Proliferative Phase Research Articles

Mechanistic insights of diabetic wound: Healing process, associated pathways and microRNA-based delivery systems.

Wounds that represent one of the most critical complications can occur in individuals suffering from diabetes mellitus, and results in the need for hospitalisation and, in severe cases, require amputation. This condition is primarily characterized by infections, persistent inflammation, and delayed healing processes, which exacerbate the overall health of the patients. As per the standard mechanism, signalling pathways such as PI3K/AKT, HIF-1, TGF-β, Notch, Wnt/β-Cat, NF-κB, JAK/STAT, TLR, and Nrf2 play major roles in inflammatory, proliferative and remodelling phases of wound healing. However, dysregulation of the above pathways has been seen during the healing of diabetic wounds. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate the expression of various genes and signalling pathways which are associated with the process of wound healing. In the past few years, there has been a great deal of interest in the potential of miRNAs as biological agents in the management of a number of disorders. These miRNAs have been shown to modulate expression of genes involved in the healing process of wounds. There have been previous reviews pertaining to clinical trials examining miRNAs in several disorders, but only a few clinical studies have examined involvement of miRNAs in healing of wounds. Considering the therapeutic promise, there are several obstacles concerning their instabilities and inefficient delivery into the target cells. Therefore, this review is an attempt to discuss precise roles of signalling pathways and miRNAs in different phases of wound healing, and their aberrant regulation in diabetic wounds, particularly. It has also compiled a range of delivery mechanisms as well as an overview of the latest findings pertaining to miRNAs and associated delivery systems for improved healing of diabetic wounds.

Plasma-Activated Water Improve Wound Healing in Diabetic Rats by Influencing the Inflammatory and Remodelling Phase

Diabetic foot ulcers have an enormous impact on patients’ quality of life and represent a major economic burden. The cause is delayed and incomplete wound healing due to hyperglycemia, reduced blood flow, infections, oxidative stress and chronic inflammation. Plasma-activated water (PAW) is emerging as a new therapeutic approach in wound treatment, as it has many of the advantages of cold atmospheric plasma but is easier to apply, thus allowing for widespread use. The aim of this study was to investigate the potential of PAW to improve wound healing in diabetic rats, with a focus on uncovering the underlying mechanisms. Two full-thickness wounds in control and diabetic animals were treated with PAW, and healing was monitored for 15 days at five time points. PAW improved wound healing in diabetic rats and mainly affected the inflammatory phase of wound healing. Application of PAW decreased the number of inflammatory cells, myeloperoxidase (MPO) and N-acetyl-b-D-glycosaminidase (NAG) activity, as well as the mRNA expression of proinflammatory genes in diabetic rats. Ten days after injury, PAW treatment increased collagen deposition in the diabetic animals by almost 10% without affecting collagen mRNA expression, and this is in correlation with a decrease in the Mmp-9/Timp-1 ratio. In conclusion, PAW treatment affects wound healing by reducing the inflammatory response and influencing extracellular matrix turnover, suggesting that it has great potential to accelerate the healing of diabetic wounds.

Single-Cell Proteomics Uncovers Dual Traits of Dermal Sheath Cells in Wound Repair.

Wound healing is a dynamic process involving multiple cell types and signaling pathways. Dermal sheath cells (DSCs), residing surrounding hair follicles, play a critical role in tissue repair, yet their regulatory mechanisms remain unclear. This study used single-cell proteomics with the AcanCreER;R26LSL-tdTomato-DTR mouse model to explore DSC function across different healing stages. All animal procedures were conducted in accordance with the Animal Research: Reporting of In Vivo Experiments guidelines. Gene set enrichment analysis (GSEA) and temporal clustering (Mfuzz) were employed to reveal dynamic functional shifts. GSEA identified enriched gene sets related to interferon-gamma response, inflammatory response, ultraviolet response, myogenesis, and xenobiotic metabolism. Temporal clustering revealed eight distinct clusters: clusters associated with the early contracting and proliferative phases were linked to metabolic activation and oxidative stress, while clusters from the later remodeling phase emphasized extracellular matrix remodeling and structural reorganization. The dynamic expression of epithelial-mesenchymal transition-related genes and keratins supported DSCs' dual epithelial and mesenchymal traits. Additionally, keratins, collagens, integrins, and actin proteins emerged as promising markers or signature molecules for DSCs. This study reveals DSCs' dual traits during wound repair, providing a basis for therapies to enhance healing.

Biomarkers associated with progression of infantile hemangioma: Exploratory study.

To identify patients with infantile hemangioma (IH) in need of early-stage treatment in this multicenter, prospective, observational study, we investigated the potential of plasma cytokines as a clinically useful marker. Plasma samples were collected at three time points from 41 patients with infantile hemangioma: baseline (days 14-60 after delivery), visit 1 (days 61-150, the proliferative phase), and visit 2 (days 151-395, the involuting phase). With a twofold or more increase in tumor volume during the baseline-visit 1 period regarded as progression, progression was seen in 15 cases (36.6%). In the first step, cytokine arrays were performed using plasma samples in five progressive and five non-progressive cases. Plasma levels of six cytokines at baseline were selected for a prediction marker of change in tumor volume during baseline-visit 1. Validation enzyme-linked immunosorbent assay indicated that the baseline growth differentiation factor 1 (GDF1) concentration tended to correlate with the proliferation ratio of total lesions or target lesion during baseline-visit 1, although without statistical significance. However, the plasma GDF1 concentrations were significantly lower in patients with a fourfold or more increase in total volume (p = 0.013). Furthermore, changes in plasma interleukin (IL)-7Rα levels showed a statistically significant inverse correlation between volume change of the target lesion during baseline-visit 1 (p = 0.0069). Our results suggest that plasma GDF1 measurement after birth is a useful marker for progression of IH. Additionally, the downregulation of IL-7Rα that begins several months after birth may also contribute to tumor growth. (UMIN-CTR: UMIN000038574).

Fibrotic Changes in Rhegmatogenous Retinal Detachment

Rhegmatogenous retinal detachment (RRD) is a sight-threatening condition involving retinal detachment and the accumulation of fluid in the subretinal space. Proliferative vitreoretinopathy (PVR) is a pathologic complication that develops after RRD surgery, and approximately 5–10% of RRD cases develop post-operative PVR. Prolonged inflammation in the wound healing process, epithelial–mesenchymal transition (EMT), retinal pigment epithelial (RPE) cell migration and proliferation, and epiretinal, intraretinal, and subretinal fibrosis are typical in the formation of PVR. RPE cells undergo EMT and become fibroblast-like cells that migrate to the retina and vitreous, promoting PVR formation. Fibroblasts transform into myofibroblasts, which promote fibrosis by overproducing the extracellular matrix (ECM). RPE cells, fibroblasts, glial cells, macrophages, T lymphocytes, and increased ECM production form contractile epiretinal membranes. Cytokine release, complement activation, RPE cells, glial cells, and endothelial cells are all involved in retinal immune responses. Normally, wounds heal within 4 to 6 weeks, including hemostasis, inflammation, proliferation, and remodeling phases. Properly initiated inflammation, complement activation, and the function of neutrophils and glial cells heal the wound in the first stage. In a retinal wound, glial cells proliferate and fill the injured area. Gliosis tries to protect the neurons and prevent damage, but it becomes harmful when it causes scarring. If healing is complicated, prolonged inflammation leads to pathological fibrosis. Currently, there is no preventive treatment for the formation of PVR, and it is worth studying in the future.

The effect of the number of endometrial CD138+ cells on the pregnancy outcomes of infertile patients in the proliferative phase.

This study was conducted to determine the influence of the number of CD138+ cells in the proliferative endometrium on pregnancy outcomes. This retrospective cohort study was conducted from January to August 2018. A total of 664 infertile women who were not diagnosed with chronic endometritis (CE) and who had not received the respective antibiotic treatment were studied. Immunostaining was performed for the plasmacyte marker CD138. The number of CD138+ cells was compared in the proliferative and mid-luteal phases of the same patients without antibiotic therapy. Infertile patients were separated into three groups based on the number of positive lesions [the number of high power fields (HPFs) containing no less than five CD138+ cells]: 0 (n = 474), 1-2 (n = 125), and ≥3 positive lesions (n = 104). The pregnancy outcomes of the infertile women undergoing in vitro fertilization-embryo transfer (IVF-ET) among the three groups were then compared. There was a much higher level of CD138+ cells during proliferation than during the mid-luteal phase (P <0.0001). Pregnancy outcomes did not differ between the groups with 0 and 1-2 positive lesions. However, the ≥3 positive lesions group (P =0.006, P =0.029) had significantly lower ongoing pregnancy and live birth rates compared with the no positive lesion group. Although the 0 and ≥3 positive lesions groups showed a trend toward higher rates of clinical pregnancy (P =0.132), these differences failed to reach statistical significance. After age, body mass index (BMI), and clinical features were adjusted for, the ≥3 positive lesions group showed significantly lower live birth rates (aOR, 1.84; 95%CI, 1.08-3.15; P =0.026), clinical pregnancy (adjusted odds ratio (aOR), 1.78; 95% CI, 1.06-2.95; P =0.028), and ongoing pregnancy (aOR, 1.85; 95% CI, 1.09-3.15; P =0.024). The analysis demonstrated that the smallest number of stromal CD138+ cells suggestive of CE patients requiring treatment was defined as ≥ 3 positive lesions during the proliferation. Different diagnostic criteria for CE should be created for the proliferative and mid-luteal phases. The analysis demonstrated that the smallest number of stromal CD138+ cells suggestive of CE patients was defined as ≥ 3 positive lesions during the proliferative phase.

Wound healing properties of a chimeric form of human GM-CSF in a rat burn injury model

Thermal burns are one of the common types of human injuries, causing in severe cases an extensive immune response both locally in the wound and having a systemic effect. The search for new means of local treatment of burn wounds remains an urgent task. The aim of this study was to investigate the wound healing properties of recombinant granulocyte-macrophage colony-stimulating factor (ryGM-CSF) and its prolonged chimeric form with human apolipoprotein AI (ryGM-CSF-apoAI) on the model of burn injury in rats. Material and methods. ryGM-CSF and ryGM-CSF-apoAI obtained by expression in yeast P. pastoris were used in this work. The study was performed on 27 Wistar rats, which were modeled burns of III degree. The wound-healing effect of recombinant cytokines was evaluated morphologically, and the expression of cytokine genes - markers of the course of the wound process and angiogenesis - was measured. Results and discussion. ryGM-CSF is known to accelerate wound healing. Human rGM-CSF on the rat burn model showed both the properties of a cytokine influencing angiogenesis, increasing the number of vessels, and being a foreign protein stimulated the immune response, increasing prolonged the number of lymphocytes and supporting inflammation. The chimeric form of cytokine ryGM-CSF-apoAI reduced inflammation, accelerated the change of wound healing phases and, as a consequence, reduced the number of neutrophils by 16 days. Unexpectedly, it induced maturation of vessels, which in this case had normal lumen, size, and were lined with endothelium. The ratio Angpt1 and Angpt2 gene mRNA content was 2-fold higher when ryGM-CSF-apoAI was used, compared to control and ryGM-CSF administration. Conclusions. With xenogeneous administration, recombinant human GM-CSF prolongs inflammation due to early lymphocytic response to foreign protein and increased neutrophil content at later wound healing periods. The chimeric form ryGM-CSF-apoAI reduces cytokine immunogenicity by promoting earlier replacement of neutrophils by macrophages and fibroblasts and stimulates maturation of high-grade blood vessels.

Recent advances in the role of neuroregulation in skin wound healing.

Neuroregulation during skin wound healing involves complex interactions between the nervous system and intricate tissue repair processes. The skin, the largest organ, depends on a complex system of nerves to manage responses to injury. Recent research has emphasized the crucial role of neuroregulation in maximizing wound healing outcomes. Recently, researchers have also explained the interactive contact between the peripheral nervous system and skin cells during the different phases of wound healing. Neurotransmitters and neuropeptides, once observed as simple signalling molecules, have since been recognized as effective regulators of inflammation, angiogenesis, and cell proliferation. The significance of skin innervation and neuromodulators is underscored by the delayed wound healing observed in patients with diabetes and the regenerative capabilities of foetal skin. Foetal skin regeneration is influenced by the neuroregulatory environment, immature immune system, abundant growth factors, and increased pluripotency of cells. Foetal skin cells exhibit greater flexibility and specialized cell types, and the extracellular matrix composition promotes regeneration. The extracellular matrix composition of foetal skin promotes regeneration, making it more capable than adult skin because neuroregulatory signals affect skin regeneration. The understanding of these systems can facilitate the development of therapeutic strategies to alter the nerve supply to the skin to enhance the process of wound healing. Neuroregulation is being explored as a potential therapeutic strategy for enhancing skin wound repair. Bioelectronic strategies and neuromodulation techniques can manipulate neural signalling, optimize the neuroimmune axis, and modulate inflammation. This review describes the function of skin innervation in wound healing, emphasizing the importance of neuropeptides released by sensory and autonomic nerve fibres. This article discusses significant discoveries related to neuroregulation and its impact on skin wound healing.

Expression of Tissue Remodeling- and Inflammation-Related Factors During the Wound-Healing Process in Humans.

Background/Objectives: There is a growing interest in the research of wound healing mechanisms worldwide. Particular attention has been paid to the expression of tissue remodeling- and inflammation-related factors. Herein, we investigate the expression patterns of TGF-β1, IL-6, TNF-a, uPA, uPA receptors, MMP-2, and MMP-9 through the four phases of the normal wound-healing process in humans. Methods: Twenty-two individuals presenting with a first episode of pilonidal sinus underwent surgical excision and the wound was left to heal by secondary intention. Sequential biopsies were collected on day 0 (operation), day 2 (inflammatory phase), day 9 (proliferative phase), and day 14 (tissue remodeling phase). The expression levels of the proteins were evaluated using reverse transcription-quantitative PCR. Statistical analyses were performed using GraphPad Prism software. One-way analysis of variance (ANOVA) with Dunn's Multiple Comparison post hoc test was used. Results: The results showed statistically significant differences in the expressions of the factors during wound healing (p < 0.05). TGF-b1 increased on days 2 and 9. TNF-a increased on day 2 and then decreased on day 9. Il-6 was increased on day 2 and decreased on days 9 and 14. uPa mRNA increased up to day 9 but its receptor exhibited high expression throughout the observation time. Finally, MMP-2 mRNA expression increased on day 2 and declined on days 9 and 14, while MMP-9 was highly expressed until the 14th postoperative day. Conclusions: Each factor investigated in this study has an important and distinct role in the normal wound repair procedure. Further investigation is required to evaluate the tissue-specific regulation of these factors and their potential use as therapeutic targets or prognostic biomarkers in wound healing.

Exploring in vitro efficacy of rCHAPk with antibiotic combinations, and promising findings of its therapeutic potential for clinical-originated MRSA wound infection.

The increasing threat of antimicrobial-resistant bacteria, particularly Staphylococcus aureus, which rapidly develops multidrug resistance and commonly colonizes wound surfaces, demands innovative strategies. Phage-encoded endolysins offer a dual-purpose approach as topical therapies for infectious skin wounds and synergistic agents to reduce high-dose antibiotic dependence. This study explores recombinant CHAPk (rCHAPk), efficiently synthesized within 3 h, displaying broad-spectrum antibacterial activity against 11 Gram-positive strains, including resistant variants, with rapid bactericidal kinetics. Application of 10 μg of rCHAPk reduced OD600 by 0.4 within 5 min against a clinical methicillin-resistant S. aureus (MRSA) strain. Combining rCHAPk (1.875 μg/mL) with oxacillin/vancomycin lowered their minimum bactericidal concentrations to 1 μg/mL from initial values over 64 μg/mL and 32 μg/mL, respectively, with a fractional inhibitory concentration index below 0.1. rCHAPk retained efficacy after one year of refrigerated storage. In in vivo experiments, rCHAPk outperformed commercial fucidin therapy in MRSA-induced murine wound models over two weeks, enhancing wound healing by modulating pro-inflammatory cytokine responses and the proliferative phase. This study, for the first time, investigates rCHAPk's in vitro combination with antibiotics and wound healing parameters, highlighting its potential as a potent antibacterial agent synergizing with antibiotics to address antibiotic-resistant bacterial wound infections.

Патоморфология, клинические проявления, методы лечения и профилактики при новой коронавирусной инфекции

The peculiarity of studying pathomorphological and clinical manifestations, prevention, and treatment strategies for COVID-19 is in the limited up-to-date information about structural changes of the affected organs. The aim was to identify pathomorphological and clinical features of COVID-19 and streamline therapeutic and preventive measures of the disease. We analyzed literature on predetermined criteria from January 1, 2020 to December 31, 2023 in the PubMed database. Lung disease in COVID-19 manifests in diffuse alveolar damage in exudative and proliferative phases. The damage to the cardiovascular system expresses in increased markers of myocardial necrosis and damage to pericytes and endothelial cells. Moreover, COVID-19 is characterized by acute tubular necrosis, submucosal vasculitis, and endothelial cell necrosis of the digestive organs. Patients may be asymptomatic or show non-respiratory (for example, palpitation, headache, nausea) and respiratory (dyspnea, tachypnea, hypoxemia) symptoms. Due to the lack of specific therapeutic intervention, oxygen therapy is indicated for patients. Keywords: COVID-19, SARS-CoV-2, pandemic, pathomorphology, RNA virus, diffuse alveolar damage

Silencing PADI-2 induces antitumor effects by downregulating NF-κB, Nrf2/HO-1 and AKT1 in A549 lung cancer cells.

This study aimed to investigate the tumorigenic role and regulatory pathways of peptidyl arginine deiminase 2 (PAD-2) in A549 lung cancer cells following treatment with small interfering RNA (PADI-2 siRNA) or the pharmacological pan-PAD inhibitor BB-Cl amidine. A549 lung cancer cells were treated with PADI-2 siRNA to knock down PADI-2 expression or with BB-Cl amidine to inhibit PAD2 activity. The effects on cell proliferation, migration, invasion, and cell cycle phases were assessed. Additionally, the expression levels of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), AKT serine/threonine kinase 1 (AKT), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin 6 (IL6), and p53 were analyzed to elucidate the underlying mechanisms involved. The manipulation of PAD-2 expression or activity significantly influenced tumor cell behavior. Knockdown of PADI-2 in A549 cells reduced cell proliferation by inhibiting the S and G2 phases and decreasing cell migration and invasion. Inhibition of PADI-2 expression also suppressed the protein levels of Nrf2 and HO-1 via suppression of the AKT/NF-κB pathway. Furthermore, this inhibition enhanced the senescence-associated secretory phenotype (SASP) through the regulation of IL6 and p53, resulted in significant upregulation of SASP factors mainly, p21, Lamin B1 and HMGB1. Downregulation of PADI-2 attenuated the proliferation, migration, and invasion of A549 lung cancer cells by modulating the Nrf2/HO-1/AKT signaling pathway. It also increased senescence in A549 lung cancer cells via IL6 and p53 key regulators. These findings highlight the potential of PADI-2 as a therapeutic target in lung cancer treatment.

The Potential Effect of Avocado Seeds to Promote Bone Formation of Tooth Extraction Sockets in Diabetic Rats.

Objective: There is a significant difference in post-extraction complications in diabetes mellitus (DM) patients as this condition can influence each phase of wound healing due to being delayed. Avocado seeds (Persea americana Mill.) contain many compounds for instance polyphenol catechin compounds, including catechin, cyanidin, chlorogenic acid and quinic acid that can accelerate bone formation after tooth extraction through various mechanism. Bone formation involve RUNX2 as differentiation factor and proliferation factor for osteoblast. and Osteoblast plays and important role and involves in the formation of woven bone. The purpose of this research is to prove the potential of avocado seed extracts as a natural intervention to accelerate bone healing in diabetic conditions by promoting anti-inflammatory and antioxidant activities, thereby improving bone formation. Materials and methods: This study is an experimental research with posttest-only control group design. The research samples were 20 white male Rattus norvegicus and were divided into two groups: control (K) and treated (KE). Then, the lower left incicives of the samples were extracted for immunohisto chemical staining to observe the expression of RUNX2, and H&amp;E staining to study osteoblast and woven bone at day 7 and 14. Data was analyzed using the SPSS Mann-Whitney and Spearman test. p &lt; 0.05 was considered statistically significant. Results: The results show significant differences between the control and treatment groups. The expression of RUNX2 and the number of osteoblasts were significantly higher in the treatment group. Additionally, there were significant correlations between RUNX2 expression, osteoblast count, and woven bone formation. This suggests that RUNX2 can enhance woven bone formation. The woven bone formed will eventually be replaced by mature bone. Conclusion: Avocado seeds have potential effect to accelerate bone formation in diabetic conditions by increasing the expression of RUNX2, osteoblast count, and woven bone formation.

Predicting inflammatory response of biomimetic nanofibre scaffolds for tissue regeneration using machine learning and graph theory.

Tissue regeneration after a wound occurs through three main overlapping and interrelated stages namely inflammatory, proliferative, and remodelling phases, respectively. The inflammatory phase is key for successful tissue reconstruction and triggers the proliferative phase. The macrophages in the non-healing wounds remain in the inflammatory loop, but their phenotypes can be changed via interactions with nanofibre-based scaffolds mimicking the organisation of the native structural support of healthy tissues. However, the organisation of extracellular matrix (ECM) is highly complex, combining order and disorder, which makes it difficult to replicate. The possibility of predicting the desirable biomimetic geometry and chemistry of these nanofibre scaffolds would streamline the scaffold design process. Fifteen families of nanofibre scaffolds, electrospun from combinations of polyesters (polylactide, polyhydroxybutyrate), polysaccharides (polysucrose, carrageenan, cellulose), and polyester ether (polydioxanone) were investigated and analysed using machine learning (ML). The Random Forest model had the best performance (92.8%) in predicting inflammatory responses of macrophages on the nanoscaffolds using tumour necrosis factor-alpha as the output. CellProfiler proved to be an effective tool to process scanning electron microscopy (SEM) images of the macrophages on the scaffolds, successfully extracting various features and measurements related to cell phenotypes M0, M1, and M2. Deep learning modelling indicated that convolutional neural network models have the potential to be applied to SEM images to classify macrophage cells according to their phenotypes. The complex organisation of the nanofibre scaffolds can be analysed using graph theory (GT), revealing the underlying connectivity patterns of the nanofibres. Analysis of GT descriptors showed that the electrospun membranes closely mimic the connectivity patterns of the ECM. We conclude that ML-facilitated, GT-quantified engineering of cellular scaffolds has the potential to predict cell interactions, streamlining the pipeline for tissue engineering.

Enhanced MRSA-infected wound healing using tannic acid cross-linked carboxymethyl chitosan/polyglutamic acid hydrogel for carbazole Delivery.

The rampant use of commercial antibiotics not only increases drug resistance but also causes a significant threat to human health. This study assessed the wound healing efficacy of hydrogels crafted from carboxymethyl chitosan (Cmc), polyglutamic acid (γ-PGA), tannic acid (TA), and carbazole (Car), with the aim of expediting the wound healing process. Hydrogels were formulated using Cmc/γ-PGA, Cmc/γ-PGA/TA, and Cmc/γ-PGA/TA/Car, followed by a thorough evaluation of their physicochemical attributes. Additionally, assessments encompassed cytotoxicity, antibacterial efficacy, wound contraction rates, histopathological parameters, immunofluorescent staining of CD31, CD86, and COL1A, along with the determination of serum concentrations of IL-1β, IL-6, and IL-10. The physicochemical analyses validated the successful synthesis of the hydrogels, which exhibited both safety and potent antibacterial properties. Topical application of Cmc/γ-PGA/TA/Car hydrogels notably accelerated wound contraction, as evidenced by heightened expression of CD31 and COL1A, alongside reduced serum concentrations of IL-1β and IL-6. In essence, the Cmc/γ-PGA/TA/Car hydrogel demonstrated a dual effect of mitigating inflammation and modulating the proliferative phase, that shows their abilities for application in the wound healing process.

Adipokines in Breast Cancer: Decoding Genetic and Proteomic Mechanisms Underlying Migration, Invasion, and Proliferation.

Adipokines, bioactive peptides secreted by adipose tissue, appear to contribute to breast cancer development and progression. While numerous studies suggest their role in promoting tumor growth, the exact mechanisms of their involvement are not yet completely understood. In this project, varying concentrations of recombinant human adipokines (Leptin, Lipocalin-2, PAI-1, and Resistin) were used to study their effects on four selected breast cancer cell lines (EVSA-T, MCF-7, MDA-MB-231, and SK-Br-3). Over a five-day proliferation phase, linear growth was assessed by calculating doubling times and malignancy-associated changes in gene and protein expression were identified using quantitative TaqMan real-time PCR and multiplex protein analysis. Migration and invasion behaviors were quantified using specialized Boyden chamber assays. We found significant, adipokine-mediated genetic and proteomic alterations, with PCR showing an up to 6-fold increase of numerous malignancy-associated genes after adipokine-supplementation. Adipokines further altered protein secretion, such as raising the concentrations of different tumor-associated proteins up to 13-fold. Effects on proliferation varied, however, with most approaches showing significant enhancement in growth kinetics. A concentration-dependent increase in migration and invasion was generally observed, with no significant reductions in any approaches. We could show a robust promoting effect of several adipokines on different breast cancer cells in vitro. Understanding the interaction between adipose tissue and breast cancer cells opens potential avenues for innovative breast cancer prevention and therapy strategies. Our findings indicate that antibodies against specific adipokines could become a beneficial component of clinical breast cancer treatment in the future.

A Comparison Between The Administration of Povidone Iodine 10% and Aloe Vera Gel on The Healing of Wistar Rat Burns (Rattus Norvegicus)

Aloe vera has long been known for its diverse properties, including wound healing. Compounds such as saponins, tannins, and polyphenols contained in aloe vera provide anti-inflammatory, antibacterial, and accelerate tissue regeneration. This study aims to compare the effectiveness between Povidone Iodine 10% and Aloe Vera Gel on burn wound healing in Wistar Rats (Rattus norvegicus). The study used an experimental design with post-test only control group design. A total of 33 rats were divided into three groups: control group without treatment, Povidone Iodine 10% group, and Aloe Vera Gel group. Observations were made on days 0, 7, and 14 with parameters of wound diameter, percentage of wound reduction, and histopathological analysis to assess the amount of blood vessel formation, fibroblasts, macrophages, and epidermal thickness. The results showed that the administration of Aloe Vera Gel is effective in healing burn wounds, especially in the inflammatory and proliferation phases.

A bacteria-responsive nanoplatform with biofilm dispersion and ROS scavenging for the healing of infected diabetic wounds.

Delayed wound healing in patients with diabetes remains a major health challenge worldwide. Uncontrolled bacterial infection leads to excessive production of reactive oxygen species (ROS) and persistent inflammatory responses, which seriously hinder conventional physiological healing processes after injury. Biofilms, as protective barriers for bacteria, pose a critical obstacle to effective bacterial eradication. Herein, an innovative therapeutic nanoplatform with in situ antibacterial and antioxidant properties is developed for enhancing infected diabetic wound healing. The enrichment of phenylboronic acid (PBA) moieties on the nanoplatform enhances biofilm penetration, actively anchors and aggregates the enclosed bacteria through the "multivalent effect", with an anchoring efficiency as high as 80%. Additionally, glycine moieties on the nanoplatform ensure spatial extensibility by charge repulsion, enabling targeted antibiotic release around bacteria. This precise antibacterial effect increases the bactericidal activities of the nanoplatform against S. aureus or P. aeruginosa by 25% and 22% respectively, effectively eliminating the bacteria and dispersing the biofilms. Furthermore, 3,4-dihydropyrimidin-2(1H)-one (DHPM) moieties act as ROS scavengers that alleviate oxidative stress and inflammatory responses, promoting tissue repair progression into the proliferative phase characterized by increased extracellular matrix deposition, angiogenesis, and granulation tissue formation, ultimately accelerating diabetic wound healing. Overall, this work presents an innovative bacterial response strategy for achieving in situ antibacterial and antioxidant effects in infected tissues and provides a promising therapeutic approach for treating infected diabetic wounds. STATEMENT OF SIGNIFICANCE: : Infected diabetic wound management remains a major world health issue. Severe bacterial infection leads to excessive oxidative stress and persistent inflammatory response, which seriously hinders the wound healing process. As a protective barrier for bacteria, biofilms are a key obstacle to effective bacterial clearance. This study provides a bacteria-responsive nanoplatform for the healing of infected diabetic wounds. The nanoplatform not only exhibits improved biofilm penetration but also actively anchors the enclosed bacteria and enables targeted antibiotic release to disperse the biofilm. The DHPM moieties of the nanoplatform act as ROS scavengers which could alleviate inflammatory responses, promote tissue repair progression into the proliferative phase, and ultimately accelerate diabetic wound repair.

Integrated 3D-Printed Hollow Microneedle Array and Lateral Flow Immunoassay for Point-of-Care Wound Healing Monitoring.

Chronic wound management requires continuous monitoring to assess healing and guide treatment. We developed a hollow microneedle array patch integrated with a lateral flow immunoassay strip to address the need for convenient, home-based diagnostics. This device extracts wound exudate directly from the wound matrix, overcoming the limitations of conventional swab sampling, which relies on surface exudate collection. The patch provides a minimally invasive, rapid solution to assess the wound healing phase. The immunoassay delivers a colorimetric signal visible to the naked eye, facilitating straightforward interpretation by clinicians within 10 min. In a clinical study involving 90 patients, matrix metalloproteinase 8 (MMP-8) was identified as a critical biomarker, achieving 80.3% sensitivity in detecting the proliferative phase. A specific lateral flow immunoassay for MMP-8 was developed with a detection limit of 0.7 ng/mL, lower than the threshold level for the proliferative healing phase (164.7 ng/mL). The hollow microneedle array patch was 3D-printed for cost-efficiency (less than €0.10 per patch) with a height of 865 ± 6 μm, allowing for a painless, easy sampling. Mechanical tests confirmed the durability of the patch, while cytotoxicity assays demonstrated its biocompatibility. Prevalidation using an ex vivo skin model showed the patch could extract 61 ± 6 μL of exudate, with a 122% recovery rate for MMP-8 detection, highlighting its efficiency in biomarker extraction. This approach represents a significant advance in decentralized wound care, offering a low-cost, user-friendly tool for at-home monitoring of chronic wounds, potentially improving early intervention and reducing hospital visits.

Anti-Scar Effects of Micropatterned Hydrogel after Glaucoma Drainage Device Implantation.

Excessive fibrosis is the primary factor for the failure of glaucoma drainage device (GDD) implantation. Thus, strategies to suppress scar formation in GDD implantation are crucial. Although it is known that in implanted medical devices, microscale modification of the implant surface can modulate cell behavior and reduce the incidence of fibrosis, in the field of ophthalmic implants, especially the modification and effects of hydrogel micropatterns have rarely been reported. Here, we designed the patterned gelatin/acrylamide double network hydrogel and developed an innovative GDD with micropattern to suppress inflammatory and fibroblast activation after GDD implantation. Pattern topography suppressed F-actin expression and mitigated actin-dependent nuclear migration of myocardin-related transcription factor A (MRTF-A) during the proliferative phase after GDD implantation. Ultimately, the expression of α-smooth muscle actin (α-SMA), a key fibrosis-related gene product, was suppressed. Moreover, the modified GDD effectively controlled intraocular pressure (IOP), mitigated fibrous formation, and remodeled extracellular matrix (ECM) collagen distribution invivo. Therefore, the novel GDD with surface patterning interventions provides a promising strategy to inhibit scar formation after GDD implantation and raise the efficacy of GDD implantation.