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The quest for enhancing the upconversion luminescence (UCL) efficiency of rare-earth doped materials has been a common target in nanophotonics research. Plasmonic nanoarchitectures have proven potential for amplifying UCL signals, prompting investigations into localized enhancement effects within noble metal nanostructures. In this work we investigate the localized enhancement of UCL in silver nanowire (AgNW) networks coated with upconversion nanoparticles (UCNPs) by employing hyperspectral microscopy to unveil distinctive regions of local enhancement. Our study reveals that three-photon upconversion processes predominantly occur at hot-spots in nanowire junctions, contributing to heightened luminescence intensity on AgNW networks. Intriguingly, our findings demonstrate that enhancement on AgNWs introduces significant artifacts for thermometry based on ratiometric analysis of the emission spectra, resulting in the observation of artificial thermal gradients. To address this challenge, we developed correction methods that were successfully applied to mitigate this effect, enabling the generation of accurate thermal maps and the realization of dynamic thermal measurements. We quantified the distance-dependent enhancement profiles and studied the effect of temperature by exploiting the heat dissipation under varying electrical voltages across the electrically percolated AgNW networks. The observations were confirmed through numerical calculations of the enhancement factor and the energy transfer rates. This comprehensive investigation sheds light on the complex interplay between plasmonic nanostructures, three-photon upconversion processes, and their influence on thermal sensing applications. The presented hyperspectral method not only allows a direct visualization of plasmonic hot-spots but also advances our understanding of localized enhancements. The correction methods applied to analyze the emission spectra also contribute to the refinement of accurate temperature mapping using UCNPs, thereby enhancing the reliability of this thermal sensing technology.
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BACKGROUND AND OBJECTIVES: The objective is to describe the demographic, clinical, functional characteristics and outcomes of older adult patients hospitalized in the acute unit of the San Ignacio University Hospital (HUSI). METHODS: Descriptive, cross-sectional observational study, based on the review of the medical records of patients hospitalized in the Geriatrics Unit of the HUSI during the period 2019-2021. VARIABLES: Demographics, comorbidities, baseline situation, main cause of entry and outcomes. The diagnosis of geriatric syndromes was made through the Barthel index, the Lawton and Brody scale, FRAIL scale, mini nutritional assessment short form and Confusion Assessment Method criteria. RESULTS: A total of 4601 patients were analyzed, whose average age was 83years (56.2% women). 72.4% had some degree of dependency for basic activities of daily living, 90.8% had some degree of dependency for instrumental activities of daily living, 32.2% had malnutrition, 15. 7% falls, 9.9% oropharyngeal dysphagia, 32.2% frailty, 28.1% delirium, 54.1% previous dementia. The main comorbidities presented were arterial hypertension, chronic obstructive pulmonary disease and diabetes. 2.9% had some complication during their hospitalization, 10.8% died, and the hospital stay was 5days. CONCLUSION: Older adult patients admitted to the acute unit of the HUSI have a high frequency of dependency, dementia and nutritional disturbances.
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Evaluación Geriátrica , Humanos , Colombia/epidemiología , Femenino , Masculino , Estudios Transversales , Anciano de 80 o más Años , Anciano , Hospitalización , Actividades Cotidianas , Fragilidad/epidemiología , Fragilidad/diagnóstico , Desnutrición/epidemiología , Desnutrición/diagnóstico , Unidades HospitalariasRESUMEN
Many contaminated tailings throughout the world cause environmental and human-health related problems due to air and water drift. Tailing phytostabilization is a promising solution, but only certain plant species may tolerate and grow in these contaminated areas. We analyzed the chemical properties of a vegetated and unvegetated area in a tailing site in Central Chile. In addition, in the vegetated area we analyzed the metals content of roots, stems, and foliage in 41-years old plantations of Pinus radiata, Acacia dealbata, and Eucalyptus globulus (the only three species that survived from a total of 34 species planted), and determined height (H), and diameter at breast height (DBH). The results indicated that, except for pH, Se, Pb, and organic matter, all components (nutrients and metals) were two- to three- fold lower in the vegetated tailing compared to that of the unvegetated tailing. The analysis of plant tissues indicated that Cu was higher in the roots of P. radiata (2,073 mg kg-1) and lower in the stems of the same species (4.1 mg kg-1). However, the ability to take up and transport Cu to the shoots was higher in A. dealbata and lower in P. radiata (bioaccumulation factor of 0.19 and 0.06, respectively).
Here we present results for the first long-term phytostabilization project of copper mine tailings in Chile. From the 34 native and exotic species established in 1980 in a mine tailing disposal site with 1,000 mg Cu kg−1, only the exotic Pinus radiata, Acacia dealbata and Eucalyptus globulus were able to survive and adapt to the tailing conditions the last 41 years. This corroborates their potential for the future phytostabilization of copper mine wastes.
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Acacia , Biodegradación Ambiental , Cobre , Eucalyptus , Minería , Pinus , Contaminantes del Suelo , Eucalyptus/metabolismo , Acacia/metabolismo , Pinus/metabolismo , Cobre/metabolismo , Contaminantes del Suelo/metabolismo , Chile , Raíces de Plantas/metabolismoRESUMEN
Nurr1 is a member of the orphan nuclear receptor family NR4A (nuclear receptor subfamily 4 group A) that modulates inflammation in several cell lineages, both positively and negatively. Macrophages are key regulators of inflammatory responses, yet information about the role of Nurr1 in human macrophages is scarce. Here we examined Nurr1 expression and activity in steady state and activated human macrophages. Pro- and anti-inflammatory macrophages were generated in vitro by culture of blood monocytes with granulocyte/macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), respectively. Nurr1 expression was predominant in macrophages with the pro-inflammatory phenotype. Nurr1 activation with the agonists 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) methane (C-DIM12) or isoxazolo-pyridinone 7e (IP7e) did not globally modify the polarization status of pro-inflammatory macrophages, but they decreased their production of TNF, IL-1ß, IL-6, IL-8, IL-12 p40, CCL2, IFN-ß, and reactive oxygen species, with variable potencies. Conversely, Nurr1 deficient macrophages increased the expression of transcripts encoding inflammatory mediators, particularly that of IL6, IFNB1, and CCL2. Mechanistically, endogenous Nurr1 interacted with NF-κB p65 in basal conditions and upon lipopolysaccharide (LPS)-mediated activation. C-DIM12 stabilized those complexes in cells exposed to LPS and concurrently decreased NF-κB transcriptional activity and p65 nuclear translocation. Expression of high levels of Nurr1 was associated with a subset of dermal macrophages that display enhanced levels of TNF and lower expression of the anti-inflammatory marker CD163L1 in skin lesions from patients with bullous pemphigoid (BP), a chronic inflammatory autoimmune blistering disorder. These results suggest that Nurr1 expression is linked with the pro-inflammatory phenotype of human macrophages, both in vivo and in vitro, where it may constitute a brake to attenuate the synthesis of inflammatory mediators.
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Factor Estimulante de Colonias de Macrófagos , FN-kappa B , Humanos , FN-kappa B/metabolismo , Factor Estimulante de Colonias de Macrófagos/metabolismo , Lipopolisacáridos/farmacología , Macrófagos , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Antiinflamatorios/metabolismoRESUMEN
Background: Hypertension and type 2 diabetes (T2D) are the most prevalent noncommunicable diseases in Mexico and worldwide. According to international practice management guidelines, the principal chronic management therapy is daily oral medication. Aim: We aim to describe the trends of antihypertensive, antidiabetic, and nonsteroidal anti-inflammatory (NSAID) drugs use among the Mexican adult population from 2004-2018. Methods: We analyzed data from the Health Workers Cohort Study (HWCS) for males and females aged >18 years. We calculated the prevalence of chronic diseases and utilization for every kind of antihypertensive, antidiabetic, and NSAIDs (measured by self-reported utilization) at baseline and two follow-ups (2004, 2010, and 2017). Trends were analyzed using Fisher's exact test. Results: Hypertension prevalence increased from 19.8 to 30.3%, higher than T2D prevalence from 7.0 to 12.8% through fourteen years of follow-up. Like the self-reported dual therapy, the proportion of patients using beta-blockers and angiotensin II receptor blockers increased. Regarding T2D, the prevalence of metformin utilization increased to 83.9%. The utilization of common NSAIDs, mainly for muscular pain, remained around 13 to 16%. Conclusions: Our findings showed a changing prevalence of drug utilization for hypertension and T2D between 2004 and 2018 and consistent use of NSAIDs in the adult Mexican population.
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Pituitary tumors (PT) are highly heterogeneous neoplasms, comprising functioning and nonfunctioning lesions. Functioning PT include prolactinomas, causing amenorrhea-galactorrhea in women and sexual dysfunction in men; GH-secreting adenomas causing acromegaly-gigantism; ACTH-secreting corticotrophinomas causing Cushing disease (CD); and the rare TSH-secreting thyrotrophinomas that result in central hyperthyroidism. Nonfunctioning PT do not result in a hormonal hypersecretion syndrome and most of them are of gonadotrope differentiation; other non-functioning PT include null cell adenomas and silent ACTH-, GH- and PRL-adenomas. Less than 5% of PT occur in a familial or syndromic context whereby germline mutations of specific genes account for their molecular pathogenesis. In contrast, the more common sporadic PT do not result from a single molecular abnormality but rather emerge from several oncogenic events that culminate in an increased proliferation of pituitary cells, and in the case of functioning tumors, in a non-regulated hormonal hypersecretion. In recent years, important advances in the understanding of the molecular pathogenesis of PT have been made, including the genomic, transcriptomic, epigenetic, and proteomic characterization of these neoplasms. In this review, we summarize the available molecular information pertaining the oncogenesis of PT.
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Adenoma , Neoplasias Hipofisarias , Masculino , Embarazo , Humanos , Femenino , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/patología , Proteómica , Adenoma/genética , Adenoma/patología , Genómica , Hormona Adrenocorticotrópica/genética , Hormona Adrenocorticotrópica/metabolismo , Perfilación de la Expresión Génica , Epigénesis GenéticaRESUMEN
Mexico is a major honey producer, but not much information exists about the health status of honey bees (Apis mellifera L.) in the country. This study was conducted to determine the sanitary status of adult honey bees in Mexico's five beekeeping regions. Samples from 369 apiaries were diagnosed to identify pathogens such as Varroa destructor, which was quantified, Acarapis woodi, Nosema spp., and five viruses. Colonies were also inspected for the presence of the small hive beetle (SHB), Aethina tumida. Varroa destructor was found in 83.5% of the apiaries, with the Pacific Coast region having the highest prevalence (>95%) and rates (4.5% ± 0.6). Acarapis woodi was detected in only one apiary from the Pacific Coast, whereas Nosema spp. were prevalent in 48.5% of the apiaries, with the highest and lowest frequencies in the Yucatan Peninsula and North regions (64.6% and 10.2%, respectively). For viruses, deformed wing virus (DWV) was detected in 26.1% of the apiaries, with the highest frequency in the Pacific Coast region (44.7%). Israeli acute paralysis virus (IAPV) was diagnosed in 3.2% of the samples and sacbrood bee virus (SBV) in 23.3% of them, with the highest frequency in the High Plateau region (36.4%). Chronic bee paralysis and Kashmir bee viruses were not detected. SHB prevalence was 25.2% nationwide, with the highest frequency in the Yucatan Peninsula (39.2%). This study shows that the most common parasites of adult honey bees in Mexico are V. destructor and Nosema spp., and that the most prevalent virus is DWV, whereas SHB is highly prevalent in the Yucatan Peninsula. This information could be useful to design disease control strategies for honey bee colonies in different regions of Mexico.
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Metabolic syndrome (MetS) predisposes individuals to chronic non-communicable diseases (NCDs) like type 2 diabetes (T2D), non-alcoholic fatty liver disease, atherosclerosis, and cardiovascular disorders caused by systemic inflammation, intestinal dysbiosis, and diminished antioxidant ability, leading to oxidative stress and compromised insulin sensitivity across vital organs. NCDs present a global health challenge characterized by lengthy and costly pharmacological treatments. Complementary and alternative medicine using herbal therapies has gained popularity. Approximately 350,000 plant species are considered medicinal, with 80% of the world's population opting for traditional remedies; however, only 21,000 plants are scientifically confirmed by the WHO. The Rubiaceae family is promissory for preventing and treating MetS and associated NCDs due to its rich content of metabolites renowned for their antioxidative, anti-inflammatory, and metabolic regulatory properties. These compounds influence transcription factors and mitigate chronic low-grade inflammation, liver lipotoxicity, oxidative stress, and insulin resistance, making them a cost-effective non-pharmacological approach for MetS prevention and treatment. This review aims to collect and update data that validate the traditional uses of the Rubiaceae family for treating MetS and associated NCDs from experimental models and human subjects, highlighting the mechanisms through which their extracts and metabolites modulate glucose and lipid metabolism at the molecular, biochemical, and physiological levels.
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This paper responds to two questions-What dimensions and indicators are relevant to the construction of social wellbeing? How are the levels of wellbeing distributed in the municipalities of Mexico City? To answer these questions, we use data from the Wellbeing Survey (N = 2,871) that is representative of Mexico City and its municipalities. We employed two methods, DM-R distances, and Mamdani's Fuzzy Inference Method. The results show that all the proposed dimensions and indicators contributed to the building of multidimensional social wellbeing; in the case of some indicators (social security, built environment, and public insecurity) they contributed less. This suggests government interventions should be designed in order to improve the gaps in those areas. The evidence also indicates that community wellbeing is a relevant dimension when measuring social wellbeing in large cities, in addition to identifying areas of intervention for the development of more efficient and inclusive public policies.
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One of the major challenges currently faced by global health systems is the prolonged COVID-19 syndrome (also known as "long COVID") which has emerged as a consequence of the SARS-CoV-2 epidemic. It is estimated that at least 30% of patients who have had COVID-19 will develop long COVID. In this study, our goal was to assess the plasma metabolome in a total of 100 samples collected from healthy controls, COVID-19 patients, and long COVID patients recruited in Mexico between 2020 and 2022. A targeted metabolomics approach using a combination of LC-MS/MS and FIA MS/MS was performed to quantify 108 metabolites. IL-17 and leptin were measured in long COVID patients by immunoenzymatic assay. The comparison of paired COVID-19/long COVID-19 samples revealed 53 metabolites that were statistically different. Compared to controls, 27 metabolites remained dysregulated even after two years. Post-COVID-19 patients displayed a heterogeneous metabolic profile. Lactic acid, lactate/pyruvate ratio, ornithine/citrulline ratio, and arginine were identified as the most relevant metabolites for distinguishing patients with more complicated long COVID evolution. Additionally, IL-17 levels were significantly increased in these patients. Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, and chronic immune dysregulation are likely to be the main hallmarks of long COVID even two years after acute COVID-19 infection.
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COVID-19 , Interleucina-17 , Humanos , Espectrometría de Masas en Tándem , Cromatografía Liquida , SARS-CoV-2 , Metaboloma , Metabolómica , Síndrome Post Agudo de COVID-19RESUMEN
In recent years, the study of extracellular vesicles (EVs) in the context of various diseases has dramatically increased due to their diagnostic and therapeutic potential. Typically, EVs are isolated in vitro from the cell culture of primary cells or cell lines or from bodily fluids. However, these cell culture methods do not represent the whole complexity of an in vivo microenvironment, and bodily fluids contain a high heterogeneous population of vesicles since they originate from different tissues. This highlights the need to develop new methods to isolate EVs directly from tissue samples. In the present study, we established a protocol for isolating EVs from hepatic and adipose tissue of mice, using a combination of ultracentrifugation and iodixanol-sucrose density gradient separation. EV isolation was confirmed with EV protein marker enrichment in Western blot assays, total protein quantification, and transmission electron microscopy. Regarding the liver tissue, we additionally implemented size exclusion chromatography (SEC) to further increase the purity grade of the EVs. The successful isolation of EVs from tissue samples will allow us to uncover a more precise molecular composition and functions, as well as their role in intercellular communication in an in vivo microenvironment.
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Vesículas Extracelulares , Animales , Ratones , Cromatografía en Gel , Hígado , Tejido Adiposo , Western BlottingRESUMEN
Metastasis remains the leading cause of mortality in prostate cancer patients. The presence of tumor cells in lymph nodes is an established prognostic indicator for several cancer types, such as melanoma, breast, oral, pancreatic, and cervical cancers. Emerging evidence highlights the role of microRNAs enclosed within extracellular vesicles as facilitators of molecular communication between tumors and metastatic sites in the lymph nodes. This study aims to investigate the potential diagnostic utility of EV-derived microRNAs in liquid biopsies for prostate cancer. By employing microarrays on paraffin-embedded samples, we characterized the microRNA expression profiles in metastatic lymph nodes, non-metastatic lymph nodes, and primary tumor tissues of prostate cancer. Differential expression of microRNAs was observed in metastatic lymph nodes compared to prostate tumors and non-metastatic lymph node tissues. Three microRNAs (miR-140-3p, miR-150-5p, and miR-23b-3p) were identified as differentially expressed between tissue and plasma samples. Furthermore, we evaluated the expression of these microRNAs in exosomes derived from prostate cancer cells and plasma samples. Intriguingly, high Gleason score samples exhibited the lowest expression of miR-150-5p compared to control samples. Pathway analysis suggested a potential regulatory role for miR-150-5p in the Wnt pathway and bone metastasis. Our findings suggest EV-derived miR-150-5p as a promising diagnostic marker for identifying patients with high-grade Gleason scores and detecting metastasis at an early stage.
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The global need for accurate and efficient cancer cell detection in biomedicine and clinical diagnosis has driven extensive research and technological development in the field. Precision, high-throughput, non-invasive separation, detection, and classification of individual cells are critical requirements for successful technology. Lab-on-a-chip devices offer enormous potential for solving biological and medical problems and have become a priority research area for microanalysis and manipulating cells. This paper reviews recent developments in the detection of cancer cells using the microfluidics-based lab-on-a-chip method, focusing on describing and explaining techniques that use optical phenomena and a plethora of probes for sensing, amplification, and immobilization. The paper describes how optics are applied in each experimental method, highlighting their advantages and disadvantages. The discussion includes a summary of current challenges and prospects for cancer diagnosis.
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Técnicas Biosensibles , Neoplasias , Dispositivos Laboratorio en un Chip , Óptica y Fotónica , Fenómenos Ópticos , Espectrometría Raman , Técnicas Biosensibles/métodos , Neoplasias/diagnósticoRESUMEN
Several vaccines against COVID-19 use a recombinant SARS-CoV-2 receptor-binding domain (RBD) as antigen, making the purification of this protein a key step in their production. In this work, citrate-coated magnetic iron oxide nanoparticles were evaluated as nano adsorbents in the first step (capture) of the purification of recombinant RBD. The nanoparticles were isolated through coprecipitation and subsequently coated with sodium citrate. The citrate-coated nanoparticles exhibited a diameter of 10 ± 2 nm, a hydrodynamic diameter of 160 ± 3 nm, and contained 1.9 wt% of citrate. The presence of citrate on the nanoparticles' surface was confirmed through FT-IR spectra and thermogravimetric analysis. The crystallite size (10.1 nm) and the lattice parameter (8.3646 Å) were determined by X-ray diffraction. In parallel, RBD-containing supernatant extracted from cell culture was exchanged through ultrafiltration and diafiltration into the adsorption buffer. The magnetic capture was then optimized using different concentrations of nanoparticles in the purified supernatant, and we found 40 mg mL-1 to be optimal. The ideal amount of nanoparticles was assessed by varying the RBD concentration in the supernatant (between 0.113 mg mL-1 and 0.98 mg mL-1), which resulted in good capture yields (between 83 ± 5% and 94 ± 4%). The improvement of RBD purity after desorption was demonstrated by SDS-PAGE and RP-HPLC. Furthermore, the magnetic capture was scaled up 100 times, and the desorption was subjected to chromatographic purifications. The obtained products recognized anti-RBD antibodies and bound the ACE2 receptor, proving their functionality after the developed procedure.
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COVID-19 , SARS-CoV-2 , Humanos , Vacunas contra la COVID-19 , Ácido Cítrico , Espectroscopía Infrarroja por Transformada de Fourier , CitratosRESUMEN
Obtaining arrays of single nanoparticles with three-dimensional complex shapes is still an open challenge. Current nanolithography methods do not allow for the preparation of nanoparticles with complex features like nanostars. In this work, we investigate the optical printing of gold nanostars of different sizes as a function of laser wavelength and power. We found that tuning the laser to the main resonances of the nanostars in the near-infrared makes it possible to avoid nanoparticles reshaping due to plasmonic heating, enabling their deposition at the single particle level and in ordered arrays.
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Nanotechnology is one of the most important and relevant disciplines today due to the specific electrical, optical, magnetic, chemical, mechanical and biomedical properties of nanoparticles. In the present study we demonstrate the efficacy of Cuphea procumbens to biogenerate silver nanoparticles (AgNPs) with antibacterial and antitumor activity. These nanoparticles were synthesized using the aqueous extract of C. procumbens as reducing agent and silver nitrate as oxidizing agent. The Transmission Electron Microscopy demonstrated that the biogenic AgNPs were predominantly quasi-spherical with an average particle size of 23.45 nm. The surface plasmonic resonance was analyzed by ultraviolet visible spectroscopy (UV-Vis) observing a maximum absorption band at 441 nm and Infrared Spectroscopy (FT IR) was used in order to structurally identify the functional groups of some compounds involved in the formation of nanoparticles. The AgNPs demonstrated to have antibacterial activity against the pathogenic bacteria Escherichia coli and Staphylococcus aureus, identifying the maximum zone of inhibition at the concentration of 0.225 and 0.158 µg/mL respectively. Moreover, compared to the extract, AgNPs exhibited better antitumor activity and higher therapeutic index (TI) against several tumor cell lines such as human breast carcinoma MCF-7 (IC50 of 2.56 µg/mL, TI of 27.65 µg/mL), MDA-MB-468 (IC50 of 2.25 µg/mL, TI of 31.53 µg/mL), human colon carcinoma HCT-116 (IC50 of 1.38 µg/mL, TI of 51.07 µg/mL) and melanoma A-375 (IC50 of 6.51 µg/mL, TI of 10.89 µg/mL). This fact is of great since it will reduce the side effects derived from the treatment. In addition, AgNPs revealed to have a photocatalytic activity of the dyes congo red (10-3 M) in 5 min and malachite green (10-3 M) in 7 min. Additionally, the degradation percentages were obtained, which were 86.61% for congo red and 82.11% for malachite green. Overall, our results demonstrated for the first time that C. procumbens biogenerated nanoparticles are excellent candidates for several biomedical and environmental applications.
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Cuphea , Nanopartículas del Metal , Humanos , Nanopartículas del Metal/química , Rojo Congo , Pruebas de Sensibilidad Microbiana , Plata/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is now considered the most common chronic liver disease worldwide. NAFLD is related to changes in lipid metabolism and is characterized by the increase or accumulation of fat in hepatocytes that may progress to nonalcoholic steatohepatitis (NASH), which leads to the appearance of inflammatory processes. Treatment consists of changes in diet, physical activity, and weight control; however, these disorders represent a health problem and require the development of novel alternatives to treatment and prevention. NAFLD/NASH are strongly associated with other disorders, such as metabolic syndrome (MetS); in fact, NAFLD is considered the hepatic manifestation of MetS. These disorders are related to other components of MetS, including dyslipidemia, which is characterized by an imbalance in blood cholesterol and triglyceride levels. Prebiotics and probiotics benefit from treating and preventing several ailments, including liver diseases. Specifically, in dyslipidemia, NAFLD, and NASH, probiotics play a fundamental role in conducting the biotransformation of primary bile acids into secondary bile acids, which generally have important activity as immunomodulators and metabolism regulators. The mechanisms of action of pre and probiotics involve the activity of bile acid receptors, such as FXR and TGR-5, and the events resulting from their activation. Therefore, prebiotics and probiotics may be reasonable options to prevent and treat metabolic- related liver diseases.
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Dislipidemias , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Probióticos , Humanos , Enfermedad del Hígado Graso no Alcohólico/terapia , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Prebióticos , Hígado/metabolismo , Probióticos/uso terapéutico , Síndrome Metabólico/metabolismo , Dislipidemias/tratamiento farmacológico , Dislipidemias/metabolismo , Ácidos y Sales Biliares/metabolismoRESUMEN
Background: Breast cancer in men is a rare and poorly studied disease, and its treatment is based on women breast cancer studies. However, clinical outcome is not the same in men and women. Basic studies and clinical trials in animal models provide detailed information on cancer, origin, development, cell signaling pathways, sites of metastasis, and target molecules. It is necessary to explore the biology of breast cancer in male animal models that allow observing their similarity. Methods: The triple-negative 4T1 breast cancer model was developed in both male and female mice and studied weekly during 4 weeks. For that, twenty 8-week-old female and male BALB/c mice were used. Sixteen mice (eight males and eight females) were inoculated into the second left thoracic mammary pad with 20,000 4T1 cells, resuspended in 20 µL phosphate-buffered saline (PBS). All samples were processed for immunodetection, characterized histopathologically and immunohistochemically. Results: In this work, we describe the development of a triple-negative 4T1 breast cancer model in male BALB/c mice. Breast tumors were characterized histopathologically at different time points and corresponded to a moderately differentiated invasive ductal carcinoma, estrogen receptor ER-/progesterone receptor PR-/human epidermal growth factor receptor 2 HER2-/Ki67+, with histological grade II (moderately differentiated; a solid mass with occasional duct formation and moderate to severe nuclear pleomorphism), infiltrating the adipose and muscular tissue, and metastasis to lungs. From the results, we did not observe differences in the time of tumor development, necrosis, color change of tumor tissue, and lung metastasis between male and female mice. Even though we did not find histological differences, response to treatment and molecular signaling may be different. Conclusions: The histogenesis of male breast tumors was similar to that of female BALB/c mice. The histological and immunohistochemical characteristics of male tumors also match the features reported for stage IV human breast cancer of men and women. The murine male breast cancer model described here can be a significant tool to explore the molecular mechanisms involved in male breast cancer tumorigenesis and metastasis and may bring new approaches for clinical treatment of triple-negative breast cancer in men.
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The orphan nuclear receptor Nur77 is involved in diverse cellular processes such as inflammation, proliferation, differentiation and survival. Stimuli like lipopolysaccharide (LPS) and tumor necrosis factor (TNF) increase Nur77 expression in human and murine macrophages, and it has been proposed that Nur77 plays a major role in dampening the inflammatory response. Here, we evaluated the expression and function of Nur77 in human anti-inflammatory and pro-inflammatory macrophages derived from blood monocytes cultured with macrophage colony-stimulating factor (M-MDMs) or granulocyte/macrophage colony-stimulating factor (GM-MDMs), respectively. Nur77 mRNA expression was significantly enhanced in M-MDMs compared with GM-MDMs, both constitutively and upon exposure to Toll-like receptor (TLR)2, 3, and 4 ligands. Nur77 activation with the agonist Cytosporone B (CsnB) significantly suppressed the production of TNF, interleukin (IL)-1ß, IL-6, and IL-8 in GM-MDMs stimulated with LPS. In contrast, it tended to enhance the production of the anti-inflammatory cytokine IL-10. This effect was associated with reduced NF-κB p65 nuclear translocation. Similarly, Nur77 knockdown enhanced TNF production in GM-MDMs. CsnB effectively stimulated the transactivation activity of Nur77 in M-MDMs, but it did not alter cytokine synthesis or p65 nuclear translocation. However, Nur77 seemed to have a role in maintaining the anti-inflammatory profile of M-MDMs, since Nur77-deficient M-MDMs constitutively produced higher levels of TNF transcripts. Thus, in the absence of exogenous agonists, Nur77 activity favors the anti-inflammatory function of M-MDMs, whereas agonistic activation of this receptor preferentially drives attenuation of inflammation in inflammatory macrophages.
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Macrófagos , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares , Fenilacetatos , Humanos , Citocinas/metabolismo , Inflamación/metabolismo , Lipopolisacáridos , Factor Estimulante de Colonias de Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/agonistas , Fenilacetatos/farmacologíaRESUMEN
Communication between neighboring or distant cells is made through a complex network that includes extracellular vesicles (EVs). Exosomes, which are a subgroup of EVs, are released from most cell types and have been found in biological fluids such as urine, plasma, and airway secretions like bronchoalveolar lavage (BAL), nasal lavage, saliva, and sputum. Mainly, the cargo exosomes are enriched with mRNAs and microRNAs (miRNAs), which can be transferred to a recipient cell consequently modifying and redirecting its biological function. The effects of miRNAs derive from their role as gene expression regulators by repressing or degrading their target mRNAs. Nowadays, various types of research are focused on evaluating the potential of exosomal miRNAs as biomarkers for the prognosis and diagnosis of different pathologies. Nevertheless, there are few reports on their role in the pathophysiology of idiopathic pulmonary fibrosis (IPF), a chronic lung disease characterized by progressive lung scarring with no cure. In this review, we focus on the role and effect of exosomal miRNAs as intercellular communicators in the onset and progression of IPF, as well as discussing their potential utility as therapeutic agents for the treatment of this disease.