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1.
Exp Cell Res ; 440(2): 114136, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38909881

RESUMEN

Considering the importance of alternative methodologies to animal experimentation, we propose an organoid-based biological model for in vitro blood vessel generation, achieved through co-culturing endothelial and vascular smooth muscle cells (VSMCs). Initially, the organoids underwent comprehensive characterization, revealing VSMCs (α-SMA + cells) at the periphery and endothelial cells (CD31+ cells) at the core. Additionally, ephrin B2 and ephrin B4, genes implicated in arterial and venous formation respectively, were used to validate the obtained organoid. Moreover, the data indicates exclusive HIF-1α expression in VSMCs, identified through various methodologies. Subsequently, we tested the hypothesis that the generated blood vessels have the capacity to modulate the osteogenic phenotype, demonstrating the ability of HIF-1α to promote osteogenic signals, primarily by influencing Runx2 expression. Overall, this study underscores that the methodology employed to create blood vessel organoids establishes an experimental framework capable of producing a 3D culture model of both venous and arterial endothelial tissues. This model effectively guides morphogenesis from mesenchymal stem cells through paracrine signaling, ultimately leading to an osteogenic acquisition phenotype, with the dynamic involvement of HIF-1α.


Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia , Músculo Liso Vascular , Miocitos del Músculo Liso , Organoides , Osteogénesis , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Osteogénesis/genética , Organoides/metabolismo , Organoides/citología , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/citología , Células Cultivadas , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/citología , Vasos Sanguíneos/crecimiento & desarrollo , Técnicas de Cocultivo/métodos , Diferenciación Celular , Células Endoteliales/metabolismo , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología
2.
AIDS Care ; 36(2): 188-194, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37919229

RESUMEN

INTRODUCTION: The current study provides people living with human immunodeficiency virus (PLHIV) the support to cope with this disease and to improve their quality of life, since their longevity has significantly increased. AIM: Investigating the effect of an educational intervention on PLHIV's strategies to cope with HIV. METHODOLOGY: Quasi-experimental, before-and-after study type, whose data were collected before and after educational intervention, was carried out with 75 PLHIV at a School Outpatient Clinic. The Brazilian version of the Ways of Coping Scale was herein used. It is a questionnaire comprising 4 disease-coping domains, namely: coping focused on problem, emotion and on seeking social support and religious practices. RESULTS: There was increased use of all coping-strategy domains after the educational intervention, as well as reduced standard deviation, and it pointed out that the recorded values were grouped closer to the mean therefore showing less variability. Coping focused on social support was the strategy mostly used after the educational intervention; it was followed by strategies focused on both emotion and problem. The least used strategy was the one focused on religion/fantasy. DISCUSSION: This study identified the need of introducing a new coping strategy focused on prejudice against patients with HIV.


Asunto(s)
Habilidades de Afrontamiento , Infecciones por VIH , Humanos , Calidad de Vida/psicología , Adaptación Psicológica , VIH , Infecciones por VIH/psicología
3.
Support Care Cancer ; 32(1): 82, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38175289

RESUMEN

OBJECTIVE: To identify predictors of sarcopenia (demographical, anthropometric measurements, tumor-related clinical characteristics, performance status, and serum C-reactive protein (CRP) and albumin levels in individuals with head and neck squamous cell carcinoma (HNSCC). MATERIAL AND METHODS: This cross-sectional study selected diagnosed with HNSCC (n = 125). Sarcopenia was defined as low muscle strength and low physical performance. Association between sarcopenia and anthropometric assessments (weight, height, body mass index, triceps skinfold, mid-upper arm circumference [MUAC], mid-upper arm muscle circumference, mid-upper arm fat area [UFA], mid-upper arm bone free muscle area, calf circumference, and appendicular skeletal muscle mass and index), tumor clinical characteristics (anatomical site, tumor size, and cervical metastasis), performance status scale (Eastern Cooperative Oncology Group Performance Status [ECOG-PS]), and CRP and albumin levels was analyzed using binary logistic regression models. RESULTS: The diagnosis of sarcopenia was identified in 28 (22.4%) individuals with HNSCC. Being an older adult increases the odds of association with sarcopenia in individuals with HNSCC (odds ratio [OR] = 1.05). Increments in MUAC measurement reduce the odds of association with sarcopenia (OR = 0.69), while the increase in the UFA measurement increases the odds of association with sarcopenia (OR = 1.33). Poor ECOG-PS scores increase the odds of association with sarcopenia in individuals with HNSCC (OR = 5.54). CONCLUSION: Early identification of easy-to-perform, cost-effective predictors of sarcopenia tends to favor the implementation of personalized therapeutic and supportive interventions in individuals with HNSCC.


Asunto(s)
Neoplasias de Cabeza y Cuello , Sarcopenia , Humanos , Anciano , Sarcopenia/epidemiología , Sarcopenia/etiología , Carcinoma de Células Escamosas de Cabeza y Cuello , Estudios Transversales , Proteína C-Reactiva , Neoplasias de Cabeza y Cuello/complicaciones
4.
J Fish Biol ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38986516

RESUMEN

The Rio de Janeiro Marine Aquarium (AquaRio) is the first to successfully maintain and reproduce the spiny butterfly ray (Gymnura altavela), providing unique information about the species' biology. Seven rays were kept in captivity between 2018 and 2023, two captured on the southeastern coast of Brazil and five born in the aquarium. The applied abiotic conditions and nutrition allowed for the survival, growth, and reproduction of these individuals. Growth parameters (asymptotic disk width-DW∞ and growth coefficient-k) were estimated based on the von Bertalanffy model using the Fabens method for males and females separately. The best models estimated DW∞ = 106.47 cm and k = 0.396 for males and DW∞ = 172.2 cm and k = 0.190 for females. Sexual dimorphism was corroborated, with females reaching larger sizes and presenting slower growth rates than males. The estimated k values were higher than those estimated for rays of similar size to G. altavela in the natural environment, probably due to the constant water temperature (around 25.5°C), food abundance, low population density, reduced predation rates, and high water quality in the captive environment. A comparison of the captivity findings with other studies on G. altavela age and growth in the Atlantic and Mediterranean indicates a broad phenotypic plasticity regarding growth. Three G. altavela reproductions were recorded, with size at birth appearing to be a key factor for pup's survival. Behavioral pattern observations associated with reproduction are also described, encompassing chasing and copulation, whereas the species' internal morphology is described through coelomic cavity ultrasound scanning.

5.
Br J Nutr ; 130(5): 783-792, 2023 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-36412162

RESUMEN

Obese mothers' offspring develop obesity and metabolic alterations in adulthood. Poor postnatal dietary patterns also contribute to obesity and its comorbidities. We aimed to determine whether in obese mothers' offspring an adverse postnatal environment, such as high-fat diet (HFD) consumption (second hit) exacerbates body fat accumulation, metabolic alterations and adipocyte size distribution. Female Wistar rats ate chow (C-5 %-fat) or HFD (maternal obesity (MO)-25 %-fat) from weaning until the end of lactation. Male offspring were weaned on either control (C/C and MO/C, maternal diet/offspring diet) or HFD (C/HF and MO/HF) diet. At 110 postnatal days, offspring were killed. Fat depots were excised to estimate adiposity index (AI). Serum glucose, triglyceride, leptin, insulin, insulin resistance index (HOMA-IR), corticosterone and dehydroepiandrosterone (DHEA) were determined. Adipocyte size distribution was evaluated in retroperitoneal fat. Body weight was similar in C/C and MO/C but higher in C/HF and MO/HF. AI, leptin, insulin and HOMA-IR were higher in MO/C and C/HF v. C/C but lower than MO/HF. Glucose increased in MO/HF v. MO/C. C/HF and MO/C had higher triglyceride and corticosterone than C/C, but lower corticosterone than MO/HF. DHEA and the DHEA/corticosterone ratio were lower in C/HF and MO/C v. C/C, but higher than MO/HF. Small adipocyte proportion decreased while large adipocyte proportions increased in MO/C and C/HF v. C/C and exacerbated in MO/HF v. C/HF. Postnatal consumption of a HFD by the offspring of obese mothers exacerbates body fat accumulation as well as the decrease of small and the increase of large adipocytes, which leads to larger metabolic abnormalities.


Asunto(s)
Leptina , Efectos Tardíos de la Exposición Prenatal , Humanos , Ratas , Femenino , Animales , Masculino , Embarazo , Dieta Alta en Grasa/efectos adversos , Madres , Corticosterona/metabolismo , Ratas Wistar , Fenómenos Fisiologicos Nutricionales Maternos , Obesidad/etiología , Obesidad/metabolismo , Tejido Adiposo/metabolismo , Peso Corporal , Glucosa/metabolismo , Triglicéridos/metabolismo , Hipertrofia/metabolismo , Insulina/metabolismo , Deshidroepiandrosterona/metabolismo
6.
J Chem Phys ; 158(20)2023 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-37212408

RESUMEN

The multifrequency formalism is generalized and exploited to quantify attractive forces, i.e., van der Waals interactions, with small amplitudes or gentle forces in bimodal and trimodal atomic force microscopy (AFM). The multifrequency force spectroscopy formalism with higher modes, including trimodal AFM, can outperform bimodal AFM for material property quantification. Bimodal AFM with the second mode is valid when the drive amplitude of the first mode is approximately an order of magnitude larger than that of the second mode. The error increases in the second mode but decreases in the third mode with a decreasing drive amplitude ratio. Externally driving with higher modes provides a means to extract information from higher force derivatives while enhancing the range of parameter space where the multifrequency formalism holds. Thus, the present approach is compatible with robustly quantifying weak long range forces while extending the number of channels available for high resolution.

7.
Oral Dis ; 29(7): 2658-2666, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35796645

RESUMEN

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is one of the most common neoplasms worldwide. The current study aimed to identify potential biomarkers associated with OSCC survival. MATERIALS AND METHODS: Differentially expressed genes (DEGs) in atypical OSCC cases were identified using two public datasets: The Cancer Genome Atlas and the Gene Expression Omnibus database. Receiver operating characteristic (ROC) analysis was performed to identify the cutoff, and the candidate DEGs related to survival. Kaplan-Meier and Cox regression analysis using the categorized genes were employed to identify genes that impact the overall survival in OSCC. RESULTS: A total of 263 OSCC samples and 105 healthy tissues were used to identify 295 upregulated and 131 downregulated genes expressed only in non-smokers. ROC analyses identified 25 candidate genes associated with death. Survival analyses demonstrated that the following DEGs, namely CSTA, FGFR2, MMP19, OLR1, PCSK1, RAMP2, and CGB5, are potential OSCC prognostic factors. CONCLUSION: We found that CSTA, FGFR2, MMP19, OLR1, PCSK1, RAMP2, and CGB5 are associated with a low survival rate in OSCC. However, further studies are needed to validate our findings and facilitate the development of these factors as potential biomarkers for OSCC survival.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas/patología , Transcriptoma , Neoplasias de la Boca/metabolismo , Regulación Neoplásica de la Expresión Génica , Análisis de Supervivencia , Biomarcadores de Tumor/genética , Neoplasias de Cabeza y Cuello/genética , Pronóstico
8.
Health Care Manag Sci ; 26(2): 217-237, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37099041

RESUMEN

Organ transplant is one of the best options for many medical conditions, and in many cases, it may be the only treatment option. Recent evidence suggests, however, that the COVID-19 pandemic might have detrimentally affected the provision of this type of healthcare services. The main purpose of this article is to use Data Envelopment Analysis and the Malmquist Index to assess the impact that the pandemic caused by the novel coronavirus SARS-CoV-2 had on the provision of solid organ transplant services. To this purpose, we use three complementary models, each focusing on specific aspects of the organ donation and transplantation process, and data from Brazil, which has one of the most extensive public organ transplant programs in the world. Using data from 17 States plus the Federal District, the results of our analysis show a significant drop in the performance of the services in terms of the organ donation and transplantation process from 2018 to 2020, but the results also indicate that not all aspects of the process and States were equally affected. Furthermore, by using different models, this research also allows us to gain a more comprehensive and informative assessment of the performance of the States in delivering this type of service and identify opportunities for reciprocal learning, expanding our knowledge on this important issue and offering opportunities for further research.


Asunto(s)
COVID-19 , Trasplante de Órganos , Obtención de Tejidos y Órganos , Humanos , SARS-CoV-2 , Pandemias , Trasplante de Órganos/métodos
9.
J Environ Manage ; 337: 117752, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-36966633

RESUMEN

Resource depletion and environmental pollution are increasingly a matter of concern for their adverse effects on ecosystems, human health, and the economy. Circular Economy (CE) practices can help us address these challenges. This paper proposes a composite circularity index (CI) to assess the level of implementation of CE practices. The main advantage of the proposed index is its ability to combine multiple indicators of circularity for different units operating in a given sector (given as inputs), using a 'Benefit of the Doubt' model. This new model is innovative in the manner it deals with ordinal scales and also by considering both relative and absolute performance indices. These indices are computed using mathematical programming tools, building on ideas from Data Envelopment Analysis models. Although the model can be applied to any sector, this work addresses the hotel industry in particular. The selection of indicators for this CI was based on seven blocks of the Circular Economy Action Plan and a literature review of circular practices. An application of the proposed index is performed by using data from Portuguese and Spanish hotels. The proposed CI allows the identification of the organizations with the best and worst performance in implementing the CE practices and clarifying the benchmarks they could follow to improve their level of circularity. Moreover, the index analysis also provides specific targets for improvement, indicating which circular practices should be improved for the lower performers to reach the implementation levels of the best performers.


Asunto(s)
Ecosistema , Industrias , Humanos , Contaminación Ambiental
10.
Plant Foods Hum Nutr ; 78(2): 342-350, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37120677

RESUMEN

Hibiscus sabdariffa L. is a worldwide component for tea and beverages, being a natural source of anthocyanins, which are associated with cardiovascular activities. To investigate this relationship, we explored different methods of aqueous extraction on the anthocyanin content and antioxidant activity of H. sabdariffa L. calyx extract (HSCE). Pharmacological effects via platelet aggregation, calcium mobilization, cyclic nucleotide levels, vasodilator-stimulated phosphoprotein Ser157 and Ser239, and on the vasomotor response of aortic rings isolated from mice are studied herewith. We found that the application of ultrasonic turbolization, 20 min, combined with acidified water was significantly more effective in the extraction process, providing extracts with the highest levels of anthocyanins (8.73 and 9.63 mg/100 g) and higher antioxidant activity (6.66 and 6.78 µM trolox/g of sample). HSCE significantly inhibited (100-1000 µg/mL) arachidonic acid-induced platelet aggregation, reduced calcium mobilization, and increased cAMP and cGMP levels with VASPSer157 and VASPSer239 phosphorylation. Vasorelaxation reduction was confirmed by the aortic rings and endothelium assays treated with nitric oxide synthase inhibitors, soluble guanylyl cyclase (sGC) oxidizing agent, or Ca2+-activated K+ channel inhibitor. The increasing of cGMP levels could be understood considering the sGC stimulation by HSCE compounds in the specific stimulus domain, which allows an understanding of the observed antiplatelet and vasorelaxant properties of H. sabdariffa L. calyx extract.


Asunto(s)
Hibiscus , Vasodilatadores , Animales , Ratones , Vasodilatadores/farmacología , Antocianinas/farmacología , Antioxidantes/farmacología , Calcio , Extractos Vegetales/farmacología , GMP Cíclico/metabolismo
11.
Socioecon Plann Sci ; 87: 101588, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37255587

RESUMEN

The topic of regional economic resilience has been the subject of intense debate in the academic and political fields over the past decade and gained a new sense of urgency because of the pandemic caused by the SARS-CoV-2 virus as territories faced relevant impacts on their economies and social structures. The economic downturn, the increase in unemployment, and the deterioration of social conditions lead policy makers to search for solutions to make their territories more resilient to this type of event. The current article discusses how multicriteria decision analysis (MCDA) was used to help a Portuguese Intermunicipal Community, formed by 16 councils, develop a strategy to make its territory more cohesive, competitive, sustainable, and resilient. In addition to discussing an innovative application of a MCDA technique, this article illustrates how, through a MCDA approach, it was possible to reach a consensus among several policymakers, despite each of them having their own political agendas.

12.
Mol Biol Rep ; 49(4): 3225-3236, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35066770

RESUMEN

BACKGROUND: Neutrophil extracellular traps (NETs) are a recently discovered neutrophil defense mechanism which modulates several inflammatory conditions contributing to metabolic profile alterations. Therefore, the present study aimed to evaluate the production of NETs in obese patients and mice, verifying the possible mechanisms associated with the release of NETs by the adipose tissue. METHODS AND RESULTS: The present study investigated NETs production in human adipose tissue and also showing the neutrophils using intravital microscopy in mouse epididymal adipose tissue. Blood and white adipose tissues were obtained from eutrophic and obese individuals and from mice. Lipid, glycemic and leukocyte profiles were evaluated, as well as the levels of NETs and its markers. Bioinformatics and proteomics analyses were performed and the identified key proteins were measured. The main findings showed that the inflammatory markers interleukin-8 (IL-8), heat shock protein 90 (HSP90) and the E1 heat shock protein family (HSPE1) can be modulated by the NETs levels in obesity. Obesity has also been associated with increased cholesterol, glucose intolerance, ionic calcium and NETs. We also observed an increase in catalase and a decreased superoxide dismutase activity. Bioinformatics and proteomics analyses revealed that IL-8, HSP90 and HSPE1 were associated with obesity, inflammation and NETs release. CONCLUSIONS: In conclusion, the present study shows an increase in NETs production during obesity associated with important inflammatory markers in adipose.


Asunto(s)
Trampas Extracelulares , Tejido Adiposo/metabolismo , Animales , Trampas Extracelulares/metabolismo , Humanos , Inflamación/metabolismo , Ratones , Neutrófilos/metabolismo , Obesidad/metabolismo
13.
Lasers Med Sci ; 37(5): 2509-2516, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35119554

RESUMEN

The aim of this study is to investigate the antineoplastic potential of photodynamic therapy (PDT) mediated by an aluminum-phthalocyanine chloride nanoemulsion (AlPc-NE), against an oral squamous cell carcinoma (OSCC) cell line in vitro. Both OSCC (SCC9) and A431 cell lines were studied in vitro. Four study groups were used: Group 1 (phosphate-buffered saline [PBS]), Group 2 (PBS + 28.3 J/cm2 irradiation), Group 3 (AlPc-NE alone), and Group 4 (AlPc-NE + 28.3 J/cm2 irradiation). To test the effect of PDT with AlPc-NE, cell viability, migration, and cell death assays were performed. Moreover, the expressions of Ki-67 and TP53 were evaluated using immunoassays. The results showed that PDT mediated by all AlPc-NE concentrations evaluated (i.e., 0.7, 0.35, and 0.17 nM AlPc) significantly reduced the viability of SCC9 cells. Migration and cell death assays also revealed that PDT with AlPc-NE significantly reduced the rate of migration and increased cell death compared to the control groups. In addition, it was found that PDT with AlPc-NE reduced Ki-67 and mutated TP53 immunoexpression. PDT with AlPc-NE is effective in reducing the viability and migration of SCC9. Moreover, PDT with AlPc-NE nanoemulsions reduces the cell proliferation and expression of mutant TP53.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de la Boca , Nanopartículas , Compuestos Organometálicos , Fotoquimioterapia , Aluminio , Carcinoma de Células Escamosas/tratamiento farmacológico , Humanos , Isoindoles , Antígeno Ki-67 , Neoplasias de la Boca/tratamiento farmacológico , Compuestos Organometálicos/farmacología , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico
14.
Lasers Med Sci ; 37(9): 3527-3536, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36001245

RESUMEN

Radiation therapy for head and neck squamous cell carcinoma (HNSCC) is associated with several complications. Although photobiomodulation (PBM) has radioprotective effects in normal tissue, it could also enhance the growth of neoplastic cells. Thus, the present study aimed to investigate the cellular response of oral squamous cell carcinoma with pre-exposure to low-level phototherapy before radiotherapy. SCC9, Cal-27, A431, and HaCaT cell lines were subjected to low-level light therapy and radiotherapy. The cells were treated with a single energy density (300 J/cm2) of a light-emitting diode (660 nm) prior to ionizing radiation at different doses (0, 2, 4, and 6 Gy). After 24 h, wound scratch, proliferation, clonogenic cell survival, cell death, and reactive oxygen species (ROS) analyses were performed to evaluate cell response. The cell lines pre-exposed to PBM at the analyzed dosage were radiosensitive. The treatment significantly reduced cell proliferation and clonogenic cell survival. Migration and cell death assays also revealed positive results, with the treatment group showing lower rate of migration and higher cell death than did the control group. Moreover, PBM effectively increased the intracellular levels of ROS. PBM at 300 J/cm2 is a promising radiosensitizing modality to reduce the radiation dose and avoid the intolerable side effects of radiotherapy for HNSCC, thus increasing the probability of successful treatment. However, further studies are needed to support and confirm the results.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Terapia por Luz de Baja Intensidad , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas de Cabeza y Cuello/etiología , Neoplasias de la Boca/radioterapia , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patología , Terapia por Luz de Baja Intensidad/métodos , Especies Reactivas de Oxígeno , Neoplasias de Cabeza y Cuello/radioterapia
15.
Environ Toxicol ; 37(9): 2314-2323, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35661558

RESUMEN

The possibility of chemical contamination is an important issue to consider when designing a cell therapy strategy. Both bisphenol A (BPA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are among the most environmentally relevant endocrine disrupting chemicals (EDCs, compounds with a high affinity for adipose tissue) recently studied. Adipose-derived stem cells (ASCs) are mesenchymal stromal cells (MSCs) obtained from adipose tissue widely used in regenerative medicine to prevent and treat diseases in several tissues and organs. Although the experimental use of tissue-engineered constructs requires careful analysis for approval and implantation, there has been a recent increase in the number of approved clinical trials for this promising strategy. This study aimed to evaluate cell viability, apoptosis, DNA damage, and the adipogenic or osteogenic differentiation potential of rat adipose-derived stem cells (rASCs) exposed to previously established non-cytotoxic doses of BPA and TCDD in vitro. Results demonstrated that 10 µM of BPA and 10 nM of TCDD were able to significantly reduce cell viability, while all exposure levels resulted in DNA damage, although did not increase the apoptosis rate. According to the analysis of adipogenic differentiation, 1 µM of BPA induced the significant formation of oil droplets, suggesting an increased adipocyte differentiation, while both 10 µM of BPA and 10 nM of TCDD decreased adipocyte differentiation. Osteogenic differentiation did not differ among the treatments. As such, BPA and TCDD in the concentrations tested can modify important processes in rASCs such as cell viability, adipogenic differentiation, and DNA damage. Together, these findings prove that EDCs play an important role as contaminants, putatively interfering in cell differentiation and thus impairing the therapeutic use of ASCs.


Asunto(s)
Dibenzodioxinas Policloradas , Adipocitos , Tejido Adiposo , Animales , Compuestos de Bencidrilo , Diferenciación Celular , Osteogénesis , Fenoles , Dibenzodioxinas Policloradas/toxicidad , Ratas , Células Madre
16.
Int J Mol Sci ; 23(23)2022 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-36499183

RESUMEN

The Developmental Origins of Health and Disease (DOHaD) concept correlates early life exposure to stressor conditions with the increased incidence of non-communicable chronic diseases, including prostate cancer (PCa), throughout the life span. However, the molecular mechanisms involved in this process remain poorly understood. In this study, the deregulation of two miRNAs (rno-miR-18a-5p and rno-miR-345-3p) was described in the ventral prostate VP of old rats born to dams fed with a low protein diet (LPD) (6% protein in the diet) during gestational and lactational periods. Integrative analysis of the (VP) transcriptomic and proteomic data revealed changes in the expression profile of 14 identified predicted targets of these two DE miRNAs, which enriched terms related to post-translational protein modification, metabolism of proteins, protein processing in endoplasmic reticulum, phosphonate and phosphinate metabolism, the calnexin/calreticulin cycle, metabolic pathways, N-glycan trimming in the ER and the calnexin/calreticulin cycle, hedgehog ligand biogenesis, the ER-phagosome pathway, detoxification of reactive oxygen species, antigenprocessing-cross presentation, RAB geranylgeranylation, collagen formation, glutathione metabolism, the metabolism of xenobiotics by cytochrome P450, and platinum drug resistance. RT-qPCR validated the deregulation of the miR-18a-5p/P4HB (prolyl 4-hydroxylase subunit beta) network in the VP of older offspring as well as in the PNT-2 cells transfected with mimic miR-18a-5p. Functional in vitro studies revealed a potential modulation of estrogen receptor α (ESR1) by miR-18a-5p in PNT-2 cells, which was also confirmed in the VP of older offspring. An imbalance of the testosterone/estrogen ratio was also observed in the offspring rats born to dams fed with an LPD. In conclusion, deregulation of the miR-18a-5p/P4HB network can contribute to the developmental origins of prostate cancer in maternally malnourished offspring, highlighting the need for improving maternal healthcare during critical windows of vulnerability early in life.


Asunto(s)
MicroARNs , Neoplasias de la Próstata , Animales , Masculino , Ratas , Perfilación de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de la Próstata/genética , Proteómica , Transcriptoma
17.
Molecules ; 27(14)2022 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-35889222

RESUMEN

Ovarian cancer (OC) is the most lethal gynecologic malignancy, and melatonin has shown various antitumor properties. Herein, we investigated the influence of melatonin therapy on energy metabolism and mitochondrial integrity in SKOV-3 cells and tested whether its effects depended on MT1 receptor activation. SKOV-3 cells were exposed to different melatonin concentrations, and experimental groups were divided as to the presence of MT1 receptors (melatonin groups) or receptor absence by RNAi silencing (siRNA MT1+melatonin). Intracellular melatonin levels increased after treatment with melatonin independent of the MT1. The mitochondrial membrane potential of SKOV-3 cells decreased in the group treated with the highest melatonin concentration. Melatonin reduced cellular glucose consumption, while MT1 knockdown increased its consumption. Interconversion of lactate to pyruvate increased after treatment with melatonin and was remarkable in siRNA MT1 groups. Moreover, lactate dehydrogenase activity decreased with melatonin and increased after MT1 silencing at all concentrations. The UCSC XenaBrowser tool showed a positive correlation between the human ASMTL gene and the ATP synthase genes, succinate dehydrogenase gene (SDHD), and pyruvate dehydrogenase genes (PDHA and PDHB). We conclude that melatonin changes the glycolytic phenotype and mitochondrial integrity of SKOV-3 cells independent of the MT1 receptor, thus decreasing the survival advantage of OC cells.


Asunto(s)
Melatonina , Neoplasias Ováricas , Receptor de Melatonina MT1 , Carcinoma Epitelial de Ovario , Femenino , Humanos , Melatonina/metabolismo , Melatonina/farmacología , Potencial de la Membrana Mitocondrial , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Piruvatos , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Receptor de Melatonina MT1/genética , Receptor de Melatonina MT1/metabolismo
18.
Prostaglandins Other Lipid Mediat ; 152: 106501, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33049402

RESUMEN

Obesity is a chronic disease caused multiple associated factors that results in excessive body fat accumulation. The Renin-Angiotensin System (RAS) unbalance is now recognized as a key factor on regulating body energy and metabolism. AIM: The aim of the present study was to evaluate the Enalapril (ACE inhibitor) effects on the metabolic function and hepatic steatosis of obese mice evaluating Angiotensin Converting Enzymes (ACEs) expression. METHODS: The experiment was performed using 32 male Swiss mice (8 weeks old) equally and randomly divided into 4 groups (n = 8): standard diet (ST), standard diet plus Enalapril (ST + ENAL), hyperlipidic diet (HF) and hyperlipidic diet plus Enalapril (HF + ENAL). Weekly measurements of animal weight and feed consumption were performed. At the end of treatment period a glucose tolerance test (GTT) and insulin sensitivity test (IST) were performed. Ultrasonography was used to evaluate hepatic and epididymal fat pad. Liver samples were submitted to HE histology and gene expression analyses were performed using Real-Time PCR. RESULTS: The main results showed a decrease in body weight after treatment with Enalapril, as well as a reduced size of epididymal fat pad (EFP). Hepatic echogenicity and steatosis measurement were lower in the obese groups treated with Enalapril also modulating ACE2/ACE expressions. CONCLUSIONS: Enalapril use improved metabolism reducing hepatic steatosis, decreasing ACE expression and increasing ACE2 expression.


Asunto(s)
Dieta Alta en Grasa , Enalapril , Hígado , Peptidil-Dipeptidasa A , Animales , Glucemia/metabolismo , Resistencia a la Insulina , Masculino , Ratones , Sistema Renina-Angiotensina/efectos de los fármacos
19.
Mol Biol Rep ; 48(5): 4625-4635, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34014471

RESUMEN

Neutrophil extracellular traps (NETs) represent an innate organism defense mechanism characterized by neutrophil release of intracellular material to capture any aggressor agent. Elevated NETs release is associated with increased inflammatory response and related diseases, such as obesity. Chronic physical training is one of the main strategies to treat and prevent obesity. The relationship between physical training and NETs is still under study. The present review, followed by a bioinformatics analysis, demonstrates the meaningful connection between physical exercise, obesity, and NETs. The bioinformatics indicated TNF-α as a leading gene after the ontological analysis followed by positive-interleukin-6 regulation, chemokines, and inflammatory response regulation. The main results pointed to a relevant regulatory effect of physical training on NETs release, indicating physical exercise as a possible therapeutic target on modulating NETs and inflammation.


Asunto(s)
Ejercicio Físico/genética , Inflamación/genética , Obesidad/genética , Factor de Necrosis Tumoral alfa/genética , Biología Computacional , Trampas Extracelulares/genética , Humanos , Inflamación/fisiopatología , Inflamación/terapia , Neutrófilos/metabolismo , Obesidad/fisiopatología , Obesidad/terapia
20.
Mol Biol Rep ; 48(2): 1725-1734, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33586053

RESUMEN

The present study aimed to evaluate the effects of resveratrol, a nutraceutical polyphenol, and Lactococcus lactis (bacteria probiotic), on metabolic parameters and hepatic proinflammatory markers expression. C57BL/6 mice were divided into 4 groups: Standard (ST), Lactococcus lactis (LL), Resveratrol (RSV), and Lactococcus lactis plus resveratrol (LL + RSV). Lactococcus lactis and resveratrol were administered by orogastric gavage. Blood parameters were assessed (total cholesterol, triglycerides, ALT and AST). IL-6 mRNA expression was evaluated by Real-time PCR and TNF-α protein expression was assessed by immunohistochemistry. The main findings showed that resveratrol and Lactococcus lactis association decreased body weight, aspartate aminotransferase and total cholesterol levels. LL and LL + RSV decreased triglycerides levels and IL-6 and TNF-α expression. These results open a perspective of using resveratrol and Lactococcus lactis to improve metabolic parameters and Lactococcus lactis in preventing inflammation and the hepatic diseases development.


Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Lactococcus lactis/metabolismo , Hígado/efectos de los fármacos , Probióticos/farmacología , Resveratrol/farmacología , Administración Oral , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Colesterol/sangre , Biología Computacional , Femenino , Regulación de la Expresión Génica/genética , Ontología de Genes , Inmunohistoquímica , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/microbiología , Interleucina-6/genética , Interleucina-6/metabolismo , Hígado/metabolismo , Hígado/patología , Ratones , Ratones Endogámicos C57BL , Resveratrol/administración & dosificación , Triglicéridos/sangre , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
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