mPPTMP195 nanoparticles enhance fracture recovery through HDAC4 nuclear translocation inhibition.

Delayed repair of fractures seriously impacts patients' health and significantly increases financial burdens. Consequently, there is a growing clinical demand for effective fracture treatment. While current materials used for fracture repair have partially addressed bone integrity issues, they still possess limitations. These challenges include issues associated with autologous material donor sites, intricate preparation procedures for artificial biomaterials, suboptimal biocompatibility, and extended degradation cycles, all of which are detrimental to bone regeneration. Hence, there is an urgent need to design a novel material with a straightforward preparation method that can substantially enhance bone regeneration. In this context, we developed a novel nanoparticle, mPPTMP195, to enhance the bioavailability of TMP195 for fracture treatment. Our results demonstrate that mPPTMP195 effectively promotes the differentiation of bone marrow mesenchymal stem cells into osteoblasts while inhibiting the differentiation of bone marrow mononuclear macrophages into osteoclasts. Moreover, in a mouse femur fracture model, mPPTMP195 nanoparticles exhibited superior therapeutic effects compared to free TMP195. Ultimately, our study highlights that mPPTMP195 accelerates fracture repair by preventing HDAC4 translocation from the cytoplasm to the nucleus, thereby activating the NRF2/HO-1 signaling pathway. In conclusion, our study not only proposes a new strategy for fracture treatment but also provides an efficient nano-delivery system for the widespread application of TMP195 in various other diseases.

Experimental Investigation of the High-Temperature Rheological and Aging Resistance Properties of Activated Crumb Rubber Powder/SBS Composite-Modified Asphalt.

Crumb rubber could form the active groups on the surface by interrupting the crosslinking bond to improve the compatibility with asphalt. While styrene-butadiene-styrene block copolymer (SBS)-modified asphalt has excellent comprehensive properties, it has poor anti-aging performance and a high cost. To explore the influence of composite modification of activated crumb rubber powder (ACR) and SBS on asphalt, modified asphalt samples with different modifiers and SBS contents were prepared. Conventional physical properties tests, a dynamic shear rheometer (DSR), and the thin-film oven test (TFOT) were used to study the conventional physical properties, high-temperature rheological properties, and aging resistance of asphalt. In addition, the action forms and distribution of modifiers in asphalt were observed by an optical microscope to characterize the micro-morphology of ACR/SBS composite-modified asphalt. Test results showed that after adding SBS, the softening point, ductility, and elastic recovery of ACR/SBS asphalt could be significantly improved, but the viscosity and softening point difference were also larger. At the same time, according to the complex shear modulus, phase angle, and rutting factor, SBS can effectively improve the high-temperature deformation resistance of ACR/SBS asphalt. The modified asphalt (ACR/SBS-2) had good high- and low- temperature performances, as well as an appropriate viscosity and low softening point difference, as a research object of aging. After short-term aging, the changes in the high- and low-temperature performances and workability of ACR/SBS asphalt were reduced. Taking the softening point as the target performance, the softening point of ACR/SBS asphalt was less affected by aging time and temperature, indicating that ACR/SBS asphalt was not sensitive to aging temperature and had good stability and aging resistance. From the micrograph by microscope, it was found that ACR/SBS asphalt could maintain a relatively stable polyphase structure for aging resistance.

Corrigendum: Transgelin Inhibits the Malignant Progression of Esophageal Squamous Cell Carcinomas by Regulating Epithelial-Mesenchymal Transition.

[This corrects the article DOI: 10.3389/fonc.2021.709486.].

Transgelin Inhibits the Malignant Progression of Esophageal Squamous Cell Carcinomas by Regulating Epithelial-Mesenchymal Transition.

OBJECTIVE: This article investigates the role of Transgelin (TAGLN) in the epithelial-mesenchymal transition (EMT) of esophageal squamous cell carcinomas (ESCC) and its possible mechanism of inhibiting the invasion of these cancers. METHODS: Tissue specimens and clinical information of patients with ESCC were collected to analyze the relationship between Transgelin expression level and prognosis of patients with ESCC. Transgelin siRNA was used to knock down Transgelin expression. The expression of Transgelin in Eca-109 and KYSE-150 cells was overexpressed by Transgelin-overexpressing plasmid. The effects of Transgelin overexpression and knockdown on the proliferation of Eca-109 and KYSE-150 cells were examined by Transwell chamber, scratch assay, and CCK-8 cell activity assay. RT-PCR and Western blot were used to detect the effect of Transgelin overexpression or knockdown on the mRNA and protein expressions of E-cadherin and Vimentin. TCGA data were used to analyze Transgelin co-expressed genes and further study the GO and KEGG enrichment analysis results under the influence of Transgelin. RESULTS: The expression of Transgelin was low in ESCC, and its expression level was positively correlated with the prognosis of patients with ESCC. The targeted Transgelin siRNA and Transgelin-overexpressing plasmid can effectively regulate the expression of Transgelin mRNA and protein in Eca-109 and KYSE-150 cells. After overexpression of Transgelin, the invasion and proliferation abilities of Eca-109 and KYSE-150 cells were significantly decreased compared with those of the control group (P < 0.05). However, Transgelin knockdown could promote the proliferation, migration, and invasion of ESCC cells. The overexpression of Transgelin inhibits EMT in ESCC. With the increase of Transgelin expression in Eca-109 and KYSE-150 cells, the expression of E-cadherin increased, while the expression of Vimentin decreased, and the difference was statistically significant (P < 0.05). CONCLUSION: Transgelin can inhibit the malignant progression of ESCC by inhibiting the occurrence of EMT.