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1.
Nutr Cancer ; 75(5): 1382-1398, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36974004

RESUMEN

Gastrointestinal toxicity, including diarrhea and inflammation, is commonly observed with the use of 5-fluorouracil (5-FU). Several studies have shown that polysaccharides are interesting bioactive macromolecules for the treatment or prevention of gastrointestinal diseases. Therefore, in this study, the effect of a polysaccharide fraction from a mixture of two Guavira species (Campomanesia adamantium and Campomanesia pubescens), referred to here as CPW, on the development of intestinal mucositis was investigated. Intestinal mucositis was induced by a single injection of 5-FU (450 mg/kg), and various doses of CPW (3-100 mg/kg) were tested. CPW attenuated disease development and prevented small bowel dysmotility and colon shortening. CPW prevented the increase in villi width, crypt depth, and mucosal thickness in the duodenum, but not in the colon. Preservation of mucus, reduction of oxidative stress, inflammation, and prevention of the 5-FU-induced enlargement and swelling of the spleen were observed. In conclusion, this study demonstrated for the first time that CPW alleviates the intestinal damage induced by 5-FU and could be used as an adjuvant strategy during chemotherapy.


Asunto(s)
Fluorouracilo , Mucositis , Ratones , Animales , Fluorouracilo/toxicidad , Mucositis/inducido químicamente , Mucositis/tratamiento farmacológico , Mucositis/prevención & control , Antimetabolitos Antineoplásicos/toxicidad , Mucosa Intestinal , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Polisacáridos/farmacología
2.
Molecules ; 28(1)2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36615553

RESUMEN

Liquidambar styraciflua L. is an aromatic species, popularly used in traditional Chinese medicine to treat diarrhea, dysentery, coughs, and skin sores. The present study was designed to investigate the chemical composition and biological potential of extracts obtained from the fruits of this plant. For the chemical evaluation, it was used mainly liquid and gas chromatography, plus NMR, and colorimetric methods. The aqueous extract (EA) originated two other fractions: an aqueous (P-EA) and an ethanolic (S-EA). The three extracts were composed of proteins, phenolic compounds, and carbohydrates in different proportions. The analyses showed that the polysaccharide extract (P-EA) contained pectic polysaccharides, such as acetylated and methyl esterified homogalacturonans together with arabinogalactan, while the fraction S-EA presented phenolic acids and terpenes such as gallic acid, protocathecuic acid, liquidambaric acid, combretastatin, and atractyloside A. EA, P-EA, and S-EA showed antioxidant activity, with IC50 values of 4.64 µg/mL, 16.45 µg/mL, and 3.67 µg/mL, respectively. The cytotoxicity followed the sequence S-EA > EA > P-EA, demonstrating that the toxic compounds were separated from the non-toxic ones by ethanol precipitation. While the fraction S-EA is very toxic to any cell line, the fraction P-EA is a promising candidate for studies against cancer due to its high toxicity to tumoral cells and low toxicity to normal cells.


Asunto(s)
Antineoplásicos , Liquidambar , Frutas , Extractos Vegetales/farmacología , Extractos Vegetales/química , Liquidambar/química , Antioxidantes/farmacología , Antioxidantes/química , Antineoplásicos/farmacología
3.
Br J Haematol ; 198(5): 866-874, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35799423

RESUMEN

Nucleophosmin1 (NPM1) is one of the most commonly mutated genes in AML and is often associated with a favourable prognosis. Immune responses play an increasing role in AML treatment decisions; however, the role of immune checkpoint inhibition is still not clear. To address this, we investigated specific immune responses against NPM1, and three other leukaemia-associated antigens (LAA), PRAME, Wilms' tumour 1 and RHAMM in AML patients. We investigated T cell responses against leukaemic progenitor/stem cells (LPC/LSC) using colony-forming immunoassays and flow cytometry. We examined whether immune checkpoint inhibition with the anti-programmed death 1 antibody increases the immune response against stem cell-like cells, comparing cells from NPM1 mutated and NPM1 wild-type AML patients. We found that the anti-PD-1 antibody, nivolumab, increases LAA stimulated cytotoxic T lymphocytes and the cytotoxic effect against LPC/LSC. The effect was strongest against NPM1mut cells when the immunogenic epitope was derived from the mutated region of NPM1 and these effects were enhanced through the addition of anti-PD-1. The data suggest that patients with NPM1 mutated AML could be treated with the immune checkpoint inhibitor anti-PD-1 and that this treatment combined with NPM1-mutation specific directed immunotherapy could be even more effective for this unique group of patients.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Leucemia Mieloide Aguda , Nucleofosmina , Linfocitos T Citotóxicos , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inmunidad , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Mutación , Nivolumab/farmacología , Nucleofosmina/genética , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores
4.
Eur J Immunol ; 51(1): 250-252, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32761616

RESUMEN

In mouse myocardial infarction, we combined lineage tracing of cardiac macrophages, mapping their ontogeny, with an analysis of their phenotype and phagocytic functions. While embryo-derived macrophages were most abundant in homeostasis, bone marrow-derived MHC-IIlo macrophages increased in both numbers and phagocytic capacity to clear necrotic cardiomyocytes early after ischemia/perfusion injury.


Asunto(s)
Antígenos de Histocompatibilidad Clase II/metabolismo , Macrófagos/inmunología , Infarto del Miocardio/inmunología , Miocardio/inmunología , Animales , Receptor 1 de Quimiocinas CX3C/metabolismo , Modelos Animales de Enfermedad , Embrión de Mamíferos/citología , Embrión de Mamíferos/inmunología , Macrófagos/patología , Ratones , Ratones Transgénicos , Infarto del Miocardio/patología , Miocardio/patología , Miocitos Cardíacos/inmunología , Miocitos Cardíacos/patología , Fagocitosis/inmunología
5.
Histochem Cell Biol ; 155(1): 75-88, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33108533

RESUMEN

Obesity due to high calorie intake induces cardiac hypertrophy and dysfunction, thus contributing to cardiovascular morbidity and mortality. Recent studies in aging suggest that oral supplementation with the natural polyamine spermidine has a cardioprotective effect. Here, the hypothesis was tested that spermidine or voluntary activity alone or in combination protect the heart from adverse effects induced by obesity. Therefore, C57Bl/6 mice (n = 8-10 per group) were subjected to control or high fat diet (HFD) and were left untreated, or either received spermidine via drinking water or were voluntarily active or both. After 30 weeks, the mice were killed and the left ventricle of the hearts was processed for light and electron microscopy. Design-based stereology was used to estimate parameters of hypertrophy, fibrosis, and lipid accumulation. HFD induced cardiac hypertrophy as demonstrated by higher volumes of the left ventricle, cardiomyocytes, interstitium, myofibrils and cardiomyocyte mitochondria. These changes were not influenced by spermidine or voluntary activity. HFD also induced myocardial fibrosis and accumulation of lipid droplets within cardiomyocytes. These HFD effects were enhanced in spermidine treated animals but not in voluntarily active mice. This was even the case in voluntarily active mice that received spermidine. In conclusion, the data confirm the induction of left ventricular hypertrophy by high-fat diet and suggest that-under high fat diet-spermidine enhances cardiomyocyte lipid accumulation and interstitial fibrosis which is counteracted by voluntary activity.


Asunto(s)
Cardiomegalia/metabolismo , Fibrosis/metabolismo , Hipertrofia Ventricular Izquierda/metabolismo , Gotas Lipídicas/metabolismo , Miocitos Cardíacos/metabolismo , Obesidad/metabolismo , Administración Oral , Animales , Cardiomegalia/inducido químicamente , Cardiomegalia/patología , Dieta Alta en Grasa/efectos adversos , Fibrosis/inducido químicamente , Fibrosis/patología , Hipertrofia Ventricular Izquierda/inducido químicamente , Hipertrofia Ventricular Izquierda/patología , Gotas Lipídicas/patología , Metabolismo de los Lípidos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Miocitos Cardíacos/patología , Obesidad/inducido químicamente , Obesidad/patología , Espermidina/administración & dosificación
6.
Cancer Immunol Immunother ; 69(4): 629-640, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32020256

RESUMEN

The efficacy of immunotherapies in cancer treatment becomes more and more apparent not only in different solid tumors but also in hematological malignancies. However, in acute myeloid leukemia (AML), mechanisms to increase the efficacy of immunotherapeutic approaches have to be further elucidated. Targeting leukemic progenitor and stem cells (LPC/LSC) by specific CTL, for instance, in an adjuvant setting or in minimal residual disease, might be an option to prevent relapse of AML or to treat MRD. Therefore, we investigated the influence of immune checkpoint inhibitors on LAA-specific immune responses by CTL against leukemic myeloid blasts and colony-forming cells including leukemic progenitor cells (CFC/LPC). In functional immunoassays like CFU/CFI (colony-forming units/immunoassays) and ELISpot analysis, we detected specific LAA-directed immune responses against CFC/LPC that are postulated to be the source population of relapse of the disease. The addition of nivolumab (anti-PD-1) significantly increases LAA-directed immune responses against CFC/LPC, no effect is seen when ipilimumab (anti-CTLA-4) is added. The combination of ipilimumab and nivolumab does not improve the effect compared to nivolumab alone. The anti-PD1-directed immune response correlates to PD-L1 expression on progenitor cells. Our data suggest that immunotherapeutic approaches have the potential to target malignant CFC/LPC and anti-PD-1 antibodies could be an immunotherapeutic approach in AML. Moreover, combination with LAA-directed vaccination strategies might also open interesting application possibilities.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ipilimumab/uso terapéutico , Leucemia Mieloide/terapia , Células Madre Neoplásicas/efectos de los fármacos , Nivolumab/uso terapéutico , Linfocitos T/inmunología , Enfermedad Aguda , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Antígeno B7-H1/metabolismo , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Antígeno CTLA-4/metabolismo , Humanos , Inmunoterapia/métodos , Ipilimumab/administración & dosificación , Leucemia Mieloide/inmunología , Leucemia Mieloide/metabolismo , Células Madre Neoplásicas/inmunología , Células Madre Neoplásicas/metabolismo , Nivolumab/administración & dosificación , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T/metabolismo , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/metabolismo , Resultado del Tratamiento
7.
Cytokine ; 123: 154760, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31226439

RESUMEN

Cystatins are natural inhibitors of cysteine peptidases. Recently, cystatins derived from plants, named phytocystatins, have been extensively studied. Among them, CsinCPI-2 proteins from Citrus sinensis were identified and recombinantly produced by our group. Thus, this study described the recombinant expression, purification, and inhibitory activity of this new phytocystatin against human cathepsins K and B and assessed the anti-inflammatory effect of CsinCPI-2 in vitro in mouse and in vivo in rats. In addition, the pro-osteogenic effect of CsinCPI-2 was investigated in vitro. The inflammatory response of mouse macrophage cells stimulated with P. gingivalis was modulated by CsinCPI-2. The in vitro results showed an inhibitory effect (p < 0.05) on cathepsin K, cathepsin B, IL-1ß, and TNF-α gene expression. In addition, CsinCPI-2 significantly inhibited in vivo the activity of TNF-α (p < 0.05) in the blood of rats, previously stimulated by E. coli lipopolysaccharide (LPS). CsinCPI-2 had a pro-osteogenic effect in human dental pulp cells, demonstrated by the increase in alkaline phosphatase (ALP) activity, deposition of mineralized nodules, and the gene expression of the osteogenic markers as bone morphogenetic protein 2 (BMP-2), runt-related transcription factor 2 (Runx-2), ALP, osteocalcin, and bone sialoprotein (BSP). These preliminary studies suggested that CsinCPI-2 has a potential anti-inflammatory, and at the same time, a pro-osteogenic effect. This may lead to new therapies for the control of diseases where inflammation plays a key role, such as periodontal disease and apical periodontitis.


Asunto(s)
Antígenos de Diferenciación/biosíntesis , Citrus/química , Cistatinas/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Macrófagos/metabolismo , Osteogénesis/efectos de los fármacos , Proteínas de Plantas/farmacología , Animales , Cistatinas/química , Humanos , Macrófagos/patología , Masculino , Ratones , Proteínas de Plantas/química , Células RAW 264.7 , Ratas , Ratas Wistar
8.
Chem Biodivers ; 16(5): e1900024, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30793846

RESUMEN

The lipophilization of ß-d-riboguanosine (1) with various symmetric as well as asymmetric ketones is described (→3a-3f). The formation of the corresponding O-2',3'-ketals is accompanied by the appearance of various fluorescent by-products which were isolated chromatographically as mixtures and tentatively analyzed by ESI-MS spectrometry. The mainly formed guanosine nucleolipids were isolated and characterized by elemental analyses, 1 H-, 13 C-NMR and UV spectroscopy. For a drug profiling, static topological polar surface areas as well as 10 logPOW values were calculated by an increment-based method as well as experimentally for the systems 1-octanol-H2 O and cyclohexane-H2 O. The guanosine-O-2',3'-ketal derivatives 3b and 3a could be crystallized in (D6 )DMSO - the latter after one year of standing at ambient temperature. X-ray analysis revealed the formation of self-assembled ribbons consisting of two structurally similar 3b nucleolipid conformers as well as integrated (D6 )DMSO molecules. In the case of 3a ⋅ DMSO, the ribbon is formed by a single type of guanosine nucleolipid molecules. The crystalline material 3b ⋅ DMSO was further analyzed by differential scanning calorimetry (DSC) and temperature-dependent polarization microscopy. Crystallization was also performed on interdigitated electrodes (Au, distance, 5 µm) and visualized by scanning electron microscopy. Resistance and amperage measurements clearly demonstrate that the electrode-bridging 3b crystals are electrically conducting. All O-2',3'-guanosine ketals were tested on their cytostatic/cytotoxic activity towards phorbol 12-myristate 13-acetate (PMA)-differentiated human THP-1 macrophages as well as against human astrocytoma/oligodendroglioma GOS-3 cells and against rat malignant neuroectodermal BT4Ca cells.


Asunto(s)
Citostáticos/síntesis química , Guanosina/química , Lípidos/química , Animales , Rastreo Diferencial de Calorimetría , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cristalografía por Rayos X , Citostáticos/química , Citostáticos/farmacología , Electricidad , Humanos , Enlace de Hidrógeno , Lípidos/síntesis química , Lípidos/farmacología , Espectroscopía de Resonancia Magnética , Conformación Molecular , Ratas , Espectrometría de Masa por Ionización de Electrospray
9.
J Food Sci Technol ; 56(3): 1551-1558, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30956335

RESUMEN

This study evaluated the fatty acid composition and the nutritional profile of Brycon cephalus and Brycon microlepis, fish species from the central Amazon basin, by different methods of quantification. The methods applied were: area normalization (MAN), internal standard (MIS), alternative theoretical (MAT) and alternative experimental (MAE). Significant differences were observed between the methods applied and the species studied. MAN supplied poor information about fatty acids composition and diet formulation, presenting only fatty acid profiles. MIS, MAT and MAE supplied fatty acids composition information on a mass basis. MAT and MAE overestimated results, whereas MIS presented the most accurate results. B. cephalus and B. microlepis showed high contents of approximately 65 mg g-1 of n-3 fatty acids. Eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) content totaled, 104.37 mg 100 g-1 and 117.89 mg 100 g-1 for B. cephalus and B. microlepis, respectively. The nutritional profile of both fish species showed favorable indices for nutritional quality of the lipid fraction, indicating that both Brycon species are healthy dietary choices.

10.
Plant Cell Rep ; 36(1): 193-201, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27837261

RESUMEN

KEY MESSAGE: Transgenic sugarcane expressing CaneCPI-1 exhibits resistance to Sphenophorus levis larvae. Transgenic plants have widely been used to improve resistance against insect attack. Sugarcane is an economically important crop; however, great losses are caused by insect attack. Sphenophorus levis is a sugarcane weevil that digs tunnels in the stem base, leading to the destruction of the crop. This insect is controlled inefficiently by chemical insecticides. Transgenic plants expressing peptidase inhibitors represent an important strategy for impairing insect growth and development. Knowledge of the major peptidase group present in the insect gut is critical when choosing the most effective inhibitor. S. levis larvae use cysteine peptidases as their major digestive enzymes, primarily cathepsin L-like activity. In this study, we developed transgenic sugarcane plants that overexpress sugarcane cysteine peptidase inhibitor 1 (CaneCPI-1) and assessed their potential through feeding bioassays with S. levis larvae. Cystatin overexpression in the transgenic plants was evaluated using semi-quantitative RT-PCR, RT-qPCR, and immunoblot assays. A 50% reduction of the average weight was observed in larvae that fed on transgenic plants in comparison to larvae that fed on non-transgenic plants. In addition, transgenic sugarcane exhibited less damage caused by larval attack than the controls. Our results suggest that the overexpression of CaneCPI-1 in sugarcane is a promising strategy for improving resistance against this insect.


Asunto(s)
Proteínas de Plantas/metabolismo , Saccharum/genética , Gorgojos/crecimiento & desarrollo , Animales , Bioensayo , Immunoblotting , Larva , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente , Reacción en Cadena de la Polimerasa , Reacción en Cadena en Tiempo Real de la Polimerasa
11.
Int J Cancer ; 137(9): 2083-92, 2015 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-25912930

RESUMEN

Leukemic stem cells (LSC) might be the source for leukemic disease self-renewal and account for disease relapse after treatment, which makes them a critical target for further therapeutic options. We investigated the role of cytotoxic T-lymphocytes (CTL) counteracting and recognizing LSC. Leukemia-associated antigens (LAA) represent immunogenic structures to target LSC. We enriched the LSC-containing fraction of 20 AML patients and hematopoietic stem cells (HSC) of healthy volunteers. Using microarray analysis and qRT-PCR we detected high expression of several LAA in AML cells but also in LSC. PRAME (p = 0.0085), RHAMM (p = 0.03), WT1 (p = 0.04) and Proteinase 3 (p = 0.04) showed significant differential expression in LSC compared with HSC. PRAME, RHAMM and WT1 are furthermore also lower expressed on leukemic bulk. In contrast, Proteinase 3 indicates a higher expression on leukemic bulk than on LSC. In colony forming unit (CFU) immunoassays, T cells stimulated against various LAA indicated a significant inhibition of CFUs in AML patient samples. The LAA PRAME, RHAMM and WT1 showed highest immunogenic responses with a range up to 58-83%. In a proof of principle xenotransplant mouse model, PRAME-stimulated CTL targeted AML stem cells, reflected by a delayed engraftment of leukemia (p = 0.0159). Taken together, we demonstrated the expression of several LAA in LSC. LAA-specific T cells are able to hamper LSC in immunoassays and in a mouse model, which suggests that immunotherapeutic approaches have the potential to target malignant stem cells.


Asunto(s)
Antígenos de Neoplasias/inmunología , Leucemia Mieloide Aguda/inmunología , Células Madre Neoplásicas/inmunología , Linfocitos T Citotóxicos/inmunología , Animales , Supervivencia Celular/inmunología , Humanos , Leucemia Mieloide Aguda/patología , Ratones Endogámicos NOD , Ratones SCID , Trasplante de Neoplasias , Células Tumorales Cultivadas
12.
Carbohydr Res ; 535: 108986, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38042036

RESUMEN

The regulation of metastasis-related cellular aspects of two structurally similar AGIs from prunes tea infusion, with different molar masses, was studied in vitro against Triple Wild-Type metastatic melanoma (TWM) from murine and human origin. The higher molar mass AGI (AGI-78KDa) induced TWMs cells death and, in murine cell line, it decreased some metastasis-related cellular processes: invasiveness capacity, cell-extracellular matrix interaction, and colonies sizes. The lower molar mass AGI (AGI-12KDa) did not induce cell death but decreased TWMs proliferation rate and, in murine cell line, it decreased cell adhesion and colonies sizes. Both AGIs alter the clonogenic capacity of human cell line. In spite to understand why we saw so many differences between AGIs effects on murine and human cell lines we performed in silico analysis that demonstrated differential gene expression profiles between them. Complementary network topological predictions suggested that AGIs can modulate multiple pathways in a specie-dependent manner, which explain differential results obtained in vitro between cell lines. Our results pointed to therapeutic potential of AGIs from prunes tea against TWMs and showed that molecular weight of AGIs may influence their antitumor effects.


Asunto(s)
Galactanos , Melanoma , Humanos , Ratones , Animales , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/metabolismo , Peso Molecular , , Línea Celular Tumoral
13.
Food Res Int ; 173(Pt 1): 113334, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37803644

RESUMEN

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of the gastrointestinal tract. The etiology is not fully understood, but environmental, microbial, and immunologic factors, as well as a genetic predisposition, play a role. UC is characterized by episodes of abdominal pain, diarrhea, bloody stools, weight loss, severe colonic inflammation, and ulceration. Despite the increase in the frequency of UC and the deterioration of the quality of life, there are still patients who do not respond well to available treatment options. Against this background, natural products such as polysaccharides are becoming increasingly important as they protect the intestinal mucosa, promote wound healing, relieve inflammation and pain, and restore intestinal motility. In this study, we investigated the effect of a polysaccharide isolated from the biomass of Campomanesia adamantium and Campomanesia pubescens (here referred to as CPW) in an experimental model of acute and chronic ulcerative colitis induced by dextran sulfate sodium (DSS). CPW reversed weight loss, increased disease activity index (DAI), bloody diarrhea, and colon shortening. In addition, CPW reduced visceral mechanical hypersensitivity, controlled oxidative stress and inflammation, and protected the mucosal barrier. CPW is not absorbed in the intestine, does not inhibit cytochrome P450 proteins, and does not exhibit AMES toxicity. These results suggest that CPW attenuates DSS-induced acute and chronic colitis in mice and may be a potential alternative treatment for UC.


Asunto(s)
Colitis Ulcerosa , Humanos , Animales , Ratones , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Calidad de Vida , Modelos Animales de Enfermedad , Inflamación , Pérdida de Peso , Diarrea
14.
Food Res Int ; 156: 111291, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35651057

RESUMEN

Inflammatory bowel disease (IBD) includes two distinct diseases: Crohn's disease (CD) and ulcerative colitis (UC). IBD is a chronic systemic disease of the gastrointestinal tract, characterized by an inflammatory process. The mechanisms by which diseases develop are still unknown, but it is known that it results from a complex interaction between genetic variability, the host's immune system, and environmental factors. One of the main complaints of patients is abdominal pain, which may be associated with the release of inflammatory mediators, changes in the normal motility of the digestive tract, and increased intestinal permeability. Currently available drugs for abdominal pain are not satisfactory, therefore, it is extremely necessary to seek new therapeutic options for the treatment of abdominal pain. Polysaccharides extracted from fruits have attracted interest, as these molecules protect the intestinal mucosa and promote wound healing, attenuating inflammation, pain, and altered intestinal motility. In this study, we investigated the ability of pectic polysaccharides obtained from guavira pomace, named CPW to reduce visceral hypersensitivity, regulate intestinal motility, and control diarrhea in mice. Acetic acid, capsaicin, or mustard oil were used to assess visceral pain in normal mice. CPW reduced abdominal writhing, cell migration, and capsaicin-induced visceral nociception. Furthermore, it regulated intestinal motility and all measured parameters of castor oil-induced diarrhea. CPW treatment reversed the increase in mucosal permeability, TEER, and tissue weight caused by acetic acid. In addition, molecular docking analysis showed that specific the CPW units binds to the 3N8V, 5COX, 2J67 and 6RBF proteins. Thus, the results suggest that CPW has attractive therapeutic characteristics for the treatment of abdominal pain and ulcerative colitis.


Asunto(s)
Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Dolor Abdominal/tratamiento farmacológico , Animales , Capsaicina , Colitis Ulcerosa/tratamiento farmacológico , Diarrea , Carbohidratos de la Dieta , Frutas , Humanos , Ratones , Simulación del Acoplamiento Molecular , Polisacáridos/farmacología
15.
Science ; 377(6603): 276-284, 2022 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-35857588

RESUMEN

γδ T cells represent a substantial fraction of intestinal lymphocytes at homeostasis, but they also constitute a major lymphocyte population infiltrating colorectal cancers (CRCs); however, their temporal contribution to CRC development or progression remains unclear. Using human CRC samples and murine CRC models, we found that most γδ T cells in premalignant or nontumor colons exhibit cytotoxic markers, whereas tumor-infiltrating γδ T cells express a protumorigenic profile. These contrasting T cell profiles were associated with distinct T cell receptor (TCR)-Vγδ gene usage in both humans and mice. Longitudinal intersectional genetics and antibody-dependent strategies targeting murine γδ T cells enriched in the epithelium at steady state led to heightened tumor development, whereas targeting γδ subsets that accumulate during CRC resulted in reduced tumor growth. Our results uncover temporal pro- and antitumor roles for γδ T cell subsets.


Asunto(s)
Neoplasias Colorrectales , Citotoxicidad Inmunológica , Intestinos , Linfocitos Intraepiteliales , Receptores de Antígenos de Linfocitos T gamma-delta , Animales , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Humanos , Intestinos/inmunología , Linfocitos Intraepiteliales/inmunología , Ratones , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Receptores de Antígenos de Linfocitos T gamma-delta/fisiología
16.
PeerJ ; 9: e11461, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34249482

RESUMEN

BACKGROUND: Sugarcane is a crop of global importance and has been expanding to areas with soils containing high levels of exchangeable aluminum (Al), which is a limiting factor for crop development in acidic soils. The study of the sugarcane physiological and nutritional behavior together with patterns of gene expression in response to Al stress may provide a basis for effective strategies to increase crop productivity in acidic soils. METHODS: Sugarcane cultivars were evaluated for physiological parameters (photosynthesis, stomatal conductance, and transpiration), nutrient (N, P, K, Ca, Mg, and S) and Al contents in leaves and roots and gene expression, of the genes MDH, SDH by qPCR, both related to the production of organic acids, and SOD, related to oxidative stress. RESULTS: Brazilian sugarcane RB867515, RB928064, and RB935744 cultivars exhibited very different responses to induced stress by Al. Exposure to Al caused up-regulation (SOD and MDH) or down-regulation (SDH, MDH, and SOD), depending on the cultivar, Al level, and plant tissue. The RB867515 cultivar was the most Al-tolerant, showing no decline of nutrient content in plant tissue, photosynthesis, transpiration, and stomatal conductance after exposure to Al; it exhibited the highest Al content in the roots, and showed important MDH and SOD gene expression in the roots. RB928064 only showed low expression of SOD in roots and leaves, while RB935744 showed important expression of the SOD gene only in the leaves. Sugarcane cultivars were classified in the following descending Al-tolerance order: RB867515 > RB928064 = RB935744. These results may contribute to the obtention of Al-tolerant cultivars that can play their genetic potential in soils of low fertility and with low demand for agricultural inputs; the selection of potential plants for breeding programs; the elucidation of Al detoxification mechanisms employed by sugarcane cultivars.

17.
Medicina (B Aires) ; 81(2): 257-268, 2021.
Artículo en Español | MEDLINE | ID: mdl-33906145

RESUMEN

Mother-to-child transmission in Toxoplasma gondii infection occurs only when the infection is acquired for the first time during pregnancy. Diagnosis of maternal infection and the newborn is achieved by a combination of serological tests, clinical features and ultrasound images. An early diagnosis of maternal infection allows treatment that offers a reduction both in transmission rate and risk of congenital damage. The aim of this expert consensus was to review the scientific literature which would enable an update of the clinical practice guideline of prevention, diagnosis and treatment of congenital toxoplasmosis in our country.


La transmisión vertical de la infección por Toxoplasma gondii ocurre cuando la madre se infecta por primera vez en el transcurso del embarazo. El diagnóstico de la infección materna y la del recién nacido se logra con el conjunto de pruebas serológicas, hallazgos clínicos y ecográficos. El reconocimiento temprano de la infección materna permite un tratamiento que reduce la tasa de transmisión y el riesgo de daño en el producto de la concepción. El objetivo de este consenso de expertos fue revisar la literatura científica para actualizar las recomendaciones de práctica clínica respecto de la prevención, el diagnóstico y el tratamiento de la toxoplasmosis congénita en nuestro país.


Asunto(s)
Complicaciones Parasitarias del Embarazo , Toxoplasma , Toxoplasmosis Congénita , Toxoplasmosis , Niño , Consenso , Femenino , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Anamnesis , Embarazo , Toxoplasmosis Congénita/diagnóstico , Toxoplasmosis Congénita/tratamiento farmacológico , Toxoplasmosis Congénita/prevención & control
18.
Front Pharmacol ; 12: 722889, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34447313

RESUMEN

The solute carrier (SLC) superfamily represents the biggest family of transporters with important roles in health and disease. Despite being attractive and druggable targets, the majority of SLCs remains understudied. One major hurdle in research on SLCs is the lack of tools, such as cell-based assays to investigate their biological role and for drug discovery. Another challenge is the disperse and anecdotal information on assay strategies that are suitable for SLCs. This review provides a comprehensive overview of state-of-the-art cellular assay technologies for SLC research and discusses relevant SLC characteristics enabling the choice of an optimal assay technology. The Innovative Medicines Initiative consortium RESOLUTE intends to accelerate research on SLCs by providing the scientific community with high-quality reagents, assay technologies and data sets, and to ultimately unlock SLCs for drug discovery.

20.
Food Res Int ; 132: 109065, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32331640

RESUMEN

Exotic fruits and their co-products may be valuable sources of antioxidant dietary fibres (DF) which are useful for food industry and human health. In this study, we aimed to characterize DF obtained from guavira fruit pomace and investigate its antioxidant potential employing TEAC assay as well as a cell model. The DF were chemically characterized as containing arabinan, highly-methoxylated homogalacturonan and arabinogalactan. The DF-containing fraction (CPW) presented ABTS free radical scavenger activity. MTT and DCFH-DA assay were performed to assess, respectively, changes in cell viability and the potential intracellular antioxidant activity against H2O2-induced oxidative stress in murine NIH 3T3 fibroblast. CPW exhibited no effects on cell viability, moreover, when administered 48 h prior the induction of H2O2 toxic effects, it protected the cells, significantly increasing the cell viability compared to control. This protection may be related to the observed reduction of reactive oxygen species levels. Thus, the pre-treatment of cells with guavira DF for 48 h remarkably induced a cytoprotection against pro-oxidant conditions, and may be a valuable functional compound recovered from an unexploited agroindutrial waste.


Asunto(s)
Antioxidantes/análisis , Antioxidantes/farmacología , Fibras de la Dieta/análisis , Frutas/química , Animales , Supervivencia Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Galactanos/química , Peróxido de Hidrógeno/toxicidad , Ratones , Células 3T3 NIH , Estrés Oxidativo , Pectinas/química , Polisacáridos/química
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