Tackling the challenges of human Chagas disease: A comprehensive review of treatment strategies in the chronic phase and emerging therapeutic approaches.

Chagas disease (CD), caused by the flagellated protozoan Trypanosoma cruzi (T. cruzi), affects approximately 7 million people worldwide and is endemic in Latin America, especially among socioeconomically disadvantaged populations. Since the 1960s, only two drugs have been commercially available for treating this illness: nifurtimox (NFX) and benznidazole (BZN). Although these drugs are effective in the acute phase (AP) of the disease, in which parasitemia is usually high, their cure rates in the chronic phase (CP) are low and often associated with several side effects. The CP is characterized by a subpatent parasitaemia and absence of clinical symptoms in the great majority of infected individuals. However, at least 30 % of the individuals will develop potentially lethal symptomatic forms, including cardiac and digestive manifestations. For such reason, in the CP the treatment is usually symptomatic and typically focuses on managing complications such as arrhythmias, heart failure, or digestive problems. Therefore, the need for new drugs or therapeutic approaches using BZN or NFX is extremely urgent. This review presents the main clinical trials, especially in the CP, which involve BZN and NFX in different treatment regimens. Additionally, other therapies using combinations of these drugs with other substances such as allopurinol, itraconazole, ravuconazole, ketoconazole, posaconazole and amiodarone are also reported. The importance of early diagnosis, especially in pediatric patients, is also discussed, emphasizing the need to identify the disease in its early stages to improve the chances of successful treatment.

Cerium oxide nanoparticles: Chemical properties, biological effects and potential therapeutic opportunities (Review).

The chemistry of pure cerium oxide (CeO2-x) nanoparticles has been widely studied since the 1970s, especially for chemical catalysis. CeO2-x nanoparticles have been included in an important class of industrial metal oxide nanoparticles and have been attributed a range of wide applications, such as ultraviolet absorbers, gas sensors, polishing agents, cosmetics, consumer products, high-tech devices and fuel cell conductors. Despite these early applications in the field of chemistry, the biological effects of CeO2-x nanoparticles were only explored in the 2000s. Since then, CeO2-x nanoparticles have gained a spot in research related to various diseases, especially the ones in which oxidative stress plays a part. Due to an innate oxidation state variation on their surface, CeO2-x nanoparticles have exhibited redox activities in diseases, such as cancer, acting either as an oxidizing agent, or as an antioxidant. In biological models, CeO2-x nanoparticles have been shown to modulate cancer cell viability and, more recently, cell death pathways. However, a deeper understanding on how the chemical structure of CeO2-x nanoparticles (including nanoparticle size, shape, suspension, agglomeration in the medium used, pH of the medium, type of synthesis and crystallite size) influences the cellular effects observed remains to be elucidated. In the present review, the chemistry of CeO2-x nanoparticles and their impact on biological models and modulation of cell signalling, particularly focusing on oxidative and cell death pathways, were investigated. The deeper understanding of the chemical activity of CeO2-x nanoparticles may provide the rationale for further biomedical applications towards disease treatment and drug delivery purposes.