Multifunctional Composite Scaffold with Nanosilver, Graphene Oxide, and Macrophage Membrane Vesicles for Sequential Treatment of Infected Bone Defects.

The management of infected bone defects poses a significant clinical challenge, and current treatment modalities exhibit various limitations. This study focuses on the development of a multifunctional composite scaffold comprising nanohydroxyapatite/polyethyleneglycol diacrylate matrix, silver nanoparticles, graphene oxide (GO), sodium alginate, and M2-type macrophage membrane vesicles (MVs) to enhance the healing of infected bone defects. The composite scaffold demonstrates several key features: first, it releases sufficient quantities of silver ions to effectively eliminate bacteria; second, the controlled release of MVs leads to a notable increase in M2-type macrophages, thereby significantly mitigating the inflammatory response. Additionally, GO acts synergistically with nanohydroxyapatite to enhance osteoinductive activity, thereby fostering bone regeneration. Through meticulous in vitro and in vivo investigations, the composite scaffold exhibits broad-spectrum antimicrobial effects, robust immunomodulatory capabilities, and enhanced osteoinductive activity. This multifaceted composite scaffold presents a promising approach for the sequential treatment of infected bone defects, addressing the antimicrobial, immunomodulatory, and osteogenic aspects. This study introduces innovative perspectives and offers new and effective treatment alternatives for managing infected bone defects.

Biomechanical improvement of anterior talofibular ligament by augmentation repair of ligament advance reinforcement system: a cadaver study.

BACKGROUND: Ankle sprain are one of the most frequent sports injuries. Some individuals will develop chronic lateral ankle instability (CLAI) after ankle sprain and suffer from recurrent ankle sprain. Current surgical treatment of CAI with anterior talofibular ligament (ATFL) rupture fails to restore the stability of the native ATFL. Ligament Advance Reinforcement System (LARS) augmentation repair of ATFL was developed to improve its primary stability after repaired. METHODS: This study was performed to evaluate whether LARS augmentation repair of ATFL had similar stability as the modified Broström repair and the intact ATFL to maintain ankle construct stability. Standardized surgical techniques were performed on eighteen fresh frozen cadaver ankle specimens. The intact ATFL group has just undergone an ATFL exploratory surgery. The modified Broström procedure is based on anatomical repair of the ATFL with a 2.9 mm suture anchor, and the LARS procedure is an augmentation procedure of the ATFL using LARS ligaments based on the modified Broström procedure. A dynamic tensile test machine was used to assess load-to-failure testing in the three groups. The ultimate failure load and stiffness were calculated and reported from the load-displacement curve. A one-way analysis of variance was used to detect significant differences (p < 0.05) between the LARS augmentation repair, the modified Broström repair and the intact ATFL, followed by least significant difference (LSD) post-hoc tests. RESULTS: The LARS augmentation repair group showed an increased in ultimate failure to load and stiffness compared to the other two groups. There were no significant differences in ultimate failure to load and stiffness between the modified Broström and the intact ATFL, the LARS ligament for ATFL augmentation allows for improved primary stability after repair and reduced stress on the repaired ATFL, which facilitates healing of the remnant ligament. CONCLUSIONS: The LARS augmentation repair of ATFL represents a stable technique that may allow for the ankle stability to be restored in patients with CAI after surgery.

MiR-601-induced BMSCs senescence accelerates steroid-induced osteonecrosis of the femoral head progression by targeting SIRT1.

BACKGROUND: The imbalance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is not only the primary pathological feature but also a major contributor to the pathogenesis of steroid-induced osteonecrosis of the femoral head (SONFH). Cellular senescence is one of the main causes of imbalanced BMSCs differentiation. The purpose of this study was to reveal whether cellular senescence could participate in the progression of SONFH and the related mechanisms. METHODS: The rat SONFH model was constructed, and rat BMSCs were extracted. Aging-related indicators were detected by SA-ß-Gal staining, qRT-PCR and Western Blot experiments. Using H2O2 to construct a senescent cell model, and overexpressing and knocking down miR-601 and SIRT1 in hBMSCs, the effect on BMSCs differentiation was explored by qRT-PCR, Western Blot experiment, oil red O staining (ORO), alizarin red staining (ARS), and luciferase reporter gene experiment. A rat SONFH model was established to test the effects of miR-601 and metformin in vivo. RESULTS: The current study showed that glucocorticoids (GCs)-induced BMSCs senescence, which caused imbalanced osteogenesis and adipogenesis of BMSCs, was responsible for the SONFH progression. Further, elevated miR-601 caused by GCs was demonstrated to contribute to BMSCs senescence through targeting SIRT1. In addition, the anti-aging drug metformin was shown to be able to alleviate GCs-induced BMSCs senescence and SONFH progression. CONCLUSIONS: Considering the role of BMSCs aging in the progression of SONFH, this provides a new idea for the prevention and treatment of SONFH.

LncRNA DGCR5-encoded polypeptide RIP aggravates SONFH by repressing nuclear localization of ß-catenin in BMSCs.

The differentiation fate of bone marrow mesenchymal stem cells (BMSCs) affects the progression of steroid-induced osteonecrosis of the femoral head (SONFH). We find that lncRNA DGCR5 encodes a 102-amino acid polypeptide, RIP (Rac1 inactivated peptide), which promotes the adipogenic differentiation of BMSCs and aggravates the progression of SONFH. RIP, instead of lncRNA DGCR5, binds to the N-terminal motif of RAC1, and inactivates the RAC1/PAK1 cascade, resulting in decreased Ser675 phosphorylation of ß-catenin. Ultimately, the nuclear localization of ß-catenin decreases, and the differentiation balance of BMSCs tilts toward the adipogenesis lineage. In the femoral head of rats, overexpression of RIP causes trabecular bone disorder and adipocyte accumulation, which can be rescued by overexpressing RAC1. This finding expands the regulatory role of lncRNAs in BMSCs and suggests RIP as a potential therapeutic target.

miR-486-5p Attenuates Steroid-Induced Adipogenesis and Osteonecrosis of the Femoral Head Via TBX2/P21 Axis.

Enhanced adipogenic differentiation of mesenchymal stem cells (MSCs) is considered as a major risk factor for steroid-induced osteonecrosis of the femoral head (SOFNH). The role of microRNAs during this process has sparked interest. miR-486-5p expression was down-regulated significantly in femoral head bone tissues of both SONFH patients and rat models. The purpose of this study was to reveal the role of miR-486-5p on MSCs adipogenesis and SONFH progression. The present study showed that miR-486-5p could significantly inhibit adipogenesis of 3T3-L1 cells by suppressing mitotic clonal expansion (MCE). And upregulated expression of P21, which was caused by miR-486-5p mediated TBX2 decrease, was responsible for inhibited MCE. Further, miR-486-5p was demonstrated to effectively inhibit steroid-induced fat formation in the femoral head and prevented SONFH progression in a rat model. Considering the potent effects of miR-486-5p on attenuating adipogenesis, it seems to be a promising target for the treatment of SONFH.

Arthroscopic internal drainage of popliteal cysts with cyst wall resection in pediatric patients.

Objectives: To evaluate the efficacy of arthroscopic internal drainage (AID) and cyst wall resection (CWR) in children with popliteal cysts. Methods: This study included 16 pediatric patients with popliteal cysts and received arthroscopy using the double posteromedial (PM) portal system during June 2020 and June 2021 at The General Hospital of Northern Theater Command. Among these pediatric patients, 14 were males and two were females, with the mean age of nine years (range: 7-12 years). The left knee was affected in 12 cases, while the right knee was involved in the rest four cases. All patients underwent MR imaging before the procedure to assess whether there was intra-articular trauma and whether the popliteal cyst communicated with the knee-joint cavity. The MRI results showed that each patient had a simple popliteal cyst that involved a single knee joint without intra-articular trauma, which was classified as Grade-1 (n=3), Grade-2 (n =10) or Grade-3 (n =3) according to the Rauschning and Lindgren grading of knee joint symptoms. Arthroscopy was performed through anterolateral (AL) and PM portals to the knee joint for AID plus CWR, and the surgical outcomes were evaluated based on the Rauschning and Lindgren criteria. Results: No major vascular or nerve injury occurred during the operation. Postoperative complications such as wound infection and lower-extremity deep venous thrombosis were not recorded in these patients. Complications involving the saphenous nerve or the great saphenous vein or pseudocyst formation were not observed during the follow-up period. All patients completed the follow-up ranging from 3-12 months and were identified to have grade-0 (n=15) and grade-1 (n=1) popliteal cysts based on the Rauschning and Lindgren criteria, indicating significant improvement compared with the preoperative levels (all p<0.05). Moreover, no recurrence was recorded after operation. Conclusion: AID plus CWR is a minimally invasive and safe approach for pediatric patients with popliteal cysts to promote postoperative recovery and reduce the recurrence rate.

Application of exposure enhancement technique combined with femoral condyle pushing technique in repairing the posterior horn of the medial meniscus under knee arthroscopy.

Objectives: To investigate the clinical efficacy of exposure enhancement technique and femoral condyle pushing technique applying in the posterior horn of the medial meniscus of the knee. Methods: From January 2016 to June 2019, 52 patients with injury in the medial meniscus treated in our department were selected. The horizontal tear of the posterior horn of the medial meniscus was repaired by exposure enhancement technique and femoral condyle pushing technique using the meniscus suture system. Postoperatively, the efficacy was evaluated using the Lysholm scoring system. Results: These 52 patients were all followed up for 3~18 months, with an average of 12.5 ± 7.3 months. The pain and activity of all patients were significantly improved compared with those before surgery. Conclusion: Exposure enhancement technique and femoral condyle pushing technique in the repair of the posterior horn of the medial meniscus presents satisfactory efficacy. It can improve the pain and activity of the knee, and enhance the stability of residual meniscus. Therefore, it is worth promoting.

Timosaponin B-II alleviates osteoarthritis-related inflammation and extracellular matrix degradation through inhibition of mitogen-activated protein kinases and nuclear factor-κB pathways in vitro.

Osteoarthritis (OA), an inflammatory response in chondrocytes, leads to extracellular matrix (ECM) degradation and cartilage destruction. Timosaponin B-II (TB-II) is the main bioactive component of Rhizoma Anemarrhenae with reported antioxidant and anti-inflammatory effects. This study investigated the anti-OA function and mechanism of TB-II on IL-1ß-stimulated SW1353 cells and primary rat chondrocytes. We firstly screened the concentration of TB-II in SW1353 cells and primary rat chondrocytes using CCK-8 assay. Thereafter, SW1353 cells and chondrocytes were, respectively, pretreated with TB-II (20 and 40 µg/mL) and TB-II (10 and 30 µg/mL) for 24 h and then stimulated with interleukin 1ß (IL-1ß, 10 ng/mL) for another 24 hours. Results showed that TB-II suppressed the production of reactive oxygen species, the protein levels of inducible nitric oxide synthase and cyclooxygenase-2 in IL-1ß-stimulated SW1353 cells and chondrocytes. IL-1ß-induced high secretion levels of nitric oxide and prostaglandin 2, TNF-α, IL-6 and MCP-1 were down-regulated by TB-II treatment, indicating an anti-inflammatory effect of TB-II on OA in vitro condition. Moreover, TB-II weakened the mRNA and protein expression of (matrix metalloproteinase) MMPs including MMP-1, MMP-3, and MMP-13, indicating the protection of TB-II against ECM degradation. Mechanically, TB-II suppressed MAPKs and NF-κB pathways under IL-1ß stimulation evidenced by the down-regulated protein expression of p-ERK, p-p38, p-JNK, p-p65 and the reduced translocation of p65 subunit to the nucleus. The present study demonstrated that TB-II might become a novel therapeutic agent for OA treatment through repressing IL-1ß-stimulated inflammation, oxidative stress and ECM degradation via suppressing the MAPKs and NF-κB pathways.

PPARα agonist relieves spinal cord injury in rats by activating Nrf2/HO-1 via the Raf-1/MEK/ERK pathway.

OBJECTIVE: To observe the inhibitory effects of the peroxisome proliferator-activated receptor alpha (PPARα) agonist palmitoylethanolamide (PEA) on inflammatory responses and oxidative stress injury in rats with spinal cord injury (SCI). METHODS: The SCI rat model was established using modified Allen's method and the changes in rats' joint motion were observed by Basso, Beattie and Bresnahan locomotor rating scale (BBB scale) at 1, 3 and 7 days after modeling, HE Staining and Nissl Staining has been carried out to evaluate the pathological lesion of spinal cords in rats. Besides, Immunohistochemical (IHC) was performed to detect the reactive oxygen species (ROS), expression levels of acrylamide (ACR) and manganese superoxide dismutase (MnSOD) in rat spinal cords, and Western Blotting was applied to measure protein expression levels of nuclear factor-kappa B (NF-κB), B cell lymphoma-2 (Bcl-2), BCL-2 associated X (BAX), phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), phosphorylated (p)-Akt, HO-1, Nrf2, trithorax-1 (TRX-1), Raf-1, MEK, ERK, p-MEK and p-ERK. RESULTS: The PPARα agonist PEA could alleviate SCI in rats, inhibit inflammatory responses, mitigate oxidative stress injury, reduce the apoptotic rate and promote SCI rats motor function recovery. In addition, the PPARα agonist PEA was able to activate the phosphorylation of MEK and ERK, stimulate Nrf-2 translocation into the nucleus and up-regulate the expressions of HO-1 and TRX-1. CONCLUSION: PPARα agonist PEA can relieve SCI in rats by inhibiting inflammatory responses and oxidative stress, which may involve a mechanism associated with the activation of Nrf2/HO-1 via the Raf-1/MEK/ERK pathway.

EIF3m promotes the malignant phenotype of lung adenocarcinoma by the up-regulation of oncogene CAPRIN1.

EIF3m is the latest identified subunit of the eukaryotic translation initiation factor 3 (eIF3), however, its function in malignant tumor is rarely reported. In the current work, we observed that EIF3m was aberrant over-expressed in lung adenocarcinoma (LADC) tissues and cell lines, and the increased EIF3m level was closely related to the poor clinical outcomes of the LADC patients. The gain- and loss-of-function assays demonstrated the proto-oncogenetic potential of EIF3m in vitro and in vivo. EIF3m induced-malignant phenotype was partly mediated by the up-regulation of CAPRIN1. The biochemical analysis showed that EIF3m could bind to the 5'UTR of CAPRIN1 and positively modulate its expression at the post-transcription level. Furthermore, we identified the interaction between EIF3m and the deubiquitinase UCHL5, which stabilized and promoted the accumulation of EIF3m in LADC cells. In summary, our findings extended the knowledge about the EIF3m function and highlight the roles of the UCHL5/EIF3m/CAPRIN1 axis during the progression of LADC.

The lncRNA BCYRN1 Functions as an Oncogene in Human Glioma by Downregulating miR-125a-5p in vitro.

INTRODUCTION: Numerous studies have demonstrated that long noncoding RNAs (lncRNAs) are deregulated in many cancers and exert their functions through multiple cancer-related biological processes. Glioma is the most common primary malignant central nervous system tumor and has a high fatality rate in adults. In current study, we aimed to determine the role and functional mechanism of the lncRNA BCYRN1 in glioma. METHODS: Gain-of-function and loss-of function approaches were used to investigate the function of BCYRN1. The effects of BCYRN1 on glioma cell proliferation, migration and invasion were evaluated using MTS, Transwell and wound-healing assays. The correlation between the expression of BCYRN1 and miR-125a-5p was verified by quantitative real-time PCR. RESULTS: The upregulation of BCYRN1 promoted the proliferation, migration and invasion of glioma cells. Meanwhile, the knockdown of BCYRN1 had the opposite effects. BCYRN1 was negatively correlated with miR-125a-5p. Additionally, TAZ, the endogenous target of miR-125a-5p, could be regulated by BCYRN1 in RNA and protein levels. A miR-125a-5p inhibitor restored BCYRN1 siRNA function in glioma. CONCLUSION: The present study indicates that BCYRN1 promotes glioma cell proliferation, invasion and migration in vitro. Mechanistically, upregulated expression of BCYRN1 in glioma acts as a sponge to sequester the endogenous tumor suppressor miR-125a-5p and to further increase the expression TAZ. Our findings suggest that BCYRN1 is a novel oncogene and a new therapeutic target for glioma.