Wound Healing Response Research Articles

A Computational Study on Effects of PID Temperature Target and RF Frequency for PID-Controlled Nonablative RF Cosmetic Systems.

Commonly adopted in cosmetic dermatology, nonablative radiofrequency (RF) devices convert high-frequency electromagnetic energy into thermal energy to induce a wound-healing response in skin tissue. However, differences in the electrical properties of different skin layers raise questions about the impact of different RF frequencies and target temperatures on treatment effectiveness. This paper presents a finite element analysis (FEA)-based computational study aimed at simulating and optimizing the effects of a proportional integral derivative (PID)-controlled RF cosmetic devices under different combinations of these two parameters during treatment. A 3D physical model for the application of a nonablative RF device was constructed using COMSOL, which included the human tissue and RF electrodes, electromagnetic and thermal boundary conditions, as well as the PID controller. FEA was performed for each of the twelve models with parameter combinations of three RF frequencies (0.1, 0.5, and 1 MHz) and three PID-controlled target temperatures (60°C, 65°C, and 70°C) plus one group without PID control. Treatment effectiveness was quantitatively assessed using the integration of tissue thermal damage fraction, i.e., thermal damage volume. In the earlier stage of heating (0-10 s), higher RF frequency resulted in a larger thermal damage volume. At 10 s, among models with a temperature target of 70°C, there is a 6.04% difference between the thermal damage volume at RF frequencies of 1.0 and 0.1 MHz. In the later stage of heating(11-80 s), the impact of RF frequency decreases. The difference in thermal damage volume caused by higher temperature targets is more significant, at 80 s, among models with an RF frequency of 1.0 MHz, the 70°C model produces 1.15 and 1.36 times more tissue thermal damage than the 65°C and 60°C models. PID controller has ensured treatment safety and uniformity, in exchange for some efficiency. Among 12 parameter combinations, the one with a temperature of 70°C and RF frequency of 1.0 MHz achieved the highest thermal damage volume, which could potentially result in the best esthetic effect. Considering users' different susceptibility to heat, engineers or physicians can select better temperature targets and RF frequencies to bring the desired cosmetic results based on thermal damage volume curves from this study.

Quantification of extra-cardiac damage following acute myocardial infarction using cis- and trans-4-[18F]fluoro-L-proline PET imaging

The preclinical surgically-induced models of myocardial infarction (MI) have been extensively utilised for studying the wound healing response in the mammalian heart. It is well-established that these invasive procedures induce marked acute systemic inflammation and adverse haemodynamic derangements, which can result in extra-cardiac tissue injury and remodelling; however, the extent of this has not yet been robustly characterised. Here, using a rat permanent coronary artery ligation (PL) model of MI and the cis- and trans-4-[18F]fluoro-l-proline positron emission tomography (PET) probes, targeting active misfolded and triple-helical collagen biosynthesis, respectively, we conducted an exploratory time-course analysis of the associated extra-cardiac tissue remodelling post-injury. Our results showed an increased cis-4-[18F]fluoro-l-proline PET signal in the liver (P = 0.02; two sample t-test) and lung (P = 0.03; two sample t-test) at the acute day 7 timepoint in the MI group compared to the Sham group (n = 3-6), which was not apparent at the later timepoints (days 14, 28, and 84). Ex vivo quantification of the deposited collagen in extra-cardiac tissues using Sirius red histochemical staining and the total hydroxyproline assay validated the apparent time course trends observed with [18F]fluoro-l-proline PET. These findings suggest that the liver and lungs are susceptible to acute injury in the rat PL model of MI and align with numerous clinical reports of extracardiac injury in MI patients. Moreover, our results highlight the suitability of [18F]fluoro-l-proline PET as a systems-based imaging technique for investigating active collagen biosynthesis across multiple organs.

LHPP deficiency aggravates liver fibrosis through TGF-β/Smad3 signaling.

Liver fibrosis is characterized by a wound-healing response and may progress to liver cirrhosis and even hepatocellular carcinoma. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a tumor suppressor that participates in malignant diseases. However, the role of LHPP in liver fibrosis has not been determined. Herein, the function and regulatory network of LHPP were explored in liver fibrosis. The expression of LHPP in human and murine fibrotic liver tissues was assessed via immunohistochemistry and Western blot analysis. In addition, liver fibrosis was induced in wild-type (WT) and LHPP-/- (KO) mice after carbon tetrachloride (CCl4) or thioacetamide (TAA) treatment. The effect of LHPP was systematically assessed by using specimens acquired from the above murine models. The functional role of LHPP was further explored by detecting the pathway activity of TGF-β/Smad3 and apoptosis after interfering with LHPP invitro. To explore whether the function of LHPP depended on the TGF-β/Smad3 pathway invivo, an inhibitor of the TGF-β/Smad3 pathway was used in CCl4-induced WT and KO mice. LHPP expression was downregulated in liver tissue samples from fibrosis patients and fibrotic mice. LHPP deficiency aggravated CCl4- and TAA-induced liver fibrosis. Moreover, through immunoblot analysis, we identified the TGF-β/Smad3 pathway as a key downstream pathway of LHPP invivo and invitro. The effect of LHPP deficiency was reversed by inhibiting the TGF-β/Smad3 pathway in liver fibrosis. These results revealed that LHPP deficiency exacerbates liver fibrosis through the TGF-β/Smad3 pathway. LHPP may be a potential therapeutic target in hepatic fibrosis.

Pediatric Rhegmatogenous Retinal Detachment and its Treatment

Pediatric rhegmatogenous retinal detachments have a different clinical presentation and different treatment algorithms than adult rhegmatogenous retinal detachments. The absence of posterior vitreus detachment and the predominance of retinal holes and dialysis in the etiology can be counted among these differences. Slow onset of visual loss and the inability of the pediatric age group to appreciate the symptoms leads to the development of variable amounts of proliferative vitreoretinopathy at clinical presentation. The presence of the crystalline lens and exaggerated wound healing response of the young eye changes the usual treatment approach of the adult detachments, and combination surgeries are frequently required. Scleral buckling surgery is the primary treatment option in the pediatric age group. It may be applied segmentally or circumferentially according to the level of the retinal breaks and the extent proliferative vitreoretinopathy present. Vitrectomy may be added according to the treatment response or the level of proliferative vitreoretinopathy present. Phakic lens status, abnormally posterior insertion of posterior vitreus base, and hyalocyte cellular remnants despite successful intraoperative posterior vitreus detachment are the obstacles that may be encountered in vitrectomy for pediatric retinal detachment. Pediatric rhegmatogenous retinal detachments require a higher number of surgeries per patient and have a lower final retinal attachment rate than adult cases. Examination and prophylactic treatment of the fellow eye must be carried out as the underlying retinal breaks and predisposing lesions are frequently bilateral with the exception of trauma in this age group.

An Advanced Hydrogel Dressing System with Progressive Delivery and Layer-to-Layer Response for Diabetic Wound Healing

Wound healing in diabetic patients presents a significant challenge due to delayed inflammatory responses, which obstruct subsequent healing stages. In response, we have developed a progressive, layer-by-layer responsive hydrogel, specifically designed to meet the dynamic requirements of diabetic wounds throughout different healing phases. This hydrogel initiates with a glucose-responsive layer formed by boronate ester bonds between 4-arm-poly (ethylene glycol) succinimidyl glutarate (4arm-PEG-SG) and 3-aminophenylboronic acid. This configuration ensures precise control over the physicochemical properties, facilitating accurate drug release during the healing process. Furthermore, we have incorporated an active pharmaceutical ingredient ionic liquid (API) composed of diclofenac and L-carnitine. This combination effectively tackles the solubility and stability issues commonly associated with anti-inflammatory drugs. To further refine drug release, we integrated matrix metalloproteinase-9 (MMP-9)-sensitive gelatin microcapsules, ensuring a controlled release and preventing the abrupt, uneven drug distribution often seen in other systems. Our hydrogel's rheological properties closely resemble human skin, offering a more harmonious approach to diabetic wound healing. Overall, this progressive layer-by-layer responsive wound management system, which is a safe, efficient, and intelligent approach, holds significant potential for the clinical treatment of diabetic wounds. Statement of SignificanceThe two main problems of diabetic wounds are the long-term infiltration of inflammation and the delayed repair process. In this experiment, a glucose-responsive hierarchical drug delivery system was designed to intelligently adjust gel properties to meet the needs of inflammation and repair stage of wound healing, accelerate the transformation of inflammation and repair stage, and accelerate the process of repair stage. In addition, in order to achieve accurate drug release in anti-inflammatory layer hydrogels and avoid sudden drug release due to poor solubility of anti-inflammatory small molecule drugs, we constructed a ionic liquid of active pharmaceutical ingredients (API-ILs) using diclofenac and L-carnitine as raw materials. It was wrapped in MMP-9 enzyme active gelatin microcapsule to construct a double-reaction anti-inflammatory layer gel to achieve accurate drug release. These findings highlight the potential of our system in treating diabetic wounds, providing a significant advance in wound treatment.

Comparison between Epiretinal Membrane Component in Proliferative Vitreoretinopathy and Other Fibroproliferative Diseases: A Scoping Review

The growth of proliferative vitreoretinopathy epiretinal membrane (PVR-ERM) is a major complication of rhegmatogenous retinal detachment (RRD). Despite surgery, adjunct treatment is necessary to control the aberrant wound healing response that occurs in PVR-ERM to prevent its recurrence. Existing studies on adjunct agents target pathways in the pathogenesis of PVR-ERM. We conducted a scoping review of composition of PVR-ERMs and other fibroproliferative ERMs. After literature search, 12 articles were included into the study. Outcome measured was gene expression, growth factors, extracellular matrix components, and enzymes.Among these studies, 9 compared PVR-ERM with PDR-ERM, 2 compared PVR-ERM with iERM, and 1 compared PVR-ERM with secondary ERM. Higher expression of certain genes or a higher concentration of particular factors can be observed throughout PVR, PDR, iERM, or secondary ERM.TGF-β, MALAT1 gene, and fibronectin are distinct factors that might play a bigger role on the pathogenesis of PVR compared to other fibroproliferative diseases.

Cloning and Expression Analysis of TGF-β Type I Receptor Gene in Hyriopsis cumingii.

The TGF-β signaling pathway plays an important role in wound healing and immune response. In this study, a TGF-β type I receptor (TGF-βRI) homolog was cloned and characterized from freshwater mussel Hyriopsis cumingii. The full-length cDNA of the TGF-β RI gene was 2017 bp, with a 1554 bp open reading frame (ORF), and encoded 517 amino acids. The predictive analysis further identified distinct regions within the TGF-βRI protein: a signal peptide, a membrane outer region, a transmembrane region, and an intracellular region. Real-time quantitative PCR results showed that the TGF-β RI gene was expressed in all tissues of healthy mussels. The transcripts of TGF-β RI in hemocytes and hepatopancreas were significantly up-regulated at different periods after stimulation with Aeromonas hydrophila and peptidoglycan (PGN) (P < 0.05). The mRNA expression of TGF-β RI progressively increased from day 1 to day 10 after trauma (P < 0.05), and it returned to the initial level by day 15. The expression levels of TGF-β , Smad5, MMP1/19, and TIMP1/2, but not Smad3/4, were significantly up-regulated at different time points after trauma. However, the expression levels of TGF-β , MMP1/19, and TIMP2 were decreased after treatment with the inhibitor SB431542. Furthermore, the recombinant TGF-βRI proteins were expressed in vitro and existed in the form of inclusion bodies. Western blotting results showed that TGF-βRI proteins were expressed constitutively in various tissues of mussels, and their expression was up-regulated after trauma, which was consistent with the mRNA expression trend. These results indicate that TGF-β RI is involved in the process of wound repair and immune response.

Tick extracellular vesicles undermine epidermal wound healing during hematophagy.

Wound healing has been extensively studied through the lens of inflammatory disorders and cancer, but limited attention has been given to hematophagy and arthropod-borne diseases. Hematophagous ectoparasites, including ticks, subvert the wound healing response to maintain prolonged attachment and facilitate blood-feeding. Here, we unveil a strategy by which extracellular vesicles (EVs) ensure blood-feeding and arthropod survival in three medically relevant tick species. We demonstrate through single cell RNA sequencing and murine genetics that wildtype animals infested with EV-deficient Ixodes scapularis display a unique population of keratinocytes with an overrepresentation of pathways connected to wound healing. Tick feeding affected keratinocyte proliferation in a density-dependent manner, which relied on EVs and dendritic epidermal T cells (DETCs). This occurrence was linked to phosphoinositide 3-kinase activity, keratinocyte growth factor (KGF) and transforming growth factor β (TGF-β) levels. Collectively, we uncovered a strategy employed by a blood-feeding arthropod that impairs the integrity of the epithelial barrier, contributing to ectoparasite fitness.

34 The influence and interaction of nutrition with the immune system in companion animal models

Abstract Understanding the impacts of nutrients in a species-specific manner has both practical and academic benefits for improving animal health. Therefore, species-specific animal models and research reagents are crucial to understanding molecular and physiological pathways. However, limitations in repeatable, descriptive models, sample size, and the ethics of companion animal research result in often needing to make inferences from human, murine, and other related immunology and nutrition research models. Recent companion animal work has focused on the impact of key nutrients in animal diets, including fat-soluble vitamins D, and E, omega-3 polyunsaturated fatty acids (PUFA), overall amino acid and energy balance over the lifespan, minerals including zinc and selenium, and feed additives such as probiotics and beta glucans. The selected research model, samples able to be collected, and available reagents for sample analysis will impact potential outcomes and inferences made from the data, including both acute to chronic impacts. From a theoretical standpoint, the balance between nutrient supplementation and impact includes understanding nutrients and responses of a model system in both deficiency and therapeutic level settings. For example, when supplementing Vitamin D, Vitamin E, or omega-3 polyunsaturated fatty acids, inclusion above currently recommended levels may optimize immune function, such as pathogen clearance, improved vaccine titer responses, or reduce inflammation. For other nutrients associated with immunomodulation such as zinc, additional chronic pharmacological supplementation may inhibit certain aspects of immune function, much like a deficiency scenario. Overstimulation of the immune system through nutrient supplementation may also impact the necessary modulation and repair roles that immune cells such as macrophages play in wound healing and anti-inflammatory responses. Continued work in nutritional immunology will further enhance our understanding of the power of nutrition and diet to improve health in companion animals.

Aberrant activation of wound healing programs within the metastatic niche facilitates lung colonization by osteosarcoma cells.

Lung metastasis is responsible for nearly all deaths caused by osteosarcoma, the most common pediatric bone tumor. How malignant bone cells coerce the lung microenvironment to support metastatic growth is unclear. The purpose of this study is to identify metastasis-specific therapeutic vulnerabilities by delineating the cellular and molecular mechanisms underlying osteosarcoma lung metastatic niche formation. Using single-cell transcriptomics (scRNA-seq), we characterized genome- and tissue-wide molecular changes induced within lung tissues by disseminated osteosarcoma cells in both immunocompetent murine models of metastasis and patient samples. We confirmed transcriptomic findings at the protein level and determined spatial relationships with multi-parameter immunofluorescence and spatial transcriptomics. Based on these findings, we evaluated the ability of nintedanib, a kinase inhibitor used to treat patients with pulmonary fibrosis, to impair metastasis progression in both immunocompetent murine osteosarcoma and immunodeficient human xenograft models. Single-nucleus and spatial transcriptomics was used to perform molecular pharmacodynamic studies that define the effects of nintedanib on tumor and non-tumor cells within the metastatic microenvironment. Osteosarcoma cells induced acute alveolar epithelial injury upon lung dissemination. scRNA-seq demonstrated that the surrounding lung stroma adopts a chronic, non-resolving wound-healing phenotype similar to that seen in other models of lung injury. Accordingly, metastasis-associated lung demonstrated marked fibrosis, likely due to the accumulation of pathogenic, pro-fibrotic, partially differentiated epithelial intermediates and macrophages. Our data demonstrated that nintedanib prevented metastatic progression in multiple murine and human xenograft models by inhibiting osteosarcoma-induced fibrosis. Fibrosis represents a targetable vulnerability to block the progression of osteosarcoma lung metastasis. Our data support a model wherein interactions between osteosarcoma cells and epithelial cells create a pro-metastatic niche by inducing tumor deposition of extracellular matrix proteins such as fibronectin that is disrupted by the anti-fibrotic TKI nintedanib. Our data shed light on the non-cell autonomous effects of TKIs on metastasis and provide a roadmap for using single-cell and spatial transcriptomics to define the mechanism of action of TKI on metastases in animal models.

Physical therapy in burn care: Development of clinical prediction rules to determine the efficacy of low-level laser therapy

This study aimed to demonstrate the benefits of low-level laser therapy (LLLT) on burn healing and to investigate whether patients' age, burn wound size, wound stage, and total burned surface area influence the burn wound healing response to LLLT. This was a quasi-experimental study with a single-group design that included eighty male and female patients with partial-thickness burn wounds recruited from burn units. The participants were placed in a single intervention group receiving LLLT. The duration of the intervention was six weeks, divided into 18 sessions (three sessions per week). The statistical analysis was conducted using version 25 of the SPSS statistical package for Windows. The results showed a statistically significant negative relationship between wound improvement from LLLT and age (p &lt; 0.05) and between total body surface area (TBSA) and wound improvement (p &lt; 0.05). Additionally, a statistically significant positive relationship was found between initial wound size and wound improvement (p &lt; 0.05). There was no statistically significant relationship between wound improvement and wound stage (p &gt; 0.05). The current study revealed that age, TBSA, and initial wound size can predict the efficacy of low-level laser treatment for burn wounds.

Effectiveness and Tolerability of Topical Curcumin for Management of Diabetic Foot Ulcer: A Pilot Clinical Study

Background: Diabetic foot ulcers (DFUs) affect 9.1 to 26.1 million individuals globally each year, with 15-25% of those with diabetes mellitus (DM) experiencing them during their lives. DFUs are a major cause of amputations, accounting for 85% of such cases in diabetic patients. Curcumin, a compound from Curcuma longa, shows potential in wound healing through mechanisms such as inhibiting the NLRP3 inflammasome pathway, promoting autophagy, and regulating microRNA expression. This study evaluated the efficacy and safety of C3-DiagardTM Cream in treating DFUs. Methods: This open-label, prospective clinical study assessed the efficacy and safety of C3-DiagardTM cream, containing 0.05mg of Harida (Curcuma longa) extract, in treating and preventing DFUs. The cream was applied twice daily for 12 weeks. Key outcomes were assessed through wound size reduction, pain (VAS score), and any adverse reactions during the treatment. Results: Fifty DM patients (36 males, 14 females; mean age 57.58±12.67 years) were enrolled. Among the patients, 75% (38 individuals) showed a wound healing response between 70% and 99%. The average wound size decreased significantly from 6.63 cm&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt; at baseline to 1.83 cm&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt; after 12 weeks, with a mean reduction of 4.8 cm&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt; (p &amp;lt; 0.05). Pain levels, measured by VAS score, significantly dropped from an average of 8 to 3 (p &amp;lt; 0.05). No adverse reactions were reported, highlighting the cream’s safety. Conclusion: C3-DiagardTM cream is effective in reducing the size of diabetic foot ulcers and alleviating pain, with a favourable safety profile. This study supports the clinical use of C3-DiagardTM as a well-tolerated treatment option for patients with DFUs.

Potential therapeutic effects of topical recombinant human erythropoietin on burn wound healing: A preliminary randomized double-blind controlled clinical trial

BackgroundBurn injuries can cause significant mortality and morbidity. This study aimed to evaluate the efficiency of topical recombinant human erythropoietin (rhEPO) on enhancing burn wound healing. MethodsIn this randomized double-blind controlled clinical trial, we enrolled 40 participants aged 18 years and older who were referred to a burn center during the first 24 h of burning. The participants with no concurrent comorbidities had superficial and deep second-degree burns, no respiratory burns, no face and perineum burns, no keloid formation, or a healed, fully epithelialized, hypertrophic burn scar. Topical rhEPO or nitrofurazone/Vitamin A was administered every other day, and the patients were scheduled for follow-up visits to receive wound cleansing, debridement, and dressing changes. Burn wound healing response to treatment was measured as the study main outcome. ResultsAt the second follow-up visit, all parameters were significantly lower in the rhEPO group compared with the control group except for itchiness. The results of the next two follow-up sessions were also the same. The total value of the modified Vancouver Scar Scale (VSS) at days 5, 7, and 14 was significantly lower in the rhEPO group compared with the routine of care group.Trial Registry Date: 2022–03-02, Trial Registry number: IRCT20190810044500N23 ConclusionsThe results of the present study suggested that topical rhEPO is a potential option in burn wounds and patient satisfaction, without causing intolerable side effects.

Interplay Between FoxM1 and Dab2 Promotes Endothelial Cell Responses in Diabetic Wound Healing.

Diabetes mellitus can cause impaired and delayed wound healing, leading to lower extremity amputations; however, the mechanisms underlying the regulation of vascular endothelial growth factor (VEGF)-dependent angiogenesis remain uncertain and could reveal new therapeutic targets. In our study, the molecular underpinnings of endothelial dysfunction in diabetes were investigated, focusing on the roles of Disabled-2 (Dab2) and Forkhead Box M1 (FoxM1) in VEGF receptor 2 (VEGFR2) signaling and endothelial cell (EC) function. Bulk RNA-sequencing analysis identified significant downregulation of Dab2 in high concentrations glucose treated primary mouse skin ECs, simulating hyperglycemic conditions in diabetes mellitus. In diabetic mice with a genetic EC deficiency of Dab2 angiogenesis was reduced in vivo and in vitro when compared with wild-type mice. Restoration of Dab2 expression by injected mRNA-containing lipid nanoparticles rescued impaired angiogenesis and wound healing in diabetic mice. At the same time, FoxM1 was downregulated in skin ECs subjected to high glucose conditions as determined by RNA-sequencing analysis. FoxM1 was found to bind to the Dab2 promoter, regulating its expression and influencing VEGFR2 signaling. The FoxM1 inhibitor FDI-6 reduced Dab2 expression and phosphorylation of VEGFR2. These findings indicate that restoring Dab2 expression through targeted therapies can enhance angiogenesis and wound repair in diabetes. To explore this therapeutic potential, we tested LyP-1-conjugated lipid nanoparticles (LNPs) containing Dab2 or control mRNAs to target ECs and found the former significantly improved wound healing and angiogenesis in diabetic mice. This study provides evidence of the crucial roles of Dab2 and FoxM1 in diabetic endothelial dysfunction and establishes targeted delivery as a promising treatment for diabetic vascular complications.

Dynamics of the thymic transcriptome at stages of acute thymic involution in Japanese Black calves with a poor prognosis

Transcriptome analysis was performed on the thymus of Japanese Black calves that were necropsied due to poor prognosis, to characterize changes associated with acute thymic involution. Gene expression profiles obtained by DNA microarray analysis of eight calf thymuses were classified into three patterns that correlated with the histopathological stage of acute thymic involution. Using principal component analysis, the first principal component of the global gene expression levels in the calf thymus was associated with the stage of acute thymic involution, suggesting that histopathological changes greatly influence the gene expression profile. Gene ontology enrichment analysis revealed that genes related to cell proliferation, wound healing, and inflammatory responses were the main contributors to the first principal component. Real-time RT-PCR showed that the thymus had lower expression of PCNA, KIFC1, and HES6, and higher expression of SYNPO2, PDGFRB, and TWIST1 during acute thymic involution. Immunohistochemistry demonstrated a decrease in the rate of Ki67-positive cells in the thymic cortex during the late stage of acute thymic involution. The rate of cleaved caspase-1-positive cells increased in the thymic cortex at an earlier stage than the increase in the rate of cleaved caspase-3-positive cells. Vimentin, which was almost absent in the non-involuted thymic cortex, appeared in the thymic cortex during acute thymic involution. These results suggest that in farmed calves with a poor prognosis, inflammatory responses and impaired thymocyte proliferation are primarily involved in acute thymic involution.

Multifunctional Nanosystem for Dual Anti-Inflammatory and Antibacterial Photodynamic Therapy in Infectious Diabetic Wounds.

Infectious diabetic wounds present a substantial challenge, characterized by inflammation, infection, and delayed wound healing, leading to elevated morbidity and mortality rates. In this work, we developed a multifunctional lipid nanoemulsion containing quercetin, chlorine e6, and rosemary oil (QCRLNEs) for dual anti-inflammatory and antibacterial photodynamic therapy (APDT) for treating infectious diabetic wounds. The QCRLNEs exhibited spherical morphology with a size of 51 nm with enhanced encapsulation efficiency, skin permeation, and localized delivery at the infected wound site. QCRLNEs with NIR irradiation have shown excellent wound closure and antimicrobial properties in vitro, mitigating the nonselective cytotoxic behavior of PDT. Also, excellent biocompatibility and anti-inflammatory and wound healing responses were observed in zebrafish models. The infected wound healing properties in S. aureus-infected diabetic rat models indicated re-epithelization and collagen deposition with no signs of inflammation. This multifaceted approach using QCRLNEs with NIR irradiation holds great promise for effectively combating oxidative stress and bacterial infections commonly associated with infected diabetic wounds, facilitating enhanced wound healing and improved clinical outcomes.

Fibrosis and Hepatocarcinogenesis: Role of Gene-Environment Interactions in Liver Disease Progression.

The liver is a complex organ that performs vital functions in the body. Despite its extraordinary regenerative capacity compared to other organs, exposure to chemical, infectious, metabolic and immunologic insults and toxins renders the liver vulnerable to inflammation, degeneration and fibrosis. Abnormal wound healing response mediated by aberrant signaling pathways causes chronic activation of hepatic stellate cells (HSCs) and excessive accumulation of extracellular matrix (ECM), leading to hepatic fibrosis and cirrhosis. Fibrosis plays a key role in liver carcinogenesis. Once thought to be irreversible, recent clinical studies show that hepatic fibrosis can be reversed, even in the advanced stage. Experimental evidence shows that removal of the insult or injury can inactivate HSCs and reduce the inflammatory response, eventually leading to activation of fibrolysis and degradation of ECM. Thus, it is critical to understand the role of gene-environment interactions in the context of liver fibrosis progression and regression in order to identify specific therapeutic targets for optimized treatment to induce fibrosis regression, prevent HCC development and, ultimately, improve the clinical outcome.

A novel mouse model of hepatocyte-specific apoptosis-induced myeloid cell-dominant sterile liver injury and repair response.

Apoptosis, inflammation, and wound healing are critical pathophysiological events associated with various liver diseases. Currently, there is a lack of in vivo approaches to study hepatocyte apoptosis-induced liver injury and repair. To address this critical knowledge gap, we developed a unique genetically modified mouse model, namely, 3-Transgene (Tg) with inducible Hepatocyte-Specific Apoptosis Phenotype (3xTg-iHAP) in this study. The 3xTg-iHAP mice possess three transgenes including Alb-Cre, Rosa26-rtTA, and tetO-Fasl on a B6 background. These mice are phenotypically normal, viable, and fertile. After subcutaneous administration of a single dose of doxycycline (5 mg/kg, Dox) to 3xTg-iHAP mice, we observed a complete histological spectrum of sterile liver wound-healing responses: asymptomatic hepatocyte apoptosis at 8 h, necrotic liver injury and sterile inflammation at 48 h, followed by hepatocyte mitosis and regeneration within 7 days. During the injury phase, the mice exhibited an increase in the biomarkers of alanine aminotransferase (ALT), chemokine (C-X-C motif) ligand 1 (CXCL1), and IL-6 in peripheral blood, as well as α-smooth muscle actin (α-SMA) protein in liver tissues. Conversely, the mice displayed a decrease in these markers in the recovery phase. Remarkably, this model shows that the sterile liver injury following elevated hepatocyte apoptosis is associated with an increase in myeloid cells in the liver. Within 7 days post-Dox administration, the liver of Dox-treated 3xTg-iHAP mice displays a normal histological structure, indicating the completion of wound healing. Together, we established a novel mouse model of injury and regeneration induced by hepatocyte apoptosis. This tool provides a robust in vivo platform for studying the pathophysiology of sterile liver inflammation, regeneration, and new therapeutic interventions for liver diseases.NEW & NOTEWORTHY Bu et al. present a triple-transgenic mouse model, namely, 3xTg-iHAP mice that are engineered to explore hepatocyte apoptosis-triggered sterile liver injury and regeneration. This model demonstrates a full spectrum of liver wound-healing responses from asymptomatic apoptosis to injury, myeloid cell-dominant sterile inflammation, and repair after induction of hepatocyte-specific apoptosis. The robust nature of this model makes it an invaluable in vivo tool for studying sterile liver inflammation, regeneration, and new therapeutic strategies.

Synthesis and Characterization of Coenzyme Q10 onto Nanoporous Calcium Silicate-Based Systems for Wound Healing

This study explores the microstructure, spectroscopic, and bonding arrangements within bioactive calcium silicate and calcium magnesium silicate systems loaded with different values (1–2.5 wt%) Coenzyme (CoQ10) ratios, synthesized using sol-gel processes. The investigation utilizes X-ray diffraction (XRD), transmission electron microscopy, and Fourier transform infrared (FTIR) spectroscopy to analyze the samples. The study explores the assignment of FTIR bonds, examining changes in the silicate-based bonds environment under the effect of the CoQ10 ratio. The observed frequency shifts and intensity variations in FTIR bonds, linked with the bioactive silicate composition, are attributed to a reduction in local symmetry resulting from introducing the calcium and magnesium oxides and CoQ10 to the silica network. The XRD and FTIR results contribute valuable insights into the structural role of silicate-based materials loaded with CoQ10, thereby enhancing our understanding of the CoQ10 release process. Approval of the CoQ10 drug loading in both calcium silicate and calcium magnesium silicate nanosystems was recognized by shifts in FTIR bands, changes in particle distribution, and the valuation of drug release activity showed by the bioactive two calcium silicate-based nanoparticles. Additionally, wound healing studies revealed the biocompatibility and wound healing response of calcium magnesium silicate nanoparticles.

Potential Wound Healing and Anti-Melanogenic Activities in Skin Cells of Aralia elata (Miq.) Seem. Flower Essential Oil and Its Chemical Composition.

Aralia elata (Miq.) Seem. (AES; family Araliaceae) is a medicinal plant and has been reported to have various bioactivities, including anticancer and hepatotoxicity protective activities. However, no studies have investigated the biological activities of AES or its extracts on skin. To address this, we aimed to explore the effect of AES-flower-derived absolute-type essential oil (AESFEO) on skin-related biological activities, especially skin wound healing and whitening-related responses in skin cells (human-derived keratinocytes [HaCaT cells] and melanocytes [B16BL6 cells]) and to identify the components of AESFEO. Cell biological activities were analyzed using WST and BrdU incorporation assays, ELISA, or by immunoblotting. In HaCaT cells, AESFEO promoted proliferation, type IV collagen production, and enhanced the phosphorylations of Erk1/2, p38 MAPK, JNK, and Akt. In B16BL6 cells, AESFEO reduced serum-induced proliferation, α-MSH-stimulated increases in melanin synthesis and tyrosinase activity, and α-MSH-induced increases in MITF, tyrosinase, TRP-1, and TRP-2 expressions. In addition, AESFEO inhibited the phosphorylation of Erk1/2, p38 MAPK, and JNK in α-MSH-stimulated B16BL6 cells. Eighteen compounds were identified in AESFEO by GC/MS. These results suggest that AESFEO has beneficial effects on keratinocyte activities related to skin wound healing and melanocyte activities related to inhibition of skin pigmentation. AESFEO may serve as a useful natural substance for developing agents that facilitate skin wound healing and inhibit melanogenesis.