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1.
Hist Philos Life Sci ; 46(1): 4, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38193992

RESUMO

Participatory and collaborative approaches in sustainability science and public health research contribute to co-producing evidence that can support interventions by involving diverse societal actors that range from individual citizens to entire communities. However, existing philosophical accounts of evidence are not adequate to deal with the kind of evidence generated and used in such approaches. In this paper, we present an account of evidence as clues for action through participatory and collaborative research inspired by philosopher Susan Haack's theory of evidence. Differently from most accounts of evidence for use in policies and interventions, our account combines action-oriented (the how) and actors-oriented (the who) considerations. We build on Haack's theory and on the analysis of examples of participatory and collaborative research in sustainability science and public health research to flesh out six procedural criteria for the generation and mobilization of evidence in and from participatory research. Action-oriented criteria invite to look at evidence from a (a) foundherentist, (b) gradational and (c) quasi-holistic perspective. Actors-oriented criteria point out that evidence generation and utilization are (d) social, (e) personal, and (f) embedded. We suggest that these criteria may reinforce participatory and collaborative approaches to evidence co-production when addressing complex problems in sustainability science and public health allowing for the generation of a kind of practical objectivity.


Assuntos
Políticas , Saúde Pública
2.
Epidemiology ; 34(4): 505-514, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37042967

RESUMO

Public health and the underlying disease processes are complex, often involving the interaction of biologic, social, psychologic, economic, and other processes that may be nonlinear and adaptive and have other features of complex systems. There is therefore a need to push the boundaries of public health beyond single-factor data analysis and expand the capacity of research methodology to tackle real-world complexities. This article sets out a way to operationalize complex systems thinking in public health, with a particular focus on how epidemiologic methods and data can contribute towards this end. Our proposed framework comprises three core dimensions-patterns, mechanisms, and dynamics-along which complex systems may be conceptualized. These dimensions cover seven key features of complex systems-emergence, interactions, nonlinearity, interference, feedback loops, adaptation, and evolution. We relate this framework to examples of methods and data traditionally used in epidemiology. We conclude that systematic production of knowledge on complex health issues may benefit from: formulation of research questions and programs in terms of the core dimensions we identify, as a comprehensive way to capture crucial features of complex systems; integration of traditional epidemiologic methods with systems methodology such as computational simulation modeling; interdisciplinary work; and continued investment in a wide range of data types. We believe that the proposed framework can support the systematic production of knowledge on complex health problems, with the use of epidemiology and other disciplines. This will help us understand emergent health phenomena, identify vulnerable population groups, and detect leverage points for promoting public health.


Assuntos
Saúde Pública , Humanos , Métodos Epidemiológicos
3.
Health Place ; 80: 102984, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36773380

RESUMO

This paper proposes a novel framework for the development of interventions in vulnerable populations. The framework combines a complex systems lens with syndemic theory. Whereas funding bodies, research organizations and reporting guidelines tend to encourage intervention research that (i) focuses on singular and predefined health outcomes, (ii) searches for generalizable cause-effect relationships, and (iii) aims to identify universally effective interventions, the paper suggests that a different direction is needed for addressing health inequities: We need to (i) start with exploratory analysis of population-level data, and (ii) invest in contextualized in-depth knowledge of the complex dynamics that produce health inequities in specific populations and settings, while we (iii) work with stakeholders at multiple levels to create change within systems.


Assuntos
Saúde Pública , Populações Vulneráveis , Humanos
4.
J Eval Clin Pract ; 29(3): 430-437, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36656768

RESUMO

Public health, just as any policy-related field, faces the evergreen problem of turning knowledge into action. Among other problems, there is a clash between the inherent complexity of public health problems and the inevitable push, by decision-makers and the public, to simplify them. The Covid-19 pandemic has shown the insufficiencies of our current epistemological, methodological and normative apparatus to handle such crises in a timely manner. Despite this, several authors have been arguing for the importance of engaging global crises such as Covid-19 in ways that do not oversimplify key dimensions of the issues involved. In this paper, we contribute to this emerging scholarship. Building on existing work in the field of environmental problem-solving, we propose an integrative approach to navigating complex trade-offs in public health interventions. Briefly put, we propose that decision making should be informed by an analysis of any given problem from four distinct, but interrelated, lenses: (i) values and valuation, (ii) process and governance, (iii) power and inequalities and (iv) scientific evidence, methods and concepts. This normative framework, we argue, can help with spelling out the complexity of public health problems and with spelling out the rationale behind public health decision making to non-specialists and the general public. We illustrate our approach using the controversy over wearing face masks in the Covid-19 pandemic.


Assuntos
Política de Saúde , Saúde Pública , Saúde Pública/ética , Saúde Pública/legislação & jurisprudência , Saúde Pública/métodos , Medicina Baseada em Evidências , Tomada de Decisões , Pandemias/prevenção & controle , COVID-19/epidemiologia , COVID-19/prevenção & controle , Valores Sociais , Equidade em Saúde
5.
Pediatr Res ; 93(5): 1208-1215, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35953512

RESUMO

BACKGROUND: Loss-of-function variants in MID1 are the most common cause of Opitz G/BBB syndrome (OS). The interpretation of intronic variants affecting the splicing is a rising issue in OS. METHODS: Exon sequencing of a 2-year-old boy with OS showed that he was a carrier of the de novo c.1286-10G>T variant in MID1. In silico predictions and minigene assays explored the effect of the variant on splicing. The minigene approach was also applied to two previously identified MID1 c.864+1G>T and c.1285+1G>T variants. RESULTS: Minigene assay demonstrated that the c.1286-10G>T variant generated the inclusion of eight nucleotides that predicted generation of a frameshift. The c.864+1G>T and c.1285+1G>T variants resulted in an in-frame deletion predicted to generate a shorter MID1 protein. In hemizygous males, this allowed reclassification of all the identified variants from "of unknown significance" to "likely pathogenic." CONCLUSIONS: Minigene assay supports functional effects from MID1 intronic variants. This paves the way to the introduction of similar second-tier investigations in the molecular diagnostics workflow of OS. IMPACT: Causative intronic variants in MID1 are rarely investigated in Opitz syndrome. MID1 is not expressed in blood and mRNA studies are hardly accessible in routine diagnostics. Minigene assay is an alternative for assessing the effect of intronic variants on splicing. This is the first study characterizing the molecular consequences of three MID1 variants for diagnostic purposes and demonstrating the efficacy of minigene assays in supporting their clinical interpretation. Review of the criteria according to the American College of Medical Genetics reassessed all variants as likely pathogenic.


Assuntos
Fissura Palatina , Hipertelorismo , Masculino , Humanos , Pré-Escolar , Mutação , Fissura Palatina/genética , Hipertelorismo/genética , Ubiquitina-Proteína Ligases/genética
6.
Longit Life Course Stud ; 15(1): 25-44, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38174547

RESUMO

The consequences of the COVID-19 pandemic are still working through health systems worldwide, and further reflections about the nature of health and disease, and about how to design and implement effective public health interventions are much needed. For numerous diseases and conditions, as well as for COVID-19, our knowledge base is rich. We know a lot about the biology of the disease, and we have plenty of statistics that relate health to socio-economic factors. In this paper, we argue that we need to add a third dimension to this knowledge base, namely a thorough description of the lifeworld of health and disease, in terms of the mixed biosocial mechanisms that operate in it. We present the concepts of lifeworld and of mixed mechanisms, and then illustrate how they can be operationalised and measured through mixed methodologies that combine qualitative and quantitative approaches. Finally, we explain the complementarity of our approach with the biological and statistical dimensions of health and disease for the design of public health interventions.


Assuntos
COVID-19 , Saúde Pública , Humanos , Pandemias/prevenção & controle , COVID-19/epidemiologia , Projetos de Pesquisa
7.
Molecules ; 27(24)2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36557909

RESUMO

(1) Background: In recent years, the consumption of sprouts, thanks to their high nutritional value, and the presence of bioactive compounds with antioxidant, antiviral and antibacterial properties, is becoming an increasingly widespread habit. Moringa oleifera Lam. (Moringa) seems to be an inexhaustible resource considering that many parts may be used as food or in traditional medicine; on the other hand, Moringa sprouts still lack a proper characterization needing further insights to envisage novel uses and applications. (2) Methods: In this study, a rapid and easy protocol to induce the in vivo and in vitro germination of Moringa seeds has been set up to obtain sprouts and cotyledons to be evaluated for their chemical composition. Moreover, the effects of sprouts developmental stage, type of sowing substrate, and gibberellic acid use on the chemical characteristics of extracts have been evaluated. (3) Results: Moringa seeds have a high germinability, both in in vivo and in vitro conditions. In addition, the extracts obtained have different total phenolic content and antioxidant activity. (4) Conclusions: This research provides a first-line evidence to evaluate Moringa sprouts as future novel functional food or as a valuable source of bioactive compounds.


Assuntos
Antioxidantes , Moringa oleifera , Antioxidantes/química , Polifenóis/farmacologia , Polifenóis/análise , Moringa oleifera/química , Extratos Vegetais/química , Sementes/química
8.
J Radiol Prot ; 42(4)2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-35973359

RESUMO

This paper provides surface-clearance levels for 413 radionuclides for the normal reuse of objects leaving the controlled area of a nuclear facility. Four sets of surface-specific clearance levels are derived based on choices of dose coefficients (DCs) in probabilistic dose assessments using the SUrface DOse QUantification model (SUDOQU; van Dillen and van Dijk 2018J. Radiol. Prot.381147-203). The general dose criteria for clearance, extended with a suitable dose constraint for the concept of the representative person, are applied in the derivations. These clearance levels apply to the total of fixed and removable radioactive contamination on the surface of objects. The results are discussed in the context of conservatism of the exposure scenarios (parameters, DCs), and guidance is given on the selection and application of the values.


Assuntos
Radioisótopos , Humanos , Doses de Radiação
9.
Genet Med ; 24(2): 439-453, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34906501

RESUMO

PURPOSE: This study aimed to describe a multisystemic disorder featuring cardiovascular, facial, musculoskeletal, and cutaneous anomalies caused by heterozygous loss-of-function variants in TAB2. METHODS: Affected individuals were analyzed by next-generation technologies and genomic array. The presumed loss-of-function effect of identified variants was assessed by luciferase assay in cells transiently expressing TAB2 deleterious alleles. In available patients' fibroblasts, variant pathogenicity was further explored by immunoblot and osteoblast differentiation assays. The transcriptomic profile of fibroblasts was investigated by RNA sequencing. RESULTS: A total of 11 individuals from 8 families were heterozygotes for a novel TAB2 variant. In total, 7 variants were predicted to be null alleles and 1 was a missense change. An additional subject was heterozygous for a 52 kb microdeletion involving TAB2 exons 1 to 3. Luciferase assay indicated a decreased transcriptional activation mediated by NF-κB signaling for all point variants. Immunoblot analysis showed a reduction of TAK1 phosphorylation while osteoblast differentiation was impaired. Transcriptomic analysis identified deregulation of multiple pleiotropic pathways, such as TGFß-, Ras-MAPK-, and Wnt-signaling networks. CONCLUSION: Our data defined a novel disorder associated with loss-of-function or, more rarely, hypomorphic alleles in a restricted linker region of TAB2. The pleiotropic manifestations in this disorder partly recapitulate the 6q25.1 (TAB2) microdeletion syndrome and deserve the definition of cardio-facial-cutaneous-articular syndrome.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , NF-kappa B , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Éxons/genética , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Fosforilação , Transdução de Sinais
10.
Genes (Basel) ; 12(12)2021 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-34946877

RESUMO

(1) Background: Classic Ehlers-Danlos syndrome (cEDS) is a heritable connective tissue disorder characterized by joint hypermobility and skin hyperextensibility with atrophic scarring. Many cEDS individuals carry variants in either the COL5A1 or COL5A2 genes. Mosaicism is relatively common in heritable connective tissue disorders but is rare in EDS. In cEDS, a single example of presumed gonosomal mosaicism for a COL5A1 variant has been published to date. (2) Methods: An 8-year-old girl with cEDS was analyzed by next-generation sequencing (NGS). Segregation was performed by Sanger sequencing in her unaffected parents. In the father, the mosaicism of the variant was further analyzed by targeted NGS and droplet digital PCR (ddPCR) in the blood and by Sanger sequencing in other tissues. (3) Results: The NGS analysis revealed the novel germline heterozygous COL5A1 c.1369G>T, p.(Glu457*) variant in the proband. Sanger chromatogram of the father's blood specimen suggested the presence of a low-level mosaicism for the COL5A1 variant, which was confirmed by NGS and estimated to be 4.8% by ddPCR. The mosaicism was also confirmed by Sanger sequencing in the father's saliva, hair bulbs and nails. (4) Conclusions: We described the second case of cEDS caused by paternal gonosomal mosaicism in COL5A1. Parental mosaicism could be an issue in cEDS and, therefore, considered for appropriate genetic counseling.


Assuntos
Colágeno Tipo V/genética , Síndrome de Ehlers-Danlos/genética , Mosaicismo , Cromossomos Sexuais/genética , Criança , Códon sem Sentido , Análise Mutacional de DNA , Feminino , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Linhagem
11.
Animals (Basel) ; 11(6)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207904

RESUMO

The quail Coturnix coturnix is a seasonal breeding species, with the annual reproductive cycle of its testes comprising an activation phase and a regression phase. Our previous results have proven that the testicular levels of both 17ß-estradiol (E2) and androgens are higher during the reproductive period compared to the non-reproductive period, which led us to hypothesize that estrogens and androgens may act synergistically to initiate spermatogenesis. The present study was, therefore, aimed to investigate the estrogen responsive system in quail testis in relation to the reproduction seasonality, with a focus on the molecular pathways elicited in both active and regressive quail testes. Western blotting and immunohistochemistry analysis revealed that the expression of ERα, which is the predominant form of estrogen receptors in quail testis, was correlated with E2 concentration, suggesting that increased levels of E2-induced ERα could play a key role in the resumption of spermatogenesis during the reproductive period, when both PCNA and SYCP3, the mitotic and meiotic markers, respectively, were also increased. In the reproductive period we also found the activation of the ERK1/2 and Akt-1 kinase pathways and an increase in second messengers cAMP and cGMP levels. In the non-reproductive phase, when the E2/ERα levels were low, the inactivation of ERK1/2 and Akt-1 pathways favored apoptotic events due to an increase in the levels of Bax and cytochrome C, with a consequent regression of the gonad.

12.
Hist Philos Life Sci ; 43(2): 59, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33864155

RESUMO

COVID-19 has revealed that science needs to learn how to better deal with the irreducible uncertainty that comes with global systemic risks as well as with the social responsibility of science towards the public good. Further developing the epistemological principles of new theories and experimental practices, alternative investigative pathways and communication, and diverse voices can be an important contribution of history and philosophy of science and of science studies to ongoing transformations of the scientific enterprise.


Assuntos
Diversidade Cultural , Conhecimento , Ciência , Responsabilidade Social , COVID-19/prevenção & controle , Comunicação , Humanos , SARS-CoV-2 , Incerteza
13.
Amino Acids ; 52(9): 1263-1273, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32930873

RESUMO

D-Aspartate, D-serine and D-alanine are a regular occurrence in mammalian endocrine tissues, though in amounts varying with the type of gland. The pituitary gland, pineal gland, thyroid, adrenal glands and testis contain relatively large amounts of D-aspartate in all species examined. D-alanine is relatively abundant in the pituitary gland and pancreas. High levels of D-serine characterize the hypothalamus. D-leucine, D-proline and D-glutamate are generally low. The current knowledge of physiological roles of D-amino acids in endocrine tissues is far from exhaustive, yet the topic is attracting increasing interest because of its potential in pharmacological application. D-aspartate is known to act at all levels of the hypothalamus-pituitary-testis axis, playing a key role in reproductive biology in several vertebrate classes. An involvement of D-amino acids in the endocrine function of the pancreas is emerging. D-Aspartate has been immunolocalized in insulin-containing secretory granules in INS-1 E clonal ß cells and is co-secreted with insulin by exocytosis. Specific immunolocalization of D-alanine in pituitary ACTH-secreting cells and pancreatic ß-cells suggests that this amino acid participates in blood glucose regulation in mammals. By modulating insulin secretion, D-serine probably participates in the control of systemic glucose metabolism by modulating insulin secretion. We anticipate that future investigation will significantly increase the functional repertoire of D-amino acids in homeostatic control.


Assuntos
Aminoácidos/metabolismo , Exocitose , Glucose/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Animais , Mamíferos
14.
Artigo em Inglês | MEDLINE | ID: mdl-32477274

RESUMO

The present investigation was undertaken to increase our insight into the molecular basis of the physiological changes in rat testis induced by food withdrawal, and to clarify whether reduced testicular function can be ameliorated by mild exercise. Male rats were selected for four separate experiments. The first of each group was chow-fed, the second was chow-fed and submitted to exercise (5 bouts in total for 30 min at 15 m/min, and 0° inclination), the third was submitted to food withdrawal (66 h) and the fourth was submitted to food withdrawal and to exercise. At the end of experiments, we investigated (i) serum and testicular sex hormone levels; (ii) protein levels of StAR, 3ß-Hydroxysteroid dehydrogenase (3ß-HSD) and P450 aromatase, which play a key role in steroid hormone biosynthesis; and (iii) protein levels of mitotic and meiotic markers of spermatogenesis in rats, in relation to testis morphology and morphometry. We found that mild exercise or food withdrawal alone induced a significant increase or decrease in both serum and testis testosterone levels, respectively. Interestingly, we found that these levels were brought back to basal levels when food withdrawal was combined with mild exercise. The changes in testosterone levels observed in our experimental groups correlated well with the expression of steroidogenic enzymes as well as with spermatogenic activity. With mild exercise the increased testosterone/17ß-estradiol (T/E2) ratio in the testis correlated with an increased spermatogenic activity. The T/E2 ratio dropped in fasted rats and was significantly reversed when food withdrawal was combined with exercise. Histological and morphometric analyses confirmed that spermatogenic activity varied in concomitance with each experimental condition. Importantly, the testis and serum T/E2 ratios correlated, confirming that exercise rescues the decline in food withdrawal-induced spermatogenesis. In conclusion, this study highlights that mild exercise normalizes the reduced spermatogenic activity caused by food withdrawal through the modulation of the steroidogenic pathway and restoring the T/E2 ratio, underlining the beneficial effects of mild exercise on the prevention and/or amelioration of reduced testis function caused by restricted caloric intake.


Assuntos
Restrição Calórica , Jejum , Hormônios Esteroides Gonadais/biossíntese , Condicionamento Físico Animal , Espermatogênese , Esteroides/biossíntese , Testículo/metabolismo , 3-Hidroxiesteroide Desidrogenases/genética , 3-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Aromatase/genética , Aromatase/metabolismo , Regulação da Expressão Gênica , Masculino , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Ratos , Ratos Wistar
15.
J Radiol Prot ; 40(1): 83-118, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31461410

RESUMO

In this paper, we describe a practical and convenient method to include the contribution of the ingrowth of radioactive progeny in dose assessments of the corresponding parent nuclides. This method modifies the dose coefficients (DCs) of parent nuclides by adding weighted DCs of the corresponding daughter nuclides to them. Based on the decay kinetics of serial nuclear transformations, the progeny weighting factors, with values between 0 and 1, are derived by analysis of the time-integrated activity of each nuclide in the (branched) decay chain headed by a parent nuclide. Using the electronic, nuclear-decay database of Publication 107 of the International Commission on Radiological Protection (ICRP 2008), DC weighting factors for annual dose assessments are calculated for all daughter radionuclides in the decay chains and are tabulated in this paper. Weighting factors based on integration periods other than one year, ranging from 1 h-70 years, are also provided (see the supplementary material). With a priori established weighting factors, dose assessments become significantly simplified by considering the decay kinetics of only the parent nuclides and by applying the modified DCs. This ensures that the ingrowth of progeny is taken into account realistically. In some cases, one requires a conservative estimate of the dose, for instance when dealing with issues of the clearance of materials under regulatory control. Therefore, we adapted the weighting-factor method to derive conservative DC weighting factors for dose evaluations. These values are calculated for various integration periods and compared with those from an existing method adopted by the Euratom Article 31 Group of Experts and by the International Atomic Energy Agency. Identical progeny weighting factors are obtained for long-lived parent radionuclides, whereas for short-lived parent radionuclides, the new method can yield significantly larger values. For example, the weighting factor of I-131 (daughter of parent Te-131) increases from 0.002 to 1.0 based on an integration period of 1 year. The progeny DC weighting factors, derived based on nuclear transformations in exit-only decay chains, may not always be suitable for use in radiological dose evaluations. For instance, when environmental removal pathways are dominant, the application of these weighting factors may have its limitations. This paper, therefore, provides guidance on the proper selection and application of weighting factors.


Assuntos
Radioisótopos do Iodo/química , Doses de Radiação , Agências Internacionais , Lesões por Radiação/prevenção & controle , Proteção Radiológica , Radioatividade
16.
BMJ Open ; 9(8): e030286, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31462483

RESUMO

Health is more than the absence of disease. It is also more than a biological phenomenon. It is inherently social, psychological, cultural and historical. While this has been recognised by major health actors for decades, open questions remain as to how to build systems that reflect the complexity of health, disease and sickness, and in a context that is increasingly technologised. We argue that an urgent change of approach is necessary. Methods and concepts from the humanities and social science must be embedded in the concepts and methods of the health sciences if we are to promote sustainable interventions capable of engaging with the recognised complexity of health, disease and sickness. Our vision is one of radical interdisciplinarity, integrating aspects of biological, psychological, social and humanities approaches across areas of urgent health need. Radical interdisciplinarity, we argue, entails the practical, methodological and conceptual integration of these approaches to health.


Assuntos
Ocupações em Saúde , Ciências Humanas , Comunicação Interdisciplinar , Ciências Sociais
17.
J Exp Zool B Mol Dev Evol ; 332(6): 198-209, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31433565

RESUMO

The quail Coturnix coturnix is a seasonal breeder with a physiological switch on/off of gonadic activity. Photoperiod and temperature are the major environmental factors regulating the spermatogenesis. To more thoroughly comprehend the steroidogenic pathways that govern the seasonal reproductive cycle, we have investigated the localization of StAR protein and steroidogenic enzymes (3ß-HSD, 17ß-HSD, P450 aromatase, and 5α-Red) as well as androgen and estrogen levels, in the testis of reproductive and nonreproductive quails. We demonstrated that StAR, 3ß-HSD, 17ß-HSD, P450 aromatase, and 5α-Red were always present in the somatic (Leydig and Sertoli cells) and germ cells (spermatogonia, spermatocytes I and II, spermatids, and spermatozoa). In addition, by western blot analysis, we demonstrated that 17ß-HSD, P450 aromatase, and 5α-Red showed the highest expression levels during the reproductive testis compared with nonreproductive one. Accordingly, we also found that during the reproductive phase the highest titres of testosterone, 17ß-estradiol, and 5α-dihydrotestosterone are recorded. In conclusion, our findings demonstrated that in C. coturnix: (a) both somatic and germ cells are involved in the local synthesis of sex hormones; (b) 17ß-HSD, P450 aromatase, and 5α-Red expressions, as well as testicular androgens and estrogens, increased in reproductive quail testis. This study strongly indicates that the steroidogenic process in quail testis exhibits seasonal changes with the promotion of both androgenic and estrogenic pathways in the reproductive period, suggesting their synergic mechanism in the spermatogenesis regulation.


Assuntos
Coturnix/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Fragmentos de Peptídeos/metabolismo , Fosfoproteínas/metabolismo , Estações do Ano , Testículo/enzimologia , Animais , Masculino , Testículo/citologia , Testículo/metabolismo
18.
J Cell Biochem ; 120(7): 11044-11055, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30762900

RESUMO

Excitatory amino acids (EAAs) are found present in the nervous and reproductive systems of animals. Numerous studies have demonstrated a regulatory role for Glutamate (Glu), d-aspartate ( d-Asp) and N-methyl- d-aspartate (NMDA) in the control of spermatogenesis. EAAs are able to stimulate the Glutamate receptors, including the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Here in, we assess expression of the main AMPAR subunits, GluA1 and GluA2/3, in the mouse testis and in spermatogonial GC-1 cells. The results showed that both GluA1 and GluA2/3 were localized in mouse testis prevalently in spermatogonia. The subunit GluA2/3 was more highly expressed compared with GluA1 in both the testis and the GC-1 cells. Subsequently, GC-1 cells were incubated with medium containing l-Glu, d-Glu, d-Asp or NMDA to determine GluA1 and GluA2/3 expressions. At 30 minutes and 2 hours of incubation, EAA-treated GC-1 cells showed significantly higher expression levels of both GluA1 and GluA2/3. Furthermore, p-extracellular signal-regulated kinase (ERK), p-Akt, proliferating cell nuclear antigen (PCNA), and Aurora B expressions were assayed in l-Glu-, d-Glu-, and NMDA-treated GC-1 cells. At 30 minutes and 2 hours of incubation, treated GC-1 cells showed significantly higher expression levels of p-ERK and p-Akt. A consequent increase of PCNA and Aurora B expressions was induced by l-Glu and NMDA, but not by d-Glu. Our study demonstrates a direct effect of the EAAs on spermatogonial activity. In addition, the increased protein expression levels of GluA1 and GluA2/3 in EAA-treated GC-1 cells suggest that EAAs could activate ERK and Akt pathways through the AMPAR. Finally, the increased PCNA and Aurora B levels may imply an enhanced proliferative activity.

19.
Eur J Clin Invest ; 48(6): e12933, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29604052

RESUMO

BACKGROUND: Cancer is believed to arise through the perturbation of pathways and the order of pathway perturbation events can enhance understanding and evaluation of carcinogenicity. This order has not been examined so far, and this study aimed to fill this gap by attempting to gather evidence on the potential temporal sequence of events in carcinogenesis. DESIGN: The methodology followed was to discuss first the temporal sequence of hallmarks of cancer from the point of view of pathological specimens of cancer (essentially branched mutations) and then to consider the hallmarks of cancer that one well-known carcinogen, benzo(a)pyrene, can modify. RESULTS: Even though the sequential order of driving genetic alterations can vary between and within tumours, the main cancer pathways affected are almost ubiquitous and follow a generally common sequence: resisting cell death, insensitivity to antigrowth signals, sustained proliferation, deregulated energetics, replicative immortality and activation of invasion and metastasis. The first 3 hallmarks can be regarded as almost simultaneous while angiogenesis and avoiding immune destruction are perhaps the only hallmarks with a varying position in the above sequence. CONCLUSIONS: Our review of hallmarks of cancer and their temporal sequence, based on mutational spectra in biopsies from different cancer sites, allowed us to propose a hypothetical temporal sequence of the hallmarks. This sequence can add molecular support to the evaluation of an agent as a carcinogen as it can be used as a conceptual framework for organising and evaluating the strength of existing evidence.


Assuntos
Benzo(a)pireno/toxicidade , Carcinógenos/toxicidade , Neoplasias/induzido quimicamente , Carcinogênese , Morte Celular , Proliferação de Células/genética , Sobrevivência Celular/genética , Humanos , Mutação , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Fatores de Tempo , Evasão Tumoral
20.
Riv Psichiatr ; 53(1): 49-52, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29493654

RESUMO

Introduction: Deficiency of growth hormone (GH) in absence of pituitary injuries is one of the causes of short stature and of the non organic failure to thrive (NOFTT) condition. Advances in developmental psychology have highlighted the role of emotions and caregiving behaviors in the organization of child's personality and psychobiology, with the mother-son attachment bond being considered a fundamental developmental experience. The objective of the present preliminary study was to assess whether there are significant correlations between attachment patterns and GH levels in a sample of subjects with NOFTT. Methods: Overall, 27 children (mean age 9.49±2.63 years) with NOFTT were enrolled. Perceived attachment security was assessed through the Security Scale (SS) and its subscales focused on maternal and paternal security. Pearson partial correlation was used to test associations between GH levels and SS measures adjusting for confounding factors (i.e. age, gender and body mass index). Results: Across all subjects, GH was significantly positively correlated with general security (r=0.425; p=0.038) and maternal security (r=0.451; p=0.027) and not significantly correlated with paternal security (r=0.237; p=0.264). Discussion: These findings preliminarily suggest that the association between GH levels and perceived attachment security may play a role in the pathophysiology of NOFTT and add to the accumulating evidence that attachment patterns may be related with specific psychoendocrine underpinnings.


Assuntos
Insuficiência de Crescimento/sangue , Insuficiência de Crescimento/psicologia , Hormônio do Crescimento Humano/sangue , Apego ao Objeto , Criança , Feminino , Humanos , Masculino
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