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1.
Methods Mol Biol ; 2206: 67-88, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32754812

RESUMO

Several studies are available addressing the mechanisms of vascular morphogenesis in order to unravel how cooperative cell behavior can follow from the underlying, genetically regulated behavior of endothelial cells and from cell-to-cell and cell-to-extracellular matrix interactions. From the morphological standpoint several aspects of the process are of interest. They include the way the pattern of vessels fills the available tissue space and how the network grows during the angiogenic process, namely how a main trunk divides into smaller branches, and how branching occurs at different distances from the root point of a vascular tree. A third morphological aspect of interest concerns the spatial relationship between vessels and tissue cells able to secrete factors modulating endothelial cells self-organization, thus influencing vascular rearrangement.In the present chapter image analysis methods allowing for a quantitative characterization of these morphological aspects will be detailed and discussed. They are almost based on concepts derived from the theoretical framework represented by spatial statistics.

2.
Sci Rep ; 10(1): 16789, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033332

RESUMO

Perfluoroalkyl substances (PFAS) are a class of compounds used in industry and consumer products. Perfluorooctanoic acid (PFOA) is the predominant form in human samples and has been shown to induce severe health consequences, such as neonatal mortality, neurotoxicity, and immunotoxicity. Toxicological studies indicate that PFAS accumulate in bone tissues and cause altered bone development. Epidemiological studies have reported an inverse relationship between PFAS and bone health, however the associated mechanisms are still unexplored. Here, we present computational, in silico and in vitro evidence supporting the interference of PFOA on vitamin D (VD). First, PFOA competes with calcitriol on the same binding site of the VD receptor, leading to an alteration of the structural flexibility and a 10% reduction by surface plasmon resonance analysis. Second, this interference leads to an altered response of VD-responsive genes in two cellular targets of this hormone, osteoblasts and epithelial cells of the colorectal tract. Third, mineralization in human osteoblasts is reduced upon coincubation of PFOA with VD. Finally, in a small cohort of young healthy men, PTH levels were higher in the exposed group, but VD levels were comparable. Altogether these results provide the first evidence of endocrine disruption by PFOA on VD pathway by competition on its receptor and subsequent inhibition of VD-responsive genes in target cells.

3.
Int J Dev Biol ; 64(7-8-9): 397-407, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33063834

RESUMO

Branching morphogenesis, the creation of branched structures in the body, is a key feature of animal and plant development. It requires the coordinated interplay of multiple types of epithelial cells with the surrounding extracellular matrix. Cell migration, proliferation, and extracellular matrix dynamics have different roles in driving budding in different organs. This historical review article summarizes the first founding literature data concerning branching morphogenesis occurring in kidney, lung, vascular system, mammary glands and neurons.

4.
J Forensic Sci ; 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32957166

RESUMO

High-quality digital three-dimensional (3D) reconstructions of microscopic findings have been used in anatomical and histopathologic research, but their use in forensic pathology may also be of interest. This paper presents an application of these methods to better characterize the pathway of a stab wound of the anterior surface of the heart in a case of suicide. A portion of the heart wall including the stab wound was serially sectioned for microscopic analysis along the full extent of the wound. Histologic sections were digitally acquired, and a 3D reconstruction was created with ImageJ software for 3D computer graphics. This showed a full-thickness wound path extending to the endocardial surface of the left ventricle, curvilinear in appearance. After correction for shrinkage, 3D reconstruction allowed estimation of the dimensions of the myocardial injury and comparison of the appearance of the wound with the suspected knife used. The curvilinear appearance was considered to reflect injury during myocardial contraction. Complete microscopic sectioning and 3D reconstruction may allow virtual sectioning through various orientations and also provide useful forensic information for selected injuries.

5.
Medicina (Kaunas) ; 56(6)2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32471194

RESUMO

Background and objectives: Possible disorders after delivery may interfere with the quality of life. The aim of this study was to ascertain whether abdominal muscles and fasciae differ in women depending on whether they experienced transverse cesarean section (CS) or vaginal delivery (VA) in comparison with healthy nulliparous (NU). Materials and methods: The thicknesses of abdominal muscles and fasciae were evaluated by ultrasound in 13 CS, 10 VA, and 13 NU women (we examined rectus abdominis (RA); external oblique (EO); internal oblique (IO); transversus abdominis (TrA); total abdominal muscles (TAM = EO + IO + TrA); inter-rectus distance (IRD); thickness of linea alba (TLA); rectus sheath (RS), which includes anterior fascia of RS and posterior fascia of RS (P-RS); loose connective tissue between sublayers of P-RS (LCT); abdominal perimuscular fasciae (APF), which includes anterior fascia of EO, fasciae between EO, IO, and TrA, and posterior fascia of TrA). Data on pain intensity, duration, and location were collected. Results: Compared with NU women, CS women had wider IRD (p = 0.004), thinner left RA (p = 0.020), thicker right RS (p = 0.035) and APF (left: p = 0.001; right: p = 0.001), and IO dissymmetry (p = 0.009). VA women had thinner RA (left: p = 0.008, right: p = 0.043) and left TAM (p = 0.024), mainly due to left IO (p = 0.027) and RA dissymmetry (p = 0.035). However, CS women had thicker LCT (left: p = 0.036, right: p < 0.001), APF (left: p = 0.014; right: p = 0.007), and right IO (p = 0.028) than VA women. There were significant correlations between pain duration and the affected fasciae/muscles in CS women. Conclusions: CS women showed significant alterations in both abdominal fasciae and muscle thicknesses, whereas VA women showed alterations mainly in muscles. Thinner RA and/or dissymmetric IO, wider IRD, and thicker LCT and APF after CS may cause muscle deficits and alteration of fascial gliding, which may induce scar, abdominal, low back, and/or pelvic pain.

6.
PLoS One ; 15(4): e0224059, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32352963

RESUMO

The aim of this study is to investigate the factors influencing consumer willingness to accept the use of insects to feed poultry, cattle, pigs, and fish. To reach this objective, we conducted an online survey with Brazilian consumers. 600 questionnaires were collected. We analyzed data using descriptive statistics and logistic regression models. In general, the use of insects to feed poultry, pigs and cattle was not widely accepted. A more widely acceptance was found for the use of insects to feed fish. The results of logistic regressions models show that positive attitudes are associated with a higher probability of accepting the use of insects to feed poultry, pigs, cattle, and fish. Perceived benefits were associated with a higher likelihood of accepting the use of insects to feed fish. However, perceived benefits were also associated with a lower likelihood of accepting the use of insects to feed poultry. Perceived challenges were associated with a higher likelihood of accepting the use of insects to feed poultry. However, perceived challenges were associated with a lower likelihood of accepting the use of insects to feed pigs.


Assuntos
Ração Animal/normas , Atitude , Comportamento do Consumidor , Insetos Comestíveis , Animais , Brasil , Bovinos , Peixes , Aves Domésticas , Opinião Pública , Suínos
7.
Int J Mol Sci ; 21(8)2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32331297

RESUMO

The demonstrated expression of endocannabinoid receptors in myofascial tissue suggested the role of fascia as a source and modulator of pain. Fibroblasts can modulate the production of the various components of the extracellular matrix, according to type of stimuli: physical, mechanical, hormonal, and pharmacological. In this work, fascial fibroblasts were isolated from small samples of human fascia lata of the thigh, collected from three volunteer patients (two men, one woman) during orthopedic surgery. This text demonstrates for the first time that the agonist of cannabinoid receptor 2, HU-308, can lead to in vitro production of hyaluronan-rich vesicles only 3-4 h after treatment, being rapidly released into the extracellular environment. We demonstrated that these vesicles are rich in hyaluronan after Alcian blue and Toluidine blue stainings, immunocytochemistry, and transmission electron microscopy. In addition, incubation with the antagonist AM630 blocked vesicles production by cells, confirming that release of hyaluronan is a cannabinoid-mediated effect. These results may show how fascial cells respond to the endocannabinoid system by regulating and remodeling the formation of the extracellular matrix. This is a first step in our understanding of how therapeutic applications of cannabinoids to treat pain may also have a peripheral effect, altering the biosynthesis of the extracellular matrix in fasciae and, consequently, remodeling the tissue and its properties.

8.
Int J Mol Sci ; 21(2)2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31936344

RESUMO

Perfluoro-alkyl substances (PFAS), particularly perfluoro-octanoic acid (PFOA), are persisting environmental chemicals showing bioaccumulation in human tissues. Recently, exposure to PFAS has been associated with increased prevalence of cardiovascular diseases (CVDs). However, a causal role of PFAS in atherosclerosis pathogenesis is under-investigated. Here, we investigated the effect of PFOA exposure on platelets' function, a key player in atherosclerosis process. PFOA accumulation in platelets was evaluated by liquid chromatography-mass spectrometry. Changes in platelets' membrane fluidity and activation after dose-dependent exposure to PFOA were evaluated by merocyanine 540 (MC540) and anti P-Selectin immune staining at flow cytometry, respectively. Intracellular calcium trafficking was analyzed with Fluo4M probe, time-lapse live imaging. Platelets' aggregation state was also evaluated with Multiplate® aggregometry analyzer in 48 male subjects living in a specific area of the Veneto region with high PFAS environmental pollution, and compared with 30 low-exposure control subjects. Platelets' membrane was the major target of PFOA, whose dose-dependent accumulation was associated in turn with increased membrane fluidity, as expected by a computational model; increased activation at resting condition; and both calcium uptake and aggregation upon activation. Finally, exposed subjects had higher serum and platelets levels of PFOA, together with increased aggregation parameters at Multiplate®, compared with controls. These data help to explain the emerging association between PFAS exposure and CVD.


Assuntos
Plaquetas/efeitos dos fármacos , Doenças Cardiovasculares/sangue , Fluorcarbonetos/toxicidade , Poluentes Químicos da Água/toxicidade , Adulto , Caprilatos/toxicidade , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/patologia , Poluição Ambiental/análise , Humanos , Itália , Masculino , Agregação Plaquetária/efeitos dos fármacos , Testes de Função Plaquetária , Fatores de Risco , Adulto Jovem
9.
Prog Mol Biol Transl Sci ; 169: 247-277, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31952688

RESUMO

The discovery of receptor-receptor interactions in the early 1980s, together with a more accurate focusing of allosteric mechanisms in proteins, expanded the knowledge on the G protein-coupled receptor (GPCR)-mediated signaling processes. GPCRs were seen to operate not only as monomers, but also as quaternary structures shaped by allosteric interactions. These integrative mechanisms can change the function of the GPCRs involved, leading to a sophisticated dynamic of the receptor assembly in terms of modulation of recognition and signaling. In this context, the heterodimeric complex formed by the adenosine A2A and the dopamine D2 receptors likely represents a prototypical example. The pharmacological evidence obtained, together with the tissue distribution of the A2A-D2 heteromeric complexes, suggested they could represent a target for new therapeutic strategies addressing significant disorders of the central nervous system. The research findings and the perspectives they offer from the therapeutic standpoint are the focus of the here presented discussion.

10.
Microvasc Res ; 128: 103935, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31655306

RESUMO

The chick embryo includes the area vasculosa is subdivided into 2 concentric zones, the inner transparent area pellucida vasculosa and the surrounding less transparent area opaca vasculosa, peripherally limited by the sinus terminalis. In this study, we have analyzed by a modern morphometric approach the total length of the vascular network, the number of vascular branches, of the branching points density, the modality of vessel ramification, and spatial arrangement of the vascular network in four consecutive stages of development of the area vasculosa. The results have shown that there is a significant 15% increase in the total length of the vascular network associated with a progressive increase of the number of vascular branches and of the branching points density. Moreover, the results indicated that vascular spatial disorder significantly decreased during development in area vasculosa, suggesting a more uniform occupancy of the tissue by the vascular pattern. Finally, a more regular pattern of branching was observed, as indicated by the significant decrease of topological disorder of the vascular tree.

11.
Sci Rep ; 9(1): 19432, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31857654

RESUMO

GPRC6A is acknowledged as a major regulator of energy metabolism and male fertility through the action of undercarboxylated osteocalcin (ucOCN), representing a possible therapeutic target. We recently showed that the sex hormone-binding globulin (SHBG) binds to GPRC6A through the likely involvement of the 141-161 domain. To confirm this model, here we investigated the possible binding and agonist activity of SHBG(141-161) domain-peptide (SHBG141-161) on GPRC6A. The binding of SHBG141-161 to GPRC6A and downstream dissociation from Gαi(GDP) protein was computationally modelled. SHBG141-161 was obtained by solid-phase synthesis, characterized by circular dichroism (CD) and the receptor binding was assessed by displacement of ucOCN on HEK-293 cells transfected with GPRC6A gene. Agonist activity of SHBG141-161 was assessed on Leydig MA-10 and Langerhans ß-TC6 cell lines through the GPRC6A-mediated release of testosterone (T) and insulin. SHBG141-161 was predicted to bind to GPRC6A and to reduce the affinity for Gαi(GDP) at computational level. Conformational properties and binding to GPRC6A of the synthetic SHBG141-161 were confirmed by CD and displacement experiments. SHBG141-161 stimulated cell secretion of T and insulin, with dose dependency from 10-13 to 10-11M for T release (respectively P = 0,041 10-13M; P = 0,032 10-12M; P = 0,008 10-11M vs basal) and for 10-12 to 10-10M for insulin (respectively P = 0,041 10-12M; P = 0,007 10-11M; P = 0,047 10-10M; P = 0,045 vs basal). Blockade with anti GPRC6A IgG abolished the response to SHBG141-161, suggesting agonist specificity. SHBG141-161 showed stimulating activity on GPRC6A, representing a template peptide with possible therapeutic use for metabolic and endocrine disorders.

12.
Medicine (Baltimore) ; 98(52): e18509, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876739

RESUMO

To evaluate progression of skin atrophy during 8 years of complete Conus-Cauda Syndrome and its recovery after 2 years of surface Functional Electrical Stimulation a cohort study was organized and implemented.Functional assessments, tissue biopsies, and follow-up were performed at the Wilhelminenspital, Vienna, Austria; skin histology and immunohistochemistry at the University of Padova, Italy on 13 spinal cord injury persons suffering up to 10 years of complete conus/cauda syndrome. Skin biopsies (n. 52) of both legs were analyzed before and after 2 years of home-based Functional Electrical Stimulation delivered by large anatomically shaped surface electrodes placed on the skin of the anterior thigh. Using quantitative histology we analyzed: 1. Epidermis atrophy by thickness and by area; 2. Skin flattening by computing papillae per mm and Interdigitation Index of dermal-epidermal junctions; 3. Presence of Langerhans cells.Linear regression analyses show that epidermal atrophy and flattening worsen with increasing years post- spinal cord injury and that 2 years of skin electrostimulation by large anatomically shaped electrodes reverses skin changes (pre-functional Electrical Stimulation vs post-functional Electrical Stimulation: thickness 39%, P < .0001; area 41%, P < .0001; papillae n/mm 35%, P < 0.0014; Interdigitation index 11%, P < 0.018), producing a significant recovery to almost normal levels of epidermis thickness and of dermal papillae, with minor changes of Langerhans cells, despite 2 additional years of complete Conus-Cauda Syndrome.In complete Conus-Cauda Syndrome patients, the well documented beneficial effects of 2 years of surface h-b Functional Electrical Stimulation on strength, bulk, and muscle fiber size of thigh muscles are extended to skin, suggesting that electrical stimulation by anatomically shaped electrodes fixed to the skin is also clinically relevant to counteract atrophy and flattening of the stimulated skin. Mechanisms, pros and cons are discussed.


Assuntos
Terapia por Estimulação Elétrica/métodos , Epiderme/patologia , Dermatopatias/terapia , Traumatismos da Medula Espinal/complicações , Medula Espinal , Adulto , Atrofia , Biópsia , Humanos , Pessoa de Meia-Idade , Pele/patologia , Dermatopatias/etiologia , Dermatopatias/patologia , Traumatismos da Medula Espinal/patologia , Síndrome , Coxa da Perna , Adulto Jovem
13.
Prev Vet Med ; 170: 104718, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31421489

RESUMO

Brazil, one of the leading countries in livestock production, has not yet developed legislation considering animal welfare issues and most of the actions to improve farm animal welfare (FAW) standards are developed by livestock industries and government focusing in meet the demands of exporting countries. Such actions resulted in FAW protocols and manuals for adoption of best management practices. In this context, farmers' decisions are of particular importance as they may comply with current FAW protocols or even decide to provide better FAW standards than required. A present example of farmers' decisions to provide better FAW standards than required by FAW protocols is in the adoption of environmental enrichment in pig farming. This practice is widely available to pig farmers, however, anecdotal evidence shows that the adoption rate is low. This study uses the theory of planned behavior (TPB) as a framework to identify the socio-psychological factors that influence pig farmers' intention to adopt environmental enrichment on their farms. The TPB hypothesizes that intention is determined by three psychological constructs: attitude, subjective norms, and perceived behavioral control. These three constructs are derived from behavioral, normative, and control beliefs, respectively. Self-identity was added as an additional construct to explain intention. A survey with 185 farmers was conducted. We used Partial-Least-Square Structural Equation Modeling (PLS-SEM) to identify the impact of attitude, subjective norms, perceived behavioral control, and self-identity on farmers' intention to adopt environmental enrichment on their farms. We used MIMIC models to identify the most important beliefs underlying farmers' intention to adopt environmental enrichment in their farms. Results show that the intention of farmers to adopt was mainly determined by their positive perceptions about their own capability to adopt environmental enrichment (perceived behavioral control), followed by their perceptions about the social pressure to adopt it (subjective norms), their positive evaluations of adoption (attitude), and self-identity. The most important behavioral beliefs were 'increase productivity', and 'decrease animals stress'. The most important normative beliefs were 'family', 'neighbor farmers', 'pig buyers', and 'experts'. The most important control belief was 'receive bonus when selling pigs'. These results revealed important implications to design public and private interventions aimed to stimulate the adoption of animal friendly practices.


Assuntos
Bem-Estar do Animal/estatística & dados numéricos , Atitude , Controle Comportamental , Fazendeiros/psicologia , Intenção , Normas Sociais , Adulto , Brasil , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos
14.
Artigo em Inglês | MEDLINE | ID: mdl-31466374

RESUMO

Humans are increasingly aware that their fate will depend on the wisdom they apply in interacting with the ecosystem. Its health is defined as the condition in which the ecosystem can deliver and continuously renew its fundamental services. A healthy ecosystem allows optimal interactions between humans and the other biotic/abiotic components, and only in a healthy ecosystem can humans survive and efficiently reproduce. Thus, both the human and ecosystem health should be considered together in view of their interdependence. The present article suggests that this relationship could be considered starting from the Hippocrates (460 BC-370 BC) work "On Airs, Waters, and Places" to derive useful medical and philosophical implications for medicine which is indeed a topic that involves scientific as well as philosophical concepts that implicate a background broader than the human body. The brain-body-ecosystem medicine is proposed as a new more complete approach to safeguarding human health. Epidemiological data demonstrate that exploitation of the environment resulting in ecosystem damage affects human health and in several instances these diseases can be detected by modifications in the heart-brain interactions that can be diagnosed through the analysis of changes in heart rate variability.


Assuntos
Encéfalo , Ecossistema , Saúde Holística , Corpo Humano , Humanos
15.
Int J Mol Sci ; 20(10)2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31109007

RESUMO

Our previous findings indicate that A2A and D2 receptors are co-expressed on adult rat striatal astrocytes and on the astrocyte processes, and that A2A-D2 receptor⁻receptor interaction can control the release of glutamate from the processes. Functional evidence suggests that the receptor⁻receptor interaction was based on heteromerization of native A2A and D2 receptors at the plasma membrane of striatal astrocyte processes. We here provide biochemical and biophysical evidence confirming that receptor⁻receptor interaction between A2A and D2 receptors at the astrocyte plasma membrane is based on A2A-D2 heteromerization. To our knowledge, this is the first direct demonstration of the ability of native A2A and D2 receptors to heteromerize on glial cells. As striatal astrocytes are recognized to be involved in Parkinson's pathophysiology, the findings that adenosine A2A and dopamine D2 receptors can form A2A-D2 heteromers on the astrocytes in the striatum (and that these heteromers can play roles in the control of the striatal glutamatergic transmission) may shed light on the molecular mechanisms involved in the pathogenesis of the disease.


Assuntos
Astrócitos/metabolismo , Receptor A2A de Adenosina/metabolismo , Receptores de Dopamina D2/metabolismo , Animais , Membrana Celular/metabolismo , Corpo Estriado/metabolismo , Ácido Glutâmico/metabolismo , Multimerização Proteica , Ratos , Ratos Sprague-Dawley , Receptor A2A de Adenosina/química , Receptores de Dopamina D2/química
16.
Artigo em Inglês | MEDLINE | ID: mdl-30833931

RESUMO

The discovery of receptor-receptor interactions (RRI) has expanded our understanding of the role that G protein-coupled receptors (GPCRs) play in intercellular communication. The finding that GPCRs can operate as receptor complexes, and not only as monomers, suggests that several different incoming signals could already be integrated at the plasma membrane level via direct allosteric interactions between the protomers that form the complex. Most research in this field has focused on neuronal populations and has led to the identification of a large number of RRI. However, RRI have been seen to occur not only in neurons but also in astrocytes and, outside the central nervous system, in cells of the cardiovascular and endocrine systems and in cancer cells. Furthermore, RRI involving the formation of macromolecular complexes are not limited to GPCRs, being also observed in other families of receptors. Thus, RRI appear as a widespread phenomenon and oligomerization as a common mechanism for receptor function and regulation. The discovery of these macromolecular assemblies may well have a major impact on pharmacology. Indeed, the formation of receptor complexes significantly broadens the spectrum of mechanisms available to receptors for recognition and signaling, which may be implemented through modulation of the binding sites of the adjacent protomers and of their signal transduction features. In this context, the possible appearance of novel allosteric sites in the receptor complex structure may be of particular relevance. Thus, the existence of RRI offers the possibility of new therapeutic approaches, and novel pharmacological strategies for disease treatment have already been proposed. Several challenges, however, remain. These include the accurate characterization of the role that the receptor complexes identified so far play in pathological conditions and the development of ligands specific to given receptor complexes, in order to efficiently exploit the pharmacological properties of these complexes.

17.
Int J Dev Neurosci ; 77: 3-17, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30465872

RESUMO

The stunning diversity of neurons and glial cells makes possible the higher functions of the central nervous system (CNS), allowing the organism to sense, interpret and respond appropriately to the external environment. This cellular diversity derives from a single primary progenitor cell type initiating lineage leading to the formation of both differentiated neurons and glial cells. The processes governing the differentiation of the progenitor pool of cells into mature nerve cells will be here briefly reviewed. They involve morphological transformations, specialized modes of cell division, migration, and controlled cell death, and are regulated through cell-cell interactions and cues provided by the extracellular matrix, as well as by humoral factors from the cerebrospinal fluid and the blood system. In this respect, a quite large body of studies have been focused on cytokines, proteins representing the main signaling network that coordinates immune defense and the maintenance of homeostasis. At the same time, they are deeply involved in CNS development as regulatory factors. This dual role in the nervous system appears of particular relevance for CNS pathology, since cytokine dysregulation (occurring as a consequence of maternal infection, exposure to environmental factors or prenatal hypoxia) can profoundly impact on neurodevelopment and likely influence the response of the adult tissue during neuroinflammatory events.


Assuntos
Citocinas/metabolismo , Microglia/metabolismo , Neurogênese/fisiologia , Neurônios/metabolismo , Transdução de Sinais/fisiologia , Animais , Astrócitos/metabolismo , Humanos
18.
Am J Physiol Lung Cell Mol Physiol ; 316(1): L6-L19, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30284924

RESUMO

Mesenchymal stem cells (MSCs) prevent the onset of bronchopulmonary dysplasia (BPD) in animal models, an effect that seems to be mediated by their secreted extracellular vesicles (EVs). The aim of this study was to compare the protective effects of intratracheally (IT) administered MSCs versus MSC-EVs in a hyperoxia-induced rat model of BPD. At birth, rats were distributed as follows: animals raised in ambient air for 2 wk ( n = 10), and animals exposed to 60% oxygen for 2 wk and treated with IT-administered physiological solution ( n = 10), MSCs ( n = 10), or MSC-EVs ( n = 10) on postnatal days 3, 7, and 10. The sham-treated hyperoxia-exposed animals showed reductions in total surface area of alveolar air spaces, and total number of alveoli ( Nalv), and an increased mean alveolar volume (Valv). EVs prompted a significant increase in Nalv ( P < 0.01) and a significant decrease in Valv ( P < 0.05) compared with sham-treated animals, whereas MSCs only significantly improved Nalv ( P < 0.05). Small pulmonary vessels of the sham-treated hyperoxia-exposed rats also showed an increase in medial thickness, which only EVs succeeded in preventing significantly ( P < 0.05). In conclusion, both EVs and MSCs reduce hyperoxia-induced damage, with EVs obtaining better results in terms of alveolarization and lung vascularization parameters. This suggests that IT-administered EVs could be an effective approach to BPD treatment.


Assuntos
Displasia Broncopulmonar/terapia , Vesículas Extracelulares/transplante , Células-Tronco Mesenquimais/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Ratos , Ratos Sprague-Dawley
19.
J Clin Endocrinol Metab ; 104(4): 1259-1271, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30403786

RESUMO

BACKGROUND: Considerable attention has been paid to perfluoroalkyl compounds (PFCs) because of their worldwide presence in humans, wildlife, and environment. A wide variety of toxicological effects is well supported in animals, including testicular toxicity and male infertility. For these reasons, the understanding of epidemiological associations and of the molecular mechanisms involved in the endocrine-disrupting properties of PFCs on human reproductive health is a major concern. OBJECTIVE: To investigate the relationship between PFC exposure and male reproductive health. DESIGN: This study was performed within a screening protocol to evaluate male reproductive health in high schools. PATIENTS: This is a cross-sectional study on 212 exposed males from the Veneto region, one of the four areas worldwide heavily polluted with PFCs, and 171 nonexposed controls. MAIN OUTCOME MEASURES: Anthropometrics, seminal parameters, and sex hormones were measured in young males from exposed areas compared with age-matched controls. We also performed biochemical studies in established experimental models. RESULTS: We found that increased levels of PFCs in plasma and seminal fluid positively correlate with circulating testosterone (T) and with a reduction of semen quality, testicular volume, penile length, and anogenital distance. Experimental evidence points toward an antagonistic action of perfluorooctanoic acid on the binding of T to androgen receptor (AR) in a gene reporter assay, a competition assay on an AR-coated surface plasmon resonance chip, and an AR nuclear translocation assay. DISCUSSION: This study documents that PFCs have a substantial impact on human health as they interfere with hormonal pathways, potentially leading to male infertility.


Assuntos
Caprilatos/toxicidade , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Fluorcarbonetos/toxicidade , Saúde Reprodutiva , Testosterona/metabolismo , Adolescente , Caprilatos/análise , Estudos Transversais , Disruptores Endócrinos/análise , Poluentes Ambientais/análise , Fluorcarbonetos/análise , Células HeLa , Humanos , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/diagnóstico , Itália , Masculino , Tamanho do Órgão/efeitos dos fármacos , Pênis/anatomia & histologia , Pênis/efeitos dos fármacos , Receptores Androgênicos/metabolismo , Sêmen/química , Sêmen/efeitos dos fármacos , Análise do Sêmen , Testículo/anatomia & histologia , Testículo/efeitos dos fármacos , Testosterona/sangue , Adulto Jovem
20.
J Mol Neurosci ; 65(4): 456-466, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30030763

RESUMO

The interaction between adenosine A2A and dopamine D2 receptors in striatal neurons is a well-established phenomenon and has opened up new perspectives on the molecular mechanisms involved in Parkinson's disease. However, it has barely been investigated in astrocytes. Here, we show by immunofluorescence that both A2A and D2 receptors are expressed in adult rat striatal astrocytes in situ, and investigate on presence, function, and interactions of the receptors in the astrocyte processes-acutely prepared from the adult rat striatum-and on the effects of homocysteine on the A2A-D2 receptor-receptor interaction. We found that A2A and D2 receptors were co-expressed on vesicular glutamate transporter-1-positive astrocyte processes, and confirmed that A2A-D2 receptor-receptor interaction controlled glutamate release-assessed by measuring the [3H]D-aspartate release-from the processes. The complexity of A2A-D2 receptor-receptor interaction is suggested by the effect of intracellular homocysteine, which reduced D2-mediated inhibition of glutamate release (homocysteine allosteric action on D2), without interfering with the A2A-mediated antagonism of the D2 effect (maintained A2A-D2 interaction). Our findings indicate the crucial integrative role of A2A-D2 molecular circuits at the plasma membrane of striatal astrocyte processes. The fact that homocysteine reduced D2-mediated inhibition of glutamate release could provide new insights into striatal astrocyte-neuron intercellular communications. As striatal astrocytes are recognized to be involved in Parkinson's pathophysiology, these findings may shed light on the pathogenic mechanisms of the disease and contribute to the development of new drugs for its treatment.


Assuntos
Astrócitos/metabolismo , Corpo Estriado/metabolismo , Homocisteína/metabolismo , Receptor A2A de Adenosina/metabolismo , Receptores de Dopamina D2/metabolismo , Regulação Alostérica , Animais , Células Cultivadas , Corpo Estriado/citologia , Ácido Glutâmico/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Receptor A2A de Adenosina/genética , Receptores de Dopamina D2/genética
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