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A proposed treatment for malaria is a combination of fosmidomycin and clindamycin. Both compounds inhibit the methylerythritol 4-phosphate (MEP) pathway, the parasitic source of farnesyl and geranylgeranyl pyrophosphate (FPP and GGPP, respectively). Both FPP and GGPP are crucial for the biosynthesis of several essential metabolites such as ubiquinone and dolichol, as well as for protein prenylation. Dietary prenols, such as farnesol (FOH) and geranylgeraniol (GGOH), can rescue parasites from MEP inhibitors, suggesting the existence of a missing pathway for prenol salvage via phosphorylation. In this study, we identified a gene in the genome of P. falciparum, encoding a transmembrane prenol kinase (PolK) involved in the salvage of FOH and GGOH. The enzyme was expressed in Saccharomyces cerevisiae, and its FOH/GGOH kinase activities were experimentally validated. Furthermore, conditional knockout parasites (Δ-PolK) were created to investigate the biological importance of the FOH/GGOH salvage pathway. Δ-PolK parasites were viable but displayed increased susceptibility to fosmidomycin. Their sensitivity to MEP inhibitors could not be rescued by adding prenols. Additionally, Δ-PolK parasites lost their capability to utilize prenols for protein prenylation. Experiments using culture medium supplemented with whole/delipidated human plasma in transgenic parasites revealed that human plasma has components that can diminish the effectiveness of fosmidomycin. Mass spectrometry tests indicated that both bovine supplements used in culture and human plasma contain GGOH. These findings suggest that the FOH/GGOH salvage pathway might offer an alternate source of isoprenoids for malaria parasites when de novo biosynthesis is inhibited. This study also identifies a novel kind of enzyme related to isoprenoid metabolism.

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The influence of the acid sites in the hydrodeoxygenation of anisole performed over Ni catalysts supported on SBA-15 modified with metal oxides (Ni/M-SBA-15, M = Ti, Zr, Al, or Nb) was demonstrated. Catalysts were characterized by SEM-EDX, nitrogen physisorption, XRD, UV-visible DRS, TPR, TPD of ammonia, IR-Py, O2 chemisorption, and high-resolution transmission electron microscopy. The mesoporous structure and the hexagonal arrangement of the supports were maintained in the catalysts. Ni catalysts supported on modified M-SBA-15 exhibited a higher metal-support interaction, an increase in the acidity and, as a consequence, improved selectivity to cyclohexane. The deoxygenation reaction rate constants increased as Ni/SBA-15 < Ni/Ti-SBA-15 < Ni/Nb-SBA-15 < Ni/Zr-SBA-15 < Ni/Al-SBA-15, which is attributed to the increase in the amount and strength of acid sites, especially of the Brønsted ones, which promotes the cleavage of the C-O bond. It is also important to keep the metal/acid sites together to obtain high activity and selectivity to hydrodeoxygenated products.

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Blastocystis spp. is a unicellular organism that resides in digestive tract of various vertebrates, with a worldwide distribution and a variable prevalence. For many years, Blastocystis spp. was considered a cyst of a flagellate, a fungus, or a saprophyte yeast of the digestive tract; in 1996, it is placed in the group of stramenopiles (heterokonts). Since its new classification, many questions have arisen around this protist about its role as a pathogen or non-pathogen organism. Recent evidence indicates that Blastocystis spp. participates in the immune inflammatory response in the intestinal microbiome generating an anti-inflammatory response, showing a lower concentration of fecal inflammatory markers in infected human hosts. Here, we review recent findings on the regulatory function of Blastocystis spp. in the immune inflammatory response to comprehend the purpose of Blastocystis spp. in health and disease, defining if Blastocystis spp. is really a pathogen, a commensal or even a mutualist in the human gut microbiome.

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Not available.

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resumen está disponible en el texto completo

Abstract: In recent decades, the growing obesity epidemic in Mexico has become one of the most important public health challenges faced by the country. With support from the World Obesity Federation, we formed a working group in 2021 to identify and summarize priority actions that Mexico can take to face this epidemic. More than 1 000 health professionals joined the development and discussion process. Recommendations from previously published, high-level documents and guidelines were taken into account. In commemoration of World Obesity Day 2022, this statement is presented as input for health care professionals to develop actions to address obesity. The statement includes 10 recommendations that include population-level and individual-level actions. It emphasizes the importance of social participation, comprehensive interventions with a person- centered perspective, planetary sustainability, on improving education and communication campaigns, as well as fostering a built environment that promotes active living, and shielding prevention and control efforts from conflicts of interest. The statement calls for obesity to be treated seriously, based on scientific evidence, in a timely and comprehensive manner, employing a life-course and ethical approach that does not perpetuate weight stigma in society.

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This is a paired prospective comparative cohort study with 58 patients, in order to analyze the clinical LD-WLI in patients with moderate or severe COVID19 pneumonia. The results of this study show that the Radiotherapy could be an option to improve the clinical response for patients with COVID-19.

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An estimated 3.5 billion people are colonized by intestinal parasites worldwide. Intestinal parasitic eukaryotes interact not only with the host but also with the intestinal microbiota. In this work, we studied the relationship between the presence of multiple enteric parasites and the community structures of gut bacteria and eukaryotes in an asymptomatic mother-child cohort from a semirural community in Mexico. Fecal samples were collected from 46 mothers and their respective children, with ages ranging from 2 to 20 months. Mothers and infants were found to be multiparasitized by Blastocystis hominis, Entamoeba dispar, Endolimax nana, Chilomastix mesnili, Iodamoeba butshlii, Entamoeba coli, Hymenolepis nana, and Ascaris lumbricoides. Sequencing of bacterial 16S rRNA and eukaryotic 18S rRNA genes showed a significant effect of parasite exposure on bacterial beta-diversity, which explained between 5.2% and 15.0% of the variation of the bacterial community structure in the cohort. Additionally, exposure to parasites was associated with significant changes in the relative abundances of multiple bacterial taxa, characterized by an increase in Clostridiales and decreases in Actinobacteria and Bacteroidales. Parasite exposure was not associated with changes in intestinal eukaryote relative abundances. However, we found several significant positive correlations between intestinal bacteria and eukaryotes, including Oscillospira with Entamoeba coli and Prevotella stercorea with Entamoeba hartmanni, as well as the co-occurrence of the fungus Candida with Bacteroides and Actinomyces, Bifidobacterium, and Prevotella copri and the fungus Pichia with Oscillospira. The parasitic exposure-associated changes in the bacterial community structure suggest effects on microbial metabolic routes, host nutrient uptake abilities, and intestinal immunity regulation in host-parasite interactions. IMPORTANCE The impact of intestinal eukaryotes on the prokaryotic microbiome composition of asymptomatic carriers has not been extensively explored, especially in infants and mothers with multiple parasitic infections. In this work, we studied the relationship between protist and helminth parasite colonization and the intestinal microbiota structure in an asymptomatic population of mother-child binomials from a semirural community in Mexico. We found that the presence of parasitic eukaryotes correlated with changes in the bacterial gut community structure in the intestinal microbiota in an age-dependent way. Parasitic infection was associated with an increase in the relative abundance of the class Clostridia and decreases of Actinobacteria and Bacteroidia. Parasitic infection was not associated with changes in the eukaryote community structure. However, we observed strong positive correlations between bacterial and other eukaryote taxa, identifying novel relationships between prokaryotes and fungi reflecting interkingdom interactions within the human intestine.

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The etiological agent of human amoebiasis is the protozoan parasite E. histolytica; the disease is still an endemic infection in some countries and the outcome of infection in the host infection can range from asymptomatic intestinal infection to intestinal or liver invasive forms of the disease. The invasive character of this parasite is multifactorial and mainly due to the differential expression of multiple pathogenic genes. The aim of the present work was to measure the differential expression of some genes in different specimens of patients with amoebic liver abscess (ALA) and specimens of genital amoebiasis (AG) by RT-qPCR. Results show that the expression of genes is different in both types of samples. Almost all studied genes were over expressed in both sets of patients; however, superoxide dismutase (Ehsod), serine threonine isoleucine rich protein (Ehstirp), peroxiredoxin (Ehprd) and heat shock protein 70 and 90 (Ehhsp-70, EHhsp-90) were higher in AG biopsies tissue. Furthermore, cysteine proteinases 5 and 2 (Ehcp5, Ehcp2), lectin (Ehgal/galnaclectin) and calreticulin (Ehcrt) genes directly associate with pathogenic mechanisms of E. histolytica had similar over expression in both AG and ALA samples. In summary the results obtained show that trophozoites can regulate the expression of their genes depending on stimuli or environmental conditions, in order to regulate their pathogenicity and ensure their survival in the host.

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Calreticulin (CRT) is a highly conserved protein in the endoplasmic reticulum that plays important roles in the regulation of key cellular functions. Little is known about the participation of E. histolytica CRT (EhCRT) in the processes of pathogenicity or in the modulation of the host immune response. The aim of this study was to evaluate the role of CRT in the proliferation and the cytokine profile in peripheral blood mononuclear cells (PBMCs) from patients with amebic liver abscess (ALA) during the acute phase (AP-ALA) of the disease compared to patients during the resolution phase (R-ALA). The PBMCs from each participant were cocultured with EhCRT and tested by the colorimetric method to evaluate their proliferation index (PI). The supernatants were subjected to an enzyme-linked immunosorbent assay (ELISA) to evaluate the concentration of cytokines. The mean values of all groups were compared using the independent t-test. When the PIs of individuals without diagnosis of liver abscess (NEG) were compared, there were no statistically significant differences in the proliferation of PBMCs between patients with AP-ALA and R-ALA when stimulated with EhCRT or concanavalin A (ConA). However, the levels of interleukins [IL-6, IL-10, granulocyte colony stimulating factor (GCSF), and transforming growth factor ß1 (TGFß1)] were higher in patients with AP-ALA, whereas in patients with R-ALA, higher levels of interferon gamma (IFNγ) were detected. These results suggest that EhCRT acts as a mitogen very similar to the activity of ConA. In addition, EhCRT is an excellent immunogen for the specific activation of PBMCs, inducing the differential expression of ILs depending on the outcome of disease, determining the type of immune response: a Th2 cytokine profile during the acute phase and a Th1 profile during the resolution phase.

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