Prevention of bacterial infection and reduction of hemorrhage, the primary challenges posed by trauma before hospitalization, are essential steps in prolonging the patient's life until they have been transported to a trauma center. Extracellular matrix (ECM) hydrogel is a promising biocompatible material for accelerating wound closure. However, due to the lack of antibacterial properties, this hydrogel is difficult to be applied to acute contaminated wounds. This study formulates an injectable dermal extracellular matrix hydrogel (porcine acellular dermal matrix (ADM)) as a scaffold for skin defect repair. The hydrogel combines vancomycin, an antimicrobial agent for inducing hemostasis, expediting antimicrobial activity, and promoting tissue repair. The hydrogel possesses a porous structure beneficial for the adsorption of vancomycin. The antimicrobial agent can be timely released from the hydrogel within an hour, which is less than the time taken by bacteria to infest an injury, with a cumulative release rate of approximately 80%, and thus enables a relatively fast bactericidal effect. The cytotoxicity investigation demonstrates the biocompatibility of the ADM hydrogel. Dynamic coagulation experiments reveal accelerated blood coagulation by the hydrogel. In vivo antibacterial and hemostatic experiments on a rat model indicate the healing of infected tissue and effective control of hemorrhaging by the hydrogel. Therefore, the vancomycin-loaded ADM hydrogel will be a viable biomaterial for controlling hemorrhage and preventing bacterial infections in trauma patients.

Background Hydrogels loaded with antimicrobial agents have been widely used for treating infected wound defects. However, hydrogels derived from a porcine dermal extracellular matrix (PADM), containing silver nanoparticles (AgNPs), have not yet been studied. Therefore, we investigated the therapeutic effect of an AgNP-impregnated PADM (AgNP–PADM) hydrogel on the treatment of infected wounds. Methods An AgNP–PADM hydrogel was synthesized by embedding AgNPs into a PADM hydrogel. We examined the porosity, moisture retention, degradation, antibacterial properties, cytotoxicity, antioxidant properties, and ability of the PADM and AgNP–PADM hydrogels to treat infected wounds in animals. Results The PADM and AgNP–PADM hydrogels were pH sensitive, which made them flow dynamically and solidify under acidic and neutral conditions, respectively. The hydrogels also exhibited porous network structures, satisfactory moisture retention, and slow degradation. Additionally, the AgNP–PADM hydrogel showed a slow and sustained release of AgNPs for at least 7 days without the particle size changing. Thus, the AgNPs exhibited adequate antibacterial ability, negligible toxicity, and antioxidant properties in vitro. Moreover, the AgNP–PADM hydrogel promoted angiogenesis and healed infected skin defects in vivo. Conclusions The AgNP–PADM hydrogel is a promising bioderived antibacterial material for clinical application to infected wound dressings.

Gastric cancer (GC) is one of the most common malignant tumors in the world. GPx4, as the core regulator of ferroptosis, has become a potential molecular target for developing anticancer agents. In the present study, we found that GPx4 was overexpressed and negatively correlated with poor prognosis in GC, while it was associated with the GC development. Molecular docking and structure-based virtual screening assays were used to screen potential GPx4 inhibitors, and we identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in GC cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cells in vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1 in vitro, which suggested that suggest that PB may increase the level of Fe 2+ by transporting Fe 3+ into the cell by TFR1 and promoting NCOA4-dependent iron autophagy. In addition, PB can also suppresses tumor growth in an orthotopic mouse model of GC via regulating the expression of GPx4, TFR1, NOCA4 and FTH1 in vivo. In summary, we confirmed that GPx4 may be a potential target for GC treatment, PB may be a novel and promising drug for the treatment of GC, which shows good antitumor efficacy without causing significant host toxicity via inducing ferroptosis in both gastric cancer cells and mouse models.

Wnt signaling involves many aspects of development, cell biology and physiology. Mutations in the Wnt gene can lead to abnormal embryonic development and cancer formation, including various aspects that affect proliferation, morphogenesis, and differentiation. The occurrence and development of tumors is a complex process involving multiple factors. The Wnt signaling pathway participates in this process as an anti-tumor target by activating multiple gene transcriptions. The emergence of Wnt pathway inhibitors and targeted drugs has opened up a new world of cancer treatment. This review focuses on the mechanism of action of the Wnt signaling pathway in different cancers. Secondly, we have organized and introduced the latest Wnt anti-tumor drugs.

MicroRNAs (miRNAs) are regulatory small noncoding RNAs that play a key role in several types of cancer. It has been reported that miR-331-3p is involved in the development and progression of various cancers, but there are few reports regarding osteosarcoma (OS). The public GEO database was used to analyze the survival difference of miR-331-3p in OS organizations. The level of cell proliferation assay was assessed by CCK-8 and colony formation. First, transwell and wound-healing assays were used to detect the transfer and invasion ability of miR-331-3p in OS. Second, TargetScan, miRDBmiR, TarBase, and dual-luciferase reporter gene assays were used to determine SOCS1 as a targeted regulator. Third, Western blot and immunohistochemistry were used to detect the expression of protein levels. Finally, a mouse model of subcutaneously transplantable tumors is used to evaluate the proliferation of OS in vivo. The low expression of miR-331-3p was negatively correlated with the overall survival of OS patients. Overexpression of miR-331-3p significantly inhibited cell proliferation, metastasis, and invasion. Moreover, miR-331-3p affected the occurrence and development of osteosarcoma by targeting the SOCS1/JAK2/STAT3 signaling pathway. Therefore, miR-331-3p reduces the expression of SOCS1 by combining with its 3′UTR, thereby activating the JAK2/STAT3 signaling pathway to regulate the progression of OS. This provides a new theoretical basis for the treatment of osteosarcoma.

No abstract

Background Osteosarcoma (OS) has become one of the highest mortality cancers in the world due to its late diagnosis, rapid metastasis and rapid recurrence. MicroRNAs can regulate a variety of signaling pathwas involved in cancer development, such as cell proliferation, apoptosis and migration. Objective In this study, we studied the biological effects and molecular regulation of mir-23b-5p on human osteosarcoma cells. Methods The proliferation of mir-23b-5p in osteosarcoma was measured by CCK8 method and EDU method. In addition, the target population was screened through the database, and the luciferase reporter gene was used to determine the association between miRNA and target gene TMEM127. We verified this result by Western blot. Results We found that mir-23b-5p promotes the progression of osteosarcoma by regulating TMEM127. Conclusions The results of this study show that mir-23b-5p affects the proliferation, metastasis and invasion of OS by targeting TMEM127.

Background: Hydrogels loaded with antimicrobial agents have been widely developed for the treatment of infected wound defects. However, hydrogels derived from a porcine dermal extracellular matrix (PADM), containing silver nanoparticles (AgNPs), have not yet been studied. Therefore, we investigated the therapeutic effect of a AgNP-impregnated PADM (AgNPs-PADM) hydrogel in the treatment of infected wound defects. Methods: A AgNPs-PADM hydrogel was synthesized by embedding AgNPs into a PADM hydrogel. We examined the porosity, moisture retention, degradation, antibacterial properties, cytotoxicity, antioxidant properties, and ability of PADM and AgNPs-PADM hydrogels to treat infected wounds in animals. Results: The PADM and AgNPs-PADM hydrogels were pH-sensitive, which made them flow dynamically under acidic conditions and become solid under neutral conditions. They also demonstrated porous network structures, satisfactory moisture retention, and slow degradation rates. Meanwhile, the AgNPs-PADM hydrogel showed a slow and sustained release of AgNPs for at least seven days without changing the size of the particles, so that they could exhibit adequate antibacterial ability, negligible toxicity, and antioxidant properties in vitro. Moreover, the AgNPs-PADM hydrogel successfully promoted the angiogenesis and wound healing of infected skin defects in vivo. Conclusions: A AgNPs-PADM hydrogel is a promising bioderived antibacterial material for clinical infected wound dressings.