Wound Healing Research Articles

The RNA N6-methyladenosine demethylase FTO regulates ATG5 to inhibit malignant progression of uveal melanoma.

This research aimed to identify the function of fat mass- and obesity-associated protein (FTO), an eraser of N6-methyladenosine (m6A), and explore its possible mechanisms in uveal melanoma (UVM). We performed quantitative real-time PCR (qPCR), Western blotting and gene correlation analysis with GEPIA2 to assess FTO expression and identify its potential targets in UVM. CCK-8, colony formation, cell cycle, cell apoptosis, wound healing and Transwell invasion assays were utilized to assess cell viability, cell cycle distribution, apoptosis, migration and invasion. Western blotting, qPCR and methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) were carried out to explore the underlying mechanism of FTO in 2 UVM cell lines. FTO, a key m6A demethylase, was found to be upregulated in human UVM tissues compared with normal choroid tissues. Knockdown of FTO in Mel270 and OMM2.3 cells significantly promoted proliferation and migration and suppressed apoptosis. Mechanistically, knockdown of FTO decreased the expression of ATG5, an autophagy-related gene, leading to attenuation of autophagosome formation, thereby inhibiting autophagy. Upon FTO knockdown, increased levels of methylated ATG5 and decreased ATG5 stability were detected. Furthermore, ATG5 dramatically alleviated FTO downregulation-induced tumor growth and metastasis. Our research highlights the importance of the m6A demethylase FTO in UVM by demonstrating that it direct regulates ATG5-induced autophagy in an m6A-dependent manner. These findings suggest that FTO may serve as a potential therapeutic target for UVM.

Psychological factors and diabetic foot ulceration: a scoping review of the bi-directional relationship between diabetic foot ulcer healing and mental health factors

Introduction Diabetic foot ulceration (DFU) is a major complication of diabetes and is associated with high morbidity and mortality rates. Psychological factors are believed to play a role in wound healing, but it remains uncertain if psychological interventions can help individuals with an active DFU, or a history of DFUs, to achieve complete or improved wound healing or prevent recurrence. Objective The objective of the proposed scoping review is to investigate the emotional consequences/burden of living with DFU and to examine how psychosocial factors may impact progression and management of ulcerations. Methods This review will be conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews and the Preferred Reporting Items for Systematic reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) will guide the reporting of results. Discussion While factors such as stress, depression, social support, and adherence to treatment have been identified as variables that may negatively affect DFU healing, there is a need for a greater understanding of how psychological and behavioural variables such as these may influence ulcer incidence, healing and recurrence in people with diabetes. This review will comprise of a broad and systematically mapped synthesis of the identified data. Findings will be used to provide a better understanding of the bi-directional relationship between DFU and psychological variables and will provide direction for the development or adaptation of a tailored psychological intervention that will aim to optimise wellbeing and improve outcomes for individuals with DFU.

Insights into the functional properties of thioredoxin domain-containing protein 12 (TXNDC12): Antioxidant activity, immunological expression, and wound-healing effect in yellowtail clownfish (Amphiprion clarkii)

Thioredoxin domain-containing protein 12 (TXNDC12) is a member of the thioredoxin-like superfamily that contributes to various thiol-dependent metabolic activities in all living organisms. In this research, the TXNDC12 gene from yellowtail clownfish (Amphiprion clarkii) was structurally characterized using in silico tools, assessed for immunological expression, and evaluated for biological activity using recombinant protein and cellular overexpression. The deduced coding sequence of AcTXNDC12 comprised a 522-bp nucleotide, encoding 173 amino acids with a predicted molecular mass of 19.198 kDa. The AcTXNDC12 protein consists of a66WCGAC70 active motif and a170GDEL173 signature. The highest tissue-specific expression of AcTXNDC12 was observed in the brain tissue, with significant modulation observed in the blood and gill tissues following stimulation of polyinosinic: polycytidylic acid, lipopolysaccharides (LPS), and Vibrio harveyi. In functional assays, recombinant AcTXNDC12 protein (rAcTXNDC12) showed insulin disulfide reduction activity, 2,2′-azino-di-(3-ethylbenzthiazoline sulfonic acid) decolorization antioxidant capacity, and ferric (Fe3+) reducing antioxidant potential. Additionally, a significant reduction in nitric oxide production was observed in AcTXNDC12-overexpressed RAW 264.7 cells upon LPS stimulation. Furthermore, genes associated with the regulation of oxidative stress, including nuclear factor erythroid 2-related factor 2 (Nrf2), catalase (Cat), peroxiredoxin 1 (Prx1), and ribonucleotide reductase catalytic subunit M1 (Rrm1) were significantly upregulated in fathead minnow cells overexpressing AcTXNDC12 in response to H2O2 treatment. The scratch wound healing assay demonstrated tissue regeneration and cell proliferation ability upon AcTXNDC12 overexpression. Altogether, the current study elucidated the antioxidant activity, immunological importance, and wound-healing effect of the AcTXNDC12 gene in yellowtail clownfish, providing valuable insights for advancing the aquaculture of A. clarkii fish.

3D nanofiber sponge based on natural insect quaternized chitosan/pullulan/citric acid for accelerating wound healing

Extensive traumatic injuries and difficult-to-heal wounds, induced by many circumstances, impose a significant social and economic burden on an annual basis. Thus, innovative wound dressings that encourage wound healing are greatly needed. In this work, we prepared a novel insect chitosan (MCS) using waste pupal shells from housefly (Musca domestica L.) culture. After conducting comparative investigations with commercially available chitosan, it was shown that MCS exhibited comparable qualities and may be used as a substitute source of commercial chitosan. A quaternized chitosan/pullulan/citric acid three-dimensional nanofiber sponge (3D-NS) of natural origin was prepared by electrostatic spinning and gas foaming techniques after MCS was quaternized. In vitro, tests showed that the 3D-NS had a higher liquid absorption capacity than the two-dimensional nanofibrous membrane (2D-NM). Additionally, the 3D-NS showed improved hemostatic, pro-cell proliferation, antibacterial, and anti-inflammatory qualities. In vitro, tests demonstrated that 3D-NS could inhibit the release of inflammatory factors, promote angiogenesis, accelerate collagen deposition, and promote wound contraction. These effects considerably facilitated the healing process of wounds in rats with full-thickness skin damage. In conclusion, the great bioactivity and physicochemical properties of 3D-NS render it an optimal candidate for developing novel wound dressings.

Regenerative Medicine Approaches for Skin Wound Healing: from Allografts to Engineered Skin Substitutes

Abstract Purpose of the Review Recent advancements in tissue engineering and regenerative medicine have paved the way for innovative solutions in skin regeneration, particularly for extensive burns and full-thickness wounds where traditional approaches are limited. The purpose of the review is to explore the integration of bioactive materials, stem cell therapies, and tissue-engineered skin substitutes and their role in revolutionizing wound healing and skin transplantation. Recent Findings Studies leveraging natural and synthetic biomaterials as scaffolds, alongside the regenerative capabilities of mesenchymal stem cells (MSCs) and other cellular therapies, underscore the potential to enhance tissue repair, minimize scarring, and improve overall clinical outcomes. The development of multifunctional biomaterials and the advent of cutting-edge techniques such as 3D bioprinting and nanomedicine further propel the field, offering personalized and effective solutions. As these technologies evolve, they hold promise for more efficient, patient-specific skin grafting, reducing the need for systemic immunosuppression and enhancing graft survival. Summary The critical advancements in biomaterials, stem cell therapies, and tissue engineering, outline a course toward more effective and personalized skin regeneration therapies.

Examination of the effectiveness of ornithine and glutamine-containing foods on wound healing

Examination of the effectiveness of ornithine and glutamine-containing foods on wound healing

Interference of FZD2 suppresses proliferation, vasculogenic mimicry and stemness in glioma cells via blocking the Notch/NF‑κB signaling pathway.

Frizzled family protein 2 (FZD2) is widely associated with tumor development and metastasis. The present study aimed to gain an insight into the role and regulatory mechanism of FZD2 in glioma. The expression level of FZD2 in normal astrocyte and glioma cells was determined by reverse transcription-quantitative PCR and western blotting, and cell transfection was conducted for FZD2 expression knockdown. Malignant behaviors including cell proliferation, migration and invasion, vasculogenic mimicry (VM) and cell stemness were determined using Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine (EdU) staining, colony formation, wound healing, Transwell, 3D culturing and sphere formation assays. The expression levels of proteins related to stemness, epithelial-mesenchymal transition (EMT) and Notch/NF-κB signaling were measured by western blotting. Then, the Notch agonist, Jagged-1 (JAG), was adopted for rescue experiments. The results demonstrated that FZD2 was highly expressed in glioma cells. Interference of FZD2 expression suppressed the proliferation of glioma cells, as evidenced by the reduced cell viability and the number of EdU+ cells and colonies. Meanwhile, the reduced sphere formation ability and decreased protein expression of Nanog, Sox2 and Oct4 following FZD2 knockdown confirmed that FZD2 repressed cell stemness in glioma. Additionally, FZD2 knockdown suppressed the migration, invasion, EMT and VM formation capabilities of glioma cells, and also blocked the Notch/NF-κB signaling pathway. Furthermore, activation of Notch by JAG treatment partially reversed the aforementioned FZD2 knockdown-mediated changes in glioma cell malignant behaviors. In conclusion, FZD2 may contribute to glioma progression through activating the Notch/NF-κB signaling pathway, providing a plausible therapeutic target for the treatment of glioma.

Unveiling the Various Analytical Techniques of Polyphenols for Pharmacological Activity and Nanotechnological Delivery in Wound Healing

Polyphenols are a diverse group of molecules known for their broad range of biological activities, making them valuable in therapeutic applications, including wound healing. Chronic wounds, which are often complicated by persistent infections and the rise of antibiotic resistance, present a significant challenge in the treatment. Traditional antibiotics are becoming less effective, necessitating the exploration of new antimicrobial agents. Polyphenols like hesperidin, chlorogenic acid, quercetin, and curcumin are promising candidates due to their natural antibacterial properties, offering an effective alternative to conventional antibiotics for treating chronic wounds. However, polyphenols face challenges such as limited stability, which can reduce their effectiveness at the wound site. Furthermore, to overcome these limitations, polymer-based systems have been developed as carriers to stabilize polyphenols and control their release over time, thereby enhancing their therapeutic efficacy. This article explores the potential of polyphenols as natural antibacterial agents and highlights various nanoparticulate systems as effective carriers for treating chronic wounds.

Impact of Polydeoxyribonucleotides on the Morphology, Viability, and Osteogenic Differentiation of Gingiva-Derived Stem Cell Spheroids

Background and Objectives: Polydeoxyribonucleotides (PDRN), composed of DNA fragments derived from salmon DNA, is widely recognized for its regenerative properties. It has been extensively used in medical applications, such as dermatology and wound healing, due to its ability to enhance cellular metabolic activity, stimulate angiogenesis, and promote tissue regeneration. In the field of dentistry, PDRN has shown potential in promoting periodontal healing and bone regeneration. This study aims to investigate the effects of PDRN on the morphology, survival, and osteogenic differentiation of gingiva-derived stem cell spheroids, with a focus on its potential applications in tissue engineering and regenerative dentistry. Materials and Methods: Gingiva-derived mesenchymal stem cells were cultured and formed into spheroids using microwells. The cells were treated with varying concentrations of PDRN (0, 25, 50, 75, and 100 μg/mL) and cultivated in osteogenic media. Cell morphology was observed over seven days using an inverted microscope, and viability was assessed with Live/Dead Kit assays and Cell Counting Kit-8. Osteogenic differentiation was evaluated by measuring alkaline phosphatase activity and calcium deposition. The expression levels of osteogenic markers RUNX2 and COL1A1 were quantified using real-time polymerase chain reaction. RNA sequencing was performed to assess the gene expression profiles related to osteogenesis. Results: The results demonstrated that PDRN treatment had no significant effect on spheroid diameter or cellular viability during the observation period. However, a PDRN concentration of 75 μg/mL significantly enhanced calcium deposition by Day 14, suggesting increased mineralization. RUNX2 and COL1A1 mRNA expression levels varied with PDRN concentration, with the highest RUNX2 expression observed at 25 μg/mL and the highest COL1A1 expression at 75 μg/mL. RNA sequencing further confirmed the upregulation of genes involved in osteogenic differentiation, with enhanced expression of RUNX2 and COL1A1 in PDRN-treated gingiva-derived stem cell spheroids. Conclusions: In summary, PDRN did not significantly affect the viability or morphology of gingiva-derived stem cell spheroids but influenced their osteogenic differentiation and mineralization in a concentration-dependent manner. These findings suggest that PDRN may play a role in promoting osteogenic processes in tissue engineering and regenerative dentistry applications, with specific effects observed at different concentrations.

Amentoflavone Induces Ferroptosis to Alleviate Proliferation, Migration, Invasion and Inflammation in Rheumatoid Arthritis Fibroblast-like Synoviocytes by Inhibiting PIN1.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that is prevalent worldwide and seriously threatens human health. RA-fibroblast-like synoviocytes (FLS) play important roles in almost all aspects of RA progression. This study aimed to study the effect of Amentoflavone (AMF), a polyphenol compound derived from extracts of Selaginella tamariscina, on the abnormal biological behaviors of RA-FLS. The immortalized human RA-FLS cell line (MH7A) was treated with AMF or transfected with small interfering RNAs (siRNAs) targeting peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1). Then, cell viability was detected by CCK-8 assay. EDU staining, wound healing and transwell assays were employed to measure the capacities of MH7A cell proliferation, migration and invasion. The levels of inflammatory factors were assessed using ELISA kits. Additionally, ferroptosis was analyzed by detecting Fe2+ content, lipid reactive oxygen species (ROS) level and expression of ferroptosis-related proteins. Pull-down assay was employed to verify the targeted binding of AMF to PIN1. Further, PIN1 overexpression or ferroptosis inhibitor Ferrostatin-1 (Fer-1) addition was conducted to elucidate the regulatory mechanism of AMF on PIN1 and ferroptosis. Results revealed that AMF intervention or PIN1 knockdown inhibited the proliferation, migration, invasion and inflammation in MH7A cells. AMF facilitated lipid peroxidation and ferroptosis in MH7A cells. Moreover, AMF targeted inhibition of PIN1 expression, and PIN1 overexpression restored the promoting effect of AMF on lipid peroxidation and ferroptosis in MH7A cells. Besides, Fer-1 reversed the impacts of AMF on the abnormal biological behaviors of MH7A cells. In summary, AMF induced ferroptosis to inhibit the proliferation, migration, invasion and inflammation in RA-FLS by inhibiting PIN1, providing a promising candidate for RA treatment.

The Efficacy of Negative Pressure Wound Therapy (NPWT) on Healing of Diabetic Foot Ulcers: A Literature Review.

Diabetes mellitus is a complex disorder that requires continuous management to control blood sugar levels and prevent complications. Diabetic foot ulcers (DFU) are the most common complication in diabetic patients. A popular therapy modality with considerable advantages in the management of diabetic foot ulcers today is negative pressure wound therapy (NPWT). This study aimed to review related articles about the efficacy as well as the complications or adverse effects of using NPWT on the healing of DFUs. Searching English databases from PubMed, Ebscohost, Proquest and Science Direct was done to identify relevant citations published between January 2017 and January 2022. A combination of terms was used with the boolean formulation of "negative pressure wound therapy OR NPWT" OR "vacuum-assisted closure or VAC" AND "diabetic foot ulcers OR diabetic foot wound" AND "wound healing" AND "Conventional dressings" and map terms were also used for the subject heading. Some potentially relevant citations of articles from the bibliographies are also reviewed. This study included 8 related articles consisting of 6 RCTs, 1 cohort study and 1 Quasy experimental study. There were various methodological techniques for using NPWT and outcome measures among studies. The results of this literature review showed that NPWT was more efficacious than the other conventional or advanced moist dressings. This therapy revealed a faster healing time with complete wound healing and formation of granulation tissue and reduction in wound size. The complications or adverse effects of NPWT, such as amputation rate, bleeding and pain, were not different from conventional or advanced moist dressings, though. NPWT was more efficacious than other conventional or advanced moist dressings for the healing of DFUs. However, complications or adverse effects of using this therapy showed no significant difference with other conventional or advanced moist dressings.

Production and Characterization of Electrospun Chitosan, Nanochitosan and Hyaluronic Acid Membranes for Skin Wound Healing.

The development of new wound dressings made from biomaterials, which offer a better cost-benefit ratio and accelerate the healing process, is increasing nowadays. Various biopolymers can be electrospun to form functional membranes for wound healing. Therefore, in this study, chitosan and nanochitosan membranes with or without hyaluronic acid were prepared using the electrospinning technique, characterized and evaluated in the healing of skin wounds in rats. Chitosan and nanochitosan solutions, with or without hyaluronic acid, were prepared at concentrations of 1%-4% using PEO (polyethylene oxide) and subjected to the electrospinning process to obtain membranes characterized by scanning electron microscopy (SEM), mechanical tests, and antimicrobial activity. The healing effect of the membranes was evaluated by monitoring the area of the lesions, contraction of the wounds, histologic analysis, and induction of pro-inflammatory cytokine (IL-1 α and TNF-α) production in rats. The nanochitosan and nanochitosan membranes with hyaluronic acid achieved greater fiber diameter and uniformity, resistance, elasticity, and thermal stability, in addition to good adhesion to the wound bed and permeation capacity. Despite not presenting antimicrobial activity in vitro, they contributed to the production of pro-inflammatory interleukins in the animals tested, provided physical protection, reduced the wound area more markedly until the seventh day of the evaluation, with an acceleration of the healing process and especially when functionalized with hyaluronic acid. These results indicate that the membranes may be promising for accelerating the healing process of chronic wounds in humans.

Comprehensive analysis of bulk, single-cell RNA sequencing, and spatial transcriptomics revealed IER3 for predicting malignant progression and immunotherapy efficacy in glioma

BackgroundAs part of stress-triggered molecules, immediate early response 3 (IER3) dysregulation has been reported to sustain pro-oncogenic pathways and precede malignant transformation. However, the role of IER3 in glioma pathology is ill-defined.MethodsImmunohistochemistry (IHC) assay and publicly available glioma datasets were used to calculate the IER3 expression level in glioma. Wound healing, invasion and cell counting kit-8 (CCK8) assays were applied to measure the cell viability and capacities of migration and invasion of glioma cells in vitro. The immunofluorescence (IF) assay was used to assess the expression associations of IER3 with CCL2 and TGFBI. Cox regression analysis and Kaplan-Meier (K-M) curve were introduced to compute the prognosis-predicting value of IER3. Variations in copy number (CNVs), single nucleotide (SNVs), and methylation profiles were analyzed to illustrate the epigenetic modifications of IER3. Gliomas were divided into two subgroups using the restricted cubic spline (RCS) method.Results IER3was overexpressed and hypomethylated in gliomas and significantly associated with the dismal prognosis of glioma samples. Samples in the high IER3 subgroup were characterized by increased infiltration of tumor-associated monocytes/macrophages (TAMMs), as well as the elevated sensitivity to Dabrafenib, an inhibitor of BRAF. In addition, this subgroup demonstrated a low mutation rate of IDH, high gain rates of BRAF, ELTD1, and PDGFA. Gliomas with relatively low IER3 expression demonstrated a less invasive subtype and were featured by favorable prognosis, increased response to immunotherapy, and adjuvant chemotherapy plus radiotherapy. The IF assay revealed that IER3 was co-localized and co-expressed with TGFBI. The glioma cells with small interfering RNA (siRNA)-silenced IER3 displayed lower migration, invasion, proliferation, and cell viability than the control group.ConclusionsIn this study, we identified IER3 upregulation as an essential biomarker that could assist in adjuvant therapy and prognosis prediction for gliomas.

Transcription factor ETS1‑mediated ECT2 expression promotes the malignant behavior of prostate cancer cells.

Prostate cancer remains the most prevalent malignancy diagnosed in men worldwide. Epithelial cell transforming sequence 2 (ECT2) is an oncogene involved in the progression of human tumors. The present study aimed to explore the involvement of ECT2 in prostate cancer and its participation in the malignant progression of prostate cancer. ECT2 expression in prostate cancer cell lines was examined via reverse transcription-quantitative PCR and western blotting. The effects of knockdown of ECT2 expression in PC-3 cells on cellular biological behaviors, including proliferation, migration and invasion, were examined using Cell Counting Kit-8, colony formation, wound healing and Transwell assays. The glycolysis level was determined based on the lactate release, glucose uptake, oxygen consumption rate and extracellular acidification rate. The binding relationship between ECT2 and ETS1 was verified using luciferase reporter and chromatin immunoprecipitation assays. The results indicated that ECT2 was highly expressed in prostate cancer cell lines. Knockdown of ECT2 expression could inhibit cell proliferation, migration, invasion and glycolysis. In addition, the transcription factor ETS1 could directly bind to the ECT2 promoter and positively regulate ECT2 expression. These data were combined with the results of rescue experiments and demonstrated that the inhibitory effects of the knockdown of ECT2 expression on the malignant behavior and glycolysis of prostate cancer cells were partially reversed by ETS1 overexpression. In conclusion, ETS1 induced transcriptional upregulation of ECT2 and enhanced the malignant biological behaviors of prostate cancer cells, thereby promoting the progression of prostate cancer. This evidence provides a theoretical basis for the treatment of prostate cancer.

Development of a gel formulation with pomegranate peel extract (Punica granatum L.) for antimicrobial and wound healing action

The aim of this study was to evaluate the feasibility of producing a gel from pomegranate peel extract for topical application, specifically for antimicrobial and wound healing purposes. Initially, the dry crude pomegranate peel extract (DCPPE) was analyzed for its phenolic profile using HPLC and by determining the total phenolic content (TPC), and total antioxidant activity (TAA). Carbomer-based gels were prepared and subjected to antimicrobial susceptibility tests to determine the optimal concentration of DCPPE (1.25 %, 2.5 %, and 3.75% w/w) in the formulations. Then, gel was produced in larger quantities and submitted to physicochemical and microbiological tests after being stored at room temperature or under refrigeration for 90 days. Gallic acid, ellagic acid, and punicalagin A and B were identified in DCPPE. The TPC was measured at 61.92 mg of gallic acid equivalent per gram (mg.GAE.g−1) and the TAA was 93.8 % (solution at 40 µL.mL−1), demonstrating superiority over butylhydroxytoluene (BHT) and gallic acid solutions at equivalent concentrations. Antimicrobial susceptibility tests indicated a significant difference (p < 0.05) for the 2.5% w/w DCPPE gel against Staphylococcus aureus and Candida albicans, which was the chosen concentration. Over a 30-day period under both storage conditions, there was no significant difference in pH values, and the reduction of TPC in the refrigerated formulation was <10 %, indicating good stability. Furthermore, the in vitro antimicrobial activity of the gel remained effective against all tested strains. These results suggest that the medicinal carbomer-based gel with DCPPE at 2.5% w/w has potential as a pharmaceutical form for antimicrobial and wound healing purposes. The utilization of DCPPE as a pharmaceutical bio-input for the gel is a sustainable approach to valorizing pomegranate peel biowaste.

Effectiveness of Polyhexamethylene biguanide Liquid for Chronic Wound Washing

Background: Chronic wounds occur due to a failure in the wound healing process and are currently one of the health problems that require proper management. Some types of chronic wounds include venous leg ulcer (VLU), diabetic foot ulcer (DFU). The use of wound washes is one of the factors that play an important role in chronic wound healing. Purpose: Effectiveness of Polyhexamethylene biguanide in cleaning wounds from old dressing residue and reducing bacterial counts. Methods: Quasi experiment without control group to 30 samples using Polyhexamethylene biguanide with BWAT wound assessment instrument (Bates Jensen Wound Assessment Tool), data processing using SPSS program with Wilcoxon test. Results: 17 (40%) were late elderly (56-65 years), 3 (20%) were early elderly (46-55 years), and 10 (20%) were seniors (&gt; 65 years). The bivariate Wilcoxon test shows that Polyhexamethylene biguanide wound cleansing liquid significantly changes mean values before and after wound care. Before wound care, the mean value was 34.65 ± 14.15, and after treatment, it was 7.87 ± 3.16. The mean difference is -5.14 (-12.24 to 2.56) with a 95% confidence interval, and the p value is 0.031. Conclusion: Polyhexamethylene biguanide was shown to be effective as a wound wash to support the healing process of chronic wounds. Suggestions based on the results of this study can be used for efficient chronic wound washing for patients.

SHR6390 Combined with Cabozantinib Inhibits Tumor Progression in the Hepatocellular Carcinoma Mouse Model.

A novel CDK4/6 inhibitor SHR6390 has shown significant anti-tumor effects. However, its role in hepatocellular carcinoma (HCC) remains unknown. To explore the inhibitory effect of combination treatment with SHR6390 and cabozantinib in HCC, and its antitumor mechanism, so as to provide a more effective therapeutic strategy for HCC patients. We investigated SHR6390, monotherapy or combined with cabozantinib, by CCK8, wound healing, transwell, western blotting, immunohistochemistry and mouse model of a subcutaneous tumor. Our results show that SHR6390 exhibited potent anti-proliferative activity against HCC in a dose-dependent manner. SHR6390 combined with cabozantinib exhibited more potent inhibition of cell viability, migration and invasion. In terms of potential mechanisms, we found that cabozantinib could lead to phosphorylation of Rb, which was reduced in SHR6390 and combined groups. SHR6390 monotherapy inhibited the growth of subcutaneous HCC tumors, besides, the combination treatment with SHR6390 and cabozantinib exerted synergistic anti-tumor activity in vivo Conclusion: SHR6390 is effective against HCC, monotherapy or combined with cabozantinib.

Comprehensive Management of Degloving Soft Tissue Injuries of the Extremity: A 12-year Retrospective Study

BackgroundDegloving soft tissue injuries (DSTIs) of the extremities, which are often underestimated in terms of their severity, present significant challenges to reconstructive surgeons. We propose a comprehensive management protocol to standardize the reconstructive approach, aiming for successful treatment of these devastating injuries. MethodsWe retrospectively analyzed data from consecutive patients with extremity DSTIs over a 12-year period. Patients were categorized into three age groups (0–17, 18–65, and > 65 years) to highlight the different treatment options based on age. Various surgical techniques were employed depending on the injury pattern. Treatment strategies for each patient were individualized based on age, underlying conditions, and injury type. Wound healing, complications, and functional outcomes were recorded. ResultsOf the hospitalized patients, 20 were lost to follow-up, and 105 were included in the analysis. The mean age at the time of injury was 40 ± 44.9 years, with a mean follow-up of 30.1 ± 12.7 months. Furthermore, 19% of patients were aged 0–17 years, 61% were aged 18–65 years, and 20% were aged > 65 years. Treatment plans were personalized based on injury characteristics, with numerous patients being treated with a combination of multiple surgical techniques. Older patients had significantly longer wound healing times and delayed return to activities of daily living compared to the other age groups. Overall, patients were generally satisfied with their outcomes. The total complication rate was 46.7%, with 79.5% being categorized as major complications. Each complication was addressed with a tailored treatment plan. ConclusionThe management of DSTIs should be individualized, taking into account the specific characteristics of each injury. Age and medical fitness play crucial roles in determining both the surgical approach and prognosis. An accurate initial evaluation and thorough debridement are essential for optimal outcomes.

Application of a customized 3D-printed osteotomy guide plate for tibial transverse transport

Enhance the efficiency of tibial transverse transport by employing customized 3D-printed osteotomy guide plates and striving to improve precision through CT evaluation for enhanced guide design. 17 diabetic foot patients were treated with the plate for tibial transverse transport. Preoperatively, we collected DICOM data from the affected tibia’s CT and designed the geometric parameters of the tibial cortical bone window. A customized 3D-printed osteotomy guide plate was then fabricated using 3D printing technology. Postoperative X-ray and CT evaluations, conducted at two and five weeks post-surgery, assessed five crucial geometric parameters of the bone window. Measurements included the distance from the upper edge of the tibial cortical bone window to the tibial plateau, the distance from the anterior edge of the tibial cortical bone window to the bone ridge, the height of the tibial cortical bone window, the center-to-center distance between the 4.0 mm diameter Schanz pin and the osteotomy Kirschner pin, and the center-to-center distance of the 4.0 mm diameter Schanz pin. These measured parameters were subsequently compared to the preoperative design parameters. The Clinical trial registration number is ChiCTR2400087174. CT measurements showed no significant differences (P > 0.05) from preoperative design parameters across the five evaluated aspects. The average osteotomy duration was 35 ± 15 min with no bone window fractures. The bone window aligned effectively with the tibial shaft, achieving complete incorporation after distraction. A 4 to 8-month postoperative follow-up confirmed full healing of the tibial surgical wound and diabetic foot wounds. Utilizing customized 3D-printed osteotomy guide plates in tibial transverse bone transport surgery enables accurate translation of preoperative virtual designs into real-time procedures, enhancing surgical efficiency and quality.

Serum-Derived Extracellular Vesicles for the Treatment of Severe Ocular Surface Disease

PurposeAutologous serum is widely used for the treatment of severe ocular surface disease with mixed efficacy. Extracellular vesicles (EVs) are small membrane bound structures present in all body fluids, including serum. This study compared the proteomic, metabolomic, and inflammatory cytokine composition of serum-derived EVs (SDEVs) to that of the soluble free protein fraction and the subsequent capacity of SDEVs to induce corneal epithelial cell migration and inflammation. MethodsSDEVs were isolated from human serum using size exclusion chromatography. SDEVs were analyzed using nanoparticle tracking analysis, transmission electron microscopy, and western blotting. The effects of SDEVs on corneal epithelial cell migration were tested using a standard scratch assay. Inflammatory cytokines in SDEVs and the free protein fraction were quantified using a microarray. A mutli-omics approach was further used to define SDEV cargo. The ability of SDEVs to modulate inflammation in corneal epithelial cells was quantified using ELISAs. ResultsWestern blot and TEM confirmed the presence of SDEVs. Proinflammatory cytokines, along with complement proteins and TGF-β, were decreased in SDEVs compared to serum. Metabolites present in SDEVs were mostly involved in amino acid biosynthesis, the TCA cycle and oxidative phosphorylation. SDEVs exhibited pro-migratory effects similar to serum however, SDEVs did not induce secretion of IL-6 or IL-8. ConclusionsSDEVs exhibit reduced levels of pro-inflammatory cytokines while retaining the beneficial wound healing properties of serum. Unlike serum, SDEVs do not induce inflammation. SDEVs may represent an alternative option for patients with severe ocular surface disease where traditional autologous serum has failed.