Machine learning and experimental analyses identified miRNA expression models associated with metastatic osteosarcoma.

Osteosarcoma (OS), as the most common primary bone cancer, has a high invasiveness and metastatic potential, therefore, it has a poor prognosis. This study identified early diagnostic biomarkers using miRNA expression profiles associated with osteosarcoma metastasis. In the first step, we used RNA-seq and online microarray data from osteosarcoma tissues and cell lines to identify differentially expressed miRNAs. Then, using seven feature selection algorithms for ranking, the first-ranked miRNAs were selected as input for five machine learning systems. Using network analysis and machine learning algorithms, we developed new diagnostic models that successfully differentiated metastatic osteosarcoma from non-metastatic samples based on newly discovered miRNA signatures. The results showed that miR-34c-3p and miR-154-3p act as the most promising models in the diagnosis of metastatic osteosarcoma. Validation for this model by RT-qPCR in benign tissue and osteosarcoma biopsies confirmed the lower expression of miR-34c-3p and miR-154-3p in OS samples. In addition, a direct correlation between miR-34c-3p expression, miR-154-3p expression and tumor grade was discovered. The combined values of miR-34c-3p and miR-154-3p showed 90 % diagnostic power (AUC = 0.90) for osteosarcoma samples and 85 % (AUC = 0.85) for metastatic osteosarcoma. Adhesion junction and focal adhesion pathways, as well as epithelial-to-mesenchymal transition (EMT) GO terms, were identified as the most significant KEGG and GO terms for the top miRNAs. The findings of this study highlight the potential use of novel miRNA expression signatures for early detection of metastatic osteosarcoma. These findings may help in determining therapeutic approaches with a quantitative and faster method of metastasis detection and also be used in the development of targeted molecular therapy for this aggressive cancer. Further research is needed to confirm the clinical utility of miR-34c-3p and miR-154-3p as diagnostic biomarkers for metastatic osteosarcoma.

Significant Interaction between Melatonin and Titanium Bone Implants: Available Evidence and Future Research Directions.

The trend in the incidence rate of bone fractures has been upward and as a result, the burden associated with orthopedic fractures has increased significantly. Titanium (Ti) implants are considered a preferred method of managing long bone fractures. However, no benefit comes without some downside, and using Ti implants is associated with several complications. In this respect, it was observed that in bones, Ti can disrupt the bone healing process by disturbing the balance of osteoclast and osteoblast activation and also increasing the production of inflammatory cytokines. Melatonin is a widely-acting molecule that possesses strong anti-oxidant features. This molecule reinforces mineral density and improves bone formation processes. In this review, we focused on the protective effect of melatonin in mitigating the Ti-related complications.

Mortality and re-fracture rates in low trauma hip fracture.

OBJECTIVES: This study aimed to estimate the incidence rate of re-fracture and all-cause mortality rate in patients with hip fractures caused by minor trauma in the first year following the event. MATERIALS AND METHODS: This is a retrospective cohort study of patients over 50 years of age conducted in a referral hospital located in Tehran (Shafa-Yahyaian). Using the hospital information system (HIS), all patients hospitalized due to hip fractures caused by minor trauma during 2013-2019 were included in the study. We investigated the occurrence of death and re-fracture in all patients one year after the primary hip fracture. RESULTS: A total of 945 patients with hip fractures during a 307,595 person-days of follow-up, were included. The mean age of the participants was 71 years (SD = 11.19), and 533 (59%) of them were women. One hundred forty-nine deaths were identified during the first year after hip fracture, resulting in a one-year mortality rate of 17.69% (95% CI: 15.06-20.77). The one-year mortality rate was 20.06% in men and 15.88% in women. Out of all the participants, 667 answered the phone call, of which 29 cases had experienced a re-fracture in the first year (incidence rate = 5.03%, 95% CI: 3.50-7.24). The incidence rates in women and men were 6.07% and 3.65%, respectively. CONCLUSION: Patients with low-trauma hip fractures have shown a high rate of mortality in the first year. Considering the increase in the incidence of hip fractures with age, comprehensive strategies are needed to prevent fractures caused by minor trauma in the elderly population.