Incluye artículos, objetos de conferencias, seminarios y jornadas, reportes técnicos, comunicaciones y otros. https://hdl.handle.net/20.500.12008/21981 2026-04-23T10:33:06Z 2026-04-23T10:33:06Z Castellano, Mauricio Blanco, Valentina Li Calzi Alcalde, Marco Costa Camacho, Bruno Alejo Witwer, Kenneth Hill, Marcelo Cayota, Alfonso Segovia, Mercedes Tosar Rovira, Juan Pablo https://hdl.handle.net/20.500.12008/54536 2026-04-22T13:02:40Z 2025-01-01T00:00:00Z

Título: Ribonuclease activity undermines immune sensing of naked extracellular RNA Autor: Castellano, Mauricio; Blanco, Valentina; Li Calzi Alcalde, Marco; Costa Camacho, Bruno Alejo; Witwer, Kenneth; Hill, Marcelo; Cayota, Alfonso; Segovia, Mercedes; Tosar Rovira, Juan Pablo Resumen: Cell membranes are thought of as barriers to extracellular RNA (exRNA) uptake. While naked exRNAs can be spontaneously internalized by certain cells, functional cytosolic delivery has been rarely observed. Here, we show that extracellular ribonucleases (RNases)—primarily from cell culture supplements—have obscured the study of exRNA functionality. When ribonuclease inhibitor (RI) is added to cell cultures, naked exRNAs can trigger pro-inflammatory responses in dendritic cells and macrophages, largely via endosomal Toll-like receptors (TLRs). Moreover, naked exRNAs can escape endosomes, engaging cytosolic RNA sensors. In addition, naked extracellular mRNAs can be spontaneously internalized and translated by various cell types in an RI-dependent manner. In vivo, RI co-injection amplifies naked-RNA-induced activation of splenic lymphocytes and myeloid leukocytes. Furthermore, naked RNA is inherently pro-inflammatory in RNase-poor compartments like the peritoneal cavity. These findings demonstrate that naked RNA is bioactive without requiring vesicular encapsulation, making a case for nonvesicular-exRNA-mediated intercellular communication. Descripción: Información suplementaria en: https://doi.org/10.1016/j.xgen.2025.100874.

2025-01-01T00:00:00Z Avanzo, Romina E. García Liñares, Guadalupe Rodríguez, Noris Romero Cordero, Ángel Heriberto https://hdl.handle.net/20.500.12008/54535 2026-04-22T13:01:14Z 2025-01-01T00:00:00Z

Título: A comprehensive revision on the use of quinoline antimalarial drugs as leishmanicidal agents Autor: Avanzo, Romina E.; García Liñares, Guadalupe; Rodríguez, Noris; Romero Cordero, Ángel Heriberto Resumen: Antimalarial drugs based on quinolines have been widely used as leishmanicidal agents for either cutaneous or visceral leishmaniasis models. Herein, we showed the leishmanicidal response against in vitro models of different Leishmania spp. and against in vivo models of eleven key antimalarials, including chloroquine, sitamaquine, amodiaquine, mefloquine, quinine, primaquine, hydroxychloroquine, tafenoquine, quinacrine and moxipraquine. Mechanistic studies and advances in clinical treatment are also discussed. This mini-review aims to show the state of the art in using antimalarial drugs to discover alternative therapies for leishmaniasis treatment.

2025-01-01T00:00:00Z Romero Cordero, Ángel Heriberto https://hdl.handle.net/20.500.12008/54534 2026-04-22T13:01:06Z 2025-01-01T00:00:00Z

Título: Are basic and lipophilic chain groups highly required in leishmanicidal quinolines to favor the phagolysosome accumulation? Autor: Romero Cordero, Ángel Heriberto Resumen: A phagolysosome is a cytoplasmic body formed through the fusion of a phagosome with a lysosome during the phagocytosis process (Alexander and Vickerman, 1975). The phagolysosome is characterized by an internal acidic environment (pH 4.5–5.0) and an internal temperature of 37°C. This internal acidic condition plays an important role in the intracellular destruction of pathogens via enzymatic hydrolytic degradation (Nguyen and Yates, 2021). This body is crucial for the survival of Leishmania parasites within the host cell (Zilberstein, 2021). Leishmania is an intracellular parasite that cycles between the midgut of female sandfly vectors and phagolysosomes of mammalian hosts. The infection initiates with the transformation of the parasite found in the midgut of a sandfly into the flagellated promastigote form. Then the parasites are injected into the human skin during a sandfly blood meal and are rapidly phagocytosed by macrophages, which fuse with lysosomes to form phagolysosomes (Zilberstein, 2021). It is documented that the presence of a chemical component such as lipophosphoglycan (LPG) could be essential in the recognition of promastigote parasite by macrophage cells (Desjardins and Descoteaux, 1997; Moradin and Descoteaux, 2012). Once within the phagolysosome, promastigotes are differentiated to a smaller aflagellated intracellular amastigote form, which is favored by the extremely harsh environment inside the phagolysosome (Berman et al., 1979; Chang and Dwyer, 1976). The parasites at this stage survive and elude the host defense mechanism within the phagolysosome (Chang and Dwyer, 1976; Moradin and Descoteaux, 2012) and then proliferate by binary cell division and invade other macrophages or phagocytic (i.e. dendritic cells) or non-professional phagocytic (i.e. fibroblasts) cells. To elude the host immune defense, Leishmania parasites developed a mechanism directed to promote a shift in the macrophage polarization, from a defensive macrophage M1 to an attenuated macrophage M2 (Carneiro et al., 2021; Naderer and McConville, 2008; Tomiotto-Pellissier, et al., 2018), which allows their survival and proliferation inside phagolysosomes. Thus, the phagolysosome emerges as an attractive target for the development of leishmanicidal agents, and it is essential to design chemical structures that will be able to accumulate into the phagolysosome taking advantage of their internal acidic characteristic and highly lipophilic membrane. With this prelude in hand, the present article seeks to show the role of some physicochemical properties [e.g., ionization constant (pKa) and lipophilicity (log P)] to favor the accumulation of quinoline systems into the lysosome and to subsequently correlate these parameters with the in vitro leishmanicidal response against intracellular amastigotes.

2025-01-01T00:00:00Z Romero Cordero, Ángel Heriberto Gonzalez, Karina N. Sabino, Marcos A. https://hdl.handle.net/20.500.12008/54533 2026-04-22T13:00:58Z 2025-01-01T00:00:00Z

Título: Application of nano and microformulations to improve the leishmanicidal response of quinoline compounds: a brief review Autor: Romero Cordero, Ángel Heriberto; Gonzalez, Karina N.; Sabino, Marcos A. Resumen: The quinolines represent an important scaffold for the development of leishmanicidal agents. In particular, the use of nano and microformulations has emerged as a powerful tool to improve the therapeutic profile of leishmanicidal drugs, favoring bioavailability, transportation to key targets, metabolic protection, and immunostimulating responses. This mini-review seeks to provide a general perspective about the use of nano/microencapsulation for the development of leishmanicidal formulations based on quinoline, giving an overview of the various cases of encapsulation, analyzing the repercussions of the type of polymeric matrix (synthetic or natural polymer), type of formulation (polymeric or metallic nanoparticles, micelles, liposomes, etc.), drug loading percentage, and release rate of quinoline drug.

2025-01-01T00:00:00Z