The Relationship between Choline Bioavailability from Diet, Intestinal Microbiota Composition, and Its Modulation of Human Diseases

© 2020 by the authors.Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which, upon absorption by the host is converted into trimethylamine-N-oxide (TMAO) in the liver. A high accumulation of both components is related to cardiovascular disease, inflammatory bowel disease, non-alcoholic fatty liver disease, and chronic kidney disease. However, the relationship between the microbiota production of these components and its impact on these diseases still remains unknown. In this review, we will address which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., the genotype) and diet affect TMA production, and the colonization of these microbes and the reversal of dysbiosis as a therapy for these diseases.This work was supported by the Ministry of Science, Innovation and Universities (PSI2017-83893-R to J.L.A.) and the Ministry of Economy and Business (PSI2015-73111-EXP to J.L.A., PSI2017-90806-REDT to J.L.A. and AGL2017-83653R to M.G.) (Spain). S.A. was the recipient of a postdoctoral Juan de la Cierva Contract (Ministry of Science, Innovation and Universities, Ref. IJCI-2017-32156).Peer reviewe

Proinflammatory Liver and Antiinflammatory Intestinal Mediators Involved in Portal Hypertensive Rats

Proinflammatory (TNF-α, IL-1β, and NO) and antiinflammatory (IL-10, CO) levels were assayed in serum, liver, and small bowel in order to verify a hypothetic inflammatory etiopathogeny of portal hypertension that could be the cause of its evolutive heterogeneity. Male Wistar rats were divided into one control group (n = 11) and one group with a triple stenosing ligation of the portal vein (n = 23) after 28 days of evolution. In one subgroup of portal hypertensive rats, portal pressure, collateral venous circulation, mesenteric vasculopathy, and liver and spleen weights were determined. In the remaining rats with portal hypertension TNF-α, IL-1β, and IL-10 were quantified in liver and ileum by enzyme-linked immunosorbent assay. NO synthase activity was studied in liver and ileum. CO and NO were measured in portal and systemic blood by spectrophotometry and Griess reaction, respectively. Portal hypertensive rats with mayor spleen weight show hepatomegaly and mayor development of collateral circulation. Ileum release of IL-10 (0.30 ± 0.12 versus 0.14 ± 0.02 pmol/mg protein; P < .01) is associated with a liver production of both proinflammatory mediators (TNF-α: 2 ± 0.21 versus 1.32 ± 0.60 pmol/mg protein; P < .05, IL-1β: 19.17 ± 2.87 versus 5.96 ± 1.84 pmol/mg protein; P = .005, and NO: 132.10 ± 34.72 versus 61.05 ± 8.30 nmol/mL; P = .005) and an antiinflammatory mediator (CO: 6.49 ± 2.99 versus 3.03 ± 1.59 pmol/mL; P = .005). In short-term prehepatic portal hypertension a gut-liver inflammatory loop, which could be fundamental in the regulation both of the portal pressure and of its complications, could be proposed

Perturbation-Based Modeling Unveils the Autophagic Modulation of Chemosensitivity and Immunogenicity in Breast Cancer Cells

In the absence of new therapeutic strategies, chemotherapeutic drugs are the most widely used strategy against metastatic breast cancer, in spite of eliciting multiple adverse effects and having low responses with an average 5-year patient survival rate. Among the new therapeutic targets that are currently in clinical trials, here, we addressed the association between the regulation of the metabolic process of autophagy and the exposure of damage-associated molecular patterns associated (DAMPs) to immunogenic cell death (ICD), which has not been previously studied. After validating an mCHR-GFP tandem LC3 sensor capacity to report dynamic changes of the autophagic metabolic flux in response to external stimuli and demonstrating that both basal autophagy levels and response to diverse autophagy regulators fluctuate among different cell lines, we explored the interaction between autophagy modulators and chemotherapeutic agents in regards of cytotoxicity and ICD using three different breast cancer cell lines. Since these interactions are very complex and variable throughout different cell lines, we designed a perturbation-based model in which we propose specific modes of action of chemotherapeutic agents on the autophagic flux and the corresponding strategies of modulation to enhance the response to chemotherapy. Our results point towards a promising therapeutic potential of the metabolic regulation of autophagy to overcome chemotherapy resistance by eliciting ICD.Universidad de Costa Rica/[803-B6-600]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET)UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiologí

Sex-Specific Effects of Early Life Stress on Brain Mitochondrial Function, Monoamine Levels and Neuroinflammation

Sex differences have been reported in the susceptibility to early life stress and its neurobiological correlates in humans and experimental animals. However, most of the current research with animal models of early stress has been performed mainly in males. In the present study, prolonged maternal separation (MS) paradigm was applied as an animal model to resemble the effects of adverse early experiences in male and female rats. Regional brain mitochondrial function, monoaminergic activity, and neuroinflammation were evaluated as adults. Mitochondrial energy metabolism was greatly decreased in MS females as compared with MS males in the prefrontal cortex, dorsal hippocampus, and the nucleus accumbens shell. In addition, MS males had lower serotonin levels and increased serotonin turnover in the prefrontal cortex and the hippocampus. However, MS females showed increased dopamine turnover in the prefrontal cortex and increased norepinephrine turnover in the striatum, but decreased dopamine turnover in the hippocampus. Sex differences were also found for pro-inflammatory cytokine levels, with increased levels of TNF-&alpha; and IL-6 in the prefrontal cortex and hippocampus of MS males, and increased IL-6 levels in the striatum of MS females. These results evidence the complex sex- and brain region-specific long-term consequences of early life stress.This work was supported by grants PSI 2017-83038-P to HGP and NC, PSI 2017-90806-REDT to JLA, PSI 2017-83893-R to JLA (Ministry of Economy and Competitiveness, Spain)

Increased basolateral amygdala metabolic activity during flavor familiarization: an experimental study

Background: Novel flavors elicit a cautious neophobic response which is attenuated as the flavor becomes familiar and safe. The attenuation of neophobia reveals the formation of a safe memory. Previous lesion studies in rats have reported that basolateral amygdala integrity is required for taste neophobia, but not neophobia to flavor, i.e., taste linked to an odorous component. Accordingly, immunohistochemical analyses show that novel tastes induced higher basolateral amygdala activity when compared to familiar ones. However, a different role of basolateral amygdala in flavor attenuation of neophobia is suggested by lesion studies using a vinegar solution. Studies assessing basolateral amygdala activity during flavor attenuation of neophobia are lacking. Thus, we quantified cytochrome oxidase as an index of basolateral amygdala activity along the first and second vinegar exposures in order to assess flavor neophobia and attenuation of neophobia. Methods: We exposed adult male Wistar rats either once or twice to a 3% cider vinegar solution or water, and compared the basolateral amygdala, piriform cortex and caudate putamen brain metabolic activity using cytochrome c-oxidase histochemistry. Results: We found increased flavor intake and cytochrome c-oxidase histochemistry activity during the second exposure in basolateral amygdala, but not in the piriform cortex and caudate/putamen. Conclusions: The main finding of the study is that BLA metabolic activity was higher in the group exposed to a familiar vinegar solution than in the groups exposed to either water or a novel vinegar solution.6 página

Phylo‐biogeographical distribution of whitefly Bemisia tabaci (Insecta: Aleyrodidae) mitotypes in Ecuador

Abstract The Bemisia tabaci complex in Ecuador was studied with respect to phylogenetic relationships and eco‐geographical distribution. Whitefly samples were collected from natural and agricultural environments in nine provinces of Ecuador (latitude, 2° N–5° S; longitude, 78°–81° W). Mitotypes were identified based on phylogenetic analysis of the 3′‐mtCOI‐tRNAleu region (832 bp) and corrected pairwise distance analysis. The distribution of mitotypes was modeled using MaxEnt, and their predicted niches were characterized according to environmental gradients. Four B. tabaci mitotypes were identified, of which three are endemic, herein ECU1–3, and the other is the introduced B mitotype. Mitotypes ECU1 (44%), ECU2 (0.74%), and ECU3 (1.47%) grouped in the American Tropics (AMTROP) species and diverged by as much as 10%, which was higher than previous estimates for the AMTROP clade of 7–8.6%. Although haplotypes of ECU1 and ECU2 are known from the American Tropics, this is the first report of the ECU3 mitotype, which may possibly be restricted to southern Ecuador. The distribution of the three ECU‐endemic mitotypes spanned the high‐altitude niches of the western slope of the Andes, rich in microclimates with variable temperature and humidity conditions. The non‐endemic B mitotype (47%) occurred only in the irrigated cropping systems located in hot and/or dry‐tropical ecological niches. Of the endemic mitotypes, ECU1 occupied the most ecological niches. Among variables contributing to ECU1 and B mitotype niche range assignments, the most significant to influence ecological range was rainfall. The B. tabaci endemic to Ecuador were more diverse with respect to mtCOI‐tRNAleu sequence than previously known, and occupied distinct microclimate niches suggestive of ecological resilience

Tolerancia al alcohol en ratas sometidas a diferentes períodos de consumo agudo y crónico de etanol

The development of tolerance to the effects of ethanol is not uniform and may vary according to the actual and previous pattern of consumption. In this experiment we assessed body temperature and the recovery of two reflexes after a high dose of ethanol in rats submitted to chronic and acute ethanol consumption. Animals were previously submitted to chronic or acute alcohol consumption from postnatal day 21 until postnatal days 56 and 84. On the testing days, the animals received a single dose of 25% ethanol (5 g/kg, i.p.) or the same amount of saline solution. The results showed that animals were affected in the day 56 to a greater extent than in the day 84 by chronic heavy consumption of ethanol solution. With moderate and acute ethanol consumption, the 56-day-old animals developed greater tolerance. However, tolerance was not developed for the motor-impairing effects, since all groups required a long time to recover reflexesEl desarrollo de tolerancia a los efectos del alcohol no es uniforme, y suele variar según el patrón de consumo previo y actual. En este trabajo se evaluó la temperatura corporal y el tiempo de recuperación de dos reflejos tras el consumo crónico y agudo de elevadas dosis de etanol. Previamente, los animales bebieron alcohol de forma crónica o aguda desde los 21 hasta los 56 y 84 días de edad. Durante los días de evaluación, los animales recibieron una única dosis de etanol al 25% (5 g/kg, i.p.), o la misma cantidad de solución salina. Los resultados mostraron una mayor afectación a los 56 días de consumo crónico elevado de etanol respecto a los 84 días. Con un consumo moderado o agudo de etanol, los animales de 56 días desarrollaron una mayor tolerancia. Sin embargo, esta tolerancia no se observó en cuanto a los déficits motores, dado que todos los grupos necesitaron un largo período de tiempo para recuperar los reflejosThis work was supported by grants PR78/02-10972 (Complutense University), MCYT BSO 2001-2757 (Ministry of Science and Technology, Spain) and PR-01-GE-2 (Principado de Asturias, Spain

Clinical insights into dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous soft tissue sarcoma, it is the second most common skin sarcoma after Kaposi's sarcoma. The cause of DFSP remains unknown. The case of a 54-year-old female patient with a diagnosis of Dermatofibrosarcoma protuberans is presented, displaying a typical clinical presentation. It is characterized by an initial lesion in the form of a reddish spot on the anterior region of the chest, which showed slow growth until the development of a multinodular and irregular lesion with multiple recurrences. The lesion is resected, confined to the superficial layers of the skin, with 3 cm margins, confirming the histopathological diagnosis of dermatofibrosarcoma protuberans with clear margins. DFSP is an uncommon cutaneous sarcoma that is typically low- to intermediate-grade, and while it has a limited likelihood of metastasis, it exhibits a notable tendency for local recurrence. The risk of recurrence is closely linked to the extent of surgical resection

El asocio papa ; fríjol arbustivo: influencia del genotipo de fríjol con tres poblaciones en su productividad.

En el CRI La Selva y en los semestres A y B de 1980 se sembró un experimento para medir el efecto de tres variedades de fríjol arbustivo en la producción del sistema de cultivo múltiple, PAPA ASOCIADA CON FRIJOL ARBUSTIVO. El efecto se midió sembrando 25000 plantas/ha de fríjol, bajo dos distribuciones dentro del cultivo normal de papa, junto con otra población de 50000 plantas de fríjol/ha bajo una sola modalidad de distribución. Las variedades de fríjol utilizadas fueron DIACOL-CATIO, L202.70 y CARGAMANTO MOCHO, esta última utilizada regionalmente. La variedad de papa fue la DIACOL-CAPIRO. El sistema de papa ; fríjol arbustivo tiene como característica esencial, que todas las labores agronómicas de la papa repercuten colateral y directamente en beneficio del fríjol. El rendimiento de la papa, 23 t/ha en promedio, fue similar bajo el efecto del asocio de las tres variedades de fríjol con cualquiera de sus poblaciones y distribución. La población de 50000 plantas de fríjol/ha de cualquiera de las tres variedades, tuvo los más altos rendimientos con repoducciones que oscilaron entre 360 y 1215 kg/ha de fríjol. En orden descendente, la variedad Cargamanto Mocho, rindió más que el Diacol-Catío y estas a su vez más que la línea 202.70 aunque la producción de las dos primeras no fue estadísticamente diferente. Al analizar el efecto de semestres, se obtuvo que los rendimientos de papa y fríjol arbustivo asociados fueron significativamente superiores en el primer semestre en comparación con el segundo.Fríjol-Phaseolus vulgarisPapa-Solanum tuberosu