freedom from hemorrhagic complications, freedom from recurrent infection, freedom from reintervention, and amputation-free survival were 82.1%, 70%, 71.9%, and 97.7%, respectively. Multivariate analysis confirmed the association of female sex with recurrent infection (HR 3.4, P=.05). Sartorius flap reconstruction after the development of a prior groin infection following vascular procedures or intravenous drug injections yielded acceptable mid-term outcomes in terms of freedom from hemorrhagic complications, and freedom from recurrent infection. Female sex seemed to affect the rate of recurrent infection.

D-Peptide cell culture scaffolds with enhanced antibacterial and controllable release properties.

The development of peptide-based hydrogels characterized by both high biostability and potent antimicrobial activity, aimed at combating multidrug-resistant bacterial infections and providing scaffolds for cell cultures, continues to pose a significant challenge. The susceptibility of antimicrobial peptides (AMPs) to degradation by cations, serum, and proteases restricted their applications in clinical environments. In this study, we designed a peptide sequence (termed D-IK1) entirely consisting of D-amino acids, an enantiomer of a previously reported AMP IK1. Our results demonstrated remarkably improved antibacterial and anticancer activities of D-IK1 as compared to IK1. D-IK1 self-assembled into hydrogels that effectively inhibited bacterial and cancer cell growth by the controlled and sustained release of D-IK1. Importantly, D-IK1 was extremely stable in salt solutions and resisted serum and protease degradation. In addition, the D-IK1 hydrogel fostered cell adhesion and proliferation, proving its viability as a 3D scaffold for cell culture applications. Our research presents a versatile, highly stable antibacterial hydrogel scaffold with potential widespread applications in cell culture, wound healing, and the eradication of multidrug-resistant bacterial infections.

Looking back to look forward: Has the time arrived for active management of obstetricians in placenta accreta spectrum?

Placenta accreta spectrum (PAS) is a relatively new obstetric condition which, until recently, was poorly understood. The true incidence is unknown because of the poor quality and heterogeneous diagnostic criteria. Classification systems have attempted to provide clarity on how to grade and diagnose PAS, but these are no longer reflective of our current understanding of PAS. This is particularly true for placenta percreta, which referred to extrauterine disease, as recent studies have demonstrated that placental villi associated with PAS have minimal potential to invade beyond the uterine serosa. It is accepted that PAS is a direct consequence of previous iatrogenic uterine injury, most commonly a previous cesarean section. Here, we "look back to look forwards"-starting with the primary predisposing factor for PAS, an iatrogenic uterine injury and subsequent wound healing. We then consider the evolution of definitions and diagnostic criteria of PAS from its first description over a century ago to current classifications. Finally, we discuss why modifications to the current classifications are needed to allow accurate diagnosis of this rare but life-threatening complication, while avoiding overdiagnosis and potential patient harm.

Bringing back Galium aparine L. from forgotten corners of traditional wound treatment procedures: an antimicrobial, antioxidant, and in-vitro wound healing assay along with HPTLC fingerprinting study

BackgroundThe wound healing process, restoring the functionality of the damaged tissue, can be accelerated by various compounds. The recent experimental analysis highlights the beneficial effects of phytochemicals in improving skin regeneration and wound healing. In traditional medicine, one of the widespread plants used for treating different injuries or skin afflictions is Galium aparine L. (GA). Besides, previously reported chemical compounds of GA suggested its therapeutic effects for the wound healing process, yet its regulatory effects on the cellular and molecular stages of the wound healing process have not been investigated.MethodsIn the present study, the phytochemical profile of the GA extract was analyzed using HPTLC fingerprinting, and further scientific evaluation of its phytochemicals was done. The wound-healing effects of GA extract were explored at the cellular and molecular levels while accounting for cell toxicity. The wound closure enhancing effect, antibacterial activity, and antioxidant activity were assessed.ResultsThe HPTLC fingerprinting of the GA extract proved its previously reported phytochemical profile including phenols, flavonoids, tannins, plant acids, ergot alkaloids, flavonoids, anthraquinones, terpenoids, sterols, salicin, lipophilic compounds, saponins, iridoids, and heterocyclic nitrogen compounds. Antimicrobial assessment, of the extract, indicated the more susceptibility of S. aureus to the inhibitory effects of GA rather than E. coli and S. epidermidis. DPPH test results revealed the antioxidant property of GA extract, which was comparable to ascorbic acid. The results of the viability assay showed no cytotoxicity effects on human umbilical endothelial cell (HUVEC) and normal human dermal fibroblast (NHDF) cell lines treated with different concentrations of whole plant extract and cell viability increased in a dose-dependent manner. The results of the scratch assay showed improved cell migration and wound closure.ConclusionsThis study shows the anti-oxidant, anti-microbial, and in vitro wound healing wound-healing effects of GA hydroalcoholic extract, which aligns with its use in traditional medicine. No cytotoxicity effects were shown. The results from this study can be the basis for further investigations such as animal models and phytochemical studies. Further evaluation of its effects on mechanisms and signaling pathways involved in the wound healing processes such as angiogenesis and cell proliferation can provide novel insights into the potential therapeutic effects of the GA extract.

Eggshell membrane and green seaweed (Ulva lactuca) micronized powders for in vivo diabetic wound healing in albino rats: a comparative study

BackgroundNonhealing diabetic wounds are a serious complication associated with extremely lethargic wound closure and a high risk of infection, leading to amputation or limb loss, as well as substantial health care costs and a poor quality of life for the patient. The effects of either eggshell membrane (ESM) and green seaweed (Ulva lactuca) extracts alone or in combination were evaluated for in vivo skin wound healing in a rat model of induced diabetes.MethodsMicronized powders of waste hen ESM, Ulva lactuca, and their 1:1 mixture were prepared using regular procedures. The mechanical, electrical, and surface morphology characteristics of powders were examined using direct compression, LCR-impedancemetry, and scanning electron microscopy. The effect of ESM, Ulva lactuca, and their mixture as compared to standard Dermazin treatments were evaluated on wounds inflicted on male Wistar Albino rats with induced diabetes. Quantitative wound healing rates at baseline and at 3, 7, 14, and 21 days of treatments among all rat groups were conducted using ANOVA. Qualitative histological analysis of epidermal re-epithelization, keratinocytes, basement membrane, infiltrating lymphocytes, collagen fibrines, and blood vessels at day 21 were performed using Image J processing program.ResultsCompressive strength measurements of tablets showed a Young’s modulus of 44.14 and 27.17 MPa for the ESM and ESM + Ulva lactuca mixture, respectively. Moreover, both samples exhibited relatively low relative permittivity values of 6.62 and 6.95 at 1 MHz, respectively, due to the porous surface morphology of ESM shown by scanning electron microscopy. On day 21, rats treated with ESM had a complete diabetic wound closure, hair regrowth, and a healing rate of 99.49%, compared to 96.79% for Dermazin, 87.05% for Ulva lactuca, 90.23% for the mixture, and only 36.44% for the negative controls. A well-formed basement membrane, well-differentiated epithelial cells, and regular thick keratinocytes lining the surface of the epidermal cells accompanied wound healing in rats treated with ESM, which was significantly better than in control rats.ConclusionGround hen ESM powder, a low-cost effective biomaterial, is better than Ulva lactuca or their mixture for preventing tissue damage and promoting diabetic wound healing, in addition to various biomedical applications.

Dermal derived matrix hydrogel loaded with curcumin improved wound healing in a diabetic rat model

There is a need in clinical practice for new wound healing techniques to address full thickness skin injuries, particularly in individuals with diabetes. Herein we investigated whether dermal derived matrix hydrogel (DMH) loaded with curcumin (Cur) could promote healing in diabetic rats. Sixty diabetic rats were randomly assigned into the non-treated group, DMH group, Cur group, and DMH+Cur group. According to the phases of wound healing, sampling was done on days 7, 14, and 21 for further assessments. Our results indicated that the wound contraction rate, new epidermal length and thickness, number of fibroblasts and vascular length, collagen deposition, and strength properties of the healed wounds were meaningfully increased in the treatment groups than in the non-treated group, and these changes were more obvious in the DMH+Cur ones. In addition, the expression of VEGF and IL-10 genes were meaningfully upregulated in all treatment groups compared to the non-treated group and were greater in the DMH+Cur group. This is while the number of neutrophils and expression levels of TNF-α and IL-1β genes decreased more significantly in the DMH+Cur group compared to the other groups. In conclusion, it was found that using both DMH and curcumin has a greater impact on diabetic wound healing.

Inula helenium extract and lidocaine-loaded electrospun wound dressings for managing skin wounds pain and their healing: An in vitro and in vivo study.

The skin injuries pose a substantial public health challenge, not only due to their physical trauma but also the accompanying pain and complexities in wound healing. In the current research, Inula helenium extract and lidocaine were loaded into electrospun PVA/calcium alginate nanofibers to promote skin wounds healing and alleviate the resulting pain. Various in vitro experiments were utilized to characterize these dressings. Wound healing potential of these constructs and their analgesic effects were studied in a rat model of skin wounds. Our developed scaffolds released the loaded drugs in a slow manner and showed antioxidative and anti-inflammatory activities. Fiber size measurement showed that drug-loaded and drug-free scaffolds had around 418.025 ± 140.11nm and 505.51 ± 93.29nm mean fiber size, respectively. Bacterial penetration assay confirmed that drug-loaded scaffolds reduced bacterial infiltration through the matrices. Wound healing study showed that on day 14th, the dressings loaded with inula helenium extract and lidocaine could close the wounds up to 91.26 ± 5.93%. In addition, these scaffolds significantly reduced the animals pain sensitivity. ELISA assay results implied that these dressings modulated inflammation and reduced tissue's oxidative stress.

Comprehensive Developmental Investigation on Simvastatin Enriched Bioactive Film Forming Spray Using the Quality by Design Paradigm: A Prospective Strategy for Improved Wound Healing

ABSTRACT The use of topical antimicrobials in wound healing presents challenges like risk of drug resistance and toxicity to local tissue. Simvastatin (SIM), a lipid-lowering agent which reduces risk of cardiovascular events, is repurposed for its pleiotropic effect in wound healing. A bioactive bioadhesive polymer-based film forming spray (FFS) formulation of SIM was designed using chitosan, collagen, hyaluronic acid and optimized by employing DoE approach. Optimized formulation demonstrated moderate viscosity (12.5 ± 0.3 cP), rapid film formation (231 ± 5.6 s), flexibility, tensile strength and sustained drug release (T80 – time for 80% drug release - 9.05 ± 0.7 h). Scanning electron microscopy (SEM) verified uniformly dispersed drug within composite polymer matrix. SIM FFS demonstrated antimicrobial activity against gram positive and gram negative bacteria. In vivo excision wound model studies in mice affirmed the beneficent role of bioactive polymers and the efficacy of SIM FFS in wound contraction and closure, tissue remodelling and re-epithelization in comparison to standard antimicrobial preparation. Cytokines TNF- alpha, IL-6 were downregulated and IL-10 was upregulated. Biochemical markers; hydroxyproline, hexosamine and histopathology were consistent with wound contraction observed. This is an exploratory effort in repurposing SIM for wound healing in a novel dosage form, underscoring its potential as an alternative to conventional topical antimicrobials.

Bioelectret Materials and Their Bioelectric Effects for Tissue Repair: A Review.

Biophysical and clinical medical studies have confirmed that biological tissue lesions and trauma are related to the damage of an intrinsic electret (i.e., endogenous electric field), such as wound healing, embryonic development, the occurrence of various diseases, immune regulation, tissue regeneration, and cancer metastasis. As exogenous electrical signals, such as conductivity, piezoelectricity, ferroelectricity, and pyroelectricity, bioelectroactives can regulate the endogenous electric field, thus controlling the function of cells and promoting the repair and regeneration of tissues. Materials, once polarized, can harness their inherent polarized static electric fields to generate an electric field through direct stimulation or indirect interactions facilitated by physical signals, such as friction, ultrasound, or mechanical stimulation. The interaction with the biological microenvironment allows for the regulation and compensation of polarized electric signals in damaged tissue microenvironments, leading to tissue regeneration and repair. The technique shows great promise for applications in the field of tissue regeneration. In this paper, the generation and change of the endogenous electric field and the regulation of exogenous electroactive substances are expounded, and the latest research progress of the electret and its biological effects in the field of tissue repair include bone repair, nerve repair, drug penetration promotion, wound healing, etc. Finally, the opportunities and challenges of electret materials in tissue repair were summarized. Exploring the research and development of new polarized materials and the mechanism of regulating endogenous electric field changes may provide new insights and innovative methods for tissue repair and disease treatment in biological applications.

Silk-fibroin-based nanofibrous scaffolds integrated with nano-engineered living bacteria enabling antibiotic-free accelerated infected wound healing

Bacteria‐infected skin wounds are an immense public health challenge for high mortality-rate and enormous financial burden worldwide. Emerging living bacterial therapy promises the desired therapeutic efficacy for wound healing, however, its indiscriminate negative effects on the bioactivity of beneficial bacteria remain enormous challenges for clinical far-ranging applications. Herein, silk fibroin-based nanofibrous scaffolds equipped with nano-engineered tannic acid (TA)-Fe(III) chelate-encapsulated Lactobacillus reuteri (denoted as Mbr/L@FeTA) were proposed for antibiotic-free accelerated bacteria‐infected wound healing. Mbr/L@FeTA exhibited excellent antimicrobial properties (99.03% and 98.60% bactericidal efficiency against Escherichia coli and Staphylococcus aureus, respectively), gratifying mechanical properties and biocompatibility. Furthermore, due to on-demand TA-Fe(III) chelate-encapsulated bacterial tactics, Mbr/L@FeTA demonstrates exceptional environmental resistance and maintains satisfactory biological-activity even when administered with antibiotics. Additionally, Mbr/L@FeTA enables the stable release of organic acids and other metabolites that significantly improve the wound microenvironment and modulate inflammatory reactions. In vivo and in vitro experiments confirmed that Mbr/L@FeTA strongly promoted cell growth and proliferation, inhibited bacteria growth at the wound-site, and further accelerated the healing process in bacteria-infected wounds. These findings suggest that Mbr/L@FeTA exhibits great potential for applications in antibiotic-free infected wound therapy and simultaneously represents a useful approach for clinical applications of living bacterial therapy.

5-aminolevulinic acid photodynamic therapy for chronic wound infection in rats with diabetes

Recent research indicated that ulcers and peripheral vascular disease resulting from drug-resistant bacterial infections are the main causes of delayed healing in chronic diabetic wounds. 5-Aminolevulinic acid (ALA) is a second-generation endogenous photosensitizer. The therapeutic effect and mechanism of ALA-mediated photodynamic therapy (ALA-PDT) on methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in diabetic rats were investigated in this study. The results revealed the promising antibacterial effects of ALA-PDT MRSA in vitro, with a minimum inhibitory concentration and minimum bactericidal concentration of 250 and 500 μM, respectively. ALA-PDT also changed the permeability and structural integrity of bacterial cell membranes by producing reactive oxygen species. Meanwhile, ALA-PDT accelerated wound healing in MRSA-infected diabetic rats, with 5 % ALA-PDT achieving complete sterilization in 14 days and wound closure in 21 days. Treatment with 5 % ALA-PDT additionally improved the histopathological appearance of skin tissue, as well as fibrosis, inflammatory cytokine release, and angiogenesis-related protein expression. These findings indicated that ALA-PDT significantly promoted the healing of MRSA-infected wounds in diabetic rats by eliminating bacteria, inhibiting inflammation, generating granulation tissues, promoting neovascularization, and restoring damaged nerves. In addition, the healing mechanism was related to the activation of inflammatory and angiogenesis pathways through the regulation of tumor necrosis factor-alpha and interleukin-6 expression and upregulation of CD206, CD31, and VEGF. These findings underscored the potential role of ALA-PDT in promoting the healing of chronic diabetic wounds.

MiR-21-5p knockdown inhibits epithelial to mesenchymal transition in A549 lung adenocarcinoma cells by upregulating RhoB.

MiR-21-5p is a highly expressed microRNA that plays an important role in various cancer-promoting processes, including anchorage-independent growth, invasion, migration metastasis, and drug resistance in lung cancer. Studies indicate that miR-21-5p may contribute to these processes by promoting epithelial-mesenchymal transition (EMT). Ras homolog gene family member B (RhoB), a gene downregulated by miR-21-5p, has also been linked to EMT in lung cancer. However, the role of the miR-21-5p/RhoB axis in EMT regulation in lung adenocarcinoma remains unclear. In this study, we aimed to investigate the regulatory role of the miR-21-5p/RhoB axis in EMT and related in vitro functional characteristics such as migration, invasion, cisplatin resistance, and the formation of tumor spheroids. A549 cells were transfected with the miR-21-5p inhibitor, RhoB siRNA, and their corresponding negative controls. Wound healing, transwell invasion, Methyl thiazole tetrazolium (MTT), and sphere formation assays were also performed to evaluate the migration, invasion, cisplatin resistance, and anchorage-independent growth of A549 cells. RT-qPCR was used to determine the mRNA expression levels of EMT markers. MiR-21-5p knockdown inhibited migration, invasion, cisplatin resistance, and sphere formation while upregulating E-cadherin and downregulating Slug. Furthermore, RhoB silencing restored EMT and related in vitro functional characteristics in A549 cells. Knockdown of miR-21-5p inhibits EMT and related in vitro functional characteristics by upregulating RhoB, suggesting that miR-21-5p may promote EMT through downregulation of RhoB.

Palmitoylation Enhances Short Polar Peptide Permeation across Stratum Corneum Lipid Bilayer: a Molecular Dynamics Study

Designing chemical molecules that target the skin for non-invasive transdermal drug delivery is of significant interest for both wound healing and skincare applications. These skin-targeting molecules must permeate the outermost protective layer of the skin, the stratum corneum (SC), which consists of dead corneocytes embedded in a lipid matrix, to fulfill their biological functions. Adsorption onto and diffusion through the lipid matrix in the SC represent two key steps for the successful permeation of a skin-targeting molecule across the SC into the underlying skin layers. Here we compare the effects of cyclization and palmitoylation on the adsorption and diffusion of a short polar peptide across a model SC lipid bilayer using molecular dynamics simulations. The cyclized peptide showed slightly better binding to the SC lipid bilayer and similar interaction energies with SC lipids compared to the unmodified peptide. In contrast, the palmitoylated peptide exhibited much stronger interaction with SC lipids via insertion of its attached fatty acid tail into the SC lipid bilayer. The average diffusivity of the cyclized peptide across the SC lipid bilayer was approximately twice that of the unmodified peptide, whereas the palmitoylated peptide’s diffusivity was about 2.7 times higher. Thus, palmitoylation appears to be a promising strategy for enhancing the binding and permeability of short polar peptides across the SC lipid matrix.

Saikosaponin-d Mediates FOXG1 to Reverse Docetaxel Resistance in Prostate Cancer through Oxidative Phosphorylation

BackgroundProstate cancer (PCa), a prevalent malignancy worldwide, is frequently identified in advanced stages due to the absence of distinctive early symptoms, thereby culminating in the development of chemotherapy-induced drug resistance. Exploring novel resistance mechanisms and identifying new therapeutic agents can facilitate the advancement of more efficacious strategies for PCa treatment. MethodsBioinformatics analysis was employed to investigate the expression of FOXG1 in PCa tissues. Subsequently, qRT-PCR was utilized to validate FOXG1 mRNA expression levels in corresponding PCa cell lines. FOXG1 knockdown was performed, and cell proliferation was assessed using CCK-8 assays, while cell migration and invasion capabilities were evaluated through wound healing and Transwell assays. Western blot and Seahorse analyzer were used to measure oxidative phosphorylation (OXPHOS) levels. Additionally, to explore potential approaches to alleviate PCa drug resistance, this study assessed the impact of biologically active saikosaponin-d (SSd) on PCa malignant progression and resistance by regulating FOXG1 expression. ResultsFOXG1 exhibited high expression in PCa tissues and cell lines. Knockdown of FOXG1 inhibited the proliferation, migration, and invasion of PCa cells, while FOXG1 overexpression had the opposite effect and promoted OXPHOS levels. The addition of an OXPHOS inhibitor prevented this outcome. Finally, SSd was shown to suppress FOXG1 expression and reverse docetaxel resistance in PCa cells through the OXPHOS pathway. ConclusionThis work demonstrated that SSd mediated FOXG1 to reverse malignant progression and docetaxel resistance in PCa through OXPHOS.

Development of magnesium hydroxide-doped nanofibrous spheres for repairing infected skin wounds

The healing of skin wounds is a continuous and coordinated process, typically accompanied by microbial colonization and growth. This may result in wound infection and subsequent delay in wound healing. Therefore, it is of particular importance to inhibit the growth of microorganisms in the wound environment. In this study, magnesium hydroxide-doped polycaprolactone (PCL/MH) nanofibrous spheres were fabricated by electrospinning and electrospray techniques to investigate their effects on infected wound healing. The prepared PCL/MH nanofibrous spheres had good porous structure and biocompatibility, providing a favorable environment for the delivery and proliferation of adipose stem cells. The incorporation of MH significantly enhanced the antimicrobial properties of the spheres, in particular, the inhibition of the growth of S. aureus and E. coli. We showed that such PCL/MH nanofibrous spheres had good antimicrobial properties and effectively promoted the regeneration of infected wound tissues, which provided a new idea for the clinical treatment of infected wounds.

S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma

BackgroundS100A8 is a member of the S100 protein family and plays a pivotal role in regulating inflammation and tumor progression. This study aimed to comprehensively assess the expression patterns and functional roles of S100A8 in glioma progression. MethodsGlioma tissues were collected from 98 patients who underwent surgical treatment at Fudan University Shanghai Cancer Center. S100A8 expression in glioma tissues was analyzed using immunohistochemistry (IHC) to establish its correlation with clinicopathological features in patients. The expression and prognostic effect of S100A8 in glioma were analyzed using TCGA and CGGA public databases. Then, we investigated the role of S100A8 in glioma through a series of in vivo and in vitro experiments including Transwell, wound healing, CCK8, and intracranial tumor models. Subsequently, bioinformatics analysis, single-cell sequencing and coimmunoprecipitation (Co-IP) were used to explore the underlying mechanism. ResultsS100A8 was upregulated in gliomas compared to paracancerous tissues, and this phenotype was significantly correlated with poor prognosis. Subgroup analysis showed that S100A8 expression was higher in the high-grade glioma (HGG) group than that in the low-grade glioma (LGG) group. S100A8 overexpression in glioma cell lines promoted cell proliferation, migration and invasion, while silencing S100A8 reversed these effects. In vivo experiments, S100A8 knockdown can significantly reduce the tumor burden of glioma cells. Notably, S100A8 was observed to stimulate microglial M2 polarization by interacting with TLR4, which subsequently induced NF-κB signaling and IL-10 secretion within the tumor microenvironment. ConclusionsS100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma. S100A8 might represent a therapeutic target for further basic research or clinical management of glioma.

In Situ Triggered Self-Contraction Bioactive Microgel Assembly Accelerates Diabetic Skin Wound Healing by Activating Mechanotransduction and Biochemical Pathway.

Chronic nonhealing skin wounds, characterized by reduced tissue contractility and inhibited wound cell survival under hyperglycemia and hypoxia, present a significant challenge in diabetic care. Here, an advanced self-contraction bioactive core-shell microgel assembly with robust tissue-adhesion (SMART-EXO) is introduced to expedite diabetic wound healing. The SMART-EXO dressing exhibits strong, reversible adhesion to damaged tissue due to abundant hydrogen and dynamic coordination bonds. Additionally, the core-shell microgel components and dynamic coordination bonds provide moderate rigidity, customizable self-contraction, and an interlinked porous architecture. The triggered in situ self-contraction of the SMART-EXO dressing enables active, tunable wound contraction, activating mechanotransduction in the skin and promoting the optimal fibroblast-to-myofibroblast conversion, collagen synthesis, and angiogenesis. Concurrently, the triggered contraction of SMART-EXO facilitates efficient loading and on-demand release of bioactive exosomes, contributing to re-epithelialization and wound microenvironment regulation in diabetic mice. RNA-seq results reveal the activation of critical signaling pathways associated with mechanosensing and exosome regulation, highlighting the combined biomechanical and biochemical mechanisms. These findings underscore SMART-EXO as a versatile, adaptable solution to the complex challenges of diabetic wound care.