Hsa_circ_0064636 regulates voltage dependent anion channel 1/ubiquitination factor E4A through miR­326/miR­503­5 in osteosarcoma.

Circular RNAs (circRNAs) are a subclass of non-coding RNAs that are important for the regulation of gene expression in eukaryotic organisms. CircRNAs exert various regulatory roles in cancer progression. However, the role of hsa_circ_0064636 in osteosarcoma (OS) remains poorly understood. In the present study, the expression of hsa_circ_0064636 in OS cell lines was measured by reverse transcription-quantitative PCR (RT-qPCR). Differentially expressed mRNAs and microRNAs (miRNA or miRs) were screened using mRNA(GSE16088) and miRNA(GSE65071) expression datasets for OS. miRNAs that can potentially interact with hsa_circ_0064636 were predicted using RNAhybrid, TargetScan and miRanda. Subsequently, RNAhybrid, TargetScan, miRanda, miRWalk, miRMap and miRNAMap were used for target gene prediction based on the overlapping miRNAs to construct a circ/miRNA/mRNA interaction network. Target genes were subjected to survival analysis using PROGgeneV2, resulting in a circRNA/miRNA/mRNA interaction sub-network with prognostic significance. miRNA and circRNA in the subnetwork may also have survival significance, but relevant data are lacking and needs to be further proved. RT-qPCR demonstrated that hsa_circ_0064636 expression was significantly increased in OS cell lines. miR-326 and miR-503-5p were identified to be target miRNAs of hsa_circ_0064636. Among the target genes obtained from the miR-326 and miR-503-5p screens, ubiquitination factor E4A (UBE4A) and voltage dependent anion channel 1 (VDAC1) were respectively identified to significantly affect prognosis; only miR-326 targets UBE4A and only miR-503 targets VDAC1. To conclude, these aforementioned findings suggest that hsa_circ_0064636 may be involved in the development of OS by sponging miR-503-5p and miR-326to inhibit their effects, thereby regulating the expression of VDAC1 and UBE4A.

Investigation of cellular communication and signaling pathways in tumor microenvironment for high TP53-expressing osteosarcoma cells through single-cell RNA sequencing.

Osteosarcoma (OS) stands as the most prevalent primary bone cancer in children and adolescents, and its limited treatment options often result in unsatisfactory outcomes, particularly for metastatic cases. The tumor microenvironment (TME) has been recognized as a crucial determinant in OS progression. However, the intercellular dynamics between high TP53-expressing OS cells and neighboring cell types within the TME are yet to be thoroughly understood. In our study, we harnessed the single-cell RNA sequencing (scRNA-seq) technology in combination with the computational tool-Cellchat, aiming to elucidate the intercellular communication networks present within OS. Through meticulous quantitative inference and subsequent analysis of these networks, we succeeded in identifying significant signaling pathways connecting high TP53-expressing OS cells with proximate cell types, namely Macrophages, Monocytes, Endothelial Cells, and PVLs. This research brings forth a nuanced understanding of the intricate patterns and coordination involved in the TME's intercellular communication signals. These findings not only provide profound insights into the molecular mechanisms underpinning OS but also indicate potential therapeutic targets that could revolutionize treatment strategies.

Injectable collagen hydrogel combines human umbilical cord mesenchymal stem cells to promote endometrial regeneration in rats with thin endometrium.

The regeneration of thin endometrium still remains as a great challenge in the field of reproductive medicine. Stem cells-based therapy has been considered as a promising strategy for the restoration of thin endometrium. However, the low transplantation and retention rate of stem cells and loss of stemness due to in vitro expansion limits the therapeutic efficacy. In our study, we combined collagen hydrogel and human umbilical cord mesenchymal stem cells (uMSCs) for improving the regeneration of thin endometrium, by using the potent pluripotency and low immunogenicity of uMSCs and collagen hydrogel that promotes the anchorage and proliferation of stem cells. Results showed that collagen hydrogel has favorable biocompatibility and the capacity to enhance the cell viability and expression of stemness-associated genes (including organic cation/carnitine transporter4 (Oct-4), Nanog homeobox (Nanog) and SRY-box transcription factor 2 (SOX2)) of uMSCs. The combination of collagen hydrogel and uMSCs prolonged the retention time of the constructs in the uterine cavity and improved endometrial thickness compared with uMSCs alone, leading to increase the fertility of the rats with thin endometrium. These highlighted therapeutic prospects of collagen hydrogel combined with uMSCs for the minimally invasive therapy of thin endometrium in the clinic.

A practical nomogram for predicting amputation rates in acute compartment syndrome patients based on clinical factors and biochemical blood markers.

BACKGROUND: Amputation is a serious complication of acute compartment syndrome (ACS), and predicting the risk factors associated with amputation remains a challenge for surgeons. The aim of this study was to analyze the risk factors for amputation in patients with ACS and develop a nomogram to predict amputation risk more accurately. METHODS: The study population consisted of 143 patients (32 in the amputation group and 111 in the limb preservation group) diagnosed with ACS. LASSO and multivariate logistic regression were used to screen predictors and create a nomogram. The model's accuracy was assessed by receiver operating characteristic (ROC) curves, C-index, calibration curves, and decision curve analysis (DCA). RESULTS: The predictors included cause of injury, vascular damage, shock, and fibrinogen in the nomogram. The C-index of the model was 0.872 (95% confidence interval: 0.854-0.962), and the C-index calculated by internal validation was 0.838. The nomogram's area under the curve (AUC) was 0.849, and the calibration curve demonstrated a high degree of agreement between the nomogram's predictions and actual observations. Additionally, the DCA indicated good clinical utility for the nomogram. CONCLUSION: The risk of amputation in ACS patients is associated with the cause of injury, vascular damage, shock, and fibrinogen. Our nomogram integrating clinical factors and biochemical blood markers enables doctors to more conveniently predict the risk of amputation in patients with ACS.

Hsa_circ_0007031 promotes the proliferation and migration of osteosarcoma cells by sponging miR-196a-5p to regulate the HOXB6.

Circular RNAs (circRNAs), a subclass of noncoding RNAs, have been demonstrated to play an essential role in osteosarcoma (OS) development. However, there is still a significant gap in investigating its biological functions and underlying molecular mechanisms, and novel targets of circRNAs have yet to be fully explored. Herein, we found that hsa_circ_0007031 is noticeably raised in OS clinical tissues and cell lines. Hsa_circ_0007031 accelerates OS cell proliferation and migration in vitro and tumor growth and metastasis in vivo and is strongly linked with the stemness of cancer stem cells in OS. Mechanistically, hsa_circ_0007031 shares miRNA response elements with Homeobox B6 (HOXB6), which is identified as a novel pro-tumorigenic gene of OS. Hsa_circ_0007031 competitively binds to miR-196a-5p to prevent miR-196a-5p from lowering the level of HOXB6, which modulates chemokines of cytokine-cytokine receptor interaction signaling pathway and finally promotes OS malignant behavior. In summary, our data unveiled that hsa_circ_0007031/miR-196a-5p/HOXB6 axis-mediated cytokine-cytokine receptor interaction facilitates the progression of OS and maintains the properties of tumor stem cells, which could be a promising therapeutic target for OS.

Identification of Candidate MicroRNA-mRNA Subnetwork for Predicting the Osteosarcoma Progression by Bioinformatics Analysis.

Osteosarcoma (OS) is the pretty common primary cancer of the bone among the malignancies in adolescents. A single molecular component or a limited number of molecules is insufficient as a predictive biomarker of OS progression. Hence, it is necessary to find novel network biomarkers to improve the prediction and therapeutic effect for OS. Here, we identified 230 DE-miRNAs and 821 DE-mRNAs through two miRNA expression-profiling datasets and three mRNA expression-profiling datasets. We found that hsa-miR-494 is closely linked with the survival of OS patients. In addition, we analyzed GO and KEGG enrichment for targets of hsa-miR-494-5p and hsa-miR-494-3p through R programming. And five mRNAs were predicted as common targets of hsa-miR-494-5p and hsa-miR-494-3p. We further revealed that upregulated TRPS1 was strongly correlated with poor outcomes in OS patients through the survival analysis based on the TARGET database. The qRT-PCR study verified that the expression of hsa-miR-494-5p and hsa-miR-494-3p was declined considerably, while TRPS1 was notably raised in OS cells when compared to the osteoblasts. Thus, we generated a new regulatory subnetwork of key miRNAs and target mRNAs using Cytoscape software. These results indicate that the novel miRNA-mRNA subnetwork composed of hsa-miR-494-5p, hsa-miR-494-3p, and TRPS1 might be a characteristic molecule for assessing the prognostic value of OS patients.