Study on the effect of self-made fracture positioning compression guide device for posterior malleolus fracture surgery: Medical prevention.

To evaluate the effectiveness of a self-designed pressure-guided fracture positioning device, a prospective study was conducted in patients with posterior ankle fractures undergoing surgery using the device. Twenty-seven cases of ankle joint fracture with posterior malleolus fracture were treated by surgery. In the process of fixing posterior malleolus fracture, a self-designed fracture positioning compression guide device was used to fix posterior malleolus bone by anterior and posterior approaches. Postoperative CT images were used to assess the fixation position as well as length of the screw and the compression of the fracture. All patients had healed ankle fractures, and the anterior-posterior screws were fixed in the central area of the posterior malleolus. Posterior malleolus fragment displacement was <2 mm. The screw effectively secured the cortex beyond the length of the posterior malleolus cortex by no more than two threads. The good rate of ankle joint function was 85.16%. Compared to traditional surgical techniques, minimally invasive fixation using the self-designed positioning compression guide device has several advantages, including smaller trauma, faster postoperative recovery, and improved patient satisfaction. The device also provides the surgeon with greater control and precision during the surgical procedure, which can contribute to better surgical outcomes.

miR-219a-5p inhibits the pyroptosis in knee osteoarthritis by inactivating the NLRP3 signaling via targeting FBXO3.

PURPOSE: This work was to identify the function and mechanism of miR-219a-5p in regulating knee osteoarthritis (KOA). METHODS: Rat fibroblast-like synoviocytes (FLSs) were isolated to construct KOA cell model by lipopolysaccharide and adenosine triphosphate treatment. miR-219a-5p and FBXO3 expression in FLSs was modulated by transfection. Flow cytometry was executed to research FLSs apoptosis. Caspase-1 and IL-1ß expression in FLSs was researched by immunofluorescence. The binding between miR-219a-5p and FBXO3 was identified by dual luciferase reporter gene assay. KOA rat model and miR-219a-5p up-modulation KOA rat model were constructed. Step size of rats was analyzed. Knee joints of rats were experienced Safranin O-fast green staining to evaluate the knee joint injury. FBXO3, pyroptosis-associated proteins, and IL-1ß and IL-18 expression in FLSs and articular cartilage tissues of rats were assessed by Western blot, qRT-PCR and Enzyme-linked immunosorbent assay. RESULTS: KOA cell model had higher apoptosis percentage, expression of pyroptosis-associated proteins, and IL-1ß and IL-18 level. miR-219a-5p up-modulation decreased the above indicators, whereas miR-219a-5p down-modulation increased the above indicators. FBXO3 expression was directly repressed by miR-219a-5p. Loss of FBXO3 suppressed the above indicators. FBXO3 counteracted the suppression of miR-219a-5p on the above indicators. miR-219a-5p agomir attenuated knee joint injury, increased step size of KOA rats, and reduced FBXO3, pyroptosis-associated proteins and level of IL-1ß and IL-18 in the articular cartilage tissues of KOA rats. CONCLUSION: miR-219a-5p suppressed the pyroptosis in KOA by inactivating the NLRP3 signaling via targeting FBXO3, which might be a promising target for ameliorating KOA in the clinic.

IARS2 regulates proliferation, migration, and angiogenesis of human umbilical vein endothelial cells.

OBJECTIVE: In this study, we aimed at investigating the role of isoleucyl-tRNA synthetase in the growth, migration, and angiogenesis of human umbilical vein endothelial cells and the underlying molecular mechanism. METHODS: To assess the role of isoleucyl-tRNA synthetase, we silenced isoleucyl-tRNA synthetase in human umbilical vein endothelial cells using lentiviral 2 specific short hairpin RNAs (short hairpin RNAs 1 and 2) and examined silencing efficiency using real time quantitative polymerase chain reaction and western blot analyses. Short hairpin RNAs 1-isoleucyl-tRNA synthetase had greater knockdown efficiency, it was used in the entire downstream analysis. Short hairpin RNAs 1- isoleucyl-tRNA synthetase silencing effects on cell proliferation, cell colony generation, cell migration, as well as angiogenesis were assessed using cell counting kit-8, colony development, cell migration, and angiogenesis tube formation assays, respectively. RESULTS: Compared to the control group, anti-isoleucyl-tRNA synthetase short hairpin RNAs significantly silenced isoleucyl-tRNA synthetase expression in human umbilical vein endothelial cells, and suppressed their proliferation, migration, and angiogenic capacity. To characterize the underlying mechanism, western blot analyses showed that isoleucyl-tRNA synthetase knockdown suppressed phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3ß, and ß-catenin. CONCLUSIONS: We have shown, for the first time, the critical role of isoleucyl-tRNA synthetase in human umbilical vein endothelial cells. Our data show that isoleucyl-tRNA synthetase knockdown suppresses human umbilical vein endothelial cell proliferation, migration, and angiogenesis. We have also shown that isoleucyl-tRNA synthetase knockdown suppresses phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3ß, and ß-catenin. Together, these data highlight isoleucyl-tRNA synthetase as a potential antitumor anti-angiogenic target.

IARS2 regulates proliferation, migration, and angiogenesis of human umbilical vein endothelial cells

SUMMARY OBJECTIVE: In this study, we aimed at investigating the role of isoleucyl-tRNA synthetase in the growth, migration, and angiogenesis of human umbilical vein endothelial cells and the underlying molecular mechanism. METHODS: To assess the role of isoleucyl-tRNA synthetase, we silenced isoleucyl-tRNA synthetase in human umbilical vein endothelial cells using lentiviral 2 specific short hairpin RNAs (short hairpin RNAs 1 and 2) and examined silencing efficiency using real time quantitative polymerase chain reaction and western blot analyses. Short hairpin RNAs 1-isoleucyl-tRNA synthetase had greater knockdown efficiency, it was used in the entire downstream analysis. Short hairpin RNAs 1- isoleucyl-tRNA synthetase silencing effects on cell proliferation, cell colony generation, cell migration, as well as angiogenesis were assessed using cell counting kit-8, colony development, cell migration, and angiogenesis tube formation assays, respectively. RESULTS: Compared to the control group, anti-isoleucyl-tRNA synthetase short hairpin RNAs significantly silenced isoleucyl-tRNA synthetase expression in human umbilical vein endothelial cells, and suppressed their proliferation, migration, and angiogenic capacity. To characterize the underlying mechanism, western blot analyses showed that isoleucyl-tRNA synthetase knockdown suppressed phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3β, and β-catenin. CONCLUSIONS: We have shown, for the first time, the critical role of isoleucyl-tRNA synthetase in human umbilical vein endothelial cells. Our data show that isoleucyl-tRNA synthetase knockdown suppresses human umbilical vein endothelial cell proliferation, migration, and angiogenesis. We have also shown that isoleucyl-tRNA synthetase knockdown suppresses phosphorylation of extracellular-regulated kinase ½ and protein-serine- threonine kinase, as well as expression of vascular endothelial growth factor, GSK-3β, and β-catenin. Together, these data highlight isoleucyl-tRNA synthetase as a potential antitumor anti-angiogenic target.

Bioinformatics analysis of miRNA and mRNA expression profiles to reveal the key miRNAs and genes in osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease and the most frequent type of arthritis. This study aimed to identify the key miRNAs and genes associated with OA progression. METHODS: The GSE105027 (microRNA [miRNA/miR] expression profile; 12 OA samples and 12 normal samples) and GSE48556 (messenger RNA [mRNA] expression profile; 106 OA samples and 33 normal samples) datasets were selected from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and miRNAs (DEMs) were analyzed using the limma and ROCR packages in R, respectively. The target genes that negatively correlated with the DEMs were predicted, followed by functional enrichment analysis and construction of the miRNA-gene and miRNA-transcription factor (TF)-gene regulatory networks. Additionally, key miRNAs and genes were screened, and their expression levels were verified by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: A total of 1696 DEGs (739 upregulated and 957 downregulated) and 108 DEMs (56 upregulated and 52 downregulated) were identified in the OA samples. Furthermore, 56 target genes that negatively correlated with the DEMs were predicted and found to be enriched in three functional terms (e.g., positive regulation of intracellular protein transport) and three pathways (e.g., human cytomegalovirus infection). In addition, three key miRNAs (miR-98-5p, miR-7-5p, and miR-182-5p) and six key genes (murine double minute 2, MDM2; glycogen synthase kinase 3-beta, GSK3B; transmembrane P24-trafficking protein 10, TMED10; DDB1 and CUL4-associated factor 12, DCAF12; caspase 3, CASP3; and ring finger protein 44, RNF44) were screened, among which the miR-7-5p → TMED10/DCAF12, miR-98-5p → CASP3/RNF44, and miR-182-5p → GSK3B pairs were observed in the regulatory network. Moreover, the expression levels of TMED10, miR-7-5p, CASP3, miR-98-5p, GSK3B, and miR-182-5p showed a negative correlation with qRT-PCR verification. CONCLUSION: MiR-98-5p, miR-7-5p, miR-182-5p, MDM2, GSK3B, TMED10, DCAF12, CASP3, and RNF44 may play critical roles in OA progression.