Inflammation-Responsive Hydrogel Accelerates Diabetic Wound Healing through Immunoregulation and Enhanced Angiogenesis.

Angiogenesis is a prominent component during the highly regulated process of wound healing. The application of exogenous vascular endothelial growth factor (VEGF) has shown considerable potential in facilitating angiogenesis. However, its effectiveness is often curtailed due to chronic inflammation and severe oxidative stress in diabetic wounds. Herein, an inflammation-responsive hydrogel incorporating Prussian blue nanoparticles (PBNPs) is designed to augment the angiogenic efficacy of VEGF. Specifically, the rapid release of PBNPs from the hydrogel under inflammatory conditions effectively alleviates the oxidative stress of the wound, therefore reprogramming the immune microenvironment to preserve the bioactivity of VEGF for enhanced angiogenesis. In vitro and in vivo studies reveal that the PBNPs and VEGF co-loaded hydrogel is biocompatible and possesses effective anti-inflammatory properties, thereby facilitating angiogenesis to accelerate the wound healing process in a type 2 diabetic mouse model.

MAP4 acts as an oncogene and prognostic marker and affects radioresistance by mediating epithelial-mesenchymal transition in lung adenocarcinoma.

PURPOSE: To explore the effect of microtubule-associated protein 4 (MAP4) on lung adenocarcinoma cells in vitro and evaluate its prognostic value. Radioresistance, indicated by reduced efficiency of radiotherapy, is a key factor in treatment failure in lung adenocarcinoma (LADC). This study aims to explore the primary mechanism underlying the relationship between MAP4 and radiation resistance in lung adenocarcinoma. METHODS: We analysed the expression of MAP4 in lung adenocarcinoma by real-time quantitative polymerase chain reaction (RT‒qPCR), immunohistochemistry (IHC) and bioinformatics online databases, evaluated the prognostic value of MAP4 in lung adenocarcinoma and studied its relationship with clinicopathological parameters. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis identified independent prognostic factors associated with lung adenocarcinoma that were used to construct a nomogram, internal validation was performed. We then evaluated the accuracy and clinical validity of the model using a receiver operating characteristic (ROC) curve, time-dependent C-index analysis, a calibration curve, and decision curve analysis (DCA). Scratch assays and transwell assays were used to explore the effect of MAP4 on the migration and invasion of lung adenocarcinoma cells. Bioinformatics analysis, RT‒qPCR, Cell Counting Kit-8 (CCK-8) assays and Western blot experiments were used to study the relationship between MAP4, epithelial-mesenchymal transition (EMT) and radiation resistance in lung adenocarcinoma. RESULTS: MAP4 expression in lung adenocarcinoma tissues was significantly higher than that in adjacent normal lung tissues. High expression of MAP4 is associated with poorer overall survival (OS) in patients with lung adenocarcinoma. Univariate Cox regression analysis showed that pT stage, pN stage, TNM stage and MAP4 expression level were significantly associated with poorer OS in LADC patients. Multivariate Cox regression analysis and LASSO regression analysis showed that only the pT stage and MAP4 expression level were associated with LADC prognosis. The nomogram constructed based on the pT stage and MAP4 expression showed good predictive accuracy. ROC curves, corrected C-index values, calibration curves, and DCA results showed that the nomogram performed well in both the training and validation cohorts and had strong clinical applicability. The results of in vitro experiments showed that the downregulation of MAP4 significantly affected the migration and invasion of lung adenocarcinoma cells. MAP4 was strongly correlated with EMT-related markers. Further studies suggested that the downregulation of MAP4 can affect the viability of lung adenocarcinoma cells after irradiation and participate in the radiation resistance of lung adenocarcinoma cells by affecting EMT. CONCLUSION: MAP4 is highly expressed in lung adenocarcinoma; it may affect prognosis by promoting the migration and invasion of cancer cells. We developed a nomogram including clinical factors and MAP4 expression that can be used for prognosis prediction in patients with lung adenocarcinoma. MAP4 participates in radiation resistance in lung adenocarcinoma by regulating the radiation-induced EMT process. MAP4 may serve as a biomarker for lung adenocarcinoma prognosis evaluation and as a new target for improving radiosensitivity.

Extracranial metastasis of glioblastoma: A case report and literature review.

INTRODUCTION: Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. Extracranial metastasis is rare, accounting for only 0.4 %-0.5 % of all GBM patients. The pathways and mechanisms involved are still unclear. CASE PRESENTATION: We reported a rare case of GBM with multiple bone metastases, highly suspected of abdominal metastasis. This 20 year old woman underwent surgery in March 2017 and underwent postoperative radiotherapy and chemotherapy. In July 2018, she underwent a second surgery due to intracranial recurrence and also underwent radiotherapy and chemotherapy after the surgery. She experienced pain in the lumbosacral region in May 2019, abdominal magnetic resonance imaging (MRI) showed metastases to the ilium, sacrum, and multiple lumbar vertebrae. In August 2019, a lump was discovered at the sternum and biopsy was performed, pathological examination confirmed it as GBM. During this period, the patient's condition was briefly controlled after receiving palliative radiotherapy, chemotherapy, and targeted treatment. Surprisingly, the patient later developed highly suspected malignant ascites, and further anti-tumor treatment was refused. She died 7 months after diagnosis of extracranial metastases. CLINICAL DISCUSSION: This patient with GBM had multiple bone metastases and highly suspected abdominal metastasis after two operations. Chemotherapy, radiotherapy and Targeted therapy extend the survival period and improve the quality of life. CONCLUSION: We believe that the patient's extracranial metastases may have occurred through blood. Young "long-term survivors" who have undergone surgery seem to have a higher risk of extracranial metastasis. Timely detection and early treatment can improve the overall quality of life of the patient.

Corrigendum to "Antibacterial coaxial hydro-membranes accelerate diabetic wound healing by tuning surface immunomodulatory functions" [Mater. Today Bio, 16 (2022)].

[This corrects the article DOI: 10.1016/j.mtbio.2022.100395.].

Modulation of Tumor Microenvironment to Enhance Radiotherapy Efficacy in Esophageal Squamous Cell Carcinoma by Inhibiting Carbonic Anhydrase IX.

The radiotherapy outcomes of patients with advanced esophageal squamous cell carcinoma (ESCC) remain poor due to hypoxia. Carbonic anhydrase IX (CAIX) is a membrane-associated enzyme that induces hypoxia, extracellular acidity, and upregulation of hypoxia-related factors in tumor microenvironment, thereby promoting tumor metastasis. CAIX is upregulated in ESCC tissues compared to normal surrounding tissues. In the current study, we aimed to investigate the effect of CAIX inhibition on the modulation of tumor microenvironment and radiotherapy efficacy in ESCC. Higher CAIX expression was correlated with poorer progression-free survival in ESCC patients. Then, the ethyl N-(4-methylphenyl) sulfonylcarbamate (S4) was used to inhibit CAIX expression in ESCC cells and mice xenografts. The pretreatment of ESCC cells with S4 significantly downregulated CAIX expression, decreased intracellular pH, reduced cell viability, resulting in decreased oxygen consumption and more sensitive response to X-ray irradiation. In mice inoculated with ESCC cells, the combination of X-ray irradiation with S4 further improved survival, delayed tumor growth, decreased hypoxia level, exaggerated DNA damage, and increased apoptosis compared with the groups treated solely with S4 or radiotherapy. In conclusion, our study showed that the inhibition of CAIX by S4 treatment altered hypoxic tumor micro-environment, exaggerated DNA damage, increased apoptosis, and thus enhanced radiotherapy efficacy in ESCC. These findings provided a potential therapeutic strategy for patients with resistant ESCC.