PLA tissue-engineered scaffolds loaded with sustained-release active substance chitosan nanoparticles: Modeling BSA-bFGF as the active substance.

The utilization of basic fibroblast growth factor (bFGF) in the development of tissue-engineered scaffolds is both challenging and imperative. In our pursuit of creating a scaffold that aligns with the natural healing process, we initially fabricated chitosan-bFGF nanoparticles (CS-bFGF NPs) through electrostatic spraying. Subsequently, polylactic acid (PLA) fiber was prepared using electrospinning technique, and the CS-bFGF NPs were uniformly embedded within the pores of porous PLA fibers. Scanning electron micrographs illustrate the smooth surface of the nanoparticles, showing a porous structure intricately attached to PLA fibers. Fourier-transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) analyses provided conclusive evidence that the CS-bFGF NPs were uniformly distributed throughout the porous PLA fibers, forming a robust physical bond through electrostatic adsorption. The resultant scaffolds exhibited commendable mechanical properties and hydrophilicity, facilitating a sustained-release for 72 h. Furthermore, the biocompatibility and degradation performance of the scaffolds were substantiated by monitoring conductivity and pH changes in pure water over different time intervals, complemented by scanning electron microscopy (SEM) observations. Cell experiments confirmed the cytocompatibility of the scaffolds. In animal studies, the group treated with 16 % NPs/Scaffold demonstrated the highest epidermal reconstruction rate. In summary, our developed materials present a promising candidate for serving as a tissue engineering scaffold, showcasing exceptional biocompatibility, sustained-release characteristics, and substantial potential for promoting epidermal regeneration.

Preparation of gastrodin modified P(VDF-TrFE)-Eudragit L100-AuNPs nanofiber membranes with piezoelectric property.

In recent years, electroactive nerve conduits made from a blend of P(VDF-TrFE) (poly (vinylidene fluoride-trifluoroethylene)) with other materials have shown significant progress. However, research combining P(VDF-TrFE) conduits with drug delivery systems remains sparse. In this study, we developed a novel gastrodin-loaded P(VDF-TrFE)-Eudragit L100-gold nanoparticles (Gas@PT-EL100-AuNPs) nanofiber membrane. Fabricated through electrospinning technique, this composite membrane aimed to investigate the impacts of gastrodin and AuNPs on its properties. Experimental results indicated that the incorporation of gold nanoparticles significantly reduced the fiber diameter of the membrane and enhanced the overall performance by improving hydrophilicity and piezoelectric properties. Specifically, the addition of AuNPs substantially enhanced the piezoelectric performance of the nanofiber membrane. Furthermore, the inclusion of gastrodin not only improved the membrane's hydrophilicity but also enabled effective release of the neuroprotective drug. These findings suggest that the Gas@PT-EL100-AuNPs nanofiber membrane is a novel biomaterial with potential applications in the repair and treatment of nerve injuries.

Transmission of Exosomal TPX2 Promotes Metastasis and Resistance of NSCLC Cells to Docetaxel.

Background: Lung cancer, most of which is non-small cell lung cancer (NSCLC), is the most common tumor in the world, and drug resistance, as a major problem in clinical treatment, has attracted extensive attention. However, the role and mechanism of Targeting protein for Xenopus kinesin-like protein 2 (TPX2), which is highly expressed in NSCLC, is still unclear. Methods: Bioinformatics analysis was used to analyze the relationship between TPX2 and the clinicopathological features of NSCLC. Stable TPX2 overexpression cell lines with were constructed by lentivirus infection, and the effect of TPX2 on proliferation, migration, invasion and chemoresistance to docetaxel was characterized by the CCK8, wound healing, transwell, colony formation assay and FACS. An in vivo lung homing mouse model was used to further confirmed the role of TPX2 on metastasis. Exosomes were extracted by differential centrifugation from the culture supernatant, and their functions were investigated by co-culture with tumor cells. Gene expression was detected via Western blot and real time PCR (RT-qPCR). Results: Overexpression of TPX2 was related to the poor prognosis of NSCLC. Promoted migration, invasion and metastasis, and reduced the sensitivity of NSCLC cells to docetaxel. The abundance of TPX2 can be packaged in vesicles and transported to other cells. In addition, overexpression of TPX2 induced the accumulation of ß-catenin and C-myc. Conclusion: Our findings indicated that intercellular transfer of exosomal TPX2 triggered metastasis and resistance against to docetaxel in lung cancer cells, through activating downstream WNT/ß-catenin signaling pathway.

Renal Clearable Mo-Based Polyoxometalate Nanoclusters: A Promising Radioprotectant against Ionizing Irradiation.

In response to diffused ionizing radiation damage throughout the body caused by nuclear leaks and inaccurate radiotherapy, radioprotectants with considerable free radical scavenging capacities, along with negligible adverse effects, are highly regarded. Herein, unlike being performed as toxic chemotherapeutic drug candidates, molybdenum-based polyoxometalate nanoclusters (Mo-POM NCs) were developed as a non-toxic potent radioprotectant with impressive free radical scavenging capacities for ionizing radiation protection. In comparison to the clinically used radioprotectant drug amifostine (AM), the as-prepared Mo-POM NCs exhibited effective shielding capacity by virtue of their antioxidant properties resulting from a valence shift of molybdenum ions, alleviating not only ionizing radiation-induced DNA damage but also disruption of the radiation-sensitive hematopoietic system. More encouragingly, without trouble with long-term retention in the body, ultra-small sized Mo-POM NCs prepared by the mimetic Folin-Ciocalteu assay can be removed from the body through the renal-urinary pathway and the hepato-enteral excretory system after completing the mission of radiation protection. This work broadened the biological applications of metal-based POM chemotherapeutic drugs to act as a neozoic radioprotectant.

METTL3/m6A/IFIT2 regulates proliferation, invasion and immunity in esophageal squamous cell carcinoma.

Epigenetic regulation plays a critical role in the development, progression, and treatment of tumors. The most common chemical modification of mRNA, called m6A, is essential for controlling mRNA stability, splicing, and translation. Methyltransferase-like 3 (METTL3) is an important m6A methyltransferase. The mechanism of action of METTL3 in esophageal squamous cell carcinoma (ESCC) remains unclear. In this investigation, we sought to clarify the function and clinical importance of METTL3 in ESCC and investigate its underlying mechanisms. We discovered that METTL3 has a significant proliferative effect in ESCC cells by using lentiviral construction of stable cell lines overexpressing METTL3 (METTL3-OE) and knocking down METTL3 (sh-METTL3). To create a xenograft tumor model, we inoculated KYSE510 cells subcutaneously into BALB/c nude mice and discovered that sh-METTL3 inhibited the tumorigenicity of esophageal cancer KYSE510 cells in the nude mouse tumor model. MeRIP-seq and RNA-seq analysis revealed IFIT2 to be a METTL3 target gene. The findings revealed that METTL3 regulates IFIT2 and thus influences malignant biological behaviors such as proliferation, migration, and invasion of ESCC, as well as the immune microenvironment of tumors.

HSD17B6 downregulation predicts poor prognosis and drives tumor progression via activating Akt signaling pathway in lung adenocarcinoma.

Lung adenocarcinoma is one of the most frequent tumor subtypes, involving changes in a variety of oncogenes and tumor suppressor genes. Hydroxysteroid 17-Beta Dehydrogenase 6 (HSD17B6) could synthetize dihydrotestosterone, abnormal levels of which are associated with progression of multiple tumors. Previously, we showed that HSD17B6 inhibits malignant progression of hepatocellular carcinoma. However, the mechanisms underlying inhibiting tumor development by HSD17B6 are not clear. Moreover, its role in lung adenocarcinoma (LUAD) is yet unknown. Here, we investigated its expression profile and biological functions in LUAD. Analysis of data from the LUAD datasets of TCGA, CPTAC, Oncomine, and GEO revealed that HSD17B6 mRNA and protein expression was frequently lower in LUAD than in non-neoplastic lung tissues, and its low expression correlated significantly with advanced tumor stage, large tumor size, poor tumor differentiation, high tumor grade, smoking, and poor prognosis in LUAD. In addition, its expression was negatively regulated by miR-31-5p in LUAD. HSD17B6 suppressed LUAD cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and radioresistance. Furthermore, HSD17B6 overexpression in LUAD cell lines enhanced PTEN expression and inhibited AKT phosphorylation, inactivating downstream oncogenes like GSK3ß, ß-catenin, and Cyclin-D independent of dihydrotestosterone, revealing an underlying antitumor mechanism of HSD17B6 in LUAD. Our findings indicate that HSD17B6 may function as a tumor suppressor in LUAD and could be a promising prognostic indicator for LUAD patients, especially for those receiving radiotherapy.