108 results on '"Macia L"'
Search Results
2. Overview of IFMIF-DONES diagnostics: Requirements and techniques
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Torregrosa-Martin, C., Ibarra, A., Aguilar, J., Ambi, F., Arranz, F., Arbeiter, F., Bagnasco, A., Becerril, S., Bernardi, D., Bolzon, B., Botta, E., Brenneis, B., Cappelli, M., Cara, P., Castellanos, J., Cosic, D., De la Morena, C., Diez, A., Ericsson, G., García, A., García, M., Garcinuño, B., Gutiérrez, J., Gutiérrez, V., Jimenez-Rey, D., Dezsi, T., Ferreira, M. Juni, Fiore, S., Krolas, W., Lorenzo, R., Luque, M., Maciá, L., Marroncle, J., Martin-Fuertes, F., Marugán, J.C., Maestre, J., Meléndez, C., Miccichè, G., Mollá, J., Moreno, A., Nitti, F.S., Núñez, C., Ogando, F., Pinna, T., Oliver, C., Podadera, I., Prieto, C., Prokopowicz, R., Qiu, Y., Rapisarda, D., Regidor, D., Rodríguez, E., Sabogal, A., Sánchez-Herranz, D., Sanmarti, M., Seguí, L., Serikov, A., Tadić, T., Talarowska, A., Wiacek, U., Weber, M., Valenzuela, J., and Zsakai, A.
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- 2023
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3. A randomized clinical trial to investigate the effect of dietary protein sources on periodontal health.
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Eberhard, J, Ruiz, K, Tan, J, Jayasinghe, TN, Khan, S, Eroglu, E, Adler, C, Simpson, SJ, Le Couteur, DG, Raubenheimer, D, Macia, L, Gosby, AK, Ribeiro, RV, Eberhard, J, Ruiz, K, Tan, J, Jayasinghe, TN, Khan, S, Eroglu, E, Adler, C, Simpson, SJ, Le Couteur, DG, Raubenheimer, D, Macia, L, Gosby, AK, and Ribeiro, RV
- Abstract
AIM: The aim was to assess two macronutrient interventions in a 2 × 2 factorial dietary design to determine their effects on oral health. MATERIALS AND METHODS: Participants (65-75 years old) with a body mass index between 20 and 35 kg/m2 of a larger randomized control trial who consented to an oral health assessment were recruited. They had ad libitum access to one of four experimental diets (omnivorous higher fat or higher carbohydrate, semi-vegetarian higher fat or higher carbohydrate) for 4 weeks. The periodontal examination included periodontal probing depth (PPD), clinical attachment level (CAL), and bleeding on probing. Oral plaque and gingival crevicular fluid (GCF) were collected before and after the intervention. RESULTS: Between baseline and follow up, the number of sites with a CAL <5 mm (mean difference [MD] -5.11 ± 9.68, p = .039) increased and the GCF amount (MD -23.42 ± 39.42 Periotron Units [PU], p = .050) decreased for the semi-vegetarian high-fat diet. For the mean proportion of sites with PPD reduction of >1 mm and CAL gain of >1 mm, significant differences were calculated between the diets investigated. The clinical parameters were not associated with changes in the oral microbiota. CONCLUSIONS: The results of this study provided evidence that a semi-vegetarian high-fat diet provides benefits to clinical parameters of periodontal health. This study is registered in ClinicalTrials.gov (ACTRN12616001606471).
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- 2022
4. Gut-derived acetate promotes B10 cells with antiinflammatory effects
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Daïen, C.I., primary, Tan, J., additional, Audo, R., additional, Mielle, J., additional, Quek, L.E., additional, Krycer, J.R., additional, Angelatos, A., additional, Duraes, M., additional, Pinget, G., additional, Ni, D., additional, Robert, R., additional, Alam, M.J., additional, Amian, M.C.B., additional, Sierro, F., additional, Parmar, A., additional, Perkins, G., additional, Hoque, S., additional, Gosby, A.K., additional, Simpson, S.J., additional, Ribeiro, R.V., additional, Mackay, C.R., additional, and Macia, L., additional
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- 2021
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5. Peripheral neuropeptide Y Y1 receptors regulate lipid oxidation and fat accretion
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Zhang, L, Macia, L, Turner, N, Enriquez, R F, Riepler, S J, Nguyen, A D, Lin, S, Lee, N J, Shi, Y C, Yulyaningsih, E, Slack, K, Baldock, P A, Herzog, H, and Sainsbury, A
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- 2010
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6. Maternal carriage of Prevotella during pregnancy associates with protection against food allergy in the offspring
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Vuillermin, PJ, O'Hely, M, Collier, F, Allen, KJ, Tang, MLK, Harrison, LC, Carlin, JB, Saffery, R, Ranganathan, S, Sly, PD, Gray, L, Molloy, J, Pezic, A, Conlon, M, Topping, D, Nelson, K, Mackay, CR, Macia, L, Koplin, J, Dawson, SL, Moreno-Betancur, M, Ponsonby, A-L, Vashee, S, Torralba, M, Gomez, A, Dwyer, T, Burgner, D, Forrester, M, Symeonides, C, Sanchez, EB, Vuillermin, PJ, O'Hely, M, Collier, F, Allen, KJ, Tang, MLK, Harrison, LC, Carlin, JB, Saffery, R, Ranganathan, S, Sly, PD, Gray, L, Molloy, J, Pezic, A, Conlon, M, Topping, D, Nelson, K, Mackay, CR, Macia, L, Koplin, J, Dawson, SL, Moreno-Betancur, M, Ponsonby, A-L, Vashee, S, Torralba, M, Gomez, A, Dwyer, T, Burgner, D, Forrester, M, Symeonides, C, and Sanchez, EB
- Abstract
In mice, the maternal microbiome influences fetal immune development and postnatal allergic outcomes. Westernized populations have high rates of allergic disease and low rates of gastrointestinal carriage of Prevotella, a commensal bacterial genus that produces short chain fatty acids and endotoxins, each of which may promote the development of fetal immune tolerance. In this study, we use a prebirth cohort (n = 1064 mothers) to conduct a nested case-cohort study comparing 58 mothers of babies with clinically proven food IgE mediated food allergy with 258 randomly selected mothers. Analysis of the V4 region of the 16S rRNA gene in fecal samples shows maternal carriage of Prevotella copri during pregnancy strongly predicts the absence of food allergy in the offspring. This association was confirmed using targeted qPCR and was independent of infant carriage of P. copri. Larger household size, which is a well-established protective factor for allergic disease, strongly predicts maternal carriage of P. copri.
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- 2020
7. SAT-160 DIETARY FIBRE AND BACTERIAL SCFA MODULATE RENAL INFLAMMATION IN DIABETIC NEPHROPATHY THROUGH ACTIVATION OF G-PROTEIN COUPLED RECEPTORS GPR43 AND GPR109A
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Li, Y., primary, Chen, X., additional, Kwan, T., additional, Loh, Y., additional, Singer, J., additional, Liu, Y., additional, Tan, J., additional, Macia, L., additional, Chadban, S., additional, and Wu, H., additional
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- 2020
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8. SUN-040 MANIPULATING THE GUT MICROBIOME BY DIETARY FIBRE TO PREVENT FOLIC ACID INDUCED KIDNEY DISEASE
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Liu, Y., primary, LI, Y., additional, Loh, Y.W., additional, Singer, J., additional, Macia, L., additional, Chadban, S., additional, and Wu, H., additional
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- 2020
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9. Simulation of ejector for vacuum generation
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Macia, L, primary, Castilla, R, additional, and Gámez, P J, additional
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- 2019
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10. SUN-303 DIETARY MANIPULATION OF THE GUT MICROBIOTA REDUCES DIABETIC KIDNEY INJURY IN MICE
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LI, Y., primary, Chen, X., additional, Kwan, T., additional, Loh, Y., additional, Singer, J., additional, Tan, J., additional, Macia, L., additional, Chadban, S., additional, and Wu, H., additional
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- 2019
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11. Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia
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Hu, M, Eviston, D, Hsu, P, Marino, E, Chidgey, A, Santner-Nanan, B, Wong, K, Richards, JL, Yap, YA, Collier, F, Quinton, A, Joung, S, Peek, M, Benzie, R, Macia, L, Wilson, D, Ponsonby, A-L, Tang, MLK, O'Hely, M, Daly, NL, Mackay, CR, Dahlstrom, JE, Vuillermin, P, Nanan, R, Saffery, R, Allen, KJ, Ranganathan, S, Burgner, D, Harrison, LC, Sly, P, Dwyer, T, Hu, M, Eviston, D, Hsu, P, Marino, E, Chidgey, A, Santner-Nanan, B, Wong, K, Richards, JL, Yap, YA, Collier, F, Quinton, A, Joung, S, Peek, M, Benzie, R, Macia, L, Wilson, D, Ponsonby, A-L, Tang, MLK, O'Hely, M, Daly, NL, Mackay, CR, Dahlstrom, JE, Vuillermin, P, Nanan, R, Saffery, R, Allen, KJ, Ranganathan, S, Burgner, D, Harrison, LC, Sly, P, and Dwyer, T
- Abstract
Maternal immune dysregulation seems to affect fetal or postnatal immune development. Preeclampsia is a pregnancy-associated disorder with an immune basis and is linked to atopic disorders in offspring. Here we show reduction of fetal thymic size, altered thymic architecture and reduced fetal thymic regulatory T (Treg) cell output in preeclamptic pregnancies, which persists up to 4 years of age in human offspring. In germ-free mice, fetal thymic CD4+ T cell and Treg cell development are compromised, but rescued by maternal supplementation with the intestinal bacterial metabolite short chain fatty acid (SCFA) acetate, which induces upregulation of the autoimmune regulator (AIRE), known to contribute to Treg cell generation. In our human cohorts, low maternal serum acetate is associated with subsequent preeclampsia, and correlates with serum acetate in the fetus. These findings suggest a potential role of acetate in the pathogenesis of preeclampsia and immune development in offspring.
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- 2019
12. The maternal microbiome during pregnancy and allergic disease in the offspring
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Vuillermin, PJ, Macia, L, Nanan, R, Tang, MLK, Collier, F, Brix, S, Vuillermin, PJ, Macia, L, Nanan, R, Tang, MLK, Collier, F, and Brix, S
- Abstract
There is substantial epidemiological and mechanistic evidence that the increase in allergic disease and asthma in many parts of the world in part relates to changes in microbial exposures and diet acting via the composition and metabolic products of the intestinal microbiome. The majority of research in this field has focused on the gut microbiome during infancy, but it is increasingly clear that the maternal microbiome during pregnancy also has a key role in preventing an allergy-prone immune phenotype in the offspring. The mechanisms by which the maternal microbiome influences the developing fetal immune system include alignment between the maternal and infant regulatory immune status and transplacental passage of microbial metabolites and IgG. Interplay between microbial stimulatory factors such as lipopolysaccharides and regulatory factors such as short-chain fatty acids may also influence on fetal immune development. However, our understanding of these pathways is at an early stage and further mechanistic studies are needed. There are also no data from human studies relating the composition and metabolic activity of the maternal microbiome during pregnancy to the offspring's immune status at birth and risk of allergic disease. Improved knowledge of these pathways may inform novel strategies for tackling the increase in allergic disorders in the modern world.
- Published
- 2017
13. Electrochemical detection of extracellular hydrogen peroxide in Arabidopsis thaliana: a real-time marker of oxidative stress
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González-Sánchez, M.I., González-Macia, L., Pérez Prior, María Teresa, Valero, E., Hancock, J., Killard, A.J., and European Commission
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Materiales ,Amperometric sensor ,Plant cells ,Pt electrode - Abstract
An electrochemical approach to directly measure thedynamic process of H2O2 release from cultures of Arabidopsis thaliana cells is reported. This approach is based on H2O2 oxidation on a Pt electrode in conjunction with continuous measurement of sample pH. For [H2O2] 1mM), the amperometric response can be described by Michaelian-type kinetics and a mathematical expression relating current intensity and pH was obtained to quantitatively determine H2O2 concentration. At pH 5.5, the detection limit of the sensor was 3.1 μ M (S/N = 3), with a response sensitivity of 0.16 AM-1cm-2 and reproducibility was within 6.1% in the range 1-5 x 10-3M (n = 5). Cell suspensions under normal physiological conditions had a pH between 5.5-5.7 and H2O2 concentrations in the range 7.0-20.5 μM (n=5). The addition of exogenous H2O2, as well as other potential stress stimuli, was made to the cells and the change in H2O2 concentration was monitored. This real-time quantitative H2O2 analysis is a potential marker for the evaluation of oxidative stress in plant cell cultures. This work has been supported by the Project POII10-0235-8597 from the Regional Ministry of Education and Science of Castilla-La Mancha (JCCM, Spain) and FP7/2007-2013 from EU (under Grant number 257372).
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- 2013
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14. Latino Parents Of Preschoolers’ Perceptions Of Healthy Living
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Sanchez I, Taverno Ross Se, Escribano C, Macia L, Patricia I. Documet, and Mirzakazemi T
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medicine.medical_specialty ,Pediatrics ,business.industry ,Family medicine ,Perception ,media_common.quotation_subject ,Intervention (counseling) ,medicine ,Physical Therapy, Sports Therapy and Rehabilitation ,Orthopedics and Sports Medicine ,business ,Focus group ,media_common - Published
- 2016
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15. ANDALE Pittsburgh - Study Protocol For A Promotora-mediated, Family-based Intervention To Prevent Obesity In Latino Children
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Russell R. Pate, Sanchez I, Ruth P. Saunders, Taverno Ross Se, Patricia I. Documet, Wisniewski Lm, and Macia L
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Gerontology ,Protocol (science) ,business.industry ,Intervention (counseling) ,medicine ,Physical Therapy, Sports Therapy and Rehabilitation ,Orthopedics and Sports Medicine ,Family based ,medicine.disease ,business ,Obesity - Published
- 2016
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16. Neuropeptide Y1 Receptor in Immune Cells Regulates Inflammation and Insulin Resistance Associated With Diet-Induced Obesity
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Macia, L, Yulyaningsih, E, Pangon, L, Nguyen, AD, Lin, S, Shi, YC, Zhang, L, Bijker, M, Grey, S, Mackay, F, Herzog, H, and Sainsbury, Amanda
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- 2012
17. Peripheral-Specific Y2 Receptor Knockdown Protects Mice From High-Fat Diet-Induced Obesity
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Shi, Y, Lin, S, Castillo, L, Aljanova, A, Enriquez, RF, Nguyen, AD, Baldock, PA, Zhang, L, Bijker, MB, Macia, L, Yulyaningsih, E, Zhang, H, Lau, J, Sainsbury, Amanda, and Herzog, H
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- 2011
18. Serum levels of human MIC-1/GDF15 vary in a diurnal pattern, do not display a profile suggestive of a satiety factor and are related to BMI
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Young, Martin, Tsai, VWW ; https://orcid.org/0000-0002-7817-3441, Macia, L, Feinle-Bisset, C, Manandhar, R, Astrup, A, Raben, A, Lorenzen, JK, Schmidt, PT, Wiklund, F, Pedersen, NL, Campbell, L ; https://orcid.org/0000-0001-7775-0246, Kriketos, A, Xu, A, Pengcheng, Z, Jia, W, Curmi, PMG ; https://orcid.org/0000-0001-5762-7638, Angstmann, CN ; https://orcid.org/0000-0002-6688-9346, Lee-Ng, KKM, Zhang, HP, Marquis, CP ; https://orcid.org/0000-0003-1656-7215, Husaini, Y, Beglinger, C, Lin, S, Herzog, H ; https://orcid.org/0000-0002-1713-1029, Brown, DA, Sainsbury, A, Breit, SN ; https://orcid.org/0000-0002-9021-9879, Lee-Ng, Michelle, Young, Martin, Tsai, VWW ; https://orcid.org/0000-0002-7817-3441, Macia, L, Feinle-Bisset, C, Manandhar, R, Astrup, A, Raben, A, Lorenzen, JK, Schmidt, PT, Wiklund, F, Pedersen, NL, Campbell, L ; https://orcid.org/0000-0001-7775-0246, Kriketos, A, Xu, A, Pengcheng, Z, Jia, W, Curmi, PMG ; https://orcid.org/0000-0001-5762-7638, Angstmann, CN ; https://orcid.org/0000-0002-6688-9346, Lee-Ng, KKM, Zhang, HP, Marquis, CP ; https://orcid.org/0000-0003-1656-7215, Husaini, Y, Beglinger, C, Lin, S, Herzog, H ; https://orcid.org/0000-0002-1713-1029, Brown, DA, Sainsbury, A, Breit, SN ; https://orcid.org/0000-0002-9021-9879, and Lee-Ng, Michelle
- Abstract
The TGF-b superfamily cytokine MIC-1/GDF15 circulates in the blood of healthy humans. Its levels rise substantially in cancer and other diseases and this may sometimes lead to development of an anorexia/cachexia syndrome. This is mediated by a direct action of MIC- 1/GDF15 on feeding centres in the hypothalamus and brainstem. More recent studies in germline gene deleted mice also suggest that this cytokine may play a role in physiological regulation of energy homeostasis. To further characterize the role of MIC-1/GDF15 in physiological regulation of energy homeostasis in man, we have examined diurnal and food associated variation in serum levels and whether variation in circulating levels relate to BMI in human monozygotic twin pairs. We found that the within twin pair differences in serum MIC-1/GDF15 levels were significantly correlated with within twin pair differences in BMI, suggesting a role for MIC-1/GDF15 in the regulation of energy balance in man. MIC-1/ GDF15 serum levels altered slightly in response to a meal, but comparison with variation its serum levels over a 24hour period suggested that these changes are likely to be due to bimodal diurnal variation which can alter serum MIC-1/GDF15 levels by about plus or minus 10% from the mesor. The lack of a rapid and substantial postprandial increase in MIC-1/ GDF15 serum levels suggests that MIC1/GDF15 is unlikely to act as a satiety factor. Taken together, our findings suggest that MIC-1/GDF15 may be a physiological regulator of energy homeostasis in man, most probably due to actions on long-term regulation of energy homeostasis.
- Published
- 2015
19. Flujometría por difusión termal para la medida del flujo sanguíneo cerebral regional en la cirugía de los aneurismas cerebrales
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Verdú-López, F., González-Darder, J.M., González-López, P., and Botella Macia, L.
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Isquemia ,Thermal diffusion flowmetry ,Aneurisma ,Oclusión temporal arterial ,Ischemia ,Temporary arterial occlusion ,Flujo sanguíneo cerebral ,Cerebral blood flow ,Monitorización intraoperatoria ,Aneurysm ,Intraoperative monitoring ,Flujometría mediante difusión termal - Abstract
Introducción. La flujometría por difusión termal (FDT) es una técnica que permite, mediante la implantación de una microsonda en una región cerebral de interés, determinar el flujo sanguíneo cerebral regional (FSCr) y su monitorización cuantitativa (ml/100g/min), continua y en tiempo real. El objetivo de nuestro trabajo es mostrar los detalles técnicos y resultados preliminares de esta técnica de monitorización durante la cirugía y el postoperatorio del tratamiento microquirúrgico de los aneurismas cerebrales, donde tendría valor para detectar y cuantificar fenómenos isquémicos relacionados con el clipaje temporal arterial o malposición del clip definitivo. Material clínico. Han sido monitorizados cinco pacientes (4 mujeres y 1 hombre; edad media de 50.8 años), dos de ellos con aneurismas de arteria cerebral media, otros dos con sendos aneurismas de arteria comunicante posterior y coroidea anterior y uno con aneurisma de carótida interna paraclinoideo. Los pacientes fueron intervenidos con técnica microquirúrgica y clipaje de los aneurismas a través de un abordaje pterional. Se utilizó monitorización neurofisiológica peroperatoria y flujometría con microdoppler. Inmediatamente antes de la craneotomía se procedió a la colocación de la microsonda de FDT a través de un minitrépano sobre la línea coronal, en territorio de la arteria cerebral anterior (2 cm de línea media) o de la cerebral media (6 cm de línea media) y en sustancia blanca, a unos 2.5 cm de profundidad. Los pacientes fueron monitorizados durante la cirugía y el tiempo en que estuvieron en la Unidad de Reanimación. Se realizaron un total de 14 clipajes temporales (rango 2-4) con un tiempo medio de clipaje de 7.2 min (rango 1.6-16) y 16 (rango 2-8) recolocaciones de los clips definitivos. En el aneurisma paraclinoideo se utilizó la técnica de aspiración retrógrada manteniendo cerrada la carótida interna 45 min. Se describen casos ilustrativos con diferentes registros demostrativos. Conclusiones. El uso de la FDT permite una valoración cuantitativa y en tiempo real del FSCr de las áreas cerebrales de interés monitorizadas durante el tratamiento microquirúrgico de los aneurismas cerebrales, lo que hace posible detectar fenómenos isquémicos y evitar que se produzcan déficits neurológicos. La detección precoz de la isquemia permitiría aplicar medidas terapéuticas más precozmente y con mayor eficacia. Introduction. The thermal diffusion flowmetry (TDF) is a technique that allows the measurement of the regional cerebral blood flow (rCBF) through an implanted microprobe in a cerebral region of interest. The monitoring is continuous, real-time and quantitative (ml/100g/min). The purpose of our clinical work has been to show the technical details and preliminary results by using this monitoring technique during the microsurgical management of cerebral aneurysms and along the postoperative period. The aim of the monitoring of the rCBF is to identify and evaluate ischemic events related with the temporary artery clipping or malposition of the final clip. Clinical materials. A total of five patients have been monitored (4 woman and one man with an average age of 50.8 years). Two patients harboured one aneurysm in the middle cerebral artery, other two patients had two aneurysms each one on the internal carotid artery in the exit of the posterior communicating and anterior choroidal artery and the fifth harboured a paraclinoid internal carotid artery aneurysm. All patients were operated on using standard microsurgical techniques through a pterional approach. Surgery was done under neurophysiological monitoring and direct microdoppler fluometry assesment. Just before craniotomy the TDF microprobe was inserted 2,5 cm deep into the white matter through a small burr-hole placed on the coronal line and 2 cm away the midline to measure in the anterior cereral artery vascular sector and 6cm away of the midline to measure in the middle cerebral artery territory. Patients were under continuous monitoring during surgery and along the postoperative period in the recovery unit. A total of 14 temporary artery clippings (between 2-4) with an average total clipping time of 7.2 minutes (ranging 1.6 to 16) and 16 definitive clip replacements (ranging 2 to 8) were done at surgery. Patient with paraclinoid aneurysm was operated on using the retrograde aspiration technique and the internal carotid artery was kept closed 45 mimutes. keeping Some illustrative cases and demonstrative records are presented. Conclusions. The use of TDF allows a quantitative real-time measurement of the rCBF in the areas of interest monitored during the microsurgical management of the cerebral aneurysms which leads to detect ischemic events helpping to avoid ischemic sequelae. The detection of ischemic events in real time would make possible the use of therapeutic measures ealier and more efficienty.
- Published
- 2010
20. Inflammation and lymphopenia trigger autoimmunity by suppression of IL-2-controlled regulatory T cell and increase of IL-21-mediated effector T cell expansion.
- Author
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Chevalier N, Thorburn AN, Macia L, Tan J, Juglair L, Yagita H, Yu D, Hansbro PM, Mackay CR, Chevalier N, Thorburn AN, Macia L, Tan J, Juglair L, Yagita H, Yu D, Hansbro PM, and Mackay CR
- Abstract
The dynamic interplay between regulatory T cells (T(regs)) and effector T cells (T(effs)) governs the balance between tolerance and effector immune responses. Perturbations of T(reg) frequency and function or imbalances in T(reg)/T(eff) levels are associated with the development of autoimmunity. The factors that mediate these changes remain poorly understood and were investigated in this study in murine autoimmune arthritis. T(regs) displayed a stable phenotype in arthritic mice and were fully functional in in vitro suppression assays. However, their expansion was delayed relative to T(effs) (T follicular helper cells and Th17 cells) during the early stages of autoimmune reactivity. This imbalance is likely to have led to insufficient T(reg) control of T(effs) and induced autoimmunity. Moreover, a counterregulatory and probably IL-7-driven increase in thymic T(reg) production and recruitment to inflamed tissues was too slow for disease prevention. Increased T(eff) over T(reg) expansion was further aggravated by inflammation and lymphopenia. Both these conditions contribute to autoimmune pathogenesis and were accompanied by decreases in the availability of IL-2 and increases in levels of IL-21. IL-2 neutralization or supplementation was used to show that T(reg) expansion mainly depended on this cytokine. IL-21R(-/-) cells were used to demonstrate that IL-21 promoted the maintenance of T(effs). Thus, at inflammatory sites in experimental arthritis, a deficit in IL-2 hampers T(reg) proliferation, whereas exaggerated IL-21 levels overwhelm T(reg) control by supporting T(eff) expansion. This identifies IL-2 and IL-21 as targets for manipulation in therapies for autoimmunity.
- Published
- 2014
21. TGF-b Superfamily Cytokine MIC-1/GDF15 Is a Physiological Appetite and Body Weight Regulator
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Morrison, Christopher, Tsai, VW-W, Macia, L, Johnen, H, Kuffner, T, Manadhar, R, Jorgensen, Lee-Ng, KKM, Hong, Ping Zhang, Wu, L, Marquis, C ; https://orcid.org/0000-0003-1656-7215, Jiang, L, Husaini, Y, Lin, S, Herzog, H, Brown, DA, Sainsbury-Salis, A, Breit, SN ; https://orcid.org/0000-0002-9021-9879, Zhang, Hong, Morrison, Christopher, Tsai, VW-W, Macia, L, Johnen, H, Kuffner, T, Manadhar, R, Jorgensen, Lee-Ng, KKM, Hong, Ping Zhang, Wu, L, Marquis, C ; https://orcid.org/0000-0003-1656-7215, Jiang, L, Husaini, Y, Lin, S, Herzog, H, Brown, DA, Sainsbury-Salis, A, Breit, SN ; https://orcid.org/0000-0002-9021-9879, and Zhang, Hong
- Abstract
The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1−/−) weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1−/− mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass. Further, infusion of human recombinant MIC-1/GDF15 sufficient to raise serum levels in MIC-1−/− mice to within the normal human range reduced body weight and food intake. Taken together, our findings suggest that MIC-1/GDF15 is involved in the physiological regulation of appetite and energy storage.
- Published
- 2013
22. Macrophage inhibitory cytokine 1 (MIC-1/GDF15) decreases food intake, body weight and improves glucose tolerance in mice on normal & obesogenic diets
- Author
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Aguila, Marcia B, Macia, L, Tsai, Vicky WW ; https://orcid.org/0000-0002-7817-3441, Nguyen, AD ; https://orcid.org/0000-0003-4603-564X, Johnen, H, Kuffner, T, Shi, Y, Lin, S, Herzog, H ; https://orcid.org/0000-0002-1713-1029, Brown, DA, Breit, SN ; https://orcid.org/0000-0002-9021-9879, Sainsbury-Salis, A, Aguila, Marcia B, Macia, L, Tsai, Vicky WW ; https://orcid.org/0000-0002-7817-3441, Nguyen, AD ; https://orcid.org/0000-0003-4603-564X, Johnen, H, Kuffner, T, Shi, Y, Lin, S, Herzog, H ; https://orcid.org/0000-0002-1713-1029, Brown, DA, Breit, SN ; https://orcid.org/0000-0002-9021-9879, and Sainsbury-Salis, A
- Abstract
Food intake and body weight are controlled by a variety of central and peripheral factors, but the exact mechanisms behind these processes are still not fully understood. Here we show that that macrophage inhibitory cytokine-1 (MIC-1/GDF15), known to have anorexigenic effects particularly in cancer, provides protection against the development of obesity. Both under a normal chow diet and an obesogenic diet, the transgenic overexpression of MIC-1/GDF15 in mice leads to decreased body weight and fat mass. This lean phenotype was associated with decreased spontaneous but not fastinginduced food intake, on a background of unaltered energy expenditure and reduced physical activity. Importantly, the overexpression of MIC-1/GDF15 improved glucose tolerance, both under normal and high fat-fed conditions. Altogether, this work shows that the molecule MIC-1/GDF15 might be beneficial for the treatment of obesity as well as perturbations in glucose homeostasis.
- Published
- 2012
23. Macrophage inhibitory cytokine-1 (MIC-1/GDF15) and mortality in end-stage renal disease
- Author
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Breit, SN ; https://orcid.org/0000-0002-9021-9879, Carrero, JJ, Tsai, VWW ; https://orcid.org/0000-0002-7817-3441, Yagoutifam, N, Luo, XW, Kuffner, T, Bauskin, AR, Wu, L, Jiang, L, Baranyi, P, Heimburer, O, Murikami, M, Apple, F, Marquis, C ; https://orcid.org/0000-0003-1656-7215, Macia, L, Lin, S, Sainsbury-Salis, A, Herzog, H, Law, MG ; https://orcid.org/0000-0002-3540-8837, Stenvinkel, P, Brown, DA, Han, Anna, Breit, SN ; https://orcid.org/0000-0002-9021-9879, Carrero, JJ, Tsai, VWW ; https://orcid.org/0000-0002-7817-3441, Yagoutifam, N, Luo, XW, Kuffner, T, Bauskin, AR, Wu, L, Jiang, L, Baranyi, P, Heimburer, O, Murikami, M, Apple, F, Marquis, C ; https://orcid.org/0000-0003-1656-7215, Macia, L, Lin, S, Sainsbury-Salis, A, Herzog, H, Law, MG ; https://orcid.org/0000-0002-3540-8837, Stenvinkel, P, Brown, DA, and Han, Anna
- Abstract
Background. Elevated macrophage inhibitory cytokine-1 (MIC-1/GDF15) levels in serum mediate anorexia and weight loss in some cancer patients and similarly elevated levels occur in chronic kidney disease (CKD). Serum MIC-1/GDF15 is also elevated in chronic inflammatory diseases and predicts atherosclerotic events independently of traditional risk factors. The relationship between chronic inflammation, decreasing body mass index (BMI) and increased mortality in CKD is not well understood and is being actively investigated. MIC-1/GDF15 may link these features of CKD. Methods. Cohorts of incident dialysis patients from Sweden (n = 98) and prevalent hemodialysis patients from the USA (n = 381) had serum MIC-1/GDF15, C-reactive protein (CRP) levels and BMI measured at study entry. Additional surrogate markers of nutritional adequacy, body composition and inflammation were assessed in Swedish patients. Patients were followed for all-cause mortality. Results. In the Swedish cohort, serum MIC-1/GDF15 was associated with decreasing BMI, measures of nutrition and markers of oxidative stress and inflammation. Additionally, high serum MIC-1/GDF15 levels identified patients with evidence of protein-energy wasting who died in the first 3 years of dialysis. The ability of serum MIC-1/GDF15 to predict mortality in the first 3 years of dialysis was confirmed in the USA cohort. In both cohorts, serum MIC-1/GDF15 level was an independent marker of mortality when adjusted for age, CRP, BMI, history of diabetes mellitus and/or cardiovascular disease and glomerular filtration rate or length of time on dialysis at study entry. Conclusions. MIC-1/GDF15 is a novel independent serum marker of mortality in CKD capable of significantly improving the mortality prediction of other established markers. MIC-1/GDF15 may mediate protein-energy wasting in CKD and represent a novel therapeutic target for this fatal complication.
- Published
- 2012
24. Macrophage inhibitory cytokine-1 (MIC-1/GDF15) and mortality in end-stage renal disease
- Author
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Breit, S. N., primary, Carrero, J. J., additional, Tsai, V. W.-W., additional, Yagoutifam, N., additional, Luo, W., additional, Kuffner, T., additional, Bauskin, A. R., additional, Wu, L., additional, Jiang, L., additional, Barany, P., additional, Heimburger, O., additional, Murikami, M.-A., additional, Apple, F. S., additional, Marquis, C. P., additional, Macia, L., additional, Lin, S., additional, Sainsbury, A., additional, Herzog, H., additional, Law, M., additional, Stenvinkel, P., additional, and Brown, D. A., additional
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- 2011
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25. Peripheral neuropeptide Y Y1 receptors regulate lipid oxidation and fat accretion
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Zhang, L, primary, Macia, L, additional, Turner, N, additional, Enriquez, R F, additional, Riepler, S J, additional, Nguyen, A D, additional, Lin, S, additional, Lee, N J, additional, Shi, Y C, additional, Yulyaningsih, E, additional, Slack, K, additional, Baldock, P A, additional, Herzog, H, additional, and Sainsbury, A, additional
- Published
- 2009
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26. Genes involved in obesity: Adipocytes, brain and microflora
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Macia, L., primary, Viltart, O., additional, Verwaerde, C., additional, Delacre, M., additional, Delanoye, A., additional, Grangette, C., additional, and Wolowczuk, I., additional
- Published
- 2006
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27. DINÂMICAS TERRITORIAIS E IMPACTOS SOCIOAMBIENTAIS EM COMUNIDADES VAZANTEIRAS ÀS MARGENS DO RIO SÃO FRANCISCO
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Mácia Larissa dos Santos Gomes, Ana Paula Glinfskói Thé, Paulo Henrique Augusto Gonçalves, Felisa Cançado Anaya, and Luciana Ribeiro Monteiro
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agronegócio ,conflitos ambientais ,desigualdades ,desenvolvimento sustentável ,comunidades tradicionais ,Social sciences (General) ,H1-99 - Abstract
O crescimento do agronegócio e os conflitos ambientais causam impactos nas dinâmicas territoriais das comunidades quilombola-pescadoras-vazanteiras. Esses grupos sociais vivem nas margens do médio rio São Francisco no Norte de Minas e se articulam para a afirmação de suas identidades étnicas diferenciadas e para terem seus direitos territoriais reconhecidos. Buscam se caracterizar através de categorias portadoras de direitos coletivos quilombolas e vazanteiras, mas são também conhecidas em terras sanfranciscanas como ilheiras, barranqueiras, beradeiras e lameiras (ARAUJO, 2009). A expansão do capitalismo e expropriação territorial desde a década de 60 têm causado conflitos ambientais que interferem no modo de vida dessas comunidades. A barragem de Três Marias pela Companhia de Energia de Minas Gerais (CEMIG) é vista como fonte das primeiras mudanças. O movimento de migração dos pescadores está intimamente ligado à construção de barragens, que colocam em risco a prática artesanal da pesca e sobrevivência das populações ribeirinhas (THÉ, 2003). O projeto Jaíba de fruticultura irrigada é indicado como uma das principais causas de conflitos ambientais à margem do rio São Francisco, causando expropriação territorial e mudanças nos costumes tradicionais. Este trabalho busca demonstrar através de pesquisa documental que a demarcação do território tradicional e o respeito ao modo de produção tradicional são as fontes de esperança das famílias que resistem à lógica “mercadológica” do modelo agroindustrial. É necessária mediação dos conflitos estimulando a participação Revista Desenvolvimento Social No 19/01, 2016. (ISSN 2179-6807) Página158 social, afirmação étnica e o acesso a políticas públicas voltadas ao desenvolvimento sustentável.
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- 2020
28. Treatment of intrinsic brain tumors located in motor eloquent areas. results of a protocol based in navegation, tractography and neurophysiological monitoring of cortical and subcortical structures
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Gonzalez-Darder, J. M., Gonzalez-Lopez, P., Talamantes-Escriba, F., Garcia-March, G., Roldan-Badia, P., VICENT QUILIS QUESADA, Verdu-Lopez, F., Bordes-Garcia, V., Botella-Macia, L., Masbout, G., Cortes-Donate, V., and Belloch-Ugarte, V.
- Subjects
Monitorización neurofisiológica intraoperatoria ,Tumor cerebral intrínseco ,Intraoperative neurophysiological monitoring ,Corteza cerebral motora ,Cerebral motor cortex ,Intrinsic brain tumor ,Neuronavegación ,Craneotomía ,Neuronavigation ,Craniotomy - Abstract
Objetivos: El papel actual del tratamiento microquirúrgico de los tumores cerebrales intrínsecos se basa en alcanzar la máxima resección volumétrica del tumor minimizando la morbilidad postoperatoria. El propósito del trabajo es estudiar los beneficios de un protocolo diseñado para tratar tumores localizados en áreas elocuentes motoras, en el que se incluye la navegación y la estimulación de tractos motores subcorticales. Material y métodos: Se han incluido 17 pacientes con tumores corticales y subcorticales de área motora tratados quirúrgicamente. Para la planificación preoperatoria se fusionaron en el sistema de navegación estudios anatómicos, de resonancia funcional motora (RNM-f) y los tractos subcorticales generados por estudios de tensor de difusión (DTI). La monitorización intraoperatoria incluía el mapeo motor por estimulación cortical y subcortical directa (ECD y EsCD) e identificación del surco central por inversión de la onda N20 con electrodos corticales multipolares. La localización de los puntos con respuesta positiva a la ECD o EsCD se correlacionaba con las áreas corticales o tractos funcionales motores definidos en los estudios preoperatorios gracias al navegador. Resultados: La resección volumétrica tumoral media fue del 89.1±14.2% del volumen tumoral calculado en los estudios preoperatorios, con resección total (≥100%) en doce pacientes. En el preoperatorio había focalidad neurológica deficitaria motora en el 58.8% de los pacientes, que aumentó al 76.5% a las 24 horas de la cirugía y se redujo a los 30 días al 41.1%. Hubo una gran correlación entre los datos anatómicos y funcionales, tanto a nivel cortical como subcortical. Sin embargo, en seis casos no se pudo identificar anatómicamente el surco central y en muchos pacientes la RNM-f ofrecía datos contradictorios. Se realizaron un total de 52 ECD con respuesta motora positiva que identificaba el área motora primaria, alcanzándose una correlación positiva del 83.7%. Se realizaron un total de 55 EsCD con respuesta motora positiva que identificaban tractos corticoespinales procedentes del área motora primaria. La distancia media entre los puntos de respuesta y la ubicación de los haces en el navegador era de 7.3±3.1mm. Conclusiones: La integración de estudios anatómicos y funcionales preoperatorios e intraoperatorios permite una resección funcional que amplía de forma significativa la resección tumoral de los tumores alojados en áreas elocuentes motoras. La navegación permite integrar y reconocer la correlación entre los datos preoperatorios y los hallazgos intraoperatorios. Las áreas funcionales motoras corticales se reconocen anatómica y funcionalmente en el preoperatorio mediante estudios de RNM y RNM-f y las subcorticales con TDI y la generación de la tractografía a partir del mismo, mientras que la confirmación intraoperatoria se consigue mediante la ECD y estudio de inversión de la onda N20 para las áreas corticales y con la EsCD para las subcorticales. El tratamiento microquirúrgico guiado por navegación y con la ayuda de los estudios descritos permite resecciones tumorales medias del 90% en lesiones tumorales de áreas motoras corticales y subcorticales elocuentes con una morbilidad neurológica alta en el postoperatorio inmediato que se reduce de forma significativa a las cuatro semanas. Los estudios en curso deben definir los márgenes de seguridad para la resección funcional que tengan en consideración el 'shift' cerebral operatorio. Finalmente, queda por demostrar el beneficio de estos protocolos en intervalo libre de enfermedad, de recidiva o en la supervivencia final de los pacientes. Objectives: The role of the microsurgical management of intrinsic brain tumors is to maximize the volumetric resection of the tumoral tissue minimizing the postoperative morbidity. The purpose of our paper has been to study the benefits of an original protocol developed for the microsurgical treatment of tumors located in eloquent motor areas where the navigation and electrical stimulation of motor subcortical pathways have been implemented. Materials and methods: A total of 17 patients operated on for resection of cortical or subcortical tumors in motor areas were included in the series. Preoperative planning for multimodal navigation was done integrating anatomic studies, motor functional MRI (f-MRI) and subcortical pathways volumes generated by diffusion tensor imaging (DTI). Intraoperative neuromonitorization included motor mapping by direct cortical and subcortical electrical stimulation (CS and sCS) and localization of the central sulcus using cortical multipolar electrodes and the N20 wave inversion technique. The location of all cortical and subcortical stimulated points with positive motor response was stored in the navigator and correlated with the cortical or subcortical motor functional structures defined preoperatively. Results: The mean tumoral volumetric resection was 89.1±14.2% of the preoperative volume, with a total resection (≥100%) in twelve patients. Preoperatively a total of 58.8% of the patients had some motor deficit, increasing 24 hours after surgery to 76.5% and decreasing to 41.1% a month later. There was a great correlation between anatomic and functional data, both cortically and subcortically. However, in six cases it was not possible to identify the central sulcus and in many cases fMRI gave contradictory information. A total of 52 cortical points submitted to CS had positive motor response, with a positive correlation of 83.7%. Also, a total of 55 subcortical points had positive motor response, being in these cases 7.3±3.1mm the mean distance from the stimulated point to the subcortical tract. Conclusions: The integration of preoperative and intraoperative anatomic and functional studies allows a safe functional resection of the brain tumors located in eloquent areas, compared to the tumoral resection based on anatomic imaging studies. Multimodal navigation allows the integration and correlation among preoperative and intraoperative anatomic and functional data. Cortical motor functional areas are anatomically and functionally located preoperatively thanks to MRI and fMRI and subcortical motor pathways with TDI and tractography. Intraoperative confirmation is done with CS and N20 inversion wave for cortical structures and with sCS for subcortical pathways. With this protocol we achieved a mean of 90% of volumetric resection in cortical and subcortical tumors located in eloquent motor areas with an increase of neurological deficits in the immediate postoperative period that significantly decreased one month later. Ongoing studies will define the safe limits for functional resection taking into account the intraoperative brain shift. Finally, it must be demonstrated if this protocol has any benefit for patients concerning disease free or everall survival.
29. Antibiotic-mediated dysbiosis leads to activation of inflammatory pathways.
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Taitz JJ, Tan J, Ni D, Potier-Villette C, Grau G, Nanan R, and Macia L
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- Animals, Mice, Female, Inflammatory Bowel Diseases immunology, Inflammatory Bowel Diseases chemically induced, Inflammatory Bowel Diseases microbiology, Inflammation immunology, Cytokines metabolism, Spleen immunology, Spleen metabolism, Vancomycin adverse effects, Vancomycin pharmacology, RNA, Ribosomal, 16S genetics, Cecum microbiology, Cecum immunology, Signal Transduction drug effects, Dysbiosis chemically induced, Dysbiosis immunology, Gastrointestinal Microbiome drug effects, Anti-Bacterial Agents adverse effects, Anti-Bacterial Agents pharmacology, Mice, Inbred C57BL
- Abstract
Introduction: The gut microbiota plays a pivotal role in influencing host health, through the production of metabolites and other key signalling molecules. While the impact of specific metabolites or taxa on host cells is well-documented, the broader impact of a disrupted microbiota on immune homeostasis is less understood, which is particularly important in the context of the increasing overuse of antibiotics., Methods: Female C57BL/6 mice were gavaged twice daily for four weeks with Vancomycin, Polymyxin B, or PBS (control). Caecal microbiota composition was assessed via 16S rRNA sequencing and caecal metabolites were quantified with NMR spectroscopy. Immune profiles of spleen and mesenteric lymph nodes (MLNs) were assessed by flow cytometry, and splenocytes assessed for ex vivo cytokine production. A generalised additive model approach was used to examine the relationship between global antibiotic consumption and IBD incidence., Results: Antibiotics significantly altered gut microbiota composition, reducing alpha-diversity. Acetate and butyrate were significantly reduced in antibiotic groups, while propionate and succinate increased in Vancomycin and PmB-treated mice, respectively. The MLNs and spleen showed changes only to DC numbers. Splenocytes from antibiotic-treated mice stimulated ex vivo exhibited increased production of TNF. Epidemiological analysis revealed a positive correlation between global antibiotic consumption and IBD incidence., Discussion: Our findings demonstrate that antibiotic-mediated dysbiosis results in significantly altered short-chain fatty acid levels but immune homeostasis in spleen and MLNs at steady state is mostly preserved. Non-specific activation of splenocytes ex vivo, however, revealed mice with perturbed microbiota had significantly elevated production of TNF. Thus, this highlights antibiotic-mediated disruption of the gut microbiota may program the host towards dysregulated immune responses, predisposing to the development of TNF-associated autoimmune or chronic inflammatory disease., Competing Interests: LM is a current employee of the Translational Science Hub Global Sanofi Vaccines R&D Brisbane, Australia. Her contribution to this manuscript was when she was an employee of the University of Sydney. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Taitz, Tan, Ni, Potier-Villette, Grau, Nanan and Macia.)
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- 2025
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30. Rapid benefits in older age from transition to whole food diet regardless of protein source or fat to carbohydrate ratio: Arandomised control trial.
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Ribeiro RV, Senior AM, Simpson SJ, Tan J, Raubenheimer D, Le Couteur D, Macia L, Holmes A, Eberhard J, O'Sullivan J, Koay YC, Kanjrawi A, Yang J, Kim T, and Gosby A
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- Humans, Aged, Male, Female, Dietary Carbohydrates metabolism, Diet, Diet, Vegetarian, Dietary Proteins pharmacology, Dietary Fats pharmacology, Dietary Fats metabolism
- Abstract
Plant-based diets reduces the risk of chronic conditions. The interaction between protein source and other macronutrients-fat (F) and carbohydrate (C)-has yet to be investigated. The aim was to assess the main and interactive effects of protein-source (plant vs. animal) and F:C (high or low) and the transition from an Australian diet to a whole food diet on various health markers in older individuals. This single-blinded, parallel, randomised experimental trial used a 2 × 2 factorial design to compare pro-vegetarian (70:30 plant to animal) versus omnivorous (50:50 plant to animal) diets at 14% protein and varying fat-to-carbohydrate ratios (high fat ~40% vs. low fat ~30%) over 4 weeks. Study foods were provided, alcohol consumption was discouraged, and dietary intake was determined through food records. Analysis included both RCT and observational data. Changes in appetite, palatability of diets, and dietary intake were assessed. Body composition, muscle strength, function, gut microbiome, and cardiometabolic health parameters were measured. Data from 113 (of the 128 randomised) individuals aged 65-75 years were analysed. Pro-vegetarian diets reduced diastolic blood pressure, total cholesterol and glucose levels. Moreover, the overall sample exhibited increased short-chain fatty acids and FGF21 levels, as well as improvements in body composition, function, and cardio-metabolic parameters irrespective of dietary treatment. Transitioning to a diet rich in fruit, vegetables, fibre, and moderate protein was associated with improved health markers in older age, with added benefits from pro-vegetarian diets. Further research on long-term effects is needed., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
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- 2024
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31. NFC-enabled potentiostat and nitrocellulose-based metal electrodes for electrochemical lateral flow assay.
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Gonzalez-Macia L, Li Y, Zhang K, Nunez-Bajo E, Barandun G, Cotur Y, Asfour T, Olenik S, Coatsworth P, Herrington J, and Güder F
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- Humans, Collodion, Electrodes, Biosensing Techniques
- Abstract
Rapid detection of pathogens at the point-of-need is crucial for preventing the spread of human, animal and plant diseases which can have devastating consequences both on the lives and livelihood of billions of people. Colorimetric, lateral flow assays consisting of a nitrocellulose membrane, are the preferred format today for low-cost on-site detection of pathogens. This assay format has, however, historically suffered from poor analytical performance and is not compatible with digital technologies. In this work, we report the development of a new class of digital diagnostics platform for precision point-of-need testing. This new versatile platform consists of two important innovations: i) A wireless and batteryless, microcontroller-based, low-cost Near Field Communication (NFC)-enabled potentiostat that brings high performance electroanalytical techniques (cyclic voltammetry, chronoamperometry, square wave voltammetry) to the field. The NFC-potentiostat can be operated with a mobile app by minimally trained users; ii) A new approach for producing nitrocellulose membranes with integrated electrodes that facilitate high performance electrochemical detection at the point-of-need. We produced an integrated system housed in a 3D-printed phone case and demonstrated its use for the detection of Maize Mosaic Virus (MMV), a plant pathogen, as a proof-of-concept application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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32. Myeloperoxidase Gene Deletion Causes Drastic Microbiome Shifts in Mice and Does Not Mitigate Dextran Sodium Sulphate-Induced Colitis.
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San Gabriel PT, O'Neil TR, Au A, Tan JK, Pinget GV, Liu Y, Fong G, Ku J, Glaros E, Macia L, Witting PK, Thomas SR, and Chami B
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- Animals, Mice, Feces microbiology, Gene Deletion, RNA, Ribosomal, 16S genetics, Mice, Inbred C57BL, Dextran Sulfate, Peroxidase metabolism, Peroxidase genetics, Colitis microbiology, Colitis chemically induced, Colitis genetics, Mice, Knockout, Gastrointestinal Microbiome, Disease Models, Animal
- Abstract
Neutrophil-myeloperoxidase (MPO) is a heme-containing peroxidase which produces excess amounts of hypochlorous acid during inflammation. While pharmacological MPO inhibition mitigates all indices of experimental colitis, no studies have corroborated the role of MPO using knockout (KO) models. Therefore, we investigated MPO deficient mice in a murine model of colitis. Wild type (Wt) and MPO-deficient mice were treated with dextran sodium sulphate (DSS) in a chronic model of experimental colitis with three acute cycles of DSS-induced colitis over 63 days, emulating IBD relapse and remission cycles. Mice were immunologically profiled at the gut muscoa and the faecal microbiome was assessed via 16S rRNA amplicon sequencing. Contrary to previous pharmacological antagonist studies targeting MPO, MPO-deficient mice showed no protection from experimental colitis during cyclical DSS-challenge. We are the first to report drastic faecal microbiota shifts in MPO-deficient mice, showing a significantly different microbiome profile on Day 1 of treatment, with a similar shift and distinction on Day 29 (half-way point), via qualitative and quantitative descriptions of phylogenetic distances. Herein, we provide the first evidence of substantial microbiome shifts in MPO-deficiency, which may influence disease progression. Our findings have significant implications for the utility of MPO-KO mice in investigating disease models.
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- 2024
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33. Breastfeeding is associated with enhanced intestinal gluconeogenesis in infants.
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Ni D, Tan J, Macia L, and Nanan R
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- Infant, Female, Animals, Humans, Gluconeogenesis, Mammals, Breast Feeding, Metabolic Syndrome
- Abstract
Background: Breastfeeding (BF) confers metabolic benefits to infants, including reducing risks of metabolic syndrome such as obesity and diabetes later in life. However, the underlying mechanism is not yet fully understood. Hence, we aim to investigate the impacts of BF on the metabolic organs of infants., Methods: Previous literatures directly studying the influences of BF on offspring's metabolic organs in both animal models and humans were comprehensively reviewed. A microarray dataset of intestinal gene expression comparing infants fed on breastmilk versus formula milk was analyzed., Results: Reanalysis of microarray data showed that BF is associated with enhanced intestinal gluconeogenesis in infants. This resembles observations in other mammalian species showing that BF was also linked to increased gluconeogenesis., Conclusions: BF is associated with enhanced intestinal gluconeogenesis in infants, which may underpin its metabolic advantages through finetuning metabolic homeostasis. This observation seems to be conserved across species, hinting its biological significance., (© 2024. The Author(s).)
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- 2024
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34. Time-resolved chemical monitoring of whole plant roots with printed electrochemical sensors and machine learning.
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Coatsworth P, Cotur Y, Naik A, Asfour T, Collins AS, Olenik S, Zhou Z, Gonzalez-Macia L, Chao DY, Bozkurt T, and Güder F
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- Plants, Machine Learning, Plant Roots, Hydrogen Peroxide, Metals
- Abstract
Traditional single-point measurements fail to capture dynamic chemical responses of plants, which are complex, nonequilibrium biological systems. We report TETRIS ( t ime-resolved e lectrochemical t echnology for plant r oot environment i n s itu chemical sensing), a real-time chemical phenotyping system for continuously monitoring chemical signals in the often-neglected plant root environment. TETRIS consisted of low-cost, highly scalable screen-printed electrochemical sensors for monitoring concentrations of salt, pH, and H
2 O2 in the root environment of whole plants, where multiplexing allowed for parallel sensing operation. TETRIS was used to measure ion uptake in tomato, kale, and rice and detected differences between nutrient and heavy metal ion uptake. Modulation of ion uptake with ion channel blocker LaCl3 was monitored by TETRIS and machine learning used to predict ion uptake. TETRIS has the potential to overcome the urgent "bottleneck" in high-throughput screening in producing high-yielding plant varieties with improved resistance against stress.- Published
- 2024
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35. Erratum: Proteomic pathways to metabolic disease and type 2 diabetes in the pancreatic islet.
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Yau B, Naghiloo S, Diaz-Vegas A, Carr AV, Van Gerwen J, Needham EJ, Jevon D, Chen SY, Hoehn KL, Brandon AE, Macia L, Cooney GJ, Shortreed MR, Smith LM, Keller MP, Thorn P, Larance M, James DE, Humphrey SJ, and Kebede MA
- Abstract
[This corrects the article DOI: 10.1016/j.isci.2021.103099.]., (© 2023 The Author(s).)
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- 2023
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36. Functional profiling of gut microbial and immune responses toward different types of dietary fiber: a step toward personalized dietary interventions.
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Tan J, Ribeiro RV, Barker C, Daien C, De Abreu Silveira E, Holmes A, Nanan R, Simpson SJ, and Macia L
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- Adult, Female, Humans, Bacteria genetics, Cross-Over Studies, Dietary Fiber analysis, Fatty Acids, Volatile pharmacology, Feces microbiology, Immunity, Leukocytes, Mononuclear, Oligosaccharides pharmacology, RNA, Ribosomal, 16S genetics, Longitudinal Studies, Gastrointestinal Microbiome, Inulin pharmacology
- Abstract
Dietary fiber plays a crucial role in maintaining gut and overall health. The objective of this study was to investigate whether different types of dietary fiber elicited specific changes in gut microbiota composition and the production of short-chain fatty acids. To test this, a longitudinal crossover study design was employed, in which healthy adult women consumed three distinct dietary fiber supplements: Inulin (fructo-oligosaccharide), Vitafiber (isomalto-oligosaccharide), and Fibremax (mixture of different fiber) during a one-week intervention period, followed by a 2-week washout period. A total of 15 g of soluble fiber was consumed daily for each supplement. Samples were collected before and after each intervention to analyze the composition of the gut microbiota by 16S rRNA sequencing and fecal levels of short-chain fatty acids measured using nuclear magnetic resonance. Phenotypic changes in peripheral blood mononuclear cells were studied in subsets of participants with higher SCFA levels post-intervention using spectral flow cytometry. The results revealed substantial stability and resilience of the overall gut bacterial community toward fiber-induced changes. However, each supplement had specific effects on gut bacterial alpha and beta diversity, SCFA production, and immune changes. Inulin consistently exerted the most pronounced effect across individuals and certain taxa were identified as potential indicators of SCFA production in response to inulin supplementation. This distinguishing feature was not observed for the other fiber supplements. Further large-scale studies are required to confirm these findings. Overall, our study implies that personalized dietary fiber intervention could be tailored to promote the growth of beneficial bacteria to maximize SCFA production and associated health benefits.
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- 2023
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37. Dysbiotic Gut Microbiota-Derived Metabolites and Their Role in Non-Communicable Diseases.
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Tan J, Taitz J, Nanan R, Grau G, and Macia L
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- Humans, Dysbiosis complications, Gastrointestinal Microbiome, Noncommunicable Diseases, Autoimmune Diseases complications, Neoplasms complications, Metabolic Diseases complications
- Abstract
Dysbiosis, generally defined as the disruption to gut microbiota composition or function, is observed in most diseases, including allergies, cancer, metabolic diseases, neurological disorders and diseases associated with autoimmunity. Dysbiosis is commonly associated with reduced levels of beneficial gut microbiota-derived metabolites such as short-chain fatty acids (SCFA) and indoles. Supplementation with these beneficial metabolites, or interventions to increase their microbial production, has been shown to ameliorate a variety of inflammatory diseases. Conversely, the production of gut 'dysbiotic' metabolites or by-products by the gut microbiota may contribute to disease development. This review summarizes the various 'dysbiotic' gut-derived products observed in cardiovascular diseases, cancer, inflammatory bowel disease, metabolic diseases including non-alcoholic steatohepatitis and autoimmune disorders such as multiple sclerosis. The increased production of dysbiotic gut microbial products, including trimethylamine, hydrogen sulphide, products of amino acid metabolism such as p-Cresyl sulphate and phenylacetic acid, and secondary bile acids such as deoxycholic acid, is commonly observed across multiple diseases. The simultaneous increased production of dysbiotic metabolites with the impaired production of beneficial metabolites, commonly associated with a modern lifestyle, may partially explain the high prevalence of inflammatory diseases in western countries.
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- 2023
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38. Determining the metabolic effects of dietary fat, sugars and fat-sugar interaction using nutritional geometry in a dietary challenge study with male mice.
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Wali JA, Ni D, Facey HJW, Dodgson T, Pulpitel TJ, Senior AM, Raubenheimer D, Macia L, and Simpson SJ
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- Humans, Male, Mice, Animals, Dietary Fats adverse effects, Diet adverse effects, Obesity metabolism, Glucose pharmacology, Fructose adverse effects, Sugars, Dietary Sucrose adverse effects
- Abstract
The metabolic effects of sugars and fat lie at the heart of the "carbohydrate vs fat" debate on the global obesity epidemic. Here, we use nutritional geometry to systematically investigate the interaction between dietary fat and the major monosaccharides, fructose and glucose, and their impact on body composition and metabolic health. Male mice (n = 245) are maintained on one of 18 isocaloric diets for 18-19 weeks and their metabolic status is assessed through in vivo procedures and by in vitro assays involving harvested tissue samples. We find that in the setting of low and medium dietary fat content, a 50:50 mixture of fructose and glucose (similar to high-fructose corn syrup) is more obesogenic and metabolically adverse than when either monosaccharide is consumed alone. With increasing dietary fat content, the effects of dietary sugar composition on metabolic status become less pronounced. Moreover, higher fat intake is more harmful for glucose tolerance and insulin sensitivity irrespective of the sugar mix consumed. The type of fat consumed (soy oil vs lard) does not modify these outcomes. Our work shows that both dietary fat and sugars can lead to adverse metabolic outcomes, depending on the dietary context. This study shows how the principles of the two seemingly conflicting models of obesity (the "energy balance model" and the "carbohydrate insulin model") can be valid, and it will help in progressing towards a unified model of obesity. The main limitations of this study include the use of male mice of a single strain, and not testing the metabolic effects of fructose intake via sugary drinks, which are strongly linked to human obesity., (© 2023. The Author(s).)
- Published
- 2023
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39. Temporal tracking of microglial and monocyte single-cell transcriptomics in lethal flavivirus infection.
- Author
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Spiteri AG, Wishart CL, Ni D, Viengkhou B, Macia L, Hofer MJ, and King NJC
- Subjects
- Animals, Mice, Monocytes, Transcriptome, Brain pathology, Microglia pathology, West Nile Fever pathology
- Abstract
As the resident parenchymal myeloid population in the central nervous system (CNS), microglia are strategically positioned to respond to neurotropic virus invasion and have been implicated in promoting both disease resolution and progression in the acute and post-infectious phase of virus encephalitis. In a mouse model of West Nile virus encephalitis (WNE), infection of the CNS results in recruitment of large numbers of peripheral immune cells into the brain, the majority being nitric oxide (NO)-producing Ly6C
hi inflammatory monocyte-derived cells (MCs). In this model, these cells enhance immunopathology and mortality. However, the contribution of microglia to this response is currently undefined. Here we used a combination of experimental tools, including single-cell RNA sequencing (scRNA-seq), microglia and MC depletion reagents, high-dimensional spectral cytometry and computational algorithms to dissect the differential contribution of microglia and MCs to the anti-viral immune response in severe neuroinflammation seen in WNE. Intriguingly, analysis of scRNA-seq data revealed 6 unique microglia and 3 unique MC clusters that were predominantly timepoint-specific, demonstrating substantial transcriptional adaptation with disease progression over the course of WNE. While microglia and MC adopted unique gene expression profiles, gene ontology enrichment analysis, coupled with microglia and MC depletion studies, demonstrated a role for both of these cells in the trafficking of peripheral immune cells into the CNS, T cell responses and viral clearance. Over the course of infection, microglia transitioned from a homeostatic to an anti-viral and then into an immune cell-recruiting phenotype. Conversely, MC adopted antigen-presenting, immune cell-recruiting and NO-producing phenotypes, which all had anti-viral function. Overall, this study defines for the first time the single-cell transcriptomic responses of microglia and MCs over the course of WNE, demonstrating both protective and pathological roles of these cells that could potentially be targeted for differential therapeutic intervention to dampen immune-mediated pathology, while maintaining viral clearance functions., (© 2023. The Author(s).)- Published
- 2023
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40. Editorial: Deciphering host-gut microbiota communication in immunity and disease.
- Author
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Tan J, Navarro S, and Macia L
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- Published
- 2023
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41. Diet-driven microbial ecology underpins associations between cancer immunotherapy outcomes and the gut microbiome.
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Simpson RC, Shanahan ER, Batten M, Reijers ILM, Read M, Silva IP, Versluis JM, Ribeiro R, Angelatos AS, Tan J, Adhikari C, Menzies AM, Saw RPM, Gonzalez M, Shannon KF, Spillane AJ, Velickovic R, Lazar AJ, Damania AV, Mishra AK, Chelvanambi M, Banerjee A, Ajami NJ, Wargo JA, Macia L, Holmes AJ, Wilmott JS, Blank CU, Scolyer RA, and Long GV
- Subjects
- Humans, Prospective Studies, Immunotherapy adverse effects, Diet, Gastrointestinal Microbiome physiology, Melanoma therapy
- Abstract
The gut microbiota shapes the response to immune checkpoint inhibitors (ICIs) in cancer, however dietary and geographic influences have not been well-studied in prospective trials. To address this, we prospectively profiled baseline gut (fecal) microbiota signatures and dietary patterns of 103 trial patients from Australia and the Netherlands treated with neoadjuvant ICIs for high risk resectable metastatic melanoma and performed an integrated analysis with data from 115 patients with melanoma treated with ICIs in the United States. We observed geographically distinct microbial signatures of response and immune-related adverse events (irAEs). Overall, response rates were higher in Ruminococcaceae-dominated microbiomes than in Bacteroidaceae-dominated microbiomes. Poor response was associated with lower fiber and omega 3 fatty acid consumption and elevated levels of C-reactive protein in the peripheral circulation at baseline. Together, these data provide insight into the relevance of native gut microbiota signatures, dietary intake and systemic inflammation in shaping the response to and toxicity from ICIs, prompting the need for further studies in this area., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2022
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42. Dysbiosis in imiquimod-induced psoriasis alters gut immunity and exacerbates colitis development.
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Pinget GV, Tan JK, Ni D, Taitz J, Daien CI, Mielle J, Moore RJ, Stanley D, Simpson S, King NJC, and Macia L
- Subjects
- Animals, Colon microbiology, Dextran Sulfate, Disease Models, Animal, Dysbiosis complications, Imiquimod adverse effects, Mice, Mice, Inbred C57BL, Colitis, Inflammatory Bowel Diseases etiology, Psoriasis chemically induced
- Abstract
Psoriasis has long been associated with inflammatory bowel disease (IBD); however, a causal link is yet to be established. Here, we demonstrate that imiquimod-induced psoriasis (IMQ-pso) in mice disrupts gut homeostasis, characterized by increased proportions of colonic CX
3 CR1 hi macrophages, altered cytokine production, and bacterial dysbiosis. Gut microbiota from these mice produce higher levels of succinate, which induce de novo proliferation of CX3 CR1 hi macrophages ex vivo, while disrupted gut homeostasis primes IMQ-pso mice for more severe colitis with dextran sulfate sodium (DSS) challenge. These results demonstrate that changes in the gut environment in psoriasis lead to greater susceptibility to IBD in mice, suggesting a two-hit requirement, that is, psoriasis-induced altered gut homeostasis and a secondary environmental challenge. This may explain the increased prevalence of IBD in patients with psoriasis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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43. Rheumatoid arthritis is associated with increased gut permeability and bacterial translocation which are reversed by inflammation control.
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Audo R, Sanchez P, Rivière B, Mielle J, Tan J, Lukas C, Macia L, Morel J, and Immediato Daien C
- Abstract
Objective: to assess how rheumatoid arthritis (RA) and Disease Modifying Anti Rheumatic Drugs (DMARDs) affect gut permeability., Methods: to explore colonic mucosa integrity, tight junction proteins ZO-1, occludin and claudin 2 were quantified by immunohistochemistry on colonic biopsies in 20 RA patients and 20 age- and sex-matched controls. Staining intensity was assessed by two blinded independent readers. To explore intestinal permeability, serum concentrations of LPS-binding protein (LBP), sCD14 and zonulin-related proteins (ZRP) were evaluated by ELISA in another cohort of 59 RA: 21 patients naive of DMARDs (17 before and after introduction of a conventional synthetic (cs) DMARDs), 38 patients with severe RA (before and after introduction of a biological (b) DMARDs), and 33 healthy controls., Results: Z0-1 protein was less expressed in colon of RA patients than controls (mean score ± SEM of 1.6 ± 0.56 vs 2.0 ± 0.43; p= 0.01), while no significant difference was detected for occludin and claudin-2. RA patients had higher serum LBP and sCD14 concentrations than controls. LBP and sCD14 levels were significantly correlated with DAS28 (r = 0.61, p= 0.005 and r = 0.57, p= 0.01, respectively) while ZRP did not. bDMARD responders had significantly reduced LBP and sCD14 concentrations unlike bDMARDs non-responders and patients treated with csDMARDs., Conclusion: RA patients have altered colonic tight junction proteins and increased serum biomarkers of intestinal permeability. There was a correlation between serological markers of intestinal permeability and disease activity as well as bDMARD response. These results suggest a link between impaired gut integrity and systemic inflammation in RA., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2022
- Full Text
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44. Dietary protein increases T-cell-independent sIgA production through changes in gut microbiota-derived extracellular vesicles.
- Author
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Tan J, Ni D, Taitz J, Pinget GV, Read M, Senior A, Wali JA, Elnour R, Shanahan E, Wu H, Chadban SJ, Nanan R, King NJC, Grau GE, Simpson SJ, and Macia L
- Subjects
- Animals, Dietary Proteins, Immunoglobulin A, Secretory metabolism, Mice, T-Lymphocytes metabolism, Extracellular Vesicles metabolism, Gastrointestinal Microbiome
- Abstract
Secretory IgA is a key mucosal component ensuring host-microbiota mutualism. Here we use nutritional geometry modelling in mice fed 10 different macronutrient-defined, isocaloric diets, and identify dietary protein as the major driver of secretory IgA production. Protein-driven secretory IgA induction is not mediated by T-cell-dependent pathways or changes in gut microbiota composition. Instead, the microbiota of high protein fed mice produces significantly higher quantities of extracellular vesicles, compared to those of mice fed high-carbohydrate or high-fat diets. These extracellular vesicles activate Toll-like receptor 4 to increase the epithelial expression of IgA-inducing cytokine, APRIL, B cell chemokine, CCL28, and the IgA transporter, PIGR. We show that succinate, produced in high concentrations by microbiota of high protein fed animals, increases generation of reactive oxygen species by bacteria, which in turn promotes extracellular vesicles production. Here we establish a link between dietary macronutrient composition, gut microbial extracellular vesicles release and host secretory IgA response., (© 2022. Crown.)
- Published
- 2022
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45. CXCR5/CXCL13 pathway, a key driver for migration of regulatory B10 cells, is defective in patients with rheumatoid arthritis.
- Author
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Rempenault C, Mielle J, Schreiber K, Corbeau P, Macia L, Combe B, Morel J, Daien CI, and Audo R
- Subjects
- Chemokine CXCL13 metabolism, Humans, Interleukin-10, Receptors, CXCR5, Synovial Fluid metabolism, Arthritis, Rheumatoid metabolism, B-Lymphocytes, Regulatory
- Abstract
Objectives: Chemokines (CKs) are key players of immune-cell homing and differentiation. CK receptors (CKRs) can be used to define T-cell functional subsets. We aimed to characterize the CKR profile of the regulatory B-cell subset B10+ cells and investigate the CKs involved in their migration and differentiation in healthy donors and patients with RA., Methods: RNA sequencing and cytometry were used to compare CKR expression between B10+ and B10neg cells. Migration of B10+ and B10neg cells and IL-10 secretion of B cells in response to recombinant CKs or synovial fluid (SF) were assessed., Results: CXCR5 was expressed at a higher level on the B10+ cell surface as compared with other B cells (referred to as B10neg cells). In line with this, its ligand CXCL13 preferentially attracted B10+ cells over B10neg cells. Interestingly, synovial fluid from RA patients contained high levels of CXCL13 and induced strong and preferential migration of B10+ cells. Besides its role in attracting B10+ cells, CXCL13 also promoted IL-10 secretion by B cells. In RA patients, the level of CXCR5 on B-cell surface was reduced. The preferential migration of RA B10+ cells toward CXCL13-rich SF was lost and CXCL13 stimulation triggered less IL-10 secretion than in healthy donors., Conclusion: Our results identify that the CXCR5/CXCL13 axis is essential for B10+ cell biology but is defective in RA. Restoring the preferential migration of B10+ within the affected joints to better control inflammation may be part of the therapeutic approach for RA., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2022
- Full Text
- View/download PDF
46. Multiplexed immunosensors for point-of-care diagnostic applications.
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Gil Rosa B, Akingbade OE, Guo X, Gonzalez-Macia L, Crone MA, Cameron LP, Freemont P, Choy KL, Güder F, Yeatman E, Sharp DJ, and Li B
- Subjects
- Immunoassay methods, Point-of-Care Systems, Point-of-Care Testing, Reproducibility of Results, Biosensing Techniques, Electrochemical Techniques methods
- Abstract
Accurate, reliable, and cost-effective immunosensors are clinically important for the early diagnosis and monitoring of progressive diseases, and multiplexed sensing is a promising strategy for the next generation of diagnostics. This strategy allows for the simultaneous detection and quantification of multiple biomarkers with significantly enhanced reproducibility and reliability, whilst requiring smaller sample volumes, fewer materials, and shorter average analysis time for individual biomarkers than individual tests. In this opinionated review, we compare different techniques for the development of multiplexed immunosensors. We review the state-of-the-art approaches in the field of multiplexed immunosensors using electrical, electrochemical, and optical methods. The barriers that prevent translating this sensing strategy into clinics are outlined together with the potential solutions. We also share our vision on how multiplexed immunosensors will continue their evolution in the coming years., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2022
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47. Your Regulatory T Cells Are What You Eat: How Diet and Gut Microbiota Affect Regulatory T Cell Development.
- Author
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Tan J, Taitz J, Sun SM, Langford L, Ni D, and Macia L
- Abstract
Modern industrial practices have transformed the human diet over the last century, increasing the consumption of processed foods. Dietary imbalance of macro- and micro-nutrients and excessive caloric intake represent significant risk factors for various inflammatory disorders. Increased ingestion of food additives, residual contaminants from agricultural practices, food processing, and packaging can also contribute deleteriously to disease development. One common hallmark of inflammatory disorders, such as autoimmunity and allergies, is the defect in anti-inflammatory regulatory T cell (Treg) development and/or function. Treg represent a highly heterogeneous population of immunosuppressive immune cells contributing to peripheral tolerance. Tregs either develop in the thymus from autoreactive thymocytes, or in the periphery, from naïve CD4
+ T cells, in response to environmental antigens and cues. Accumulating evidence demonstrates that various dietary factors can directly regulate Treg development. These dietary factors can also indirectly modulate Treg differentiation by altering the gut microbiota composition and thus the production of bacterial metabolites. This review provides an overview of Treg ontogeny, both thymic and peripherally differentiated, and highlights how diet and gut microbiota can regulate Treg development and function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tan, Taitz, Sun, Langford, Ni and Macia.)- Published
- 2022
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48. PLX5622 Reduces Disease Severity in Lethal CNS Infection by Off-Target Inhibition of Peripheral Inflammatory Monocyte Production.
- Author
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Spiteri AG, Ni D, Ling ZL, Macia L, Campbell IL, Hofer MJ, and King NJC
- Subjects
- Animals, Mice, Microglia, Organic Chemicals, Receptors, Colony-Stimulating Factor metabolism, Severity of Illness Index, Monocytes, West Nile Fever
- Abstract
PLX5622 is a CSF-1R inhibitor and microglia-depleting reagent, widely used to investigate the biology of this central nervous system (CNS)-resident myeloid population, but the indirect or off-target effects of this agent remain largely unexplored. In a murine model of severe neuroinflammation induced by West Nile virus encephalitis (WNE), we showed PLX5622 efficiently depleted both microglia and a sub-population of border-associated macrophages in the CNS. However, PLX5622 also significantly depleted mature Ly6C
hi monocytes in the bone marrow (BM), inhibiting their proliferation and lethal recruitment into the infected brain, reducing neuroinflammation and clinical disease scores. Notably, in addition, BM dendritic cell subsets, plasmacytoid DC and classical DC, were depleted differentially in infected and uninfected mice. Confirming its protective effect in WNE, cessation of PLX5622 treatment exacerbated disease scores and was associated with robust repopulation of microglia, rebound BM monopoiesis and markedly increased inflammatory monocyte infiltration into the CNS. Monoclonal anti-CSF-1R antibody blockade late in WNE also impeded BM monocyte proliferation and recruitment to the brain, suggesting that the protective effect of PLX5622 is via the inhibition of CSF-1R, rather than other kinase targets. Importantly, BrdU incorporation in PLX5622-treated mice, suggest remaining microglia proliferate independently of CSF-1 in WNE. Our study uncovers significantly broader effects of PLX5622 on the myeloid lineage beyond microglia depletion, advising caution in the interpretation of PLX5622 data as microglia-specific. However, this work also strikingly demonstrates the unexpected therapeutic potential of this molecule in CNS viral infection, as well as other monocyte-mediated diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Spiteri, Ni, Ling, Macia, Campbell, Hofer and King.)- Published
- 2022
- Full Text
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49. Impact of Dietary Fiber on West Nile Virus Infection.
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Ni D, Tan J, Niewold P, Spiteri AG, Pinget GV, Stanley D, King NJC, and Macia L
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- Animals, Brain metabolism, Cytokines metabolism, Dietary Fiber, Mice, West Nile Fever, West Nile virus physiology
- Abstract
Dietary fiber supports healthy gut bacteria and their production of short-chain fatty acids (SCFA), which promote anti-inflammatory cell development, in particular, regulatory T cells. It is thus beneficial in many diseases, including influenza infection. While disruption of the gut microbiota by antibiotic treatment aggravates West Nile Virus (WNV) disease, whether dietary fiber is beneficial is unknown. WNV is a widely-distributed neurotropic flavivirus that recruits inflammatory monocytes into the brain, causing life-threatening encephalitis. To investigate the impact of dietary fiber on WNV encephalitis, mice were fed on diets deficient or enriched with dietary fiber for two weeks prior to inoculation with WNV. To induce encephalitis, mice were inoculated intranasally with WNV and maintained on these diets. Despite increased fecal SCFA acetate and changes in gut microbiota composition, dietary fiber did not affect clinical scores, leukocyte infiltration into the brain, or survival. After the brain, highest virus loads were measured in the colon in neurons of the submucosal and myenteric plexuses. Associated with this, there was disrupted gut homeostasis, with shorter colon length and higher local inflammatory cytokine levels, which were not affected by dietary fiber. Thus, fiber supplementation is not effective in WNV encephalitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ni, Tan, Niewold, Spiteri, Pinget, Stanley, King and Macia.)
- Published
- 2022
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50. Community health workers promote perceived social support among Latino men: Respaldo .
- Author
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Ruiz-Sánchez HC, Macia L, Boyzo R, and Documet PI
- Abstract
Promotores or community health workers are trusted community members who offer information and support to marginalized groups in society. Latinx immigrants in new growth communities or emerging communities (areas with a small yet growing Latinx population) confront many challenges in their settling processes. De la Mano con la Salud was a community-based participatory project that trained Latino immigrant men as promotores. Promotores recruited 182 Latino immigrant men helped them to attain their own goals, connected them with health and social services and connected them to the larger community. We present data from 23 in-depth interviews with project participants conducted after six months of enrollment. Qualitative analysis confirmed participants' vulnerabilities and showed that promotores addressed many of the health, legal, and occupational needs of participants. Emerging themes showed that 1) participants had a thirst for a united Latinx community; and 2) felt that promotores had their back ( respaldo ). The need for community may reflect the current invisibility of this Latinx population, as well as the desires for recognition and ethnic identity affirmation. Respaldo strongly resembles perceived social support, which is the kind of support most associated with health outcomes. Future research can determine what intervention components best foster respaldo ., Competing Interests: None., (© 2021 The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
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