Survivin/BIRC5 as a novel molecular effector at the crossroads of glucose metabolism and radioresistance in head and neck squamous cell carcinoma.

BACKGROUND: Metabolic reprogramming and abnormal glucose metabolism are hallmarks of head and neck squamous cell carcinoma (HNSCC). Certain oncogenes can promote cancer-related metabolic changes, but understanding their crosstalk in HNSCC biology and treatment is essential for identifying predictive biomarkers and developing target therapies. METHODS: We assessed the value of survivin/BIRC5 as a radioresistance factor potentially modulated by glucose for predicting therapeutic sensitivity and prognosis of HNSCC in a cohort of 32 patients. Additionally, we conducted in vitro experiments to explore the role of survivin/BIRC5 in glucose metabolism concerning radiation response. RESULTS: Tumoral BIRC5 expression is associated with serum glucose and predicts locoregional disease-free survival and lower BIRC5 mRNA levels are associated with better outcomes. Upregulation of BIRC5 by radiation depends on glucose levels and provokes a pro-tumoral and radioresistant phenotype in surviving cells. CONCLUSIONS: Survivin/BIRC5 might be independently associated with the risk of recurrence in patients with HNSCC.

Competências auto percebidas pelos enfermeiros de família: Controlo e prevenção da infeção por Vírus Imunodeficiência Humana / Family nurses' self-perceived competencies: Control and prevention of Human Immunodeficiency Virus infection / Competencias autopercibidas por los enfermeros de familia: Control y prevención de la infección por el virus de la inmunodeficiencia humana

Resumo Enquadramento: A infeção pelo Vírus da Imunodeficiência Humana (VIH) constitui um problema de saúde pública. O Enfermeiro de Família desempenha um papel significativo na Prevenção e Controlo da Infeção (PCI). Objetivo: Analisar a auto perceção dos enfermeiros face às competências que detêm na PCI por VIH e a sua relação com a formação na área. Metodologia: Estudo quantitativo e descritivo-correlacional. Amostra selecionada a partir dos enfermeiros de família da Administração Regional de Saúde do Norte que aceitaram participar no estudo. Utilizou-se um formulário que integrou a ECAPC-VIH_CSP. Recorreu-se à estatística descritiva e inferencial através do IBM SPSS Statistics, versão 25.0. Resultados: Os enfermeiros apresentaram um nível medio (M = 4,44 ± 1,24) de auto perceção de competências na PCI por VIH. Os enfermeiros com formação específica apresentam maior perceção da competência. Conclusão: Os resultados evidenciam um nível medio de competências na PCI por VIH auto percebidas pelos enfermeiros. Conclui-se da necessidade da formação dos enfermeiros para o desenvolvimento das competências para a qualidade e segurança na PCI por VIH.

Abstract Background: Human Immunodeficiency Virus (HIV) infection is a public health issue. Family nurses play a significant role in HIV Infection Prevention and Control (IPC). Objective: To analyze nurses' self-perceived competencies in HIV IPC and determine their association with training in the area. Methodology: Quantitative and descriptive-correlational study. The sample was selected from family nurses from the Northern Regional Health Administration who agreed to participate. A form that included the ECAPC-VIH_CSP scale was applied. Data were analyzed through descriptive and inferential statistics in IBM SPSS Statistics, version 25.0. Results: Nurses had an average level (M = 4.44 ± 1.24) of self-perceived competencies in HIV IPC. Nurses with specific training had higher self-perceived competence. Conclusion: The results show that nurses had an average level of self-perceived competencies in HIV IPC. Nurses require training to develop competencies in HIV IPC, improving the quality and safety of care.

Resumen Marco contextual: La infección por el virus de la inmunodeficiencia humana (VIH) es un problema de salud pública. El enfermero de familia desempeña un papel importante en la prevención y el control de las infecciones (PCI). Objetivo: Analizar la autopercepción de los enfermeros sobre sus competencias en PCI del VIH y su relación con la formación en este ámbito. Metodología: Estudio cuantitativo y descriptivo-correlacional. Muestra seleccionada entre los enfermeros de familia de la Administración Sanitaria Regional del Norte que aceptaron participar en el estudio. Se utilizó un formulario que integró el ECAPC-VIH_CSP. Se utilizó la estadística descriptiva e inferencial a través del IBM SPSS Statistics, versión 25.0. Resultados: Los enfermeros presentaron un nivel medio (M = 4,44 ± 1,24) de autopercepción de competencias en la PCI del VIH. Los enfermeros con formación específica mostraron una mayor percepción de la competencia. Conclusión: Los resultados mostraron un nivel medio de competencias autopercibidas en la PCI del VIH entre el personal de enfermería. Se concluye que es necesario formar al personal de enfermería para que desarrolle competencias de calidad y seguridad en la PCI del VIH.

Protective effects of the succinate/SUCNR1 axis on damaged hepatocytes in NAFLD.

OBJECTIVE: Succinate and succinate receptor 1 (SUCNR1) are linked to fibrotic remodeling in models of non-alcoholic fatty liver disease (NAFLD), but whether they have roles beyond the activation of hepatic stellate cells remains unexplored. We investigated the succinate/SUCNR1 axis in the context of NAFLD specifically in hepatocytes. METHODS: We studied the phenotype of wild-type and Sucnr1-/- mice fed a choline-deficient high-fat diet to induce non-alcoholic steatohepatitis (NASH), and explored the function of SUCNR1 in murine primary hepatocytes and human HepG2 cells treated with palmitic acid. Lastly, plasma succinate and hepatic SUCNR1 expression were analyzed in four independent cohorts of patients in different NAFLD stages. RESULTS: Sucnr1 was upregulated in murine liver and primary hepatocytes in response to diet-induced NASH. Sucnr1 deficiency provoked both beneficial (reduced fibrosis and endoplasmic reticulum stress) and detrimental (exacerbated steatosis and inflammation and reduced glycogen content) effects in the liver, and disrupted glucose homeostasis. Studies in vitro revealed that hepatocyte injury increased Sucnr1 expression, which when activated improved lipid and glycogen homeostasis in damaged hepatocytes. In humans, SUCNR1 expression was a good determinant of NAFLD progression to advanced stages. In a population at risk of NAFLD, circulating succinate was elevated in patients with a fatty liver index (FLI) ≥60. Indeed, succinate had good predictive value for steatosis diagnosed by FLI, and improved the prediction of moderate/severe steatosis through biopsy when added to an FLI algorithm. CONCLUSIONS: We identify hepatocytes as target cells of extracellular succinate during NAFLD progression and uncover a hitherto unknown function for SUCNR1 as a regulator of hepatocyte glucose and lipid metabolism. Our clinical data highlight the potential of succinate and hepatic SUCNR1 expression as markers to diagnose fatty liver and NASH, respectively.

SUCNR1 signaling in adipocytes controls energy metabolism by modulating circadian clock and leptin expression.

Adipose tissue modulates energy homeostasis by secreting leptin, but little is known about the factors governing leptin production. We show that succinate, long perceived as a mediator of immune response and lipolysis, controls leptin expression via its receptor SUCNR1. Adipocyte-specific deletion of Sucnr1 influences metabolic health according to nutritional status. Adipocyte Sucnr1 deficiency impairs leptin response to feeding, whereas oral succinate mimics nutrient-related leptin dynamics via SUCNR1. SUCNR1 activation controls leptin expression via the circadian clock in an AMPK/JNK-C/EBPα-dependent manner. Although the anti-lipolytic role of SUCNR1 prevails in obesity, its function as a regulator of leptin signaling contributes to the metabolically favorable phenotype in adipocyte-specific Sucnr1 knockout mice under standard dietary conditions. Obesity-associated hyperleptinemia in humans is linked to SUCNR1 overexpression in adipocytes, which emerges as the major predictor of adipose tissue leptin expression. Our study establishes the succinate/SUCNR1 axis as a metabolite-sensing pathway mediating nutrient-related leptin dynamics to control whole-body homeostasis.

The ANGPTL3-4-8 Axis in Normal Gestation and in Gestational Diabetes, and Its Potential Involvement in Fetal Growth.

Dyslipidemia in gestational diabetes has been associated with worse perinatal outcomes. The ANGPTL3-4-8 axis regulates lipid metabolism, especially in the transition from fasting to feeding. In this study, we evaluated the response of ANGPTL3, 4, and 8 after the intake of a mixed meal in women with normal glucose tolerance and gestational diabetes, and we assessed their gene expressions in different placental locations. Regarding the circulating levels of ANGPTL3, 4, and 8, we observed an absence of ANGPTL4 response after the intake of the meal in the GDM group compared to its presence in the control group. At the placental level, we observed a glucose tolerance-dependent expression pattern of ANGPTL3 between the two placental sides. When we compared the GDM pregnancies with the control pregnancies, a downregulation of the maternal side ANGPTL3 expression was observed. This suggests a dysregulation of the ANGPTL3-4-8 axis in GDM, both at the circulating level after ingestion and at the level of placental expression. Furthermore, we discerned that the expressions of ANGPTL3, 4, and 8 were related to birth weight and placental weight in the GDM group, but not in the control group, which suggests that they may play a role in regulating the transplacental passage of nutrients.

Aprendizagem do cuidar a família na comunidade: Usabilidade do Modelo Dinâmico de Avaliação e Intervenção Familiar / Learning to care for the family in the community: Usability of the Dynamic Model of Family Assessment and Intervention / Aprendizaje del cuidado a la familia en la comunidad: Usabilidad del Modelo Dinámico de Evaluación e Intervención Familiar

Resumo Enquadramento: O Modelo Dinâmico de Avaliação e Intervenção Familiar é mobilizado no processo de ensino aprendizagem dos estudantes da licenciatura em enfermagem, como orientador no processo de cuidados às famílias na comunidade. Objetivo: Analisar as dimensões valorizadas pelos estudantes do curso de licenciatura em enfermagem, no desenvolvimento de competências na avaliação e intervenção familiar. Metodologia: Estudo exploratório-descritivo com 350 estudantes da licenciatura em Enfermagem. Uso de formulário para identificar aspetos valorizados na utilização do modelo referencial teórico e operativo em ensino clínico. Análise de conteúdo com categorização a priori e a posteriori. Cumpridos os pressupostos éticos. Resultados: Identificam-se cinco dimensões: Clareza (mais valorizada); Simplicidade; Generalidade; Consequências deriváveis (frequência de nomeação intermédia) e Precisão empírica (menos valorizada). Emerge interligação entre etapas do processo de cuidados e modelo como instrumento de mudança e referencial na tomada de decisão no contexto clínico. Conclusão: As dimensões confirmam a importância atribuída pelos estudantes à estrutura e sentido na aprendizagem dos cuidados à família sendo preditivas da aprendizagem integrada, entre teoria e prática em enfermagem.

Abstract Background: The Dynamic Model of Family Assessment and Intervention is used in the teaching-learning process of undergraduate nursing students to guide the process of caring for families in the community. Objective: To analyze the dimensions valued by undergraduate nursing students in the development of family assessment and intervention skills. Methodology: An exploratory-descriptive study was conducted with 350 undergraduate nursing students. A form was used to identify aspects valued in using the theoretical and operational model in clinical teaching. Data were subjected to content analysis, with a priori and a posteriori categorization. All ethical assumptions were met. Results: Five dimensions were identified: Clarity (most valued); Simplicity; Generality; Derivable consequences (intermediate frequency), and Empirical precision (least valued). Interconnection emerges between stages of the care process and the model as an instrument of change and reference in decision-making in clinical settings. Conclusion: The dimensions confirm the importance attributed by students to the structure and meaning in learning about family care and are predictors of integrated learning between nursing theory and practice.

Resumen Marco contextual: El Modelo Dinámico de Evaluación e Intervención Familiar se articula en el proceso de enseñanza-aprendizaje de los estudiantes del grado en Enfermería, como guía en el proceso de cuidados a las familias en la comunidad. Objetivo: Analizar las dimensiones valoradas por los estudiantes del grado en Enfermería en el desarrollo de competencias en la evaluación e intervención familiar. Metodología: Estudio exploratorio-descriptivo con 350 estudiantes del grado en Enfermería. Se utilizó un formulario para identificar los aspectos valorados en el uso del modelo referencial teórico y operativo en la enseñanza clínica. Análisis de contenido con categorización a priori y a posteriori. Se cumplieron todos los supuestos éticos. Resultados: Se identifican cinco dimensiones, Clareza (más valorada); Simplicidad; Generalidad; Consecuencias derivables (frecuencia intermedia) y Precisión empírica (menos valorada). Surge interconexión entre etapas del proceso de cuidados y modelo como instrumento de cambio y referencia para la toma de decisiones en el contexto clínico. Conclusión: Las dimensiones confirman la importancia atribuida por los estudiantes a la estructura y el significado en el aprendizaje de los cuidados a la familia, y son predictivas del aprendizaje integrado entre la teoría y la práctica en enfermería.

Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes.

Background: Coronavirus-19 (COVID-19) disease is driven by an unchecked immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus which alters host mitochondrial-associated mechanisms. Compromised mitochondrial health results in abnormal reprogramming of glucose metabolism, which can disrupt extracellular signalling. We hypothesized that examining mitochondrial energy-related signalling metabolites implicated in host immune response to SARS-CoV-2 infection would provide potential biomarkers for predicting the risk of severe COVID-19 illness. Methods: We used a semi-targeted serum metabolomics approach in 273 patients with different severity grades of COVID-19 recruited at the acute phase of the infection to determine the relative abundance of tricarboxylic acid (Krebs) cycle-related metabolites with known extracellular signaling properties (pyruvate, lactate, succinate and α-ketoglutarate). Abundance levels of energy-related metabolites were evaluated in a validation cohort (n=398) using quantitative fluorimetric assays. Results: Increased levels of four energy-related metabolites (pyruvate, lactate, a-ketoglutarate and succinate) were found in critically ill COVID-19 patients using semi-targeted and targeted approaches (p<0.05). The combined strategy proposed herein enabled us to establish that circulating pyruvate levels (p<0.001) together with body mass index (p=0.025), C-reactive protein (p=0.039), D-Dimer (p<0.001) and creatinine (p=0.043) levels, are independent predictors of critical COVID-19. Furthermore, classification and regression tree (CART) analysis provided a cut-off value of pyruvate in serum (24.54 µM; p<0.001) as an early criterion to accurately classify patients with critical outcomes. Conclusion: Our findings support the link between COVID-19 pathogenesis and immunometabolic dysregulation, and show that fluorometric quantification of circulating pyruvate is a cost-effective clinical decision support tool to improve patient stratification and prognosis prediction.

Reasons for Living Inventory for Young Adults: Psychometric Properties Among Portuguese Sample.

A main protective factor against suicide in young adults is their reasons for living; therefore, suicide risk screening should consider these reasons. However, few psychometric instruments assess reasons for living, and none have been adapted for young adults in Portugal. Thus, we assess the psychometric characteristics of the Reasons for Living Inventory for Young Adults-II (RFL-YA-II) in participants (n = 936; Mage = 21.77; SD = 2.88) from Portugal. Participants answered measures concerning suicidal ideation, depression, hopelessness, and positive and negative affect. The results of an exploratory factorial analysis replicated the original 4-factor model of the RFL-YA-II, and a confirmatory factorial analysis indicated satisfactory indices. In terms of reliability and convergent, discriminant, and concurrent validity, our results are consistent with previous research. Moreover, our results indicate that the RFL-YA-II is a valid and reliable instrument to study the protective factors against suicidal behavior in Portuguese young adults, and should thus be integrated into preventive strategies.

Crohn's Disease Increases the Mesothelial Properties of Adipocyte Progenitors in the Creeping Fat.

Our understanding of the interplay between human adipose tissue and the immune system is limited. The mesothelium, an immunologically active structure, emerged as a source of visceral adipose tissue. After investigating the mesothelial properties of human visceral and subcutaneous adipose tissue and their progenitors, we explored whether the dysfunctional obese and Crohn's disease environments influence the mesothelial/mesenchymal properties of their adipocyte precursors, as well as their ability to mount an immune response. Using a tandem transcriptomic/proteomic approach, we evaluated the mesothelial and mesenchymal expression profiles in adipose tissue, both in subjects covering a wide range of body-mass indexes and in Crohn's disease patients. We also isolated adipose tissue precursors (adipose-derived stem cells, ASCs) to assess their mesothelial/mesenchymal properties, as well as their antigen-presenting features. Human visceral tissue presented a mesothelial phenotype not detected in the subcutaneous fat. Only ASCs from mesenteric adipose tissue, named creeping fat, had a significantly higher expression of the hallmark mesothelial genes mesothelin (MSLN) and Wilms' tumor suppressor gene 1 (WT1), supporting a mesothelial nature of these cells. Both lean and Crohn's disease visceral ASCs expressed equivalent surface percentages of the antigen-presenting molecules human leucocyte antigen-DR isotype (HLA-DR) and CD86. However, lean-derived ASCs were predominantly HLA-DR dim, whereas in Crohn's disease, the HLA-DR bright subpopulation was increased 3.2-fold. Importantly, the mesothelial-enriched Crohn's disease precursors activated CD4+ T-lymphocytes. Our study evidences a mesothelial signature in the creeping fat of Crohn's disease patients and its progenitor cells, the latter being able to present antigens and orchestrate an immune response.

Primes and Consequences: A Systematic Review of Meritocracy in Intergroup Relations.

Psychological interest in Meritocracy as an important social norm regulating most of the western democratic societies has significantly increased over the years. However, the way Meritocracy has been conceptualized and operationalized in experimental studies has advanced in significant ways. As a result, a variety of paradigms arose to understand the social consequences of Meritocracy for intergroup relations; in particular, to understand the adverse consequences of Meritocracy for disadvantaged group members. The present research seeks to understand whether there is strong support for the idea that (manipulated) Meritocracy disproportionally affects members of low status groups, and also to understand which specific components of this norm have been successfully manipulated and to what consequences. And this is particularly important given the recent call for greater transparency in how the success of experimental manipulations is reported. Thus, we carried out a systematic review examining the content of different prime tasks, summarizing prime manipulation checks' effectiveness, and analyzing whether priming Meritocracy leads to less favorable orientations toward low status groups. Results across 33 studies revealed that despite the existing differences in the components highlighted, the salience of any of the Meritocracy dimensions facilitates the use of internal causal attributions, negative evaluations and stereotyping toward low status groups, affecting negatively decisions involving low-status group members, particularly in specific domains, as organizational contexts. These results carry both practical and theoretical implications for future research on the role of Meritocracy in intergroup settings.

Justifying treatment bias: The legitimizing role of threat perception and immigrant-provider contact in healthcare.

OBJECTIVE: Immigrants tend to receive a lower quality of healthcare, which can be a sign of healthcare bias. We examined whether this bias in medical care is associated with a legitimizing process involving two psychosocial factors: threat perception and level of intergroup contact. METHOD: One hundred eighty six Portuguese health professionals (55.6% clinicians; 44.4% nurses; 78.5% female; Mage = 45.83, range = 23 and 71) completed a questionnaire on prejudiced attitudes toward immigrants, perceptions of health-specific threats, bias in medical practice and level of contact with immigrant patients. RESULTS: For healthcare providers who have more contact with immigrant patients, the perceived health threat mediated the relationship between prejudiced attitudes and treatment bias. In contrast, for healthcare providers with less contact with immigrant patients, the perceived threat was not associated with treatment bias. CONCLUSIONS: These findings help to understand the persistence of lower quality medical treatment among immigrants, providing guidelines for future research. In particular, they suggest that perceiving immigrants as a threat to public health is indicative of the providers' engagement in a legitimizing process of self-reported biased treatment, making this engagement necessary only for providers with greater levels of contact with immigrant patients. (PsycINFO Database Record

Crohn's Disease Disturbs the Immune Properties of Human Adipose-Derived Stem Cells Related to Inflammasome Activation.

Crohn's disease (CD) is characterized by the expansion of mesenteric fat, also known as "creeping fat." We explored the plasticity and immune properties of adipose-derived stem cells (ASCs) in the context of CD as potential key players in the development of creeping fat. Mesenteric CD-derived ASCs presented a more proliferative, inflammatory, invasive, and phagocytic phenotype than equivalent cells from healthy donors, irrespective of the clinical stage. Remarkably, ASCs from the subcutaneous depot of patients with CD also showed an activated immune response that was associated with a reduction in their immunosuppressive properties. The invasive phenotype of mesenteric CD ASCs was governed by an inflammasome-mediated inflammatory state since blocking inflammasome signaling, mainly the secretion of interleukin-1ß, reversed this characteristic. Thus, CD alters the biological functions of ASCs as adipocyte precursors, but also their immune properties. Selection of ASCs with the best immunomodulatory properties is advocated for the success of cell-based therapies.

Reações adversas na cavidade oral em decorrência do uso de medicamentos / Side effects in oral cavity in consequent of medication use

Introdução: as reações adversas a medicamentos constituem um problema importante na prática do profissional da área da saúde, já que essas reações são causas de hospitalização, aumento no tempo de permanência hospitalar e da morbimortalidade. Muitas das reações adversas aos fármacos apresentam-se na cavidade oral. Objetivo: descrever os principais medicamentos com potencial de efeitos colaterais na cavidade oral, agrupando os que causam efeitos adversos semelhantes. Método: trata-se de estudo bibliográfico e descritivo por meio de utilização de estudos originais e atualizados a partir dos bancos de dados oficiais SciELO, PUBMED e LILACS. Priorizaram-se artigos em língua portuguesa, inglesa e espanhola, que incluíam revisões bibliográficas, meta-análises e relatos de casos publicados entre 2000 e 2015. Foram utilizados como descritores os termos: manifestações orais e medicamentos, lesões orais e medicamentos, mucosa oral e medicamentos e reação medicamentosa na cavidade oral. Resultados e Discussão: dezenove artigos foram analisados detalhadamente e mostram predominância de relatos de caso. Vários medicamentos foram associados com alterações patológicas nos tecidos orais, sobretudo os medicamentos utilizados em oncologia e medicamentos com ação no sistema nervoso central. As reações adversas às drogas dependem do fármaco e são bastante variáveis, e dentre as encontradas destacam-se ulceração de mucosa, hiperplasia gengival, xerostomia e diminuição do fluxo salivar. Conclusão: algumas lesões são comuns a diferentes medicamentos e, dessa forma, é fundamental a observação correta da possibilidade de sequela associada à terapia medicamentosa. Uma anamnese adequada com um levantamento do histórico médico completo do paciente é essencial para o profissional de saúde estar apto a fazer o diagnóstico das alterações e concluir o tratamento adequado para a solução do problema. (AU)

Introduction: adverse drug reactions are an important problem in the practice of health professionals, since these reactions may cause hospitalization, increase in length of hospital stay and morbidity and mortality. Many adverse drug reactions occur in the oral cavity. Objective: to describe the main drugs with potential side effects in the oral cavity, grouping those that cause similar adverse effects. Methods: bibliographic and descriptive study through use of original studies from three databases: SciELO, PubMed and LILACS. Selected papers were in Portuguese, English and Spanish, which included literature reviews, meta-analysis and case reports published between 2000 and 2015. The terms used were: oral medications and manifestations, oral lesions and medicines, oral mucosa and drugs and adverse drug reaction in the oral cavity. Results and Discussion: nineteen articles were analyzed in detail and case reports were predominant. Several drugs have been associated with pathological changes in oral tissue, in particular drugs used in oncology and those acting on the central nervous system. Adverse drug reactions depend on the medication and are quite variable. Among the found reaction are: ulcerative mucosa, gingival hyperplasia, xerostomia and decreased salivary flow. Conclusion: some lesions are common to different drugs, making critical the proper observation of possible sequelae associated with drug therapy. Detailed anamnesis with a complete medical history of the patient is essential for the proper diagnosis and a better therapeutic decision. (AU)

Aquaporin-5: from structure to function and dysfunction in cancer.

Aquaporins, a highly conserved group of membrane proteins, are involved in the bidirectional transfer of water and small solutes across cell membranes taking part in many biological functions all over the human body. In view of the wide range of cancer malignancies in which aquaporin-5 (AQP5) has been detected, an increasing interest in its implication in carcinogenesis has emerged. Recent publications suggest that this isoform may enhance cancer cell proliferation, migration and survival in a variety of malignancies, with strong evidences pointing to AQP5 as a promising drug target and as a novel biomarker for cancer aggressiveness with high translational potential for therapeutics and diagnostics. This review addresses the structural and functional features of AQP5, detailing its tissue distribution and functions in human body, its expression pattern in a variety of tumors, and highlighting the underlying mechanisms involved in carcinogenesis. Finally, the actual progress of AQP5 research, implications in cancer biology and potential for cancer detection and prognosis are discussed.

Detecting Aquaporin Function and Regulation.

Water is the major component of cells and tissues throughout all forms of life. Fluxes of water and solutes through cell membranes and epithelia are essential for osmoregulation and energy homeostasis. Aquaporins are membrane channels expressed in almost every organism and involved in the bidirectional transfer of water and small solutes across cell membranes. Aquaporins have important biological roles and have been implicated in several pathophysiological conditions suggesting a great translational potential in aquaporin-based diagnostics and therapeutics. Detecting aquaporin function is critical for assessing regulation and screening for new activity modulators that can prompt the development of efficient medicines. Appropriate methods for functional analysis comprising suitable cell models and techniques to accurately evaluate water and solute membrane permeability are essential to validate aquaporin function and assess short-term regulation. The present review describes established assays commonly used to assess aquaporin function in cells and tissues, as well as the experimental biophysical strategies required to reveal functional regulation and identify modulators, the first step for aquaporin drug discovery.

Water Transport in Yeasts.

Water moves across membranes through the lipid bilayer and through aquaporins, in this case in a regulated manner. Aquaporins belong to the MIP superfamily and two subfamilies are represented in yeasts: orthodox aquaporins considered to be specific water channels and aquaglyceroporins (heterodox aquaporins). In Saccharomyces cerevisiae genome, four aquaporin isoforms were identified, two of which are genetically close to orthodox aquaporins (ScAqy1 and ScAqy2) and the other two are more closely related to the aquaglyceroporins (ScFps1 and ScAqy3). Advances in the establishment of water channels structure are reviewed in this chapter in relation with the mechanisms of selectivity, conductance and gating. Aquaporins are important for key aspects of yeast physiology. They have been shown to be involved in sporulation, rapid freeze-thaw tolerance, osmo-sensitivity, and modulation of cell surface properties and colony morphology, although the underlying exact mechanisms are still unknown.

Adipocyte membrane glycerol permeability is involved in the anti-adipogenic effect of conjugated linoleic acid.

Conjugated linoleic acid (CLA), a group of minor fatty acids from ruminant origin, has long been recognized as a body fat lowering agent. Given the trans(t)10,cis(c)12-CLA well documented interference on lipolysis, we hypothesized for adipocytes altered permeation to glycerol when supplemented with this isomer. 3T3-L1 murine differentiated adipocytes were medium supplemented with linoleic acid (LA) and individual or combined c9,t11 and t10,c12-CLA isomers. Adipocytes treated with the t10,c12-CLA isomer and CLA mixture showed reduced triacylglycerols content (p < 0.001), re-enforcing the t10,c12-CLA as the anti-adipogenic CLA isomer. This finding was supported by decreased Δ9-desaturase index and adipocyte differentiation markers for the t10,c12-CLA group (p < 0.001), which suggest reduced lipogenesis and differentiation, respectively. The glycerol permeability was higher in all CLA treated cells compared to control and LA groups (p < 0.05). The increase in glycerol permeability agrees with both reduced triacylglycerols and non-osmotic cellular volume in the t10,c12-CLA and CLA mixture groups. Taken together, our data suggest that the increased adipocyte plasma membrane glycerol fluxes may be part of the anti-adipogenic response to CLA treatments.

Aquaporin-5 is expressed in adipocytes with implications in adipose differentiation.

Aquaporins (AQPs) are membrane channels widely distributed in nature. Typically, multiple isoforms are expressed in a single tissue. The adipose tissue is no exception where several AQP members have been identified. The importance of overlapped AQPs expression is unclear, yet interisoforms interactions might be required for key cellular functions. Recently, AQP5 was described as a regulator of other AQP isoforms. Therefore, we hypothesized for a role of AQP5 in adipocyte biology. Gene expression analysis revealed the presence of AQP5 in both 3T3-L1 fibroblasts and adipocytes, being more abundant in the later. AQP5 depletion impaired adipocyte differentiation, which was confirmed by decreased expression of specific differentiation markers. By overexpressing the human AQP5 in mature adipocytes it was possible to ascertain its role as a water channel in a gain-of-function scenario. To our knowledge, this is the first time that AQP5 is reported on adipose tissue. Our data revealed AQP5 as a new player in adipose tissue biology.

Aquaglyceroporins: implications in adipose biology and obesity.

Aquaporins (AQPs) are membrane water/glycerol channels that are involved in many physiological processes. Their primary function is to facilitate the bidirectional transfer of water and small solutes across biological membranes in response to osmotic gradients. Aquaglyceroporins, a subset of the AQP family, are the only mammalian proteins with the ability to permeate glycerol. For a long time, AQP7 has been the only aquaglyceroporin associated with the adipose tissue, which is the major source of circulating glycerol in response to the energy demand. AQP7 dysregulation was positively correlated with obesity onset and adipocyte glycerol permeation through AQP7 was appointed as a novel regulator of adipocyte metabolism and whole-body fat mass. Recently, AQP3, AQP9, AQP10 and AQP11 were additionally identified in human adipocytes and proposed as additional glycerol pathways in these cells. This review contextualizes the importance of aquaglyceroporins in adipose tissue biology and highlights aquaglyceroporins' unique structural features which are relevant for the design of effective therapeutic compounds. We also refer to the latest advances in the identification and characterization of novel aquaporin isoforms in adipose tissue. Finally, considerations on the actual progress of aquaporin research and its implications on obesity therapy are suggested.

A gold coordination compound as a chemical probe to unravel aquaporin-7 function.

Aquaporins (AQPs) are membrane water/glycerol channels that are involved in many physiological functions. Aquaporin-based modulators are predicted to have potential utility in the treatment of several diseases, as well as chemical tools to assess AQPs function in biological systems. We recently reported gold(III) compounds as human AQP3 inhibitors, with Auphen as the most potent of the series. In this work, we assessed the modulation of aquaporin-7 (AQP7) expressed in an adipocyte cell model and show that Auphen significantly inhibits mouse and human AQP7. By homology modeling and molecular docking it was possible to identify the thioether groups of methionine residues, in particular Met47, as likely candidates for binding to the gold(III) complex. Our data point to Auphen as a useful chemical tool to detect AQP7 function. It might constitute a basis to develop inhibitors with improved affinity towards different aquaglyceroporin isoforms.