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Objective. To investigate the effects of berberine (Berb) on dexamethasone- (Dex-) induced injury of human tendon cells and its potential mechanism. Methods. CCK-8 assay was used to explore the appropriate concentration of Dex-induced injury of tendon cells and the doses of Berb attenuates Dex cytotoxicity; cell wound healing assay was used to detect the effects P < 0.05 of Berb and Dex on the migration ability of tendon cells; flow cytometry was used to measure cell apoptosis; DCF DA fluorescent probe was used to measure the ROS activity of cells. Western blotting was used to detect the expression of phenotype related factors including smooth muscle actin α (SMA-α), type I collagen (Col I), col III, apoptosis-related factors, caspase-3, cleaved caspase-3, caspase-9, cleaved caspase-9, and PI3K/AKT. Results. CCK-8 assay showed that 1–100 μM Dex significantly inhibited the proliferation of tendon cells in a concentration-dependent manner P < 0.05 , where the inhibitory effect of 100 μM Dex was most significant P < 0.005 , and the pretreatment of 150, 200 μM Berb could reverse those inhibitions (all P < 0.05 ). Compared with the control group, Dex significantly inhibited cell migration P < 0.05 , while Berb pretreatment could enhance cell migration P < 0.05 . Flow cytometry and ROS assay showed that Dex could induce apoptosis and oxidative stress response of tendon cells (all P < 0.05 ), while Berb could reverse those responses P < 0.05 . Western blot showed that Dex could inhibit the expression of the col I and III as well as α-SMA (all P < 0.05 ) and enhance the expression of apoptosis-related factors including cleaved caspase-3 and cleaved caspase-9 (all P < 0.05 ). Besides, Dex could also inhibit the activation of the PI3K/AKT signaling pathway (all P < 0.05 ), thus affecting cell function, while Berb treatment significantly reversed the expression of those above proteins (all P < 0.05 ). Conclusion. Berb attenuated DEX induced reduction of proliferation and migration, oxidative stress, and apoptosis of tendon cells by activating the PI3K/AKT signaling pathway and regulated the expression of phenotype related biomarkers in tendon cells. However, further studies are still needed to clarify the protective effects of Berb in vivo.

Objective. To investigate the effect of Mn3O4 nanoparticles (Mn3O4NPs) on inflammatory factors induced by lipopolysaccharide (LPS) in human tendon cells and its mechanism. Methods. The Mn3O4NPs were synthesized by a hydrothermal method. RT-qPCR was used to detect the expression levels of miRNAs related to inflammation in human tendon cells. The expression level of NLRP1 (NOD-like receptor containing pyrin domain 1) was measured by Western blotting. ELISA assay was used to measure the level of TNF-α, IL-1β, IL-4, and IL-10. The relationship between miR-181a-5p and NLRP1 was verified by dual-luciferase reporter assay. Results. Mn3O4NPs produced in this study were brown spherical particles with an average size of 7-10 nm. Mn3O4NP treatment significantly reduced the levels of TNF-α and IL-1β but increased the levels of IL-4 and IL-10 in the human tendon cells induced by LPS. In addition, Mn3O4NP treatment remarkably increased the expression level of miR-181a-5p. NLRP1 is one of the targets of miR-181a-5p, and miR-181a-5p downregulated its expression. Further study showed that Mn3O4NPs could alleviate the inflammatory response of human tendon cells induced by LPS by upregulating miR-181a-5p and thus downregulating the expression of NLRP1. Conclusion. Mn3O4NPs affect the expression of inflammatory cytokines in the human tendon cells induced by LPS by modulating the molecular axis of miR-181a-5p/NLRP1.

Background Patients with osteosarcoma and synchronous lung metastasis (SLM) have poor survival. This study aimed to explore the epidemiology data and construct a predictive nomogram to identify cases at risk of SLM occurrence among pediatric and young adulthood osteosarcoma patients. Methods All data were extracted from Surveillance, Epidemiology, and End Results 17 registries. The age-standardized incidence rate (ASIR) and annual percentage change was evaluated, and reported for the overall population and by age, gender, race, and primary site. Univariate and multivariate logistic regression analyses were used to identify risk factors associated with SLM occurrence, then significant factors were used to develop the nomogram. The area under the receiver operating characteristic curve (AUC) and calibration curve were used to evaluated the predictive power of the nomogram. Survival analysis was assessed by the Kaplan-Meier method and the log-rank test. Multivariate Cox analysis was used to determine the prognostic factors. Results A total of 278 out of 1965 patients (14.1%) presented with SLM at diagnosis. The ASIR increased significant from 0.46 to 0.66 per 1,000,000 person-years from year 2010 to 2019, with an annual percentage change of 3.5, mainly in patients with age 10–19 years, male and appendicular location. All patients were randomly assigned into train cohort and validation cohort with a spilt of 7:3. In the train cohort, higher tumor grade, bigger tumor size, positive lymph nodes and other site-specific metastases (SSM) were identified as significant risk factors associated with SLM occurrence. Then a nomogram was developed based on the four factors. The AUC and calibration curve in both train and validation cohorts demonstrated that the nomogram had moderate predictive power. The median cancer-specific survival was 25 months. Patients with age 20–39 years, male, positive lymph nodes, other SSM were adverse prognostic factors, while surgery was protective factor. Conclusions This study performed a comprehensive analysis regarding pediatric and young adulthood osteosarcoma patients had SLM. A visual, clinically operable, and easy-to-interpret nomogram model was developed for predicting the risk of SLM, which could be used in clinic and help clinicians make better decisions.