Cutaneous Leishmaniasis (CL) is a Neglected Tropical Disease characterized by skin ulcers caused by Leishmania spp. protozoans and there is no safe and effective vaccine to reduce its negative consequences. In a previous work by our group, we identified T cell epitopes of Leishmania (Viannia) braziliensis which stimulated patients’ T cells in vitro. In the present work, the peptides were tested as two pools for their ability to rescue memory T cells during natural infection by Leishmania. We analyzed the frequency of central memory (TCM, CD45RA-CD62L+) and effector memory (TEM, CD45RA + CD62L-) cells during active CL and post-treatment. In parallel, we investigated cell proliferation levels and the cytokines produced after stimulation. Interestingly, we observed higher frequencies (%) in CD4+ TEM during CL, and CD8+ TEM and CD8+ TCM during CL and post-treatment. Cell proliferation was increased, and a significant difference in expression was observed on T-bet and RORγT. Besides that, IFN-γ, IL-2, and IL-10 were detected in patient samples. Collectively, this dataset suggests that during CL there is an increase in the frequency of TCM and TEM, especially in the CD8 compartment. These results indicate a potentially immunogenic profile of the peptide pools, which can support the development of anti-Leishmania formulations.

Visceral leishmaniasis (VL), caused by protozoa of the genus Leishmania, remains a significant public health concern due to its potentially lethal nature if untreated. Current chemotherapy options are limited by severe toxicity and drug resistance. Derivatives of 1,2,4-oxadiazole have emerged as promising drug candidates due to their broad biological activity. This study investigated the effects of novel 1,2,4-oxadiazole derivatives (Ox1–Ox7) on Leishmania infantum, the etiological agent of VL. In silico predictions using SwissADME suggest that these compounds have high oral absorption and good bioavailability. Among them, Ox1 showed the most promise, with higher selectivity against promastigotes and lower cytotoxicity towards L929 fibroblasts and J774.G8 macrophages. Ox1 exhibited selectivity indices of 18.7 and 61.7 against L. infantum promastigotes and amastigotes, respectively, compared to peritoneal macrophages. Ultrastructural analyses revealed severe morphological damage in both parasite forms, leading to cell death. Additionally, Ox1 decreased the mitochondrial membrane potential in promastigotes, as shown by flow cytometry. Molecular docking and dynamic simulations indicated a strong affinity of Ox1 for the L. infantum CYP51 enzyme. Overall, Ox1 is a promising and effective compound against L. infantum.

Aims: This work describes the encapsulation of ceftazidime and tobramycin in zein nanoparticles (ZNPs) and the characterization of their antibacterial and antibiofilm activities against Gram-negati... Plain language summary A nanotechnology product was developed to treat diseases caused by bacteria. This prototype showed the ideal characteristics and could be administered by ingestion through th... Tweetable abstract Zein nanoparticles containing ceftazidime and tobramycin reduce cytotoxicity and improve antibacterial and antibiofilm activity. They are a promising alternative for the treatmen... Graphical abstract

Leishmaniasis remains a global health challenge, and the search for effective and selective therapeutic agents is crucial. This study evaluated the in vitro antileishmanial and cytotoxic activities of thiosemicarbazone compounds (LT-70, LT-73, LT-75, and LT-89) against Leishmania infantum promastigote and axenic amastigote forms. The compounds demonstrated strong leishmanicidal activity, with IC₅₀ values ranging from 10.5 to 14 µM. At the lowest tested concentration (20 µM) the compounds produced percent inhibitions of 100% (LT-70), 100% (LT-73), 100% (LT-75) and 100% (LT-89). Cytotoxicity assays on J774.A1 macrophages revealed CC₅₀ values from 60 µM to >75 µM, with LT-73 and LT-75 showing low toxicity (CC₅₀ > 75µM). Selectivity index (SI) ranged from 7.1 for LT-75 and 5.8 for LT-73, indicating potential for further development. Ultrastructural analysis by SEM and TEM revealed cellular and organelle damage, including membrane rupture and mitochondrial swelling, especially after LT-73 and LT-75 treatment. Immunomodulatory assays indicated induction of TNF-α and IFN-γ production, with significant IL-6 reduction. Flow cytometry data suggest mitochondrial dysfunction and apoptosis-like features, particularly for LT-73. Membrane potential assays suggested mitochondrial depolarization by LT-73. LT thiosemicarbazone derivatives present specific structural modifications that enhance antileishmanial selectivity and reveal a dual mechanism of action combining mitochondrial dysfunction and immunomodulatory effects. These findings support the potential of thiosemicarbazone derivatives as promising antileishmanial agents with selective cytotoxicity and immunomodulatory effects.

Asymptomatic Leishmania infantum, when associated with HIV, can become severe and potentially fatal. In this co-infection, the worst prognosis may be influenced by the host’s immunological aspects, which are crucial in determining susceptibility. Chemokines play an important role in this process by influencing the cellular composition at affected sites and impacting the disease’s outcome. Therefore, the aim of this study was to evaluate proinflammatory chemokines in HIV patients with the asymptomatic L. infantum infection. In this cross-sectional study, the levels of CCL2, CCL5, CXCL8, MIG, and IP-10 were measured in 160 serum samples from co-infected patients (n = 53), patients with HIV (n = 90), and negative controls (n = 17). Quantification was determined by flow cytometry. The obtained data were statistically analyzed using the Kruskal–Wallis test, followed by the Dunn’s post-test and the Spearman’s correlation coefficient. Significance was set at p < 0.05. The chemokines CCL2, CCL5, MIG, and IP-10 exhibited higher levels in the HIV group compared to co-infection. However, the elevated levels of all these chemokines and their increased connectivity in co-infected patients appear to be important in identifying proinflammatory immune responses associated with the asymptomatic condition. Furthermore, a weak negative correlation was observed between higher levels of CXCL8 and lower viral loads in co-infected patients.