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1.
Heliyon ; 9(11): e21435, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38027698

RESUMO

Background: In recent decades, scientific production related to Emotional Regulation (ER) has increased significantly. Deficits in ER have been linked to various mental health problems. The aim of this work is to evaluate the Spanish adaptation of the Feel-Kj scale to the RASCH model. Method: Children from 9 to 16 years old took part of this study. One hundred and eighteen children between 9 and 16 years old and one hundred and fifteen from 13 to 16. The 254 participants were attending 25 schools located in de Valencian Community in Spain. Results: Both infit and outfit MNSQ statistics provided evidence for the construct validity of the FEEL-KJ questionnaire. The infit and outfit mean values (1.01 and 1.02, respectively) were close to the perfect fit value of 1. Conclusions: From these results it can be sensed that the FEEL-KJ will be a valid and reliable instrument to apply in the Spanish speaking population, although it is necessary to make some minor adjustments in terms of translation.

2.
Cytotechnology ; 75(2): 135-141, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36969572

RESUMO

Mycoplasma contamination is a significant problem in cell culture replication and maintenance. From more than 200 known species, a limited number of Mycoplasma species have been detected in cell cultures, representing new species or variants that can escape detection systems. A qPCR commercial kit was used for Mycoplasma detection in cell cultures. Furthermore, an amplified Mycoplasma species was sequenced and summited for sequence assembly, clustering, and evolutionary analysis study. Our work has identified a new and unusual variant or species of Mycoplasma that possesses a high degree of homology with species related with M. mycoides cluster. This variant is usually associated with cattle but has been detected contaminating a cell culture. Mycoplasma testing (even for unusual species) in cell cultures is essential to ensure the validity and reproducibility of research that uses cell cultures and to ensure the quality of cell line deposits in biobanks. For this reason, it is necessary to perform continuous checks for the absence of Mycoplasma in cell cultures and engage in the continuous adaptation of relevant detection systems.

3.
Bioeng Transl Med ; 8(2): e10443, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36925706

RESUMO

Psoriasis vulgaris is an inflammatory disease characterized by distinctive skin lesions and dysregulated angiogenesis. Recent research uses stem cell secretion products (CM); a set of bioactive factors with therapeutic properties that regulate several cellular processes, including tissue repair and angiogenesis. The aim of this work was to evaluate the effect of CM of Wharton's gelatin MSC (hWJCM) in a treatment based on the bioactivation of a hyaluronic acid matrix (HA hWJCM) in a psoriasiform-like dermatitis (PD) mouse model. A preclinical study was conducted on PD mice. The effect of hWJCM, Clobetasol (Clob) gold standard, HA Ctrl, and HA hWJCM was tested topically evaluating severity of PD, mice weight as well as skin, liver, and spleen appearance. Treatment with either hWJCM, HA Ctrl or HA hWJCM, resulted in significant improvement of the PD phenotype. Moreover, treatment with HA hWJCM reduced the Psoriasis Area Severity Index (PASI), aberrant angiogenesis, and discomfort associated with the disease, leading to total recovery of body weight. We suggest that the topical application of HA hWJCM can be an effective noninvasive therapeutic solution for psoriasis, in addition to other skin diseases, laying the groundwork for future studies in human patients.

4.
Cell Metab ; 34(10): 1457-1471.e4, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36198292

RESUMO

Diet modification and exercise training are primary lifestyle strategies for obesity management, but poor adherence rates limit their effectiveness. Time-restricted eating (TRE) and high-intensity interval training (HIIT) improve cardiometabolic health in at-risk individuals, but whether these two interventions combined induce superior improvements in glycemic control than each individual intervention is not known. In this four-armed randomized controlled trial (ClinicalTrials.gov NCT04019860), we determined the isolated and combined effects of 7 weeks of TRE (≤10-h daily eating window, with ad libitum energy intake) and HIIT (three exercise sessions per week), compared with a non-intervention control group, on glycemic control and secondary cardiometabolic outcomes in 131 women (36.2 ± 6.2 years) with overweight/obesity. There were no statistically significant effects after isolated TRE, HIIT, or a combination (TREHIIT) on glucose area under the curve during an oral glucose tolerance test (the primary outcome) compared with the control group (TRE, -26.3 mmol/L; 95% confidence interval [CI], -82.3 to 29.7, p = 0.36; HIIT, -53.8 mmol/L; 95% CI, -109.2 to 1.6, p = 0.057; TREHIIT, -41.3 mmol/L; 95% CI, -96.4 to 13.8, p = 0.14). However, TREHIIT improved HbA1c and induced superior reductions in total and visceral fat mass compared with TRE and HIIT alone. High participant adherence rates suggest that TRE, HIIT, and a combination thereof may be realistic diet-exercise strategies for improving markers of metabolic health in women at risk of cardiometabolic disease.


Assuntos
Doenças Cardiovasculares , Sobrepeso , Composição Corporal , Doenças Cardiovasculares/complicações , Exercício Físico , Feminino , Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Obesidade/metabolismo , Sobrepeso/complicações , Sobrepeso/terapia
5.
Proc Natl Acad Sci U S A ; 119(39): e2115015119, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36122233

RESUMO

The conservation status of large-bodied mammals is dire. Their decline has serious consequences because they have unique ecological roles not replicated by smaller-bodied animals. Here, we use the fossil record of the megafauna extinction at the terminal Pleistocene to explore the consequences of past biodiversity loss. We characterize the isotopic and body-size niche of a mammal community in Texas before and after the event to assess the influence on the ecology and ecological interactions of surviving species (>1 kg). Preextinction, a variety of C4 grazers, C3 browsers, and mixed feeders existed, similar to modern African savannas, with likely specialization among the two sabertooth species for juvenile grazers. Postextinction, body size and isotopic niche space were lost, and the δ13C and δ15N values of some survivors shifted. We see mesocarnivore release within the Felidae: the jaguar, now an apex carnivore, moved into the specialized isotopic niche previously occupied by extinct cats. Puma, previously absent, became common and lynx shifted toward consuming more C4-based resources. Lagomorphs were the only herbivores to shift toward C4 resources. Body size changes from the Pleistocene to Holocene were species-specific, with some animals (deer, hare) becoming significantly larger and others smaller (bison, rabbits) or exhibiting no change to climate shifts or biodiversity loss. Overall, the Holocene body-size-isotopic niche was drastically reduced and considerable ecological complexity lost. We conclude biodiversity loss led to reorganization of survivors and many "missing pieces" within our community; without intervention, the loss of Earth's remaining ecosystems that support megafauna will likely suffer the same fate.


Assuntos
Cervos , Ecossistema , Animais , Biodiversidade , Fósseis , Coelhos , Texas
6.
Mol Psychiatry ; 27(9): 3708-3718, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35705634

RESUMO

Schizophrenia (SZ) is a complex neuropsychiatric disorder, affecting 1% of the world population. Long-standing clinical observations and molecular data have pointed to a possible vascular deficiency that could be acting synergistically with neuronal dysfunction in SZ. As SZ is a neurodevelopmental disease, the use of human-induced pluripotent stem cells (hiPSC) allows disease biology modeling while retaining the patient's unique genetic signature. Previously, we reported a VEGFA signaling impairment in SZ-hiPSC-derived neural lineages leading to decreased angiogenesis. Here, we present a functional characterization of SZ-derived brain microvascular endothelial-like cells (BEC), the counterpart of the neurovascular crosstalk, revealing an intrinsically defective blood-brain barrier (BBB) phenotype. Transcriptomic assessment of genes related to endothelial function among three control (Ctrl BEC) and five schizophrenia patients derived BEC (SZP BEC), revealed that SZP BEC have a distinctive expression pattern of angiogenic and BBB-associated genes. Functionally, SZP BEC showed a decreased angiogenic response in vitro and higher transpermeability than Ctrl BEC. Immunofluorescence staining revealed less expression and altered distribution of tight junction proteins in SZP BEC. Moreover, SZP BEC's conditioned media reduced barrier capacities in the brain microvascular endothelial cell line HCMEC/D3 and in an in vivo permeability assay in mice. Overall, our results describe an intrinsic failure of SZP BEC for proper barrier function. These findings are consistent with the hypothesis tracing schizophrenia origins to brain development and BBB dysfunction.


Assuntos
Células-Tronco Pluripotentes Induzidas , Esquizofrenia , Humanos , Animais , Camundongos , Células-Tronco Pluripotentes Induzidas/metabolismo , Barreira Hematoencefálica/metabolismo , Esquizofrenia/metabolismo , Encéfalo , Linhagem Celular
7.
J Public Health Dent ; 82(3): 280-288, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35567374

RESUMO

OBJECTIVES: The purpose of this study was to evaluate the cost-effectiveness of two preventive interventions aimed at increasing the proportion of caries-free preschool children of low socioeconomic status using a decision analytic model. METHODS: Two scenarios were tested, one with a school milk program (SMP) and one without (non-SMP). Fluoride varnish (FV) and a probiotic (PB) were compared to a do-nothing alternative among children in public nurseries/schools over a 4-year period. FV was applied biannually and a PB (Lactobacillus rhamnosus) added to milk powder prepared daily. A Markov decision tree model was utilized. Several sources of data were used to populate the model. Probabilistic and deterministic sensitivity analyses were performed, and a public provider perspective was used. RESULTS: In the SMP scenario, PB was more effective and less costly than FV and, compared with do-nothing, increased the proportion of caries-free children by 14.5%, with a cost of USD 12.5 per child (June 2018). PB presented an incremental cost-effectiveness ratio (ICER) or cost per extra caries-free child of USD 86.2. In the non-SMP scenario, both interventions were cost-effective. FV (compared with do-nothing) increased the percentage of caries-free children by 8.3% with an ICER of USD 338.3 and PB (compared with FV) increased the effect by 6.2% with an ICER of USD 1400.2. CONCLUSIONS: The findings showed that PB was most effective and less costly than FV in the SMP scenario only. This type of analysis and its results provide essential information for decision-makers to improve the oral health of preschool children.


Assuntos
Cárie Dentária , Probióticos , Cariostáticos , Pré-Escolar , Análise Custo-Benefício , Cárie Dentária/prevenção & controle , Fluoretos , Fluoretos Tópicos/uso terapêutico , Humanos
8.
BMJ Open ; 11(2): e040020, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33550228

RESUMO

INTRODUCTION: Overweight and obesity in reproductive-aged women is a global problem due to the increased risk of subfertility, pregnancy complications and cardiometabolic diseases. High-intensity interval training and time-restricted eating are two primary lifestyle interventions that, independently, have positive effects on a range of health outcomes. Whether these two strategies have synergistic effects is currently unknown. Our primary aim is to determine the isolated and combined effect of high-intensity interval training and time-restricted eating on glycaemic control in reproductive-aged women with overweight/obesity. METHODS AND ANALYSIS: The study is a randomised controlled trial with four parallel groups. Women (N=120) aged 18-45 years with body mass index ≥27 kg/m2 will be randomly allocated (1:1:1:1) to either: (1) high-intensity interval training, (2) time-restricted eating, (3) a combination of high-intensity interval training and of time-restricted eating, or (4) a control group. The duration of each intervention will be 7 weeks. The primary outcome measure will be glycaemic control, determined by the total area under the plasma glucose curve over 2 hours after a 75-gram oral glucose tolerance test. Secondary outcome measurements will include markers of cardiovascular and metabolic health (peak oxygen uptake, blood pressure, blood lipids, body composition, insulin sensitivity), sleep quality, physical activity, diet and adherence rates to the intervention. ETHICS AND DISSEMINATION: The Regional Committee Medical Research Ethics, Norway has approved the trial protocol. This study will provide important new knowledge to both the scientific community and the general population about the isolated and combined effects of two novel diet-exercise strategies on cardiovascular and metabolic health among women with overweight/obesity. TRIAL REGISTRATION NUMBER: NCT04019860.


Assuntos
Treinamento Intervalado de Alta Intensidade , Adolescente , Adulto , Feminino , Controle Glicêmico , Humanos , Pessoa de Meia-Idade , Noruega , Obesidade/terapia , Sobrepeso/terapia , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
9.
Head Face Med ; 17(1): 2, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499906

RESUMO

Oro-Pharyngeal Dysphagia - or simply dysphagia - is the difficulty (persistent) in swallowing/passing food and/or liquid from the mouth to the pharynx into the esophagus and finally the stomach; a deglutition disorder (a symptom, by definition, often due to neuro-degenerative/-muscular, drug-induced or localized structural pathologies such as head and neck tumors, lesions and associated surgical and/or radiation injuries) linked to severe consequences on Quality of Life (QoL), including malnutrition, dehydration, and even sudden death. Likewise, Temporo-Mandibular Jaw and Joint disorder(s) - or simply TMD - is a multifactorial etiological condition, regularly encountered in the dental office. Whether due to malocclusion, bruxism, stress and/or trauma, TMD destabilizes the whole cranio-mandibular system structurally and functionally, via affecting mastication, teeth, supporting structures, comfort and aesthetics, and thus, QoL, again. While several treatment regimens do exist for such conditions, some of which have been standardized for use over the years, most continue to lack proper evidence-based literature support. Hence, (1) caution is to be exercised; and (2) the need for alternative therapeutic strategies is amplified, subsequently, the door for innovation is wide open. Indeed, neuromuscular electrical stimulation or "NMES", is perhaps a fine example. Herein, we present the interested oro-dental health care provider with an up-dated revision of this therapeutic modality, its potential benefits, risks and concerns, to best handle the dysphagic patient: an intra-disciplinary approach or strategy bridging contemporary dentistry with speech and language therapy; a rather obscure and un-discovered yet critical allied health profession. A pre-clinical and clinical prospectus on employing inventive NMES-based regimens and devices to manage TMD is also highlighted.


Assuntos
Transtornos de Deglutição , Qualidade de Vida , Deglutição , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Diamante , Estética Dentária , Humanos , Boca
10.
BMC Res Notes ; 13(1): 77, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070402

RESUMO

OBJECTIVE: Peripheral blood is the most promising source of RNA biomarkers for diagnostic and epidemiological studies, because the presence of disease and prognostic information is reflected in the gene expression pattern. Quality RNA is used by a number of different downstream applications, so the selection of the most appropriate RNA stabilization and purification method is important. We have analyzed the RNA purified from 300 blood samples from 25 donors processed by two technicians using three methodologies with Tempus and PaxGene tubes. RESULTS: The best quality sample results were obtained with the Tempus Spin RNA Isolation Kit and the PaxGene Blood miRNA Kit, although larger amounts of RNA were obtained with the Tempus Spin RNA Isolation Kit. Lower Cq values were observed for RNA and miRNA genes in samples that were tested with PaxGene Blood miRNA Kit and Tempus Spin RNA Isolation Kit respectively. We identify the Tempus Spin RNA Isolation Kit as the most robust methodology, whilst the MagMax for Stabilized Blood Tubes RNA Isolation Kit showed the most instability. For biobanks, which process a large cohort and conduct epidemiological studies, the Tempus Spin RNA Isolation Kit is the most appropriate methodology. The study demonstrates the robustness of real-life procedures.


Assuntos
Coleta de Amostras Sanguíneas/instrumentação , Coleta de Amostras Sanguíneas/métodos , Estudos Epidemiológicos , RNA/sangue , RNA/isolamento & purificação , Humanos , RNA/genética , Estabilidade de RNA , Reprodutibilidade dos Testes
11.
Int J Mol Sci ; 20(6)2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30897795

RESUMO

Gestational diabetes mellitus (GDM) is a common metabolic disorder, defined by high blood glucose levels during pregnancy, which affects foetal and post-natal development. However, the cellular and molecular mechanisms of this detrimental condition are still poorly understood. A dysregulation in circulating angiogenic trophic factors, due to a dysfunction of the feto-placental unit, has been proposed to underlie GDM. But even the detailed study of canonical pro-angiogenic factors like vascular endothelial growth factor (VEGF) or basic Fibroblast Growth Factor (bFGF) has not been able to fully explain this detrimental condition during pregnancy. Netrins are non-canonical angiogenic ligands produced by the stroma have shown to be important in placental angiogenesis. In order to address the potential role of Netrin signalling in GDM, we tested the effect of Netrin-1, the most investigated member of the family, produced by Wharton's Jelly Mesenchymal Stem Cells (WJ-MSC), on Human Umbilical Vein Endothelial Cells (HUVEC) angiogenesis. WJ-MSC and HUVEC primary cell cultures from either healthy or GDM pregnancies were exposed to physiological (5 mM) or high (25 mM) d-glucose. Our results reveal that Netrin-1 is secreted by WJ-MSC from healthy and GDM and both expression and secretion of the ligand do not change with distinct experimental glucose conditions. Noteworthy, the expression of its anti-angiogenic receptor UNC5b is reduced in GDM HUVEC compared with its expression in healthy HUVEC, accounting for an increased Netrin-1 signalling in these cells. Consistently, in healthy HUVEC, UNC5b overexpression induces cell retraction of the sprouting phenotype.


Assuntos
Células Endoteliais da Veia Umbilical Humana/metabolismo , Netrina-1/metabolismo , Receptores de Superfície Celular/metabolismo , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismo , Feminino , Humanos , Neovascularização Fisiológica/genética , Neovascularização Fisiológica/fisiologia , Receptores de Netrina , Netrina-1/genética , Gravidez , Receptores de Superfície Celular/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
Stem Cell Res Ther ; 8(1): 203, 2017 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-28962669

RESUMO

BACKGROUND: Wharton's jelly-derived mesenchymal stem cells (WJ-MSC) show remarkable therapeutic potential to repair tissue upon injury via paracrine signaling by secreting diverse trophic factors that promote angiogenesis. However, the mechanisms and signaling pathways that regulate the induction of these specific factors are still mostly unknown. Emerging evidence suggests that Sonic hedgehog (SHH) plays a central role in angiogenesis and tissue maintenance. However, its contribution to the angiogenic potential of MSC has not been fully addressed. The aim of this work was to characterize the expression of the SHH pathway components in WJ-MSC primary cultures and to evaluate their angiogenic responsiveness to SHH signaling. METHODS: Primary cell cultures obtained from human umbilical cords were treated with pharmacological modulators of the SHH pathway. We evaluated the modulation of diverse trophic factors in cell lysates, conditioned medium, and functional in vitro assays. In addition, we determined the angiogenic potential of the SHH pathway in the chicken chorioallantoic membrane, an in vivo model. RESULTS: Our results show that WJ-MSC express components of the canonical SHH pathway and are activated by its signaling. In fact, we provide evidence of basal autocrine/paracrine SHH signaling in WJ-MSC. SHH pathway stimulation promotes the secretion of angiogenic factors such as activin A, angiogenin, angiopoietin 1, granulocyte-macrophage colony-stimulating factor, matrix metallometallopeptidase -9, and urokinase-type plasminogen activator, enhancing the pro-angiogenic capabilities of WJ-MSC both in vitro and in vivo. CONCLUSION: WJ-MSC are a cell population responsive to SHH pathway stimulation. Basal SHH signaling is in part responsible for the angiogenic inductive properties of WJ-MSC. Overall, exogenous activation of the SHH pathway enhances the angiogenic properties of WJ-MSC, making this cell population an ideal target for treating tissue injury.


Assuntos
Proteínas Hedgehog/metabolismo , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica , Ativinas/genética , Ativinas/metabolismo , Angiopoietina-1/genética , Angiopoietina-1/metabolismo , Animais , Diferenciação Celular , Linhagem Celular , Células Cultivadas , Galinhas , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Proteínas Hedgehog/genética , Humanos , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Ativadores de Plasminogênio/genética , Ativadores de Plasminogênio/metabolismo , Transdução de Sinais , Geleia de Wharton/citologia
13.
Stem Cells ; 35(12): 2430-2441, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28895234

RESUMO

Novel bone regeneration approaches aim to obtain immature osteoblasts from somatic stem cells. Umbilical cord Wharton's jelly mesenchymal stem cells (WJ-MSCs) are an ideal source for cell therapy. Hence, the study of mechanisms involved in WJ-MSC osteoblastic differentiation is crucial to exploit their developmental capacity. Here, we have assessed epigenetic control of the Runt-related transcription factor 2 (RUNX2) osteogenic master regulator gene in WJ-MSC. We present evidence indicating that modulation of RUNX2 expression through preventing Jumonji AT-rich interactive domain 1B (JARID1B) histone demethylase activity is relevant to enhance WJ-MSC osteoblastic potential. Hence, JARID1B loss of function in WJ-MSC results in increased RUNX2/p57 expression. Our data highlight JARID1B activity as a novel target to modulate WJ-MSC osteoblastic differentiation with potential applications in bone tissue engineering. Stem Cells 2017;35:2430-2441.


Assuntos
Histona Desmetilases com o Domínio Jumonji/metabolismo , Células-Tronco Mesenquimais/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Epigenômica , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Células-Tronco Mesenquimais/citologia , Osteoblastos/citologia , Osteoblastos/metabolismo , Cordão Umbilical/citologia , Geleia de Wharton/citologia
14.
Stem Cell Res Ther ; 8(1): 43, 2017 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-28241866

RESUMO

BACKGROUND: Angiogenesis, the process in which new blood vessels are formed from preexisting ones, is highly dependent on the presence of classical angiogenic factors. Recent evidence suggests that axonal guidance proteins and their receptors can also act as angiogenic regulators. Netrin, a family of laminin-like proteins, specifically Netrin-1 and 4, act via DCC/Neogenin-1 and UNC5 class of receptors to promote or inhibit angiogenesis, depending on the physiological context. METHODS: Mesenchymal stem cells secrete a broad set of classical angiogenic factors. However, little is known about the expression of non-canonical angiogenic factors such as Netrin-1. The aim was to characterize the possible secretion of Netrin ligands by Wharton's jelly-derived mesenchymal stem cells (WJ-MSC). We evaluated if Netrin-1 presence in the conditioned media from these cells was capable of inducing angiogenesis both in vitro and in vivo, using human umbilical vein endothelial cells (HUVEC) and chicken chorioallantoic membrane (CAM), respectively. In addition, we investigated if the RhoA/ROCK pathway is responsible for the integration of Netrin signaling to control vessel formation. RESULTS: The paracrine angiogenic effect of the WJ-MSC-conditioned media is mediated at least in part by Netrin-1 given that pharmacological blockage of Netrin-1 in WJ-MSC resulted in diminished angiogenesis on HUVEC. When HUVEC were stimulated with exogenous Netrin-1 assayed at physiological concentrations (10-200 ng/mL), endothelial vascular migration occurred in a concentration-dependent manner. In line with our determination of Netrin-1 present in WJ-MSC-conditioned media we were able to obtain endothelial tubule formation even in the pg/mL range. Through CAM assays we validated that WJ-MSC-secreted Netrin-1 promotes an increased angiogenesis in vivo. Netrin-1, secreted by WJ-MSC, might mediate its angiogenic effect through specific cell surface receptors on the endothelium, such as UNC5b and/or integrin α6ß1, expressed in HUVEC. However, the angiogenic response of Netrin-1 seems not to be mediated through the RhoA/ROCK pathway. CONCLUSIONS: Thus, here we show that stromal production of Netrin-1 is a critical component of the vascular regulatory machinery. This signaling event may have deep implications in the modulation of several processes related to a number of diseases where angiogenesis plays a key role in vascular homeostasis.


Assuntos
Membrana Corioalantoide/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Fatores de Crescimento Neural/farmacologia , Proteínas Supressoras de Tumor/farmacologia , Geleia de Wharton/metabolismo , Animais , Bioensaio , Movimento Celular , Embrião de Galinha , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/citologia , Meios de Cultivo Condicionados/química , Meios de Cultivo Condicionados/farmacologia , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Integrina alfa6beta1/genética , Integrina alfa6beta1/metabolismo , Células-Tronco Mesenquimais/citologia , Fatores de Crescimento Neural/genética , Fatores de Crescimento Neural/metabolismo , Receptores de Netrina , Netrina-1 , Cultura Primária de Células , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Transdução de Sinais , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Geleia de Wharton/citologia
15.
Cell Tissue Bank ; 18(2): 271-280, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28255773

RESUMO

Establishment of continuous cell lines from human normal and tumor tissues is an extended and useful methodology for molecular characterization of cancer pathophysiology and drug development in research laboratories. The exchange of these cell lines between different labs is a common practice that can compromise assays reliability due to contamination with microorganism such as mycoplasma or cells from different flasks that compromise experiment reproducibility and reliability. Great proportions of cell lines are contaminated with mycoplasma and/or are replaced by cells derived for a different origin during processing or distribution process. The scientific community has underestimated this problem and thousand of research experiment has been done with cell lines that are incorrectly identified and wrong scientific conclusions have been published. Regular contamination and authentication tests are necessary in order to avoid negative consequences of widespread misidentified and contaminated cell lines. Cell banks generate, store and distribute cell lines for research, being mandatory a consistent and continuous quality program. Methods implementation for guaranteeing both, the absence of mycoplasma and authentication in the supplied cell lines, has been performed in the Andalusian Health System Biobank. Specifically, precise results were obtained using real time PCR detection for mycoplasma and 10 STRs identification by capillary electrophoresis for cell line authentication. Advantages and disadvantages of these protocols are discussed.


Assuntos
Bancos de Espécimes Biológicos , Técnicas de Cultura de Células/métodos , Linhagem Celular/microbiologia , DNA Bacteriano/isolamento & purificação , Mycoplasma/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , DNA Bacteriano/genética , Humanos , Mycoplasma/genética , Infecções por Mycoplasma/microbiologia , Controle de Qualidade
16.
J Cell Physiol ; 232(9): 2519-2527, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27689934

RESUMO

Wharton's Jelly mesenchymal stem cells (WJ-MSCs) are an attractive potential source of multipotent stem cells for bone tissue replacement therapies. However, the molecular mechanisms involved in their osteogenic conversion are poorly understood. Particularly, epigenetic control operating at the promoter regions of the two master regulators of the osteogenic program, RUNX2/P57 and SP7 has not yet been described in WJ-MSCs. Via quantitative PCR profiling and chromatin immunoprecipitation (ChIP) studies, here we analyze the ability of WJ-MSCs to engage osteoblast lineage. In undifferentiated WJ-MSCs, RUNX2/P57 P1, and SP7 promoters are found deprived of significant levels of the histone post-translational marks that are normally associated with transcriptionally active genes (H3ac, H3K27ac, and H3K4me3). Moreover, the RUNX2 P1 promoter lacks two relevant histone repressive marks (H3K9me3 and H3K27me3). Importantly, RUNX2 P1 promoter is found highly enriched in the H3K4me1 mark, which has been shown recently to mediate gene repression of key regulatory genes. Upon induction of WJ-MSCs osteogenic differentiation, we found that RUNX2/P57, but not SP7 gene expression is strongly activated, in a process that is accompanied by enrichment of activating histone marks (H3K4me3, H3ac, and H3K27ac) at the P1 promoter region. Histone mark analysis showed that SP7 gene promoter is robustly enriched in epigenetic repressive marks that may explain its poor transcriptional response to osteoblast differentiating media. Together, these results point to critical regulatory steps during epigenetic control of WJ-MSCs osteogenic lineage commitment that are relevant for future applications in regenerative medicine. J. Cell. Physiol. 232: 2519-2527, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Diferenciação Celular , Linhagem da Célula , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Epigênese Genética , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/metabolismo , Osteogênese , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo , Transcriptoma , Geleia de Wharton/metabolismo , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Histonas/metabolismo , Humanos , Metilação , Fenótipo , Fator de Transcrição Sp7 , Fatores de Transcrição/genética , Transcrição Gênica , Ativação Transcricional , Geleia de Wharton/citologia
17.
Eur Psychiatry ; 33: 9-17, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26852375

RESUMO

BACKGROUND: Patient's relatives usually care for patients with schizophrenia, and as informal caregivers they experience negative consequences. The aim of the EDUCA-III trial is to test the efficacy of a psychoeducational intervention program (PIP) versus standard care to reduce the caregiver burden at post-intervention (4 months), and at follow-up (8 months). METHOD: A two-arm, evaluator blind, multicentre, randomized controlled trial. The PIP group had 12 weekly group sessions. The control intervention group had the usual support and standard care. Primary outcomes were change scores since baseline on the Zarit Burden Interview (ZBI) and the Involvement Evaluation Questionnaire (IEQ). RESULTS: One hundred and nine caregivers were randomized to PIP and 114 to control condition from 23 research sites. The decrease of ZBI scores was significantly higher on the PIP arm at 4 months (mean difference [MD]=-4.33; 95% CI -7.96, -0.71), and at 8 months (MD=-4.46; 95% CI -7.79, -1.13). There were no significant decreases in the IEQ scores (MD at 4 months=-2.80; 95% CI -6.27, 0.67; MD at 8 months=-2.85; 95% CI -6.51, 0.81). CONCLUSIONS: The PIP condition seems to reduce caregiver burden. TRIAL REGISTRATION: ISRCTN32545295.


Assuntos
Cuidadores , Educação em Saúde , Esquizofrenia/terapia , Estresse Psicológico/prevenção & controle , Adaptação Psicológica , Idoso , Cuidadores/educação , Cuidadores/psicologia , Efeitos Psicossociais da Doença , Aconselhamento , Avaliação Educacional/métodos , Eficiência Organizacional , Feminino , Educação em Saúde/métodos , Educação em Saúde/organização & administração , Humanos , Masculino , Pessoa de Meia-Idade , Apoio Social , Inquéritos e Questionários
18.
Proc Natl Acad Sci U S A ; 113(4): 874-9, 2016 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-26504225

RESUMO

Globally, large-bodied wild mammals are in peril. Because "megamammals" have a disproportionate influence on vegetation, trophic interactions, and ecosystem function, declining populations are of considerable conservation concern. However, this is not new; trophic downgrading occurred in the past, including the African rinderpest epizootic of the 1890s, the massive Great Plains bison kill-off in the 1860s, and the terminal Pleistocene extinction of megafauna. Examining the consequences of these earlier events yields insights into contemporary ecosystem function. Here, we focus on changes in methane emissions, produced as a byproduct of enteric fermentation by herbivores. Although methane is ∼ 200 times less abundant than carbon dioxide in the atmosphere, the greater efficiency of methane in trapping radiation leads to a significant role in radiative forcing of climate. Using global datasets of late Quaternary mammals, domestic livestock, and human population from the United Nations as well as literature sources, we develop a series of allometric regressions relating mammal body mass to population density and CH4 production, which allows estimation of methane production by wild and domestic herbivores for each historic or ancient time period. We find the extirpation of megaherbivores reduced global enteric emissions between 2.2-69.6 Tg CH4 y(-1) during the various time periods, representing a decrease of 0.8-34.8% of the overall inputs to tropospheric input. Our analyses suggest that large-bodied mammals have a greater influence on methane emissions than previously appreciated and, further, that changes in the source pool from herbivores can influence global biogeochemical cycles and, potentially, climate.


Assuntos
Clima , Ecossistema , Extinção Biológica , Herbivoria , Mamíferos/metabolismo , Metano/análise , Anaerobiose , Distribuição Animal , Animais , Animais Domésticos , Animais Selvagens , Bison , Digestão , Surtos de Doenças/história , Surtos de Doenças/veterinária , Europa (Continente) , Fermentação , Efeito Estufa , História Antiga , Atividades Humanas , Humanos , Gelo , Metano/metabolismo , Dispersão Vegetal , Plantas Comestíveis , Peste Bovina/história
19.
Vertex ; XXVII(129): 374-382, 2016 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-28282075

RESUMO

This article complements a previous one, in which theoretical concepts about etiologic categories, suspicion criteria and timely referral to the specialist were explained. This time we will focus on genetic counselling (GC), describing this process and its characteristics, in particular we will emphasize on psychiatry genetic counseling (PGC). PGC has particular characteristics considering the fact that there are still no tools (genetic testing) for diagnosis and that most mental pathologies are multifactorial inheritance disorders. This is complex, since it results from the interaction of genetics and environmental circumstances. Uncertainty is a given due to the number of factors involved in its appearance and, despite great strides, these should be further investigated. PGC seems to be a useful tool for both patients and families for better adapting to the disease and to cope with consequences derived from it. In conclusion, we consider of great importance to create an enabling collaborative workspace between psychiatrists and clinical geneticists in order to provide patients and their families a comprehensive approach to their problems.


Assuntos
Aconselhamento Genético , Genética Médica , Psiquiatria , Humanos , Transtornos Mentais/genética , Incerteza
20.
Rev Panam Salud Publica ; 37(4-5): 265-72, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26208195

RESUMO

OBJECTIVE: To examine the impact that domestic violence (DV) has on hindering the success of urban migrants in Peru and any association with maternal depression, impaired parenting, social capital, and child development. METHODS: This was a cross-sectional study consisting of structured interviews with 97 mothers and their school-aged children in El Porvenir, a predominantly migrant area of the city of Trujillo, Peru. Data collection occurred in February-June 2011. Proven tools previously validated for use in Spanish were used to assess the following variables: maternal depression, social capital, domestic violence, parenting behaviors, child socioemotional development, and child cognitive development. Correlational, multiple regression, tests of interaction, and indirect/mediator models were used for analysis. RESULTS: Sixty-five percent of women reported currently experiencing DV. DV strongly predicted depression (P < 0.001). Women who reported DV were less likely to be employed (P < 0.05), had lower cognitive social capital (P < 0.01), engaged in fewer caregiving activities (P < 0.05), had less maternal energy (P < 0.05), and were less warm (P < 0.05). DV was associated with internalizing behaviors in children (P < 0.01), with impaired parenting partially mediating this relationship. CONCLUSIONS: DV compromises women's mental health and parenting ability. High rates of DV among urban migrants affect the whole community by hindering employment potential and reducing trust among community members. Interventions targeting DV-related variables (e.g., substance abuse and limited job opportunities for men) could reduce the deleterious effects of DV on urban migrant communities across Latin America.


Assuntos
Saúde da Criança , Violência Doméstica , Saúde Materna , Mães/estatística & dados numéricos , Marginalização Social/psicologia , Migrantes/estatística & dados numéricos , Adulto , Criança , Filho de Pais com Deficiência , Estudos Transversais , Depressão/epidemiologia , Depressão/etiologia , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/etiologia , Violência Doméstica/estatística & dados numéricos , Emoções , Feminino , Humanos , Mães/psicologia , Poder Familiar/psicologia , Peru/epidemiologia , Abuso Físico/estatística & dados numéricos , Gravidez , Capital Social , Migrantes/psicologia , Desemprego/psicologia , Desemprego/estatística & dados numéricos , População Urbana/estatística & dados numéricos
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