MSI2 expression in adrenocortical carcinoma: Association with unfavorable prognosis and correlation with steroid and immune-related pathways.

Adrenocortical carcinoma (ACC) is a rare, but highly aggressive cancer of the adrenal cortex with a generally poor prognosis. Despite being rare, completely resected ACCs present a high risk of recurrence. Musashi-2 (MSI2) has recently been recognized as a potential prognostic biomarker and therapeutic target in many cancers. However, no studies have evaluated the clinical significance of MSI2 expression in ACC. Here, we addressed MSI2 expression and its association with ACC prognosis and clinicopathological parameters. MSI2 expression was analyzed in TCGA, GSE12368, GSE33371, and GSE49278 ACC datasets; and its correlation with other genes and immune cell infiltration were investigated by using the R2: Genomics Analysis and Visualization Platform and TIMER databases, respectively. Enrichment analysis was performed with the DAVID Functional Annotation Tool. Kaplan-Meier curves, log-rank tests, and Cox regression analyses were used to explore the prognostic role of MSI2 in ACC. Our findings demonstrated the potential value of MSI2 overexpression as an independent predictor of poor prognosis in patients with completely resected ACC (hazard ratio 6.715, 95% confidence interval 1.266 - 35.620, p =.025). In addition, MSI2 overexpression was associated with characteristics of unfavorable prognosis, such as cortisol excess (p = .002), recurrence (p =.003), and death (p =.015); positively correlated with genes related to steroid biosynthesis (p < .05); and negatively correlated with immune-related pathways (p < .05). Our findings demonstrate that MSI2 has value as a prognostic marker for completely resected ACC and reinforce the investigation of its role as a possible therapeutic target for patients with ACC.

Applicability of plant-based products in the treatment of Trypanosoma cruzi and Trypanosoma brucei infections: a systematic review of preclinical in vivo evidence.

Chagas disease and sleeping sickness are neglected tropical diseases closely related to poverty, for which the development of plant-derived treatments has not been a promising prospect. Thus, we systematicaly review the preclinical in vivo evidence on the applicability of plant-based products in the treatment of Trypanosoma cruzi and Trypanosoma brucei infections. Characteristics such as disease models, treatments, toxicological safety and methodological bias were analysed. We recovered 66 full text articles from 16 countries investigating 91 plant species. The disease models and treatments were highly variable. Most studies used native (n = 36, 54·54%) or exotic (n = 30, 45·46%) plants with ethnodirected indication (n = 45, 68·18%) for trypanosomiasis treatment. Complete phytochemical screening and toxicity assays were reported in only 15 (22·73%) and 32 (48·49%) studies, respectively. The currently available preclinical evidence is at high risk of bias. The absence of or incomplete characterization of animal models, treatment protocols, and phytochemical/toxicity analyses impaired the internal validity of the individual studies. Contradictory results of a same plant species compromise the external validity of the evidence, making it difficult determine the effectiveness, safety and biotechnological potential of plant-derived products in the development of new anti-infective agents to treat T. cruzi and T. brucei infections.