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Despite the intense global efforts towards an effective treatment of glioblastoma (GB), current therapeutic options are unsatisfactory with a median survival time of 12-15 months after diagnosis, which has not improved significantly over more than a decade. The high tumoral heterogeneity confers resistance to therapies, which has hindered a successful clinical outcome, GB remaining among the deadliest cancers. A hallmark of GB is its high recurrence rate, which has been attributed to the presence of a small subpopulation of tumor cells called GB stem-like cells (GSC). In the present work, the efficacy of a multimodal strategy combining microRNA (miRNA) modulation with new generation multitargeted tyrosine kinase inhibitors (imatinib and axitinib) was investigated aiming at tackling this subpopulation of GB cells. MiR-128 and miR-302a were selected as attractive therapeutic candidates on the basis of previous findings reporting that reestablishment of their decreased expression levels in GSC resulted in cell differentiation, which could represent a possible strategy to sensitize GSC to chemotherapy. Our results show that overexpression of miR-128 or miR-302a induced GSC differentiation, which enhanced senescence mediated by axitinib treatment, thus further impairing GSC proliferation. We also provided evidence for the capacity of GSC to efficiently internalize functionalized stable nucleic acid lipid particles, previously developed and successfully applied in our laboratory to target GB. Taken together, our findings will be important in the future design of a GB-targeted multimodal miRNA-based gene therapy, combining overexpression of miR-128 or miR-302a with axitinib treatment, endowed with the ability to overcome drug resistance., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The delivery of therapeutic proteins remains a challenge, despite recent technological advances. While the delivery of proteins to the lungs is the gold standard for topical and systemic therapy through the lungs, the issue still exists. While pulmonary delivery is highly attractive due to its non-invasive nature, large surface area, possibility of topical and systemic administration, and rapid absorption circumventing the first-pass effect, the absorption of therapeutic proteins is still ineffective, largely due to the immunological and physicochemical barriers of the lungs. Most studies using spray-drying for the nanoencapsulation of drugs focus on the delivery of conventional drugs, which are less susceptible to bioactivity loss, compared to proteins. Herein, the development of polymeric nanoparticles by spray-drying for the delivery of therapeutic proteins is reviewed with an emphasis on its advantages and challenges, and the techniques to evaluate their in vitro and in vivo performance. The protein stability within the carrier and the features of the carrier are properly addressed.

Objective African-Americans have been shown to have low prevalence of hypothyroidism. Brazil has a high ethnic admixture allowing further exploration into whether environmental factors can explain the ethnic differences. Design A survey, representative of the population of Rio de Janeiro, a large metropolitan city in Brazil. Factors studied included race, parity, income, schooling, and smoking. Population The survey was carried out in Rio de Janeiro whereby households (1500) were selected using three-stage probability sampling. A total of 1298 (86.5%) women participated in the survey (non-response: 13.5%). Measurements TSH from blood drawn at the households. Anti-thyroperoxidase (anti-TPO) antibodies and free T4 were also measured. Results Overall prevalence of hypothyroidism (TSH > 4 mUI/ml or taking medication) was 12.3%. Prevalence was 6.9% in black people, 8.8% in Mulatto people, and 16.7% among white people. The mean serum TSH of the population was 2.65 (95% confidence interval 2.33-2.97). The TSH distribution of black and Mulatto people was shifted to the left compared to white people. After adjustment for age, income, smoking and presence of anti-TPO, Black and Mulatto people were still protected from hypothyroidism. The adjusted odds ratio for black compared to white people was 0.45 (95% CI 0.30-0.68) and for Mulatto people was 0.34 (95% CI 0.18-0.63). Serum TSH levels were significantly lower in smokers than in non-smokers, but there was no association between number of cigarettes smoked and serum TSH level. Conclusions This is the first time it has been demonstrated that Mulatto people have a prevalence of hypothyroidism which lies between that of white and black people, independent of the prevalence of anti-TPO and smoking.