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1.
PLoS One ; 18(8): e0289472, 2023.
Article in English | MEDLINE | ID: mdl-37531359

ABSTRACT

In recent years, insufficiently characterised controls have been a contributing factor to irreproducibility in biomedical research including neuroscience and metabolism. There is now a growing awareness of phenotypic differences between the C57BL/6 substrains which are commonly used as control animals. We here investigated baseline metabolic characteristics such as glucose regulation, fasted serum insulin levels and hepatic insulin signalling in five different C57BL/6 substrains (N, J, JOla, JRcc) of both sexes, obtained from two commercial vendors, Charles River Laboratories (Crl) and Envigo (Env). Our results indicate systematic and tissue-specific differences between substrains, affected by both vendor and sex, in all parameters investigated, and not necessarily mediated by the presence of the NntC57BL/6J mutation. Not only were there differences between 6J and 6N as expected, all three 6J substrains exhibited different profiles, even from the same breeder. Two distinct metabolic profiles were identified, one in which low insulin levels resulted in impaired glucose clearance (6JCrl; both sexes) and the other, where sustained elevations in fasted basal insulin levels led to glucose intolerance (male 6JRccEnv). Further, 6JRccEnv displayed sex differences in both glucose clearance and hepatic insulin signalling markers. In comparison, the two 6N substrains of either sex, irrespective of vendor, did not exhibit considerable differences, with 6NCrl animals presenting a good choice as a healthy baseline 'control' for many types of experiments. Overall, our data emphasise the importance of selecting and characterising control subjects regarding background, sex, and supplier to ensure proper experimental outcomes in biomedical research.


Subject(s)
Glucose , Insulin , Animals , Male , Female , Mice , Phenotype , Insulin/genetics , Mice, Inbred C57BL
2.
Einstein (Sao Paulo) ; 19: eRW5772, 2021.
Article in English, Portuguese | MEDLINE | ID: mdl-33729289

ABSTRACT

Ground-glass opacity is a very frequent and unspecified finding in chest computed tomography. Therefore, it admits a wide range of differential diagnoses in the acute context, from viral pneumonias such as influenza virus, coronavirus disease 2019 and cytomegalovirus and even non-infectious lesions, such as vaping, pulmonary infarction, alveolar hemorrhage and pulmonary edema. For this diagnostic differentiation, ground glass must be correlated with other findings in imaging tests, with laboratory tests and with the patients' clinical condition. In the context of a pandemic, it is extremely important to remember the other pathologies with similar findings to coronavirus disease 2019 in the imaging exams.


Subject(s)
COVID-19/diagnostic imaging , Lung Diseases/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Cytomegalovirus Infections/diagnostic imaging , Diagnosis, Differential , Humans , Influenza, Human/diagnostic imaging , Pneumonia, Viral/classification , Tomography, X-Ray Computed
3.
Proc Nutr Soc ; 80(2): 126-138, 2021 05.
Article in English | MEDLINE | ID: mdl-33138875

ABSTRACT

Life expectancy in most developed countries has been rising over the past century. In the UK alone, there are about 12 million people over 65 years old and centenarians have increased by 85% in the past 15 years. As a result of the ageing population, which is due mainly to improvements in medical treatments, public health, improved housing and lifestyle choices, there is an associated increase in the prevalence of pathological conditions, such as metabolic disorders, type 2 diabetes, cardiovascular and neurodegenerative diseases, many types of cancer and others. Statistics suggest that nearly 54% of elderly people in the UK live with at least two chronic conditions, revealing the urgency for identifying interventions that can prevent and/or treat such disorders. Non-pharmacological, dietary interventions such as energetic restriction (ER) and methionine restriction (MR) have revealed promising outcomes in increasing longevity and preventing and/or reversing the development of ageing-associated disorders. In this review, we discuss the evidence and mechanisms that are involved in these processes. Fibroblast growth factor 1 and hydrogen sulphide are important molecules involved in the effects of ER and MR in the extension of life span. Their role is also associated with the prevention of metabolic and cognitive disorders, highlighting these interventions as promising modulators for improvement of health span.


Subject(s)
Diabetes Mellitus, Type 2 , Aged , Aged, 80 and over , Aging , Cognition , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/prevention & control , Humans , Life Expectancy , Longevity
4.
Einstein (Säo Paulo) ; 19: eRW5772, 2021. graf
Article in English | LILACS | ID: biblio-1154099

ABSTRACT

ABSTRACT Ground-glass opacity is a very frequent and unspecified finding in chest computed tomography. Therefore, it admits a wide range of differential diagnoses in the acute context, from viral pneumonias such as influenza virus, coronavirus disease 2019 and cytomegalovirus and even non-infectious lesions, such as vaping, pulmonary infarction, alveolar hemorrhage and pulmonary edema. For this diagnostic differentiation, ground glass must be correlated with other findings in imaging tests, with laboratory tests and with the patients' clinical condition. In the context of a pandemic, it is extremely important to remember the other pathologies with similar findings to coronavirus disease 2019 in the imaging exams.


RESUMO A opacidade em vidro fosco é uma alteração muito frequente e pouco específica na tomografia computadorizada de tórax. Ela admite grande leque de diagnósticos diferenciais no contexto agudo, desde pneumonias virais, como as causadas pelo vírus influenza, pela doença do coronavírus 2019 e pelo citomegalovírus, até mesmo lesões de origem não infecciosa, como vaping , infarto pulmonar, hemorragia alveolar e edema pulmonar. Para essa diferenciação diagnóstica, deve-se correlacionar o vidro fosco com os demais achados nos exames de imagem, exames laboratoriais e quadro clínico do paciente. É de suma importância, no contexto de pandemia, recordar as demais patologias com os achados semelhantes aos da doença do coronavírus 2019 nos exames de imagem.


Subject(s)
Humans , Pneumonia, Viral/diagnostic imaging , COVID-19/diagnostic imaging , Lung Diseases/diagnostic imaging , Pneumonia, Viral/classification , Tomography, X-Ray Computed , Cytomegalovirus Infections/diagnostic imaging , Diagnosis, Differential , Influenza, Human/diagnostic imaging
8.
Einstein (Sao Paulo) ; 18: eRW5741, 2020.
Article in English, Portuguese | MEDLINE | ID: mdl-32578687

ABSTRACT

The disease caused by the new coronavirus, or COVID-19, has been recently described and became a health issue worldwide. Its diagnosis of certainty is given by polymerase chain reaction. High-resolution computed tomography, however, is useful in the current context of pandemic, especially for the most severe cases, in assessing disease extent, possible differential diagnoses and searching complications. In patients with suspected clinical symptoms and typical imaging findings, in which there is still no laboratory test result, or polymerase chain reaction is not available, the role of this test is still discussed. In addition, it is important to note that part of the patients present false-negative laboratory tests, especially in initial cases, which can delay isolation, favoring the spread of the disease. Thus, knowledge about the COVID-19 and its imaging manifestations is extremely relevant for all physicians involved in the patient care, clinicians or radiologists.


Subject(s)
Coronavirus Infections/diagnostic imaging , Lung/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Thorax/diagnostic imaging , Tomography, X-Ray Computed , Betacoronavirus , COVID-19 , Diagnosis, Differential , Humans , Lymphadenopathy/diagnostic imaging , Pandemics , Pleural Effusion/diagnostic imaging , SARS-CoV-2
9.
Front Immunol ; 11: 128, 2020.
Article in English | MEDLINE | ID: mdl-32153562

ABSTRACT

There are several unmet needs in modern immunology. Among them, vaccines against parasitic diseases and chronic infections lead. Trypanosoma cruzi, the causative agent of Chagas disease, is an excellent example of a silent parasitic invasion that affects millions of people worldwide due to its progression into the symptomatic chronic phase of infection. In search for novel vaccine candidates, we have previously introduced Traspain, an engineered trivalent immunogen that was designed to address some of the known mechanisms of T. cruzi immune evasion. Here, we analyzed its performance in different DNA prime/protein boost protocols and characterized the systemic immune response associated with diverse levels of protection. Formulations that include a STING agonist, like c-di-AMP in the boost doses, were able to prime a Th1/Th17 immune response. Moreover, comparison between them showed that vaccines that were able to prime polyfunctional cell-mediated immunity at the CD4 and CD8 compartment enhanced protection levels in the murine model. These findings contribute to a better knowledge of the desired vaccine-elicited immunity against T. cruzi and promote the definition of a vaccine correlate of protection against the infection.


Subject(s)
Immunity/immunology , Protozoan Vaccines/immunology , Trypanosoma cruzi/immunology , Vaccination/methods , Animals , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes/immunology , Cytokines/metabolism , Female , Immunization, Secondary , Male , Mice , Models, Animal , Treatment Outcome
11.
Einstein (Säo Paulo) ; 18: eRW5741, 2020. graf
Article in English | LILACS | ID: biblio-1133785

ABSTRACT

ABSTRACT The disease caused by the new coronavirus, or COVID-19, has been recently described and became a health issue worldwide. Its diagnosis of certainty is given by polymerase chain reaction. High-resolution computed tomography, however, is useful in the current context of pandemic, especially for the most severe cases, in assessing disease extent, possible differential diagnoses and searching complications. In patients with suspected clinical symptoms and typical imaging findings, in which there is still no laboratory test result, or polymerase chain reaction is not available, the role of this test is still discussed. In addition, it is important to note that part of the patients present false-negative laboratory tests, especially in initial cases, which can delay isolation, favoring the spread of the disease. Thus, knowledge about the COVID-19 and its imaging manifestations is extremely relevant for all physicians involved in the patient care, clinicians or radiologists.


RESUMO A doença causada pelo novo coronavírus, ou COVID-19, foi descrita recentemente e tornou-se uma questão de saúde mundial. Seu diagnóstico de certeza é dado pela reação em cadeia da polimerase. A tomografia computadorizada de alta resolução, entretanto, mostra-se útil no contexto atual de pandemia, especialmente nos casos mais graves, na avaliação da extensão da doença, em possíveis diagnósticos diferenciais e na pesquisa de complicações. Em pacientes com quadro clínico suspeito e achados de imagem típicos, nos quais ainda não há resultado laboratorial ou a reação em cadeia da polimerase não se encontra disponível, ainda se discute o papel desse exame. Importante ressaltar que parte dos pacientes apresenta exames laboratoriais falsos-negativos, notadamente em casos iniciais, o que pode retardar medidas de isolamento, favorecendo a propagação da doença. Dessa forma, o conhecimento da COVID-19 e de suas manifestações nos exames de imagem é de extrema importância para os médicos envolvidos no atendimento, sejam clínicos ou radiologistas.


Subject(s)
Humans , Pneumonia, Viral/diagnostic imaging , Thorax/diagnostic imaging , Tomography, X-Ray Computed , Coronavirus Infections/diagnostic imaging , Lung/diagnostic imaging , Pleural Effusion/diagnostic imaging , Diagnosis, Differential , Pandemics , Lymphadenopathy/diagnostic imaging , Betacoronavirus , SARS-CoV-2 , COVID-19
12.
Estud. Interdiscip. Psicol ; 10(3): 160-180, dez. 2019.
Article in Portuguese | LILACS | ID: biblio-1123678

ABSTRACT

A regulação emocional em intervenções psicoterapêuticas pode ser eficaz para lidar com situações, como o desconforto, não permitindo que o estado emocional afete a qualidade dos atendimentos. O intuito deste estudo é abordar o estado emocional dos psicoterapeutas em situações intensas do trabalho clínico. Para isso, recorreu-se à pesquisa de cunho descritivo e exploratório, em dados qualitativos. Foram realizadas cinco entrevistas, seguindo um roteiro de entrevistas semiestruturadas com perguntas abertas. Na sequência, o material foi transcrito e submetido à análise de conteúdo de Bardin (1977). Apesar de a regulação emocional fazer parte da rotina dos entrevistados, o uso das estratégias advém das experiências do cotidiano e, em menor proporção, das aprendizagens de formação. Considera-se que ampliar a compreensão do impacto da regulação emocional na prática clínica é necessário para a criação de estratégias de enfrentamento que cuidem da saúde mental do psicoterapeuta e do usuário do serviço (AU).


The Emotional regulation in psychotherapeutic interventions can be effective in dealing with situations such as discomfort, not allowing the emotional status to affect the quality of care. The intention of this study is to address the emotional status of the psychotherapists in intense clinical work situations. To do so, we use a research of descriptive and exploratory nature, in qualitative data. Five interviews were conducted, following a script of semi-structured interviews with open questions. Consequently, the material was transcribed and subjected to the content analysis of Bardin (1977). Although emotional regulation is part of the routine of interviewees, the use of strategies comes from everyday experiences and, in a smaller scale, from learning experiences. It is considered that broadening the understanding of the impact of emotional regulation in clinical practice is necessary for the creation of confrontation strategies that take care of the mental health of the psychotherapist and the service user (AU).


La regulación emocional en intervenciones psicoterapéuticas puede ser eficaz para lidiar con situaciones como la incomodidad, no permitiendo que el estado emocional afecte la calidad de las atenciones. La intención de este estudio es abordar el estado emocional de los psicoterapeutas en situaciones intensas del trabajo clínico. Para ello, se recurrió a la investigación de naturaleza descriptiva y exploratoria, en datos cualitativos. Se realizaron cinco entrevistas, siguiendo un guión de entrevistas semiestructuradas con preguntas abiertas. En consecuencia, el material fue transcrito y sometido al análisis de contenido de Bardin (1977). A pesar de que la regulación emocional forma parte de la rutina de los entrevistados, el uso de las estrategias proviene de las experiencias de lo cotidiano y, en menor proporción, de los aprendizajes de formación. Se considera que ampliar la comprensión del impacto de la regulación emocional en la práctica clínica es necesario para la creación de estrategias de enfrentamiento que cuidan la salud mental del psicoterapeuta y del usuario del servicio (AU).


Subject(s)
Psychotherapy , Emotional Adjustment , Professional Practice
13.
Materials (Basel) ; 12(14)2019 Jul 23.
Article in English | MEDLINE | ID: mdl-31340461

ABSTRACT

The worldwide regulatory demand for the elimination of non-phthalate compounds for poly(vinyl chloride) (PVC) plasticization has intensified the search for alternatives. Concomitantly, sustainability concerns have highlighted sugar-based 2,5-furandicarboxylic acid as one key renewable-chemical for the development of several products, namely di(2-ethylhexyl) 2,5-furandicarboxylate (DEHF) plasticizer. This study addresses the use of DEHF under a realistic scenario of the co-existence of both DEHF and entirely fossil-based plasticizers. More precisely, original PVC blends using mixtures of non-toxic DEHF and di(2-ethylhexyl) terephthalate ester (DEHT) were designed. The detailed structural, thermal, and mechanical characterization of these materials showed that they all have a set of interesting properties that are compatible with those of commercial DEHT, namely a low glass transition (19.2-23.8 °C) and enhanced elongation at break (up to 330%). Importantly, migration tests under different daily situations, such as for example exudation from food/beverages packages and medical blood bags, reveal very low weight loss percentages. For example, in both distilled water and phosphate buffered saline (PBS) solution, weight loss does not exceed ca. 0.3% and 0.2%, respectively. Viability tests show, for the first time, that up to 500 µM of DEHF, a promising cytotoxic profile is observed, as well as for DEHT. Overall, this study demonstrates that the combination of DEHF and DEHT plasticizers result in a noticeable plasticized PVC with an increased green content with promising cytotoxic results.

14.
Materials (Basel) ; 12(2)2019 Jan 21.
Article in English | MEDLINE | ID: mdl-30669649

ABSTRACT

Poly(ether ester)s (PEEs) represent a promising class of segmented co-polymers, nevertheless the synthesis of PEEs based on renewable 2,5-furandicarboxylic acid (FDCA) is still scarce. In this context, a series of poly(1,4-butylene 2,5-furandicarboxylate)-co-poly(poly(propylene oxide) 2,5-furandicarboxylate) co-polyesters with different composition of stiff poly(1,4-butylene 2,5-furandicarboxylate) (PBF) and soft poly(poly(propylene oxide) 2,5-furandicarboxylate) (PPOF) moieties were synthesized, via a two-step bulk polytransesterification reaction. The molar ratio of PBF/PPOF incorporated was varied (10 to 50 mol%) in order to prepare several novel materials with tuned properties. The materials were characterised in detail through several techniques, namely ATR FTIR, ¹H and 13C NMR, TGA, DSC, DMTA and XRD. Their hydrolytic and enzymatic degradation evaluation was also assessed. These new co-polymers showed either a semi-crystalline nature when higher PBF/PPOF ratios were used, and for approximately equal amounts of PBF and PPOF an amorphous co-polyester was obtained instead.

15.
Exp Physiol ; 104(4): 514-528, 2019 04.
Article in English | MEDLINE | ID: mdl-30653762

ABSTRACT

NEW FINDINGS: What is the central question of this study? Does glucocorticoid excess disrupt brown adipose tissue (BAT) phenotype and function? What is the main finding and its importance? Glucocorticoid excess induced an extensive remodelling of interscapular BAT, resulting in a white-like phenotype in association with metabolic disturbances. Glucocorticoids might be an important modulator of BAT physiology and BAT may have a role in pathophysiology of metabolic disturbances induced by glucocorticoid excess. ABSTRACT: In mammals, brown adipose tissue (BAT) is centrally involved in energy metabolism. To test the hypothesis that glucocorticoid excess disrupts BAT phenotype and function, male Wistar rats were treated with corticosterone in drinking water for 21 days. To confirm induction of glucocorticoid excess and metabolic disturbances, adrenal weight, corticotrophin releasing hormone mRNA levels and corticosterone serum levels were measured and a glucose tolerance test and serum triacylglycerol analyses were performed. Adipose tissue deposits were excised, weighed and evaluated by a set of biochemical, histological and molecular procedures, including thin-layer chromatography, histochemistry, immunohistochemistry, quantitative real-time polymerase chain reaction, high-resolution oxygraphy, ATP synthesis and enzymatic activity measurements. The approach was successful in induction of glucocorticoid excess and metabolic disturbances. Lower body weight and increased adiposity were observed in corticosterone-treated rats. Interscapular brown adipose tissue (iBAT) showed higher sensitivity to glucocorticoids than other fat deposits. The treatment induced lipid accumulation, unilocular rearrangement, increased collagen content and decreased innervation in iBAT. Furthermore, expression of Prdm16 (P < 0.05), Ucp1 (P <0.05) and Slc7a10 (P <0.05) mRNA decreased, while expression of Fasn (P <0.05) and Lep (P <0.05) mRNA increased in brown adipose tissue. Also, the levels of UCP1 diminished (P <0.001, 2.5-fold). Finally, lower oxygen consumption (P <0.05), ATP synthesis (P <0.05) and mitochondrial content (P <0.05) were observed in iBAT of glucocorticoid-treated rats. Glucocorticoid excess induced an extensive remodelling of interscapular brown adipose tissue, resulting in a white-like phenotype in association with metabolic disturbances.


Subject(s)
Adipose Tissue, Brown/drug effects , Corticosterone/pharmacology , Adipose Tissue, Brown/metabolism , Adiposity/drug effects , Animals , Energy Metabolism/drug effects , Glucocorticoids/metabolism , Glucose Tolerance Test/methods , Male , Membrane Proteins/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondrial Proteins/metabolism , RNA, Messenger/metabolism , Rats , Rats, Wistar , Transcription Factors/metabolism , Uncoupling Protein 1/metabolism
16.
PLoS Negl Trop Dis ; 12(3): e0006384, 2018 03.
Article in English | MEDLINE | ID: mdl-29601585

ABSTRACT

BACKGROUND: Chagas disease, also known as American Trypanosomiasis, is a chronic parasitic disease caused by the flagellated protozoan Trypanosoma cruzi that affects about 8 million people around the world where more than 25 million are at risk of contracting the infection. Despite of being endemic on 21 Latin-American countries, Chagas disease has become a global concern due to migratory movements. Unfortunately, available drugs for the treatment have several limitations and they are generally administered during the chronic phase of the infection, when its efficacy is considered controversial. Thus, prophylactic and/or therapeutic vaccines are emerging as interesting control alternatives. In this work, we proposed Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a new antigen for vaccine development against Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: In a murine model, we analyzed the immune response triggered by different immunization protocols based on Tc80 and evaluated their ability to confer protection against a challenge with the parasite. Immunized mice developed Tc80-specific antibodies which were able to carry out different functions such as: enzymatic inhibition, neutralization of parasite infection and complement-mediated lysis of trypomastigotes. Furthermore, vaccinated mice elicited strong cell-mediated immunity. Spleen cells from immunized mice proliferated and secreted Th1 cytokines (IL-2, IFN-γ and TNF-α) upon re-stimulation with rTc80. Moreover, we found Tc80-specific polyfunctional CD4 T cells, and cytotoxic T lymphocyte activity against one Tc80 MHC-I peptide. Immunization protocols conferred protection against a T. cruzi lethal challenge. Immunized groups showed a decreased parasitemia and higher survival rate compared with non-immunized control mice. Moreover, during the chronic phase of the infection, immunized mice presented: lower levels of myopathy-linked enzymes, parasite burden, electrocardiographic disorders and inflammatory cells. CONCLUSIONS/SIGNIFICANCE: Considering that an early control of parasite burden and tissue damage might contribute to avoid the progression towards symptomatic forms of chronic Chagas disease, the efficacy of Tc80-based vaccines make this molecule a promising immunogen for a mono or multicomponent vaccine against T. cruzi infection.


Subject(s)
Chagas Disease/prevention & control , Protozoan Vaccines/immunology , Serine Endopeptidases/immunology , Trypanosoma cruzi/enzymology , Trypanosoma cruzi/immunology , Animals , Antibodies, Protozoan/blood , Antigens, Protozoan/immunology , CD4-Positive T-Lymphocytes/immunology , Chagas Disease/immunology , Chagas Disease/parasitology , Cytokines/immunology , Immunity, Cellular , Mice , Mice, Inbred BALB C , Parasite Load , Prolyl Oligopeptidases , Protozoan Proteins , Protozoan Vaccines/administration & dosage , Protozoan Vaccines/genetics , Serine Endopeptidases/genetics , Spleen/cytology , Spleen/immunology , T-Lymphocytes, Cytotoxic/immunology , Vaccination
17.
Polymers (Basel) ; 10(8)2018 Jul 24.
Article in English | MEDLINE | ID: mdl-30960735

ABSTRACT

Polyesters made from 2,5-furandicarboxylic acid (FDCA) have been in the spotlight due to their renewable origins, together with the promising thermal, mechanical, and/or barrier properties. Following the same trend, (nano)composite materials based on FDCA could also generate similar interest, especially because novel materials with enhanced or refined properties could be obtained. This paper presents a case study on the use of furanoate-based polyesters and bacterial cellulose to prepare nanocomposites, namely acetylated bacterial cellulose/poly(butylene 2,5-furandicarboxylate) and acetylated bacterial cellulose/poly(butylene 2,5-furandicarboxylate)-co-(butylene diglycolate)s. The balance between flexibility, prompted by the furanoate-diglycolate polymeric matrix; and the high strength prompted by the bacterial cellulose fibres, enabled the preparation of a wide range of new nanocomposite materials. The new nanocomposites had a glass transition between -25⁻46 °C and a melting temperature of 61⁻174 °C; and they were thermally stable up to 239⁻324 °C. Furthermore, these materials were highly reinforced materials with an enhanced Young's modulus (up to 1239 MPa) compared to their neat copolyester counterparts. This was associated with both the reinforcing action of the cellulose fibres and the degree of crystallinity of the nanocomposites. In terms of elongation at break, the nanocomposites prepared from copolyesters with higher amounts of diglycolate moieties displayed higher elongations due to the soft nature of these segments.

18.
Cell Metab ; 25(6): 1320-1333.e5, 2017 Jun 06.
Article in English | MEDLINE | ID: mdl-28591635

ABSTRACT

Decreased growth hormone (GH) and thyroid hormone (TH) signaling are associated with longevity and metabolic fitness. The mechanisms underlying these benefits are poorly understood, but may overlap with those of dietary restriction (DR), which imparts similar benefits. Recently we discovered that hydrogen sulfide (H2S) is increased upon DR and plays an essential role in mediating DR benefits across evolutionary boundaries. Here we found increased hepatic H2S production in long-lived mouse strains of reduced GH and/or TH action, and in a cell-autonomous manner upon serum withdrawal in vitro. Negative regulation of hepatic H2S production by GH and TH was additive and occurred via distinct mechanisms, namely direct transcriptional repression of the H2S-producing enzyme cystathionine γ-lyase (CGL) by TH, and substrate-level control of H2S production by GH. Mice lacking CGL failed to downregulate systemic T4 metabolism and circulating IGF-1, revealing an essential role for H2S in the regulation of key longevity-associated hormones.


Subject(s)
Hydrogen Sulfide/metabolism , Hypothalamo-Hypophyseal System/metabolism , Liver/metabolism , Animals , Cystathionine gamma-Lyase/genetics , Cystathionine gamma-Lyase/metabolism , Dextrothyroxine/metabolism , Female , Growth Hormone/genetics , Growth Hormone/metabolism , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/metabolism , Mice , Mice, Knockout
19.
PLoS Negl Trop Dis ; 11(2): e0005300, 2017 02.
Article in English | MEDLINE | ID: mdl-28234897

ABSTRACT

The development of new adjuvants enables fine modulation of the elicited immune responses. Ideally, the use of one or more adjuvants should result in the induction of a protective immune response against the specific pathogen. We have evaluated the immune response and protection against Trypanosoma cruzi infection in mice vaccinated with recombinant Tc52 or its N- and C-terminal domains (NTc52 and CTc52) adjuvanted either with the STING (Stimulator of Interferon Genes) agonist cyclic di-AMP (c-di-AMP), a pegylated derivative of α-galactosylceramide (αGC-PEG), or oligodeoxynucleotides containing unmethylated CpG motifs (ODN-CpG). All groups immunized with the recombinant proteins plus adjuvant: Tc52+c-di-AMP, NTc52+c-di-AMP, CTc52+c-di-AMP, NTc52+c-di-AMP+αGC-PEG, NTc52+CpG, developed significantly higher anti-Tc52 IgG titers than controls. Groups immunized with c-di-AMP and Tc52, NTc52 or CTc52 showed the highest Tc52-specific IgA titers in nasal lavages. All groups immunized with the recombinant proteins plus adjuvant developed a strong specific cellular immune response in splenocytes and lymph node cells with significant differences for groups immunized with c-di-AMP and Tc52, NTc52 or CTc52. These groups also showed high levels of Tc52-specific IL-17 and IFN-γ producing cells, while NTc52+CpG group only showed significant difference with control in IFN-γ producing cells. Groups immunized with c-di-AMP and Tc52, NTc52 or CTc52 developed predominantly a Th17 and Th1immune response, whereas for NTc52+CpG it was a dominant Th1 response. It was previously described that αGC-PEG inhibits Th17 differentiation by activating NKT cells. Thus, in this work we have also included a group immunized with both adjuvants (NTc52+c-di-AMP+αGC-PEG) with the aim to modulate the Th17 response induced by c-di-AMP. This group showed a significant reduction in the number of Tc52-specific IL-17 producing splenocytes, as compared to the group NTc52+c-di-AMP, which has in turn correlated with a reduction in protection against infection. These results suggest that the Th17 immune response developed after immunizing with NTc52+c-di-AMP could have a protective role against T. cruzi infection. Groups NTc52+c-di-AMP, Tc52+c-di-AMP and NTc52PB, were the ones that showed better protection against infection with lower parasitemia and weight loss, and higher survival.


Subject(s)
Chagas Disease/prevention & control , Protozoan Proteins/immunology , Th1 Cells/immunology , Th17 Cells/immunology , Trypanosoma cruzi/immunology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/chemistry , Animals , Antibodies, Protozoan/immunology , Chagas Disease/immunology , Chagas Disease/parasitology , Cyclic AMP/administration & dosage , Cyclic AMP/chemistry , Female , Humans , Immunization , Mice , Mice, Inbred C3H , Protein Domains , Protozoan Proteins/administration & dosage , Protozoan Proteins/chemistry , Protozoan Proteins/genetics , Trypanosoma cruzi/chemistry , Trypanosoma cruzi/genetics
20.
Environ Microbiol ; 18(12): 4471-4484, 2016 12.
Article in English | MEDLINE | ID: mdl-27348213

ABSTRACT

Alginates are abundant polysaccharides in brown algae that constitute an important energy source for marine heterotrophic bacteria. Despite the key role of alginate degradation processes in the marine carbon cycle, little information is available on the bacterial populations involved in these processes. The aim of this work was to gain a better understanding of alginate utilization capabilities in cold coastal environments. Sediment metagenomes from four high-latitude regions of both Hemispheres were interrogated for alginate lyase gene homologue sequences and their genomic context. Sediments contained highly abundant and diverse bacterial assemblages with alginolytic potential, including members of Bacteroidetes and Proteobacteria, as well as several poorly characterized taxa. The microbial communities in Arctic and Antarctic sediments exhibited the most similar alginolytic profiles, whereas brackish sediments showed distinct structures with a higher proportion of novel genes. Examination of the gene neighbourhood of the alginate lyase homologues revealed distinct patterns depending on the potential lineage of the scaffolds, with evidence of evolutionary relationships among alginolytic gene clusters from Bacteroidetes and Proteobacteria. This information is relevant for understanding carbon fluxes in cold coastal environments and provides valuable information for the development of biotechnological applications from brown algae biomass.


Subject(s)
Alginates/metabolism , Bacteria/genetics , Bacteria/metabolism , Geologic Sediments/microbiology , Metagenomics , Antarctic Regions , Arctic Regions , Ecosystem , Glucuronic Acid/metabolism , Hexuronic Acids/metabolism , Metagenome , Polysaccharide-Lyases , Polysaccharides/metabolism
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