Intervertebral disc degeneration (IVDD) is a prevalent musculoskeletal disorder that involves the excessive accumulation of reactive oxygen species (ROS), resulting in mitochondrial dysfunction and matrix metabolism imbalance in nucleus pulposus cells (NPCs). Selenium, an indispensable trace element, plays a crucial role in maintaining mitochondrial redox homeostasis by being incorporated into antioxidant selenoproteins as selenocysteine. In this study, we employed a straightforward synthesis method to produce selenium nanoparticles (SeNPs) with consistent size and distribution, and evaluated their potential protective effects in ameliorating IVDD. In a simulated inflammatory environment induced by interleukin-1beta (IL-1β) in vitro, SeNPs demonstrated a protective effect on the matrix synthesis capacity of NPCs through the up-regulation of aggrecan and type II collagen, while concurrently suppressing the expression of matrix degradation enzymes including MMP13 and ADAMTS5. Additionally, SeNPs preserved mitochondrial integrity and restored impaired mitochondrial energy metabolism by activating glutathione peroxidase1 (GPX1) to rebalance redox homeostasis. In a rat lumbar disc model induced by puncture, the local administration of SeNPs preserved the hydration of nucleus pulposus tissue, promoted matrix deposition, and effectively mitigated the progression of IVDD. Our results indicate that the enhancement of GPX1 by SeNPs may offer a promising therapeutic approach for IVDD by restoring mitochondrial function and redox homeostasis.
In clinical studies, we discovered that when using headless cannulated compression screw fixation, many patients complain of heel pain and frequently need to have the screws removed, whereas this occurrence is uncommon with plate fixation. This study aims to compare the clinical outcome of a mini T-plate and headless cannulated compression screws in calcaneal osteotomy. We reviewed the medical records of patients who had calcaneal osteotomy performed by one senior chief surgeon in our hospital between January 2014 and May 2021. Thirty-nine patients met the selection criteria: 22 were fixed using a mini T-plate through a modified small “L” incision on the lateral aspect of the calcaneus and 17 were fixed using double screws through an oblique incision on the lateral aspect of the calcaneus. Then, we compared the patient demographics, surgical statistics, and postoperative complications in calcaneal osteotomy between a mini T-plate and double 6.5-mm headless cannulated compressed screws. Each patient attained radiographic union. The average age was 49.23±13.80 (range: 24–76) years and the average follow-up duration was 47.07±8.64 (range: 36–66) weeks. The average operation duration and times of intraoperative fluoroscopy were significantly lower in the mini T-plate group (P<0.05). There was a savings of $838.88 per patient when using double screws for fixation. The incidence of hardware-related pain and implant removal was lower in the mini T-plate group (P<0.05). There is no significant difference between the two groups in terms of delayed incision healing and clinical neurological complications (P>0.05). In calcaneal osteotomy, the operation duration, times of intraoperative fluoroscopy, hardware-related pain, and implant removal rate were lower with mini T-plate fixation than with double screws fixation. Therefore, we consider that the mini T-plate would be a good alternative to double screws in calcaneal osteotomy.
A two-dimensional (2D) cell culture-based model is widely applied to study tumorigenic mechanisms and drug screening. However, it cannot authentically simulate the three-dimensional (3D) microenvironment of solid tumors and provide reliable and predictable data in response to in vivo, thus leading to the research illusions and failure of drug screening. In this study, honeycomb-like gelatin methacryloyl (GelMA) hydrogel microspheres are developed by synchronous photocrosslinking microfluidic technique to construct a 3D model of osteosarcoma. The in vitro study shows that osteosarcoma cells (K7M2) cultured in 3D GelMA microspheres have stronger tumorous stemness, proliferation and migration abilities, more osteoclastogenetic ability, and resistance to chemotherapeutic drugs (DOX) than that of cells in 2D cultures. More importantly, the 3D-cultured K7M2 cells show more tumorigenicity in immunologically sound mice, characterized by shorter tumorigenesis time, larger tumor volume, severe bone destruction, and higher mortality. In conclusion, honeycomb-like porous microsphere scaffolds are constructed with uniform structure by microfluidic technology to massively produce tumor cells with original phenotypes. Those microspheres could recapitulate the physiology microenvironment of tumors, maintain cell-cell and cell-extracellular matrix interactions, and thus provide an effective and convenient strategy for tumor pathogenesis and drug screening research.
Transforming growth factor β (TGF‐β) is part of the transforming growth factor β superfamily which is involved in many physiological processes and closely related to the carcinogenesis. Here, we discuss the TGF‐β structure, function, and its canonical Smads signaling pathway. Importantly, TGF‐β has been proved that it plays both tumor suppressor as well as an activator role in tumor progression. In an early stage, TGF‐β inhibits cell proliferation and is involved in cell apoptosis. In an advanced tumor, TGF‐β signaling pathway induces tumor invasion and metastasis through promoting angiogenesis, epithelial–mesenchymal transition, and immune escape. Furthermore, we are centered on updated research results into the inhibitors as drugs which have been studied in preclinical or clinical trials in tumor carcinogenesis to prevent the TGF‐β synthesis and block its signaling pathways such as antibodies, antisense molecules, and small‐molecule tyrosine kinase inhibitors. Thus, it is highlighting the crucial role of TGF‐β in tumor therapy and may provide opportunities for the new antitumor strategies in patients with cancer.