Publications by authors named "Ricardo Mondragon Flores"

Drug repositioning is an efficient strategy to search for new treatment alternatives that is especially valuable for neglected parasitic diseases such as leishmaniasis. Tamoxifen and raloxifene are selective estrogen receptor modulators (SERMs) that have shown antileishmanial activity. Clomiphene is a SERM structurally similar to tamoxifen, whose antileishmanial potential is unknown.

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Integral membrane pyrophosphatases (mPPases) hydrolyze pyrophosphate. This enzymatic mechanism is coupled with the pumping of H + and/or Na + across membranes, which can be either K + -dependent or K + -independent. Inorganic proton-translocating pyrophosphatases (H + -PPases) can transport protons across cell membranes and are reported in various organisms such as plants, bacteria, and protozoan parasites.

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Indazoles have previously been identified as molecules with antiprotozoal activity. In this study, we evaluate the in vitro activity of thirteen 3-alkoxy-1-benzyl-5-nitroindazole derivatives (series D) against , and . In vitro, cytotoxicity against mouse peritoneal macrophages and growth inhibitory activity in promastigotes were evaluated for all compounds, and those showing adequate activity and selectivity were tested against intracellular amastigotes.

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Arpin was discovered as an inhibitor of the Arp2/3 complex localized at the lamellipodial tip of fibroblasts, where it regulated migration steering. Recently, we showed that arpin stabilizes the epithelial barrier in an Arp2/3-dependent manner. However, the expression and functions of arpin in endothelial cells (EC) have not yet been described.

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  • Chronic infections trigger the growth of neural progenitor cells (NPCs) in the brain, influenced by factors like inflammation and changes in cytokines.
  • In a study with CD-1 adult male mice infected with the ME49 strain, researchers examined brain tissues to observe the proliferation of NPCs using immunofluorescence techniques and confocal microscopy.
  • Findings revealed a significant increase in NPC proliferation in the infected mice compared to the control group, offering insights into the effects of chronic toxoplasmosis on brain cell dynamics.
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  • Hutchinson-Gilford progeria syndrome (HGPS) is a rare disease caused by a mutant form of Lamin A called progerin, leading to premature aging.
  • Recent studies show that HGPS cells have issues with protein export due to the CRM1 pathway, and inhibiting this pathway with a drug called LMB can improve cell health by reducing senescence.
  • In this study, LMB not only enhances mitochondrial function in HGPS cells but also promotes mitochondrial biogenesis and mitophagy, making it a potential treatment strategy for HGPS and related diseases involving mitochondrial dysfunction.
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  • The study focuses on Toxoplasma gondii's cytoskeleton, which is crucial for its ability to invade cells, yet some structural details remain unclear.
  • Using a detergent extraction process and electron microscopy, researchers successfully isolated and examined the cytoskeleton of Toxoplasma tachyzoites, uncovering both known and new structures.
  • Notably, the research characterized previously unexamined nanofibers and structural components, providing insights into Toxoplasma's biology and potential targets for therapeutic intervention to block its ability to invade host cells.
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The intestinal epithelial barrier (IEB) depends on stable interepithelial protein complexes such as tight junctions (TJ), adherens junctions (AJ), and the actin cytoskeleton. During inflammation, the IEB is compromised due to TJ protein internalization and actin remodeling. An important actin regulator is the actin-related protein 2/3 (Arp2/3) complex, which induces actin branching.

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Protein phosphorylation and dephosphorylation are increasingly recognized as important processes for regulating multiple physiological mechanisms. Phosphorylation is carried out by protein kinases and dephosphorylation by protein phosphatases. Phosphoprotein phosphatases (PPPs), one of three families of protein serine/threonine phosphatases, have great structural diversity and are involved in regulating many cell functions.

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Toxoplasma gondii is one of the most successful intracellular parasites in the world. The dynamic, adhesion, invasion, and even replication capabilities of Toxoplasma are based on dynamic machinery located in the pellicle, a three membrane complex that surrounds the parasite. Among the proteins that carry out these processes are inner membrane complex (IMC) proteins, gliding-associated proteins (GAP), diverse myosins, actin, tubulin, and SRS proteins.

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Toxoplasma gondii shows high dissemination and migration properties across biological barriers infecting immunologically privileged organs. Toxoplasma uses different routes for dissemination; however, the mechanisms are not fully understood. Herein, we studied the effects of proteases present in excretion/secretion products (ESPs) of Toxoplasma on MDCK cell monolayers.

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The apicomplexan parasite () causes toxoplasmosis in humans. Pyrimethamine and sulfadiazine that are the drugs of choice to treat the disease, produce severe side effects as well as failure treatments because of drug resistance; thus, novel anti-Toxoplasma compounds are needed and natural compounds can be a good source to obtain them, as medicinal plants have been used to control other apicomplexan parasites. () is a fern used in some rural areas of Mexico to treat among other malaises, mouth ulcers, gastrointestinal problems and parasites.

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Due the proteins from bone remains are highly resistant to pass of time and environmental conditions, they could tell us about the events that probably happened in the past. In the forensic and physical anthropology context, burnt bone remains are one of the most common pieces of recovered evidence and, generally, they are associated with funerary practices, criminal scenes or massive catastrophic events. In the present study, bone pieces of pigs were calcined at different calcination temperatures, and proteins were searched using biochemical, immunochemical and ultrastructure visualization under these experimentally conditions.

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After the cell invasion, the parasite Toxoplasma gondii locates within a parasitophorous vacuole to proliferate. It continuously modifies the composition of the parasitophorous vacuole by the secretion of GRA and ROP proteins, some of which become inserted into the vacuole membrane, remain as soluble proteins or involved in the intravacuolar network. In this report, we analyze the excretion/secretion products and the vesicles released by extracellular tachyzoites, this structures were morphologically analyzed by electron microscopy and characterized by mass spectrometry.

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After host cell invasion, Toxoplasma secretes a variety of dense granule proteins (GRA proteins) from its secretory dense granules, which are involved in the biogenesis of the parasitophorous vacuole (PV). TgGRA8 is predicted to contain proline-rich domains, which are structural features of some cytoskeleton-related proteins. In agreement with this observation, previous proteomic analyses revealed the presence of TgGRA8 in the Toxoplasma sub-pellicular cytoskeleton.

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Article Synopsis
  • Toxoplasma gondii infects all nucleated cells in warm-blooded organisms, spreading through the body and crossing barriers like the intestine and blood-brain barrier.
  • This study aimed to identify and characterize proteases in Toxoplasma extracts, discovering at least nine metalloproteases and three serine proteases involved in altering cell structures.
  • Proteomic analysis revealed 19 proteases in the excretion/secretion products, suggesting that these enzymes aid in the parasite’s ability to spread through host tissues.
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Conjugated linoleic acid (CLA) constitutes a group of isomers derived from linoleic acid. Diverse studies have suggested that these unsaturated fatty acids have beneficial effects on human health. However, it has also been reported that their consumption can generate alterations in hepatic tissue.

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is an opportunistic fungus that is part of the normal microflora commonly found in the human digestive tract and the normal mucosa or skin of healthy individuals. However, in immunocompromised individuals, it becomes a serious health concern and a threat to their lives and is ranked as the leading fungal infection in humans worldwide. As existing treatments for this infection are non-specific or under threat of developing resistance, there is a dire necessity to find new targets for designing specific drugs to defeat this fungus.

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The biochemical and structural changes that occur during the conversion of Toxoplasma gondii tachyzoites to bradyzoites and the formation of tissue cyst are not well understood. Maintaining cells infected with T. gondii type II and III strains under stress conditions induces the tachyzoite-bradyzoite in vitro differentiation, along with the formation of cyst-like structures.

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Leishmaniasis is a neglected tropical disease caused by the parasite of the genus Leishmania. About 13 million people are infected worldwide, and it is estimated that 350 million are at risk of infection. Clinical manifestations depend on the parasite species and factors related to the host such as the immune system, nutrition, housing, and financial resources.

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Lactoferrin (LF) is a protein with antimicrobial activity, which is conferred in part by 2 regions contained in its N-terminal lobe. These regions have been used to develop the following synthetic peptides: lactoferricin17-30, lactoferrampin265-284, and LF chimera (a fusion of lactoferricin17-30 and lactoferrampin265-284). We have reported that these LF peptides have antibacterial activity against several pathogenic bacteria; however, the exact mechanism of action has not been established.

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Quinoxalinone derivatives, identified as VAM2 compounds (7-nitroquinoxalin-2-ones), were evaluated against Toxoplasma gondii tachyzoites of the RH strain. The VAM2 compounds were previously synthesized based on the design obtained from an in silico prediction with the software TOMOCOMD-CARDD. From the ten VAM2 drugs tested, several showed a deleterious effect on tachyzoites.

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Background: One of the main phenomena occurring in cellular membranes during virus infection is a change in membrane permeability. It has been observed that numerous viral proteins can oligomerize and form structures known as viroporins that alter the permeability of membranes. Previous findings have identified such proteins in cells infected with Japanese encephalitis virus (JEV), a member of the same family that Dengue virus (DENV) belongs to (Flaviviridae).

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Unlabelled: Toxoplasma, the causative agent of toxoplasmosis in animals and humans, has a subpellicular cytoskeleton that is involved in motility, cell shape and invasion. Knowledge of components of the cytoskeleton is necessary to understand the invasion mechanisms as well as for the identification of possible therapeutic targets. To date, most cytoskeletal components of Toxoplasma remain unidentified due mainly to the lack of reproducible methods for their isolation.

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Calcium deposits have been related to articular cartilage (AC) degeneration and have been observed in late stages of osteoarthritis (OA). However, the role of those deposits, whether they induce the OA pathogenesis or they appear as a consequence of such process, is still unknown. In this work, we present the kinetics of expression and tissue localisation of osteopontin (OPN), a mineralisation biomarker, and calcium deposits in samples from (normal, sham) and osteoarthritic cartilage (in a rat model).

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