CircPVT1 promotes migration and invasion by regulating miR-490-5p/HAVCR2 axis in osteosarcoma cells.

Circular RNAs (circRNAs) play an important role in the progression of osteosarcoma. However, the precise function of circPVT1 in osteosarcoma remains elusive. This study aims to explore the molecular mechanism underlying the involvement of circPVT1 in osteosarcoma cells. We quantified circPVT1 expression using qRT-PCR in both control and osteosarcoma cell lines. To investigate the roles of circPVT1, miR-490-5p and HAVCR2 in vitro, we separately conducted overexpression and inhibition experiments for circPVT1, miR-490-5p and HAVCR2 in HOS and U2OS cells. Cell migration was assessed through wound healing and transwell migration assays, and invasion was measured via the Matrigel invasion assay. To elucidate the regulatory mechanism of circPVT1 in osteosarcoma, a comprehensive approach was employed, including fluorescence in situ hybridization, qRT-PCR, Western blot, bioinformatics, dual-luciferase reporter assay and rescue assay. CircPVT1 expression in osteosarcoma cell lines surpassed that in control cells. The depletion of circPVT1 resulted in a notable reduction in the in vitro migration and invasion of osteosarcoma cells. Mechanism experiments revealed that circPVT1 functioned as a miR-490-5p sequester, and directly targeted HAVCR2. Overexpression of miR-490-5p led to a significant attenuation of migration and invasion of osteosarcoma cells, whereas HAVCR2 overexpression had the opposite effect, promoting these abilities. Additionally, circPVT1 upregulated HAVCR2 expression via sequestering miR-490-5p, thereby orchestrating the migration and invasion in osteosarcoma cells. CircPVT1 orchestrates osteosarcoma migration and invasion by regulating the miR-490-5p/HAVCR2 axis, underscoring its potential as a promising therapeutic target for osteosarcoma.

Identification of circRNA biomarkers in osteosarcoma: An updated systematic review and meta-analysis.

Circular RNAs (circRNAs) play a crucial role in cancer development and progression. This study aimed to identify potential circRNA biomarkers for osteosarcoma. Articles published from January 2010 to September 2023 were searched across eight databases to compare circRNA expression profiles in osteosarcoma and control samples (human, animal and cell lines). Meta-analysis was conducted under a random effects model. Subgroup analysis of circRNAs in different samples and tissues was performed. Diagnostic value was evaluated using receiver operator characteristic curves. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis explored functions of circRNA host genes. A circRNA-miRNA-mRNA axis depicted the regulatory mechanism in osteosarcoma. Among 1356 circRNAs with differential expression were identified across 226 original studies, only 74 were reported in at least three published sub-studies. Meta-analysis identified 58 dysregulated circRNAs (52 upregulated and 6 downregulated). Eleven circRNAs consistently showed dysregulation in tissues and cell lines, with hsa_circ_0005721 showing potential as a circulating biomarker in osteosarcoma. Sensitivity analysis demonstrated 97 % consistency. The overall area under the curve was 0.87 (95 % CI, 0.83-0.89). GO and KEGG enrichment analyses revealed host gene involvement in cancer. The circRNA-miRNA-mRNA axis revealed the regulatory axis and interactions within osteosarcoma specifically. This study demonstrates circRNAs as potential diagnostic biomarkers for osteosarcoma. Consistently reported dysregulated circRNAs are potential biomarkers in osteosarcoma pathogenesis, with hsa_circ_0005721 as a potential circulating biomarker for diagnosis and treatment.

PITX1 suppresses osteosarcoma metastasis through exosomal LINC00662-mediated M2 macrophage polarization.

Paired-like homeodomain transcription factor 1 (PITX1) is frequently downregulated in cancers, including osteosarcoma (OS). However, its role in OS remains unknown. Therefore, we aimed to explore the functions and potential mechanisms of PITX1 in OS malignant progression. Elevated PITX1 suppressed OS cell proliferation and migration, based on transwell, proliferation, and colony formation assays. Pathway enrichment analysis of differentially-expressed genes between PITX1-overexpressing and control OS cells indicated that PITX1 expression was associated with the FAK/Src and PI3k/Akt signaling pathways. Mechanistically, ubiquitination assays and rescue experiments showed that PITX1 interacted with transcription factor STAT3, leading to decreased STAT3 transcriptional activity, which repressed the expression of LINC00662. Specific knockdown of LINC00662 reduced the tumor growth and invasion of OS cells induced by downregulated PITX1. Moreover, exosomal LINC00662, derived from PITX1 knockdown OS cell lines activated M2 macrophages in cell co-culture assays. M2 macrophage secreted several cytokines, among which CCL22 was found to cause OS cell EMT. Collectively, our data indicate that PITX1 suppresses OS cell proliferation and metastasis by downregulating LINC00662. Moreover, LINC00662 can be packaged into OS cell-derived exosomes to mediate M2 macrophage polarization to promote OS metastasis via CCL22.

Which is the best analgesia treatment for total knee arthroplasty: Adductor canal block, periarticular infiltration, or liposomal bupivacaine? A network meta-analysis.

STUDY OBJECTIVE: To review all randomized controlled trials (RCTs) comparing the analgesic efficacy of adductor canal block (ACB), periarticular infiltration (PAI), and any other mode of these treatments in analgesia, such as PAI with liposomal bupivacaine (LB), continuous adductor canal block (cACB) or ACB + PAI, after total knee arthroplasty (TKA). DESIGN: Systematic review and network meta-analysis of RCTs. PATIENTS: We searched PubMed, Embase, and the Cochrane database to detect all relevant RCTs on investigating the analgesic effects of ACB, PAI and LB for TKA published until April 2020. INTERVENTIONS: Use of different analgesic methods of ACB, PAI, cACB, ACB + PAI and LB. MEASUREMENTS: The primary endpoint was visual analog scale (VAS) score at rest and movement. The secondary endpoints were opioids consumption, length of hospitalization and knee range of motion (ROM). We used Cochrane risk of bias to assess the quality of evidence for outcomes. RESULTS: Forty-two studies involving 3785 patients with 5 different methods containing ACB, PAI, ACB + PAI, continuous ACB (cACB), LB, were evaluated. According to surface under the cumulative ranking curve value, 24 h resting VAS score was the lowest the ACB + PAI (88.4%), followed by cACB (73.4%); Resting VAS score at 48 h and movement VAS score at 24 h and 48 h was the lowest in the cACB (99.9%, 92% and 100%). Total opioids consumption was the least in LB (81.4%) before cACB (60.8%). ROM was the largest in the ACB + PAI (84.1%) before cACB (78.8%). CONCLUSION: Although all analgesic methods available were not evaluated, and further studies are needed to establish our results, the 24 h resting VAS score was lowest in ACB + PAI and 48 h resting and movement VAS score was lowest in cACB. CLINICAL TRIAL REGISTRATION: PROSPERO (CRD 42020168102).

Room Temperature Versus Warm Irrigation Fluid Used for Patients Undergoing Arthroscopic Shoulder Surgery: A Systematic Review and Meta Analysis.

PURPOSE: The aim of this study was to analyze whether warm irrigation fluid could reduce postoperative adverse effects in patients undergoing arthroscopic shoulder surgery compared with room temperature irrigation fluid. DESIGN: A systematic review and meta-analysis of clinical trials was performed. METHODS: A computerized search of electronic databases was performed. The inclusion criteria were studies comparing the clinical effects of room temperature and warm irrigation fluid on patients undergoing arthroscopic shoulder surgery. FINDINGS: Warm irrigation fluid reduced the degree of core body temperature drop and the incidence of hypothermia. A statistically lower incidence of shivering also occurred in the warm irrigation fluid group. CONCLUSIONS: The use of warm irrigation fluid better maintains core body temperature and reduces incidence of shivering than room temperature irrigation fluid. Therefore, warm irrigation fluid is a better choice for arthroscopic shoulder surgery.