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BACKGROUND: Obesity represents a global health crisis, yet a dichotomy is emerging with classification according to the metabolic state into metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). This study aimed to identify distinctive systemic clinical/endocrinological parameters between MHO individuals, employing a comprehensive comparative analysis of 50 biomarkers. Our emphasis was on routine analytes, ensuring cost-effectiveness for widespread use in diagnosing metabolic health. SUBJECTS/METHODS: The study included 182 women diagnosed with obesity referred for bariatric surgery at the Endocrinology, Diabetes, and Metabolism Service of São João Hospital and University Centre in Portugal. MUO was defined by the presence of at least one of the following metabolic disorders: diabetes, hypertension, or dyslipidemia. Patients were stratified based on the diagnosis of these pathologies. RESULTS: Significantly divergent health-related parameters were observed between MHO and MUO patients. Notable differences included: albumin (40.1 ± 2.2 vs 40,98 ± 2.6 g/L, p value = 0.017), triglycerides (110.7 ± 51.1 vs 137.57 ± 82.6 mg/dL, p value = 0.008), glucose (99.49 ± 13.0 vs 119.17 ± 38.9 mg/dL, p value < 0.001), glycated hemoglobin (5.58 ± 0.4 vs 6.15 ± 1.0%, p value < 0.001), urea (31.40 ± 10.0 vs 34.61 ± 10.2 mg/dL, p value = 0.014), total calcium (4.64 ± 0.15 vs 4.74 ± 0.17 mEq/L, 1 mEq/L = 1 mg/L, p value < 0.001), ferritin (100.04 ± 129.1 vs 128.55 ± 102.1 ng/mL, p value = 0.005), chloride (104.68 ± 1.5 vs 103.04 ± 2.6 mEq/L, p value < 0.001), prolactin (13.57 ± 6.3 vs 12.47 ± 7.1 ng/mL, p value = 0.041), insulin (20.36 ± 24.4 vs 23.87 ± 19.6 µU/mL, p value = 0.021), c peptide (3.78 ± 1.8 vs 4.28 ± 1.7 ng/mL, p value = 0.003), albumin/creatinine ratio (15.41 ± 31.0 vs 48.12 ± 158.7 mg/g creatinine, p value = 0.015), and whole-body mineral density (1.27 ± 0.1 vs 1.23 ± 0.1 g/cm2, p value = 0.016). CONCLUSIONS: Our findings highlight potential additional parameters that should be taken into consideration alongside the commonly used biomarkers for classifying metabolic health in women. These include albumin, urea, total calcium, ferritin, chloride, prolactin, c-peptide, albumin-creatinine ratio, and whole-body mineral density. Moreover, our results also suggest that MHO may represent a transitional phase preceding the development of the MUO phenotype.
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Biomarcadores , Obesidad Metabólica Benigna , Humanos , Femenino , Adulto , Persona de Mediana Edad , Biomarcadores/sangre , Portugal/epidemiología , Obesidad/metabolismo , Glucemia/metabolismo , Glucemia/análisisRESUMEN
The unfoldase ClpC1 is one of the most exciting drug targets against tuberculosis. This AAA+ unfoldase works in cooperation with the ClpP1P2 protease and is the target of at least four natural product antibiotics: cyclomarin, ecumicin, lassomycin, and rufomycin. Although these molecules are promising starting points for drug development, their mechanisms of action remain largely unknown. Taking advantage of a middle domain mutant, we determined the first structure of Mycobacterium tuberculosis ClpC1 in its apo, cyclomarin-, and ecumicin-bound states via cryo-EM. The obtained structure displays features observed in other members of the AAA+ family and provides a map for further drug development. While the apo and cyclomarin-bound structures are indistinguishable and have N-terminal domains that are invisible in their respective EM maps, around half of the ecumicin-bound ClpC1 particles display three of their six N-terminal domains in an extended conformation. Our structural observations suggest a mechanism where ecumicin functions by mimicking substrate binding, leading to ATPase activation and changes in protein degradation profile.
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Mycobacterium tuberculosis , Tuberculosis , Humanos , Antibacterianos/farmacología , Antibacterianos/metabolismo , Proteínas Bacterianas/metabolismo , Mycobacterium tuberculosis/metabolismo , Chaperonas Moleculares/metabolismoRESUMEN
BACKGROUND: The gut microbiota is relatively stable; however, various factors can precipitate an imbalance that is known to be associated with various diseases. We aimed to conduct a systematic literature review of studies reporting the effects of ionizing radiation on the composition, richness, and diversity of the gut microbiota of animals. METHODS: A systematic literature search was performed in PubMed, EMBASE, and Cochrane library databases. The standard methodologies expected by Cochrane were utilized. RESULTS: We identified 3531 non-duplicated records and selected twenty-nine studies after considering the defined inclusion criteria. The studies were found to be heterogeneous, with significant differences in the chosen populations, methodologies, and outcomes. Overall, we found evidence of an association between ionizing radiation exposure and dysbiosis, with a reduction of microbiota diversity and richness and alterations in the taxonomic composition. Although differences in taxonomic composition varied across studies, Proteobacteria, Verrucomicrobia, Alistipes, and Akkermancia most consistently reported to be relatively more abundant after ionizing radiation exposure, whereas Bacteroidetes, Firmicutes, and Lactobacillus were relatively reduced. CONCLUSIONS: This review highlights the effect of ionizing exposure on gut microbiota diversity, richness, and composition. It paves the way for further studies on human subjects regarding gastrointestinal side effects in patients submitted to treatments with ionizing radiation and the development of potential preventive, therapeutic approaches.
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INTRODUCTION: Obesity and breast cancer are two major pathologies closely associated with increasing incidence and mortality rates, especially amongst women. The association between both diseases have been thoroughly discussed but much is still to uncover. AIM: The aim of this study is to analyse tumour characteristics and clinical outcomes of overweight and obese women to disclosure potential associations and better understand the impact of obesity in breast cancer. MATERIALS AND METHODS: Clinicopathological information of 2246 women were extracted from the institutional database of comprehensive cancer centre in Portugal diagnosed between 2012 and 2016. Women were stratified according to body mass index as normal, overweight, and obese. Patients' demographic information and tumour features (age, family history, topographic localization, laterality, histological type, and receptor status) were taken as independent variables and overall survival, tumour stage, differentiation grade and bilaterality were considered clinical outcomes. RESULTS: The main results reveal that overweight and obesity are predominantly associated with worse outcomes in breast cancer patients. Obese patients present larger (p-value: 0.002; OR 1.422; 95% CI 1.134-1.783) and more poorly differentiated tumours (p-value: 0.002; OR 1.480; 95% CI 1.154-1.898) and tend to have lower overall survival although without statistical significance (p-value: 0.117; OR 1.309; 95% CI 0.934-1.833). Overweighted women are more likely to have bilateral breast cancer (p-value: 0.017; OR 3.076; 95% CI 1.225-7.722) than obese women. The results also reveal that overweight women present less distant metastasis (p-value: 0.024; OR 0.525; 95%CI 0.299-0.920). Topographic localization and laterality did not achieve statistical significance.
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Neoplasias de la Mama , Sobrepeso , Humanos , Femenino , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Estudios Retrospectivos , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/diagnóstico , Índice de Masa CorporalRESUMEN
OBJECTIVE: The effect of diabetes on adhesive capsulitis (AC) and its impact on the outcomes of ultrasound (US)-guided hydrodistension of the glenohumeral joint are still unclear. We aimed to identify predictors of US-guided hydrodistension outcomes, while assessing the performance of the method in diabetic compared to non-diabetic patients. MATERIALS AND METHODS: A total of 135 patients with AC who underwent US-guided hydrodistension were prospectively included. Demographics and factors linked to chronic inflammation and diabetes were recorded and patients were followed-up for 6 months. Functionality and pain were evaluated with the Disabilities of the Arm, Shoulder and Hand (DASH) and the Visual Analogue Scale (VAS) score. Statistical analysis was performed with Mann-Whitney U test, linear, and binary logistic regression. RESULTS: Diabetes was identified in 25/135 patients (18.5%). Diabetic patients had worse DASH and VAS score at presentation (P < 0.0001) and presented with a higher grade of AC (P < 0.0001) and lower range of motion (P < 0.01) compared to non-diabetics. Higher DASH (P = 0.025) and VAS scores (P = 0.039) at presentation were linked to worse functionality at 6 months. Presence and duration of diabetes, and the number of hydrodistension repeats, correlated with worse VAS and DASH scores at 6 months. The number of procedure repeats was the only independent predictor of complete pain resolution at 6 months (OR 0.418, P = 003). CONCLUSION: Diabetes is linked to more severe AC at presentation and worse outcomes in patients undergoing US-guided hydrodistension. In resistant cases, repeating the intervention is independently linked to worse outcomes for at least 6 months post-intervention.
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Bursitis , Diabetes Mellitus , Articulación del Hombro , Humanos , Estudios Longitudinales , Resultado del Tratamiento , Bursitis/diagnóstico por imagen , Bursitis/terapia , Dolor de Hombro , Rango del Movimiento Articular , Ultrasonografía Intervencional/métodosRESUMEN
Although biofloc technology is already recognized as advantageous and practical for aquaculture for the effects of maintaining water quality and improving the health status and resistance of cultivated animals against pathogens, little is known about the way of action involved. This study aimed to evaluate the performance of bacterial groups as inducers in the formation of flocs compared to a system with spontaneous formation. Therefore, three microsystems were built in 3L tanks with constant aeration to induce the biofloc aggregation with addition of bacterial consortiuns with differentiated functions. It was used a control, without addition of bacterial consortium; B1 with addition of probiotic bacteria consortium; and B2, with adding nitrifying bacteria consortium. During the experimental period were evaluated physicochemical variables and quantifications of bacterial cultivable groups: Heterotrophic Bacteria and Vibrio. Also was the microscopic characterization of the flakes and tests of antimicrobial activity against pathogenic bacteria. Systems B1 and B2 showed promising results in relation to control (spontaneous bioflocs), showing more homogeneous flake formation, antimicrobial activity against the tested pathogens and greater biological diversity in the systems. The bacteria used in these tests were able to optimize the formation of microbial aggregates, showing potential for application in cultivation systems, in order to obtain improvements in productivity.
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Antiinfecciosos , Acuicultura , Animales , Bacterias , Biodiversidad , Estado de SaludRESUMEN
Nitrite is an important food additive for cured meats; however, high nitrite levels pose adverse health effects to humans. Hence, monitoring nitrite concentration is critical to comply with limits imposed by regulatory agencies. Laser-induced graphene (LIG) has proven to be a scalable manufacturing alternative to produce high-performance electrochemical transducers for sensors. Herein, we expand upon initial LIG studies by fabricating hydrophilic and hydrophobic LIG that are subsequently converted into ion-selective sensors to monitor nitrite in food samples with comparable performance to the standard photometric method (Griess method). The hydrophobic LIG resulted in an ion-selective electrode with improved potential stability due partly to a decrease in the water layer between the electrode and the nitrite poly(vinyl) chloride-based ion-selective membrane. These resultant nitrite ion-selective sensors displayed Nernstian response behavior with a sensitivity of 59.5 mV dec-1, a detection limit of 0.3 ± 0.1 mg L-1 (mean ± standard deviation), and a broad linear sensing range from 10-5 to 10-1 M, which was significantly larger than currently published nitrite methods. Nitrite levels were determined directly in food extract samples of sausage, ham, and bacon for 5 min. These sensor metrics are significant as regulatory agencies limit nitrite levels up to 200 mg L-1 in finished products to reduce the potential formation of nitrosamine (carcinogenic compound). These results demonstrate the versatility of LIG as a platform for ion-selective-LIG sensors and simple, efficient, and scalable electrochemical sensing in general while demonstrating a promising alternative to monitor nitrite levels in food products ensuring regulatory compliance.
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Grafito , Electrodos de Iones Selectos , Humanos , Grafito/química , Nitritos , Agua , Rayos LáserRESUMEN
Radium-223 (Ra-223) is a targeted nuclear medicine therapy for castration-resistant prostate cancer with bone metastases. Its major route of elimination is the intestine. There is overwhelming evidence that the gut microbiota is altered by ionizing radiation (IR) from radiotherapy treatments. Nevertheless, it is known that extrapolation of outcomes from radiotherapy to nuclear medicine is not straightforward. The purpose of this study was to prospectively determine the effect of Ra-223 on selected important bacteria from the gut microbiota. Stool samples from three prostate cancer patients and two healthy individuals were obtained, processed, and analysed. We specifically measured the relative change of the abundance of important bacteria, determined by the 2-ΔΔC method. We found that Ra-223 influenced the gut microbiota composition. The most relevant changes were increases of Proteobacteria and Atopobacter; and decreases of Bacteroidetes, Prevotella, Lactobacillus, Bifidobacterium, Clostridium coccoides, and Bacteroides fragilis. Additionally, our experiment confirms that the composition of gut microbiota from prostate cancer patients is altered. No significant correlation was found between each subject's gut microbiome profile and their clinical indices. Despite its limited sample, the results of this pilot study suggest that ionizing radiation from Ra-223 alters the gut microbiota composition and that the gut microbiota of prostate cancer patients has an increase of the bacteria with known prejudicial effects and a decrease of the ones with favorable effects.
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Early-life consumption of high-fat and sugar-rich foods is recognized as a major contributor for the onset of metabolic dysfunction and its related disorders, including diabetes and nonalcoholic fatty liver disease. The lifelong impact of early unhealthy eating habits that start at younger ages remains unclear. Therefore, to better understand the effects of diet, it is essential to evaluate the structural and functional changes induced in metabolic organs and potential mechanisms underlying those changes. To investigate the long-term effects of eating habits, young male rats were exposed to high-sugar and high-energy diets. After 14 weeks, body composition was assessed, and histopathological changes were analyzed in the liver and adipose tissue. Serum biochemical parameters were also determined. Expression of inflammatory markers in the liver was evaluated by immunohistochemistry. Our results revealed that serum levels of glucose, creatinine, aspartate transaminase (AST), alanine transaminase (ALT), and lipid profile were increased in rats red high-sugar and high-energy diets. Histopathological alterations were observed, including abnormal hepatocyte organization and lipid droplet accumulation in the liver, and abnormal structure of adipocytes. In both unhealthy diet groups, hepatic expression of Toll-like receptor 4 (TLR4), cyclooxygenase 2 (COX-2), and E-selectin were increased, as well as a biomarker of oxidative stress. Together, our data demonstrated that unhealthy diets induced functional and structural changes in the metabolic organs, suggesting that proinflammatory and oxidative stress mechanisms trigger the hepatic alterations and metabolic dysfunction.
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Dieta Alta en Grasa , Hígado , Tejido Adiposo/metabolismo , Animales , Conducta Alimentaria , Hígado/patología , Masculino , Ratas , Azúcares/metabolismo , Azúcares/farmacologíaRESUMEN
Bariatric surgery (BS) is the most effective therapy for severe obesity, which improves several comorbidities (such as diabetes, hypertension, dyslipidemia, among others) and results in marked weight loss. Despite these consensual beneficial effects, sleeve gastrectomy and Roux-en-Y gastric bypass (the two main bariatric techniques) have also been associated with changes in bone metabolism and progressive bone loss. The objective of this literature review is to examine the impact of bariatric surgery on bone and its main metabolic links, and to analyze the latest findings regarding the risk of fracture among patients submitted to bariatric surgery.
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Cirugía Bariátrica , Derivación Gástrica , Laparoscopía , Obesidad Mórbida , Cirugía Bariátrica/métodos , Densidad Ósea , Gastrectomía/efectos adversos , Gastrectomía/métodos , Derivación Gástrica/efectos adversos , Derivación Gástrica/métodos , Humanos , Laparoscopía/métodos , Resultado del TratamientoRESUMEN
Current solid-contact ion-selective electrodes (ISEs) suffer from signal-to-noise drift and short lifespans partly due to water uptake and the development of an aqueous layer between the transducer and ion-selective membrane. To address these challenges, we report on a nitrate ISE based on hydrophobic laser-induced graphene (LIG) coated with a poly(vinyl) chloride-based nitrate selective membrane. The hydrophobic LIG was created using a polyimide substrate and a double lasing process under ambient conditions (air at 23.0 ± 1.0 °C) that resulted in a static water contact angle of 135.5 ± 0.7° (mean ± standard deviation) in wettability testing. The LIG-ISE displayed a Nernstian response of - 58.17 ± 4.21 mV dec-1 and a limit-of-detection (LOD) of 6.01 ± 1.44 µM. Constant current chronopotentiometry and a water layer test were used to evaluate the potential (emf) signal stability with similar performance to previously published work with graphene-based ISEs. Using a portable potentiostat, the sensor displayed comparable (p > 0.05) results to a US Environmental Protection Agency (EPA)-accepted analytical method when analyzing water samples collected from two lakes in Ames, IA. The sensors were stored in surface water samples for 5 weeks and displayed nonsignificant difference in performance (LOD and sensitivity). These results, combined with a rapid and low-cost fabrication technique, make the development of hydrophobic LIG-ISEs appealing for a wide range of long-term in situ surface water quality applications.
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This study aimed to determine the effect of three widely used radiopharmaceuticals with intestinal excretion on selected relevant bacteria that are part of the human gut microbiota, using an ex vivo approach. Fecal samples obtained from healthy volunteers were analyzed. Each sample was divided into four smaller aliquots. One served as the non-irradiated control. The other three were homogenized with three radiopharmaceutical solutions ([131I]NaI, [99mTc]NaTcO4, and [223Ra]RaCl2). Relative quantification of each taxa was determined by the 2-ΔΔC method, using the ribosomal gene 16S as an internal control (primers 534/385). Twelve fecal samples were analysed: three controls and nine irradiated. Our experiment showed fold changes in all analyzed taxa with all radiopharmaceuticals, but results were more significant with I-131, ranging from 1.87-83.58; whereas no relevant differences were found with Tc-99m and Ra-223, ranging from 0.98-1.58 and 0.83-1.97, respectively. This study corroborates limited existing research on how ionizing radiation changes the gut microbiota composition, providing novel data regarding the ex vivo effect of radiopharmaceuticals. Our findings justify the need for future larger scale projects.
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Microbioma Gastrointestinal , Radio (Elemento) , Heces/microbiología , Humanos , Radioisótopos de Yodo , ARN Ribosómico 16S/genética , Radiación Ionizante , RadiofármacosRESUMEN
The intestinal epithelium is a principal site for environmental agents' detection. Several inflammation- and stress-related signalling pathways have been identified as key players in these processes. However, it is still unclear how the chronic intake of inadequate nutrients triggers inflammatory signalling pathways in different intestinal regions. We aimed to evaluate the impact of unhealthy dietary patterns, starting at a younger age, and the association with metabolic dysfunction, intestinal inflammatory response, and obesity in adulthood. A rat model was used to evaluate the effects of the consumption of sugary beverages (HSD) and a Western diet (WD), composed of ultra-processed foods. Both diets showed a positive correlation with adiposity index, but a positive correlation was found between the HSD diet and the levels of blood glucose and triglycerides, whereas the WD diet correlated positively with triglyceride levels. Moreover, a distinct inflammatory response was associated with either the WD or HSD diets. The WD induced an increase in TLR2, TLR4, and nuclear factor-kappa B (NF-κB) intestinal gene expression, with higher levels in the colon and overexpression of the inducible nitric oxide synthase. In turn, the HSD diet induced activation of the TLR2-mediated NF-κB signalling pathway in the small intestine. Altogether, these findings support the concept that early intake of unhealthy foods and nutrients are a main exogenous signal for disturbances of intestinal immune mechanisms and in a region-specific manner, ultimately leading to obesity-related disorders in later life.
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FN-kappa B , Receptor Toll-Like 4 , Animales , Glucemia , Dieta Occidental , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Obesidad , Ratas , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , TriglicéridosRESUMEN
Date seed is a by-product of Phoenix dactylifera L. fruit which is well recognized for its polyphenols content and numerous health-beneficial effects. Due to the increasing interest in natural phytochemicals with antioxidant activities, the present study aimed to extract polyphenols from both raw and roasted date seeds and investigate the anti-angiogenic effect of these two extracts (raw and roasted date seed polyphenols extracts (DSPE) at 25 and 50 µg/mL) using human microvascular endothelial cells (HMVEC). Our results showed that both raw and roasted DSPE suppressed some angiogenesis features in a dose-dependent manner including cell proliferation, migration, and capillary-like structure formation, of which raw DSPE was more potent inhibitor than roasted DSPE. Reduction in reactive oxygen species, as well as enhancement of superoxide dismutase activity occurred using both raw and roasted date seed polyphenols extracts. However, no changes were observed in advanced oxidation protein products versus control. Taken together, our data indicated that raw and roasted DSPE possess antioxidant activity, which suggested their potential use as a source of polyphenols with anti-angiogenic properties. Nevertheless, further studies are required to explore the underlying mechanisms responsible for their anti-angiogenic activities.
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Phoeniceae , Humanos , Phoeniceae/química , Polifenoles/farmacología , Polifenoles/análisis , Antioxidantes/análisis , Células Endoteliales/química , Productos Avanzados de Oxidación de Proteínas/análisis , Especies Reactivas de Oxígeno , Semillas/química , Extractos Vegetales/química , Superóxido DismutasaRESUMEN
We aimed to identify the main challenges in the gynecological care and management of patients with intellectual disability by gynecologists. Gynecologists answered to online questionnaires about situations in which the professional reports their confidence in caring for patients with intellectual disability. Were studied 143 responses, 75% women. Among them, 53.8% felt apprehensive to conduct a routine gynecological screening, 60% were confident in advising about contraceptive services and examining the genitals. The greatest difficulty was indicating drugs to suppress menstruation and managing patients with severe intellectual disability. The female doctors were more prepared in the care of disability patients and recent certified gynecologists were more insecure. The main difficulty was time for examinations (39.2%) and the main solution was to improve medical training (64.2%). The main challenges of the gynecologist included the amount of time needed to provide clinical services, the lack of knowledge and skill; and ethical concerns.
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Interactions between cell types, growth factors, and extracellular matrix components involved in angiogenesis are crucial for new vessel formation leading to tissue regeneration. This study investigated whether cocultures of fibroblasts and endothelial cells (ECs; from macro- or microvasculature) play a role in the formation of microvessel-like structures by ECs, as well as modulate fibroblast differentiation and growth factors production (vascular endothelial cell growth factor, basic fibroblast growth factor, active transforming growth factor-ß1, and interleukin-8), which are important for vessel sprouting and maturation. Data obtained revealed that in vitro coculture systems of fibroblasts and human ECs stimulate collagen synthesis and growth factors production by fibroblasts that ultimately affect the formation and distribution of microvessel-like structures in cell cultures. In this study, areas with activated fibroblasts and high alkaline phosphatase (ALP) activity were also observed in cocultures. Molecular docking assays revealed that ALP has two binding positions for collagen, suggesting its impact in collagen proteins' aggregation, cell migration, and microvessel assembly. These findings indicate that bioinformatics and coculture systems are complementary tools for investigating the participation of proteins, like collagen and ALP in angiogenesis.
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Fosfatasa Alcalina/metabolismo , Movimiento Celular , Colágeno/metabolismo , Endotelio Vascular/fisiología , Fibroblastos/fisiología , Microvasos/fisiología , Neovascularización Fisiológica , Fosfatasa Alcalina/química , Sitios de Unión , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Endotelio Vascular/citología , Fibroblastos/citología , Humanos , Técnicas In Vitro , Microvasos/citología , Conformación ProteicaRESUMEN
The umbilical cord has been proved to be an easy-access, reliable, and useful source of mesenchymal stem cells (MSC) for clinical applications due to its primitive, immunomodulatory, non-immunogenic, secretory and paracrine, migratory, proliferative, and multipotent properties. This set of characteristics has recently attracted great research interest in the fields of nanotechnology and regenerative medicine and cellular therapy. Accumulating evidence supports a pronounced therapeutic potential of MSC in many different pathologies, from hematology to immunology, wound-healing, tissue regeneration, and oncology. Diabetes mellitus, branded the epidemic of the century, is considered a chronic metabolic disorder, representing a major burden for health system sustainability and an important public health challenge to modern societies. The available treatments for type 2 diabetes mellitus (T2DM) still rely mainly on combinations of oral antidiabetic agents with lifestyle and nutritional adjustments. Despite the continuous development of novel and better hypoglycemic drugs, their efficacy is limited in the installment and progression of silent T2DM complications. T2DM comorbidities and mortality rates still make it a serious, common, costly, and long-term manageable disease. Recently, experimental models, preclinical observations, and clinical studies have provided some insights and preliminary promising results using umbilical cord MSCs to treat and manage diabetes. This review focuses on the latest research and applications of human-derived umbilical cord MSC in the treatment and management of T2DM, exploring and systematizing the key effects of both umbilical cord MSC and its factor-rich secretome accordingly with the major complications associated to T2DM.
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Diabetes Mellitus Tipo 2/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/metabolismo , Cordón Umbilical/metabolismo , HumanosRESUMEN
There is a great demand for the development of novel wound dressings to overcome the time and costs of wound care performed by a vast number of clinicians, especially in the current overburdened healthcare systems. In this study, Cyanoflan, a biopolymer secreted by a marine unicellular cyanobacterium, was evaluated as a potential biomaterial for wound healing. Cyanoflan effects on cell viability, apoptosis, and migration were assessed in vitro, while the effect on tissue regeneration and biosafety was evaluated in healthy Wistar rats. The cell viability and apoptosis of fibroblasts and endothelial cells was not influenced by the treatment with different concentrations of Cyanoflan, as observed by flow cytometry. Moreover, the presence of Cyanoflan did not affect cell motility and migratory capacity, nor did it induce reactive oxygen species production, even revealing an antioxidant behavior regarding the endothelial cells. Furthermore, the skin wound healing in vivo assay demonstrated that Cyanoflan perfectly adapted to the wound bed without inducing systemic or local oxidative or inflammatory reaction. Altogether, these results suggest that Cyanoflan is a promising biopolymer for the development of innovative applications to overcome the many challenges that still exist in skin wound healing.
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Materiales Biocompatibles/farmacología , Biopolímeros/farmacología , Cianobacterias/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/aislamiento & purificación , Biopolímeros/administración & dosificación , Biopolímeros/aislamiento & purificación , Línea Celular , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Masculino , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Piel/efectos de los fármacos , Piel/patologíaRESUMEN
Cylindrospermopsin (CYN) is a cyanotoxin that has raised serious concerns about public health in many parts of the world. It can bioaccumulate and affect the health of aquatic organisms, but despite this, few studies have been conducted on CYN uptake and clearance in fish. In this paper, the authors evaluate the uptake and clearance of CYN in the muscle tissue and viscera of juvenile tilapia (Oreochromis niloticus) after exposure to aqueous extracts and whole cells of Cylindrospermopsis raciborskii (CYN-producer). CYN blended with commercial fish food, and three experiments were conducted. In the first trial, fish food, and aqueous extracts containing 0.31 µg CYN g-1 of food per day, was administered to tilapia for 15 days. In the second trial, fish were provided food and intact cells (5.4 µg CYN g-1 of food per day) for 15 days. In the last trial, they were provided fish food and aqueous extracts (0.8 µg CYN g-1 of food per day) for 12 days, and for the next 10 days, the animals were fed food without toxic cell extracts (to simulate a clearance period). The concentration of CYN in muscle tissue and viscera was analysed using ELISA. In the case of juvenile tilapia, the presence of CYN was higher in viscera than in muscle tissue, and the toxin remained in the tissues even after 10 days without the addition of contaminated food. The results suggest that tilapia represents a potential source of CYN transfer through the food web, and this shows the need for a continuous monitoring of this compound in organisms that are used for human and animal consumption.
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Cíclidos , Alcaloides , Animales , Toxinas de Cianobacterias , Cylindrospermopsis , Laboratorios , UraciloRESUMEN
The Euterpe oleracea fruit (açaí) is a promising source of polyphenols with health-promoting properties. To our knowledge, few studies have focused on the influence of açaí phytochemicals on angiogenesis, with a significant impact on cancer. This study aimed at investigating the phytochemical profile of a purple açaí hydroethanolic extract (AHE) obtained from a commercial dietary powder supplement by high-performance liquid chromatography coupled to diode array detection and electrospray ionization mass spectrometry, and evaluate its in vitro effects on distinct angiogenic steps during vessel growth and on oxidative markers in human microvascular endothelial cells (HMEC-1). The phenolic profile of AHE revealed the presence of significant levels of anthocyanins, mainly cyanidin-3-O-rutinoside, and other flavonoids with promising health effects. The in vitro studies demonstrated that AHE exerts antiangiogenic activity with no cytotoxic effect. The AHE was able to decrease HMEC-1 migration and invasion potential, as well as to inhibit the formation of capillary-like structures. Additionally, AHE increased antioxidant defenses by upregulating superoxide dismutase and catalase enzymatic activities, accompanied by a reduction in the production of reactive oxygen species. These data bring new insights into the potential application of angiogenic inhibitors present in AHE on the development of novel therapeutic approaches for angiogenesis-dependent diseases.