Kruppel-Like Factor 4-Dependent Staufen1-Mediated mRNA Decay Regulates Cortical Neurogenesis

Kruppel-like factor 4 (Klf4) is a zinc-finger-containing protein that plays a critical role in diverse cellular physiology. While most of these functions attribute to its role as a transcription factor, it is postulated that Klf4 may play a role other than transcriptional regulation. Here we demonstrate that Klf4 loss in neural progenitor cells (NPCs) leads to increased neurogenesis and reduced self-renewal in mice. In addition, Klf4 interacts with RNA-binding protein Staufen1 (Stau1) and RNA helicase Ddx5/17. They function together as a complex to maintain NPC self-renewal. We report that Klf4 promotes Stau1 recruitment to the 3′-untranslated region of neurogenesis-associated mRNAs, increasing Stau1-mediated mRNA decay (SMD) of these transcripts. Stau1 depletion abrogated SMD of target mRNAs and rescued neurogenesis defects in Klf4-overexpressing NPCs. Furthermore, Ddx5/17 knockdown significantly blocked Klf4-mediated mRNA degradation. Our results highlight a novel molecular mechanism underlying stability of neurogenesis-associated mRNAs controlled by the Klf4/Ddx5/17/Stau1 axis during mammalian corticogenesis

Deubiquitinase USP47/UBP64E Regulates β-Catenin Ubiquitination and Degradation and Plays a Positive Role in Wnt Signaling

Wnt signaling plays important roles in development and tumorigenesis. A central question about the Wnt pathway is the regulation of β-catenin. Phosphorylation of β-catenin by CK1α and GSK3 promotes β-catenin binding to β-TrCP, leading to β-catenin degradation through the proteasome. The phosphorylation and ubiquitination of β-catenin have been well characterized; however, it is unknown whether and how a deubiquitinase is involved. In this study, by screening RNA interference (RNAi) libraries, we identified USP47 as a deubiquitinase that prevents β-catenin ubiquitination. Inactivation of USP47 by RNAi increased β-catenin ubiquitination, attenuated Wnt signaling, and repressed cancer cell growth. Furthermore, USP47 deubiquitinates itself, whereas β-TrCP promotes USP47 ubiquitination through interaction with an atypical motif in USP47. Finally, in vivo studies in the Drosophila wing suggest that UBP64E, the USP47 counterpart in Drosophila, is required for Armadillo stabilization and plays a positive role in regulating Wnt target gene expression

Preparation and in vitro osteogenic evaluation of high-strength ceramic artificial bone loaded with anti-tuberculosis drug PaMZ

The objective of this study was to prepare a high-strength ceramic artificial bone loaded with the anti-tuberculosis drug PaMZ (delamanid, moxifloxacin, and pyrazinamide) and evaluate its physical characteristics and osteogenic potential. We utilized 3D printing technology to fabricate artificial bones and then obtained a high-strength ceramic artificial bone by high-temperature firing. Then, a triple combination of anti-tuberculosis drugs, including delamanid (Pa), moxifloxacin (M), pyrazinamide (Z), and polylactic acid-co-glycolic acid mixed in a ratio of 3:12:45:140, was incorporated onto the surface of the ceramic artificial bone. Consequently, a high-strength ceramic artificial bone, loaded with anti-tuberculosis drugs, was successfully obtained. The physical characteristics of the drug-loaded artificial bone were assessed using an electronic universal testing machine and scanning electron microscopy. The osteogenic performance of the artificial bone was evaluated through rat bone marrow mesenchymal stem cell (rBMSCs) co-culture experiment, cell counting kit-8 (CCK-8) cell proliferation assay, alkaline phosphatase staining, and alizarin red staining. The drug-loaded ceramic artificial bone exhibited favorable physical characteristics, void interconnection, a porosity of 30.6% ± 0.7%, and a compressive strength of 17.65 ± 0.46 MPa. The rBMSCs co-culture experiment and CCK-8 cell proliferation experiment demonstrated excellent cell compatibility, while alkaline phosphatase and alizarin red staining indicated good in vitro osteogenic performance. In summary, the high-strength ceramic artificial bone loaded with the anti-tuberculosis drug PaMZ exhibited a favorable morphological structure and compressive strength. In addition, it demonstrated good biocompatibility and osteogenic properties

Comparative study on the selection of drainage methods in posterior lumbar interbody fusion

Abstract Objective To compare and analyze the clinical effects of bilateral natural pressure drainage and negative pressure drainage after posterior lumbar interbody fusion (PLIF) to provide a reference for selecting drainage methods after lumbar surgery. Methods A retrospective cohort study, 281 patients who underwent single-segment PLIF in our hospital from January 2017 to December 2020 and met the inclusion and exclusion criteria were included in the study, including 132 males and 149 females, aged 22–85 years, with an average of (53.62 ± 11.23) years. According to different postoperative incision drainage methods determined by the random number table method before surgery, they were divided into the natural pressure drainage group and negative pressure drainage group, both of which were bilateral drainage. The general observation indexes and perioperative-related indexes were recorded and analyzed. Results There were 143 cases in the natural pressure drainage group and 138 cases in the negative pressure drainage group. There was no significant difference in age, gender, body mass index, disease type, blood pressure on the day of surgery, preoperative albumin, hemoglobin, platelet, prothrombin time, and intraoperative bleeding between the two groups (P > 0.05). The albumin on the first postoperative day in the natural pressure drainage group was higher than that in the negative pressure drainage group [(33.24 ± 3.52) vs. (32.17 ± 5.03), P  0.05). Conclusion Bilateral natural pressure drainage and negative pressure drainage can achieve good drainage effects after PLIF, but patients with natural pressure drainage have less loss of albumin and hemoglobin, less drainage volume, and shorter drainage tube indwelling time, which is worthy of clinical application

sj-docx-1-npx-10.1177_1934578X241228966 - Supplemental material for Momordin Ic Inhibits the Partially Malignant Phenotype of Osteosarcoma Cells by Inducing Apoptosis and Autophagy

Supplemental material, sj-docx-1-npx-10.1177_1934578X241228966 for Momordin Ic Inhibits the Partially Malignant Phenotype of Osteosarcoma Cells by Inducing Apoptosis and Autophagy by Ruiqing Xu, Rui Huang, Jiandang Shi, Dawei Chu and Pengyu Yang in Natural Product Communications</p

Dexamethasone promotes the endoplasmic reticulum stress response of bone marrow mesenchymal stem cells by activating the PERK‐Nrf2 signaling pathway

Abstract The pathogenesis of steroid‐induced avascular necrosis of femoral head (SANFH) is complex, and there is a lack of effective early prevention method. The aim of the present study was to evaluate the effect of dexamethasone (DEX) on the biological behavior of bone marrow mesenchymal stem cells (BMSCs) and to explore the possibility of DEX in the clinical treatment of SANFH. The effect of DEX on the proliferation of BMSCs was evaluated by Counting Kit‐8 assay, western blot assay, and enzyme‐linked immunosorbent assay. Flow cytometry and western blot assay were performed to detect the effect of DEX on the apoptosis of BMSCs. Quantitative real‐time PCR and western blot assay were performed to detect the effect of DEX on the expression of endoplasmic reticulum stress (ERS)‐related genes. Immunoblotting analysis was conducted for detecting the nuclear‐cytoplasmic distribution of Nrf2. DEX could significantly inhibit the proliferation of BMSCs and promote apoptosis of BMSCs. DEX could increase the expression of PERK, ATF6, and IRE1a, and induce nuclear translocation of Nrf2. The addition of ML385 could reverse the effect of DEX on BMSCs. DEX could activate the PERK‐Nrf2 pathway to promote ERS and finally affect the cell proliferation and apoptosis of BMSCs

MiR-192-5p Alleviated Fibrosis and Inflammatory Responses of Tendon Cells by Targeting NFAT5

Objective. To explore the effect of microRNA (miR)-192-5p on the inflammatory and fibrotic responses of tendon cells. Methods. Tendon cells were treated with transforming growth factor-β1 (TGF-β1). The expression of miR-192-5p and nuclear factor of activated T cells 5 (NFAT5) in tendon cells were detected by RT-qPCR. The expressions of inflammatory and fibrosis-related factors were detected by RT-qPCR and Western blot. MiR-192-5p binds to NFAT5 targeting by TargetScan and dual-luciferase reporter gene assay. The expression of the NFAT5 gene was detected by RT-qPCR and Western blot. Detection of apoptosis in tendon cells by flow cytometry. Results. MiR-192-5p was downregulated in tendon cells, and the expression level gradually decreased with the prolong of TGF-β1 treatment. The expression of NFAT5 increased with the treatment time of TGF-β1. The expression of miR-192-5p decreased collagen III (COLIII), α smooth muscle actin (α-SMA), matrix metalloproteinase- (MMP-) 1, and MMP-8 expression, thereby inhibiting TGF-β1-induced fibrosis in tendon cells. The expression of miR-192-5p decreased the expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β, thereby alleviating TGF-β1-induced inflammatory response and reduce apoptosis in tendon cells. NFAT5 is a direct target of miR-192-5p in tendon cells. The upregulation of NFAT5 reversed the effect of miR-192-5p on the fibrotic activity and inflammatory response of TGF-β1-stimulated tendon cells. Conclusions. MiR-192-5p alleviates fibrosis and inflammatory responses of tendon cells by targeting NFAT5