MicroRNAs signatures, bioinformatics analysis of miRNAs, miRNA mimics and antagonists, and miRNA therapeutics in osteosarcoma.

MicroRNAs (miRNAs) involved in key signaling pathways and aggressive phenotypes of osteosarcoma (OS) was discussed, including PI3K/AKT/MTOR, MTOR AND RAF-1 signaling, tumor suppressor P53- linked miRNAs, NOTCH- related miRNAs, miRNA -15/16 cluster, apoptosis related miRNAs, invasion-metastasis-related miRNAs, and 14Q32-associated miRNAs cluster. Herrin, we discussed insights into the targeted therapies including miRNAs (i.e., tumor-suppressive miRNAs and oncomiRNAs). Using bioinformatics tools, the interaction network of all OS-associated miRNAs and their targets was also depicted.

Novel molecular insights and new therapeutic strategies in osteosarcoma.

Osteosarcoma (OS) is one of the most prevalent malignant cancers with lower survival and poor overall prognosis mainly in children and adolescents. Identifying the molecular mechanisms and OS stem cells (OSCs) as new concepts involved in disease pathogenesis and progression may potentially lead to new therapeutic targets. Therefore, therapeutic targeting of OSCs can be one of the most important and effective strategies for the treatment of OS. This review describes the new molecular targets of OS as well as novel therapeutic approaches in the design of future investigations and treatment.

Evaluation of gene expression level of CDC5L and MACC1 in poor prognosis and progression of osteosarcoma.

Current evidences have indicated that osteosarcoma is strongly associated with abnormal genetic and epigenetic changes that lead to the abnormal expression of oncogenes or methylation of tumor suppressor genes. In the present study, MACC1 and CDC5L mRNA levels in the patients with osteosarcoma were evaluated using quantitative real-time PCR. Our results demonstrated that CDC5L mRNA levels were higher in tumor tissues than in adjacent normal tissues (2.713 ± 0.738 vs. 1.071 ± 0.629; P < 0.05). Moreover, MACC1 was upregulated in tumor bone tissues than in adjacent normal tissues (3.221 ± 0. 624 vs. 1.427 ± 0.456; P < 0.05). Our result demonstrated that high expression of CDC5L was significantly related to advanced TNM stage (P = 0.032). No significant difference was determined between CDC5L mRNA expression and other clinicopathological parameters including age, gender, tumor diameter, location, tumor grade, and histological type. In addition, overexpression of MACC1 was strongly correlated with advanced TNM stage (P = 0.027) and high tumor grade (P = 0.035). Our findings indicated that mRNA level of CDC5L is correlated with advanced TNM stage, and MACC1 may be involved in progression of osteosarcoma.

Evaluation of the Etiologies of Implant Fracture in Patients With Fractures of the Implants of Lower Limbs' Long Bones.

BACKGROUND: Orthopedics implants are important tools for treatment of bone fractures. Despite available recommendations for designing and making the implants, there are multiple cases of fracture of these implants in the body. Hence, in this study the frequency of failure of implants in long bones of lower extremities was evaluated. METHODS AND MATERIALS: In this cross-sectional study, two types of fractured implants in the body were analyzed and underwent metalogical, mechanical, and modeling and stress-bending analysis. RESULTS: The results revealed that the main cause of fractures was decreased mechanical resistance due to inappropriate chemical composition (especially decreased percentages of Nickel and Molybdenum). CONCLUSIONS: It may be concluded that following the standard chemical composition and use of optimal making method are the most important works for prevention of failure of implants.

Determination of copper status by five biomarkers in serum of healthy women.

BACKGROUND: The essential trace element copper is relevant for many important physiological processes. Changes in copper homeostasis can result from disease and affect human health. A reliable assessment of copper status by suitable biomarkers may enable fast detection of subtle changes in copper metabolism. To this end, additional biomarkers besides serum copper and ceruloplasmin (CP) concentrations are required. OBJECTIVES: The aim of this study was to investigate the emerging copper biomarkers CP oxidase (CPO) activity, exchangeable copper (CuEXC) and labile copper in serum of healthy women and compare them with the conventional biomarkers total serum copper and CP. METHOD AND MAIN FINDINGS: This observational study determined CPO activity, the non CP-bound copper species CuEXC and labile copper, total serum copper and CP in sera of 110 healthy women. Samples were collected at four time points over a period of 24 weeks. The concentrations of total serum copper and CP were within the reference ranges. The comparison of all five biomarkers provided insight into their relationship, the intra- and inter-individual variability as well as the age dependence. The correlation and Principal Component Analyses (PCA) indicated that CP, CPO activity and total copper correlated well, followed by CuEXC, while the labile copper pool was unrelated to the other parameters. CONCLUSIONS: This study suggests that the non-CP-bound copper species represent copper pools that are differently regulated from total copper or CP-bound copper, making them interesting complementary biomarkers to enable a more complete assessment of body copper status with potential relevance for clinical application.

Combined copper and zinc deficiency is associated with reduced SARS-CoV-2 immunization response to BNT162b2 vaccination.

The essential trace elements copper, selenium and zinc are of relevance for immunity and immune response to vaccination. In this longitudinal study, adult healthcare workers (n = 126) received two doses of an mRNA vaccine (BNT162b2), and longitudinal serum samples were prepared. Vaccine-induced antibodies and their neutralizing activity were analyzed, and the trace elements copper, zinc, and selenium along with the copper transporter ceruloplasmin were measured. Subjects with combined deficiency of copper and zinc, i.e. both in the lowest tertiles at baseline, displayed particularly low antibody titers at three (Double Q1: 13 AU/mL vs. not double Q1: 29 AU/mL) and six (Double Q1: 200 AU/mL vs. not double Q1: 425 AU/mL) weeks after vaccination (p < 0.05). The results indicate the potential importance of an adequate trace element status of copper and zinc for raising a strong vaccine-induced SARS-CoV-2 antibody response, and highlights the importance of considering combined micronutrient insufficiencies, as single deficiencies may synergize.

Diagnostic investigations of PLA2G16 and CDH11 expression levels as independent prognostic markers of human osteosarcoma.

INTRODUCTION: The aim of this study was to facilitate and deepen the understanding of the associations of the clinical significance of PLA2G16 and CDH11 in patients with osteosarcoma. MATERIAL AND METHODS: We collected 50 paired osteosarcoma tissues and adjacent normal bone tissues and evaluated the expression of PLA2G16 and CDH11 by quantitavise reverse transcriptase real-time polymerase chain reaction. RESULTS: PLA2G16 expression was upregulated in osteosarcoma tissues when compared with adjacent normal bone tissues, and the difference was statistically significant (4.78 ±0.70 vs. 1.31 ±0.65; p < 0.05). Our data indicated that high expression of PLA2G16 was significantly related to advanced TNM stage and metastasis or recurrence (p < 0.05). The expression level of CDH11 was lower in osteosarcoma tissues (median relative expression level ± SD: 6.29 ±1.43) than adjacent normal bone tissues (mean ± SD: 13.72 ±3.08, p < 0.05). Our findings demonstrated that decreased expression of CDH11 was strongly linked to advanced TNM stage, and metastasis or recurrence (p < 0.05). Log-rank analysis showed that patients with high expression of PLA2G16 have shorter overall survival than those with low expression. Moreover, shorter overall survival was significantly correlated with decreased expression of CDH11. Multivariate Cox proportional hazards analysis showed that PLA2G16 (p = 0.028; HR = 2.621; 95% CI) and CDH11 (p = 0.023; HR = 2.81; 95% CI) expression and also metastasis or recurrence (p = 0.03; HR = 2.531; 95% CI) were independent prognostic factors for poor overall survival of osteosarcoma patients. CONCLUSIONS: These findings suggest that PLA2G16 and CDH11 expression can be independent prognostic factors for poor overall survival of patients with osteosarcoma.