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Gadolinium-based contrast agents (GBCAs) are used in around 40 % of MRI procedures. Despite initial perceptions of minimal risk, their long-term use has emphasized the need to reduce toxicity and develop more efficient GBCAs with extended blood retention. Advancements in nanomaterials have led to improved GBCAs, enhancing MRI diagnostics. This study synthesizes and characterizes nanostructured gadolinium(III) micelles as superior MRI contrast agents. The complexes, [Gd(L)2], where L is a ligand of the N-alkyl-N-methylglucamine surfactant series (L8, L10 or L12, L10), form nanostructured micelles in aqueous solution. Gd(L8)2 and Gd(L10)2 relaxivities remained stable across concentrations. Compared to Gd-DTPA, Gd(III) micelles showed enhanced T1-weighted MRI contrast. Gd(L12)2 micelles exhibited cytotoxicity against B16F10 melanoma cells (IC 50 42.5 ± 2.2 μM) and L292L929 fibroblasts (IC 50 52.0 ± 2.5 μM), with a selectivity index of 1.2. In vivo application in mice brain T2-weighted images suggests nanostructured Gd(III) micelles are promising MRI contrast agents for targeting healthy organs or tumors., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Millions of people worldwide are affected by cutaneous leishmaniasis (CL), a disease that has a significant impact on morbidity and mortality. Understanding the immune responses responsible for tissue damage or the process of lesion healing plays a pivotal role in shaping optimal treatment strategies. In this study, we investigated immunological phenotypes for three groups: glucantime treated (n = 30) and untreated (n = 30) CL patients infected with Leishmania tropica (L. tropica), and healthy controls (n = 20). T-lymphocytes (CD4+ and CD8+), and B lymphocytes (CD14+ and CD19+) were isolated using antibody-conjugated microbeads and magnetic field isolation to achieve high purity. A higher significant difference was observed between T-lymphocytes (CD4+ and CD8+), and B-lymphocytes (CD14+ and CD19+) cells in CL-infected groups before and after treatment (p < 0.0001). When compared, there was also a significant difference among T-lymphocytes (CD4+ and CD8+), B lymphocytes (CD14+ and CD19+) p < 0.0001, p < 0.0005, and p < 0.0007, respectively between CL-infected individuals (before and after treatment) to controls. Our findings suggest that an increased proportion of these cells seen in treated patients may mediate healing, while it is also possible that they may contribute to tissue injury. Understanding the immune system and lesion size of CL can help develop immunotherapies and comprehend the evolution of this parasitic disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The pathophysiology of Cutaneous Leishmaniasis (CL), an infection caused by Leishmania tropica (L. tropica) and Leishmania major (L. major) is primarily determined by inflammation-mediated immune cells. The immune response mainly depends on cells and molecules related to T-cells that influence susceptibility and disease development. Understanding the immunological mechanisms that cause tissue injury or lesion healing is critical for developing appropriate treatment strategies. In the present study, T-cells profile and cell-free mitochondrial DNA (CF mt-DNA) were investigated in CL patients infected with L. tropica (n = 34) and L. major (n = 2) and compared with non-infected healthy controls (n = 20). There was a significant (p<0.0001) difference between CD4+ T-cells among L. tropica and L. major CL-infected groups as compared to control while no significant difference (p = 0.8597) was found in the percentages of CD8+ T-cells. When L. tropica and L. major CL-infected individuals were compared to controls, the levels of IL-4 and expression of CF mt-DNA were significantly higher (p<0.0001). Higher levels of CF mt-DNA were detected in CL patients, irrespective of the infective Leishmania species. We proposed that the levels of CF mt-DNA and IL-4 in CL-infected individuals can be used to determine the disease progression. A better understanding of these biomarkers and evaluation of the immune responses in CL patients might benefit the development of vaccines and immunotherapies., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022. Published by Elsevier B.V.)

Leishmaniasis being one of the six major tropical diseases that affects nearly 0.7-1.3 million people annually, has so far limited and high toxic therapeutic options. Herein, we report the synthesis, in silico, and in vitro evaluations of novel coumarin-incorporated isatin hydrazones (Spf-1 - Spf-10) as highly potent and safe antileishmanial agents. Molecular docking was initially carried out to decipher the binding confirmation of lead molecules towards the active cavity of the target protein (Leishmanolysin gp63) of Leishmania tropica. Among all the docked compounds, only Spf-6, Spf-8, and Spf-10 showed high binding affinities due to a pattern of strong conventional hydrogen bonds and hydrophobic π-interactions. The molecular dynamics simulations showed the stable pattern of such bonding and structure-based confirmation with a time scale of 50 ns towards the top compound (Spf-10) and protein. These analyses affirmed the high stability of the system. Three out of ten compounds evaluated for their antileishmanial activity against Leishmania tropica promastigotes and amastigotes were found to be active at micromolar concentrations (IC 50 range 0.1-4.13 μmol/L), and most importantly, they were also found to be highly biocompatible when screened for their toxicity in human erythrocytes., (Copyright © 2021 Elsevier Inc. All rights reserved.)