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Throughout life, whether through external consumption or internal production, we are exposed to different reactive metabolites considered toxic to the body. Pham et al.1 uncover metabolic regulation by one such harmful metabolite: formaldehyde.
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Formaldehído , Formaldehído/metabolismoRESUMEN
Marine hydrocarbonoclastic bacteria can use polycyclic aromatic hydrocarbons as carbon and energy sources, that makes these bacteria highly attractive for bioremediation in oil-polluted waters. However, genomic and metabolic differences between species are still the subject of study to understand the evolution and strategies to degrade PAHs. This study presents Rhodococcus ruber MSA14, an isolated bacterium from marine sediments in Baja California, Mexico, which exhibits adaptability to saline environments, a high level of intrinsic pyrene tolerance (> 5 g L- 1), and efficient degradation of pyrene (0.2 g L- 1) by 30% in 27 days. Additionally, this strain demonstrates versatility by using naphthalene and phenanthrene as individual carbon sources. The genome sequencing of R. ruber MSA14 revealed a genome spanning 5.45 Mbp, a plasmid of 72 kbp, and three putative megaplasmids, lengths between 110 and 470 Kbp. The bioinformatics analysis of the R. ruber MSA14 genome revealed 56 genes that encode enzymes involved in the peripheral and central pathways of aromatic hydrocarbon catabolism, alkane, alkene, and polymer degradation. Within its genome, R. ruber MSA14 possesses genes responsible for salt tolerance and siderophore production. In addition, the genomic analysis of R. ruber MSA14 against 13 reference genomes revealed that all compared strains have at least one gene involved in the alkanes and catechol degradation pathway. Overall, physiological assays and genomic analysis suggest that R. ruber MSA14 is a new haloalkalitolerant and hydrocarbonoclastic strain toward a wide range of hydrocarbons, making it a promising candidate for in-depth characterization studies and bioremediation processes as part of a synthetic microbial consortium, as well as having a better understanding of the catabolic potential and functional diversity among the Rhodococci group.
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Biodegradación Ambiental , Genoma Bacteriano , Genómica , Sedimentos Geológicos , Hidrocarburos Policíclicos Aromáticos , Rhodococcus , Rhodococcus/genética , Rhodococcus/metabolismo , Hidrocarburos Policíclicos Aromáticos/metabolismo , Sedimentos Geológicos/microbiología , Naftalenos/metabolismo , Filogenia , Fenantrenos/metabolismo , Tolerancia a la Sal , PirenosRESUMEN
Gastric cancer (GC) remains a significant global health challenge, with high mortality rates, especially in developing countries. Current treatments are invasive and have considerable risks, necessitating the exploration of safer alternatives. Quercetin (QRC), a flavonoid present in various plants and foods, has demonstrated multiple health benefits, including anticancer properties. This study investigated the therapeutic potential of QRC in the treatment of GC. We utilized advanced molecular techniques to assess the impact of QRC on GC cells, examining its effects on cellular pathways and gene expression. Our findings indicate that QRC significantly inhibits GC cell proliferation and induces apoptosis, suggesting its potential as a safer therapeutic option for GC treatment. Further research is required to validate these results and explore the clinical applications of QRC in cancer therapy.
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Apoptosis , Proliferación Celular , Biología Computacional , Quercetina , Neoplasias Gástricas , Quercetina/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Humanos , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Biología Computacional/métodos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacosRESUMEN
The hormone prolactin acquires antiangiogenic and antivasopermeability properties after undergoing proteolytic cleavage to vasoinhibin, an endogenous prolactin fragment of 123 or more amino acids that inhibits the action of multiple proangiogenic factors. Preclinical and clinical evidence supports the therapeutic potential of vasoinhibin against angiogenesis-related diseases including diabetic retinopathy, peripartum cardiomyopathy, rheumatoid arthritis, and cancer. However, the use of vasoinhibin in the clinic has been limited by difficulties in its production. Here, we removed this barrier to using vasoinhibin as a therapeutic agent by showing that a short linear motif of just three residues (His46-Gly47-Arg48) (HGR) is the functional determinant of vasoinhibin. The HGR motif is conserved throughout evolution, its mutation led to vasoinhibin loss of function, and oligopeptides containing this sequence inhibited angiogenesis and vasopermeability with the same potency as whole vasoinhibin. Furthermore, the oral administration of an optimized cyclic retro-inverse vasoinhibin heptapeptide containing HGR inhibited melanoma tumor growth and vascularization in mice and exhibited equal or higher antiangiogenic potency than other antiangiogenic molecules currently used as anti-cancer drugs in the clinic. Finally, by unveiling the mechanism that obscures the HGR motif in prolactin, we anticipate the development of vasoinhibin-specific antibodies to solve the on-going challenge of measuring endogenous vasoinhibin levels for diagnostic and interventional purposes, the design of vasoinhibin antagonists for managing insufficient angiogenesis, and the identification of putative therapeutic proteins containing HGR.
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Proteínas de Ciclo Celular , Retinopatía Diabética , Inhibidores de la Angiogénesis/farmacología , Animales , Ratones , Oligopéptidos/farmacología , ProlactinaRESUMEN
Agave angustifolia is a xerophytic species widely used in Mexico as an ingredient in sweet food and fermented beverages; it is also used in traditional medicine to treat wound pain and rheumatic damage, and as a remedy for psoriasis. Among the various A. angustifolia extracts and extract fractions that have been evaluated for their anti-inflammatory effects, the acetonic extract (AaAc) and its acetonic (F-Ac) and methanolic (F-MeOH) fractions were the most active in a xylene-induced ear edema model in mice, when orally administered. Four fractions resulting from chemically resolving F-Ac (F1-F4) were locally applied to mice with phorbol 12-myristate 13-acetate (TPA)-induced ear inflammation; F1 inhibited inflammation by 70% and was further evaluated in a carrageenan-induced mono-arthritis model. When administered at doses of 12.5, 25, and 50 mg/kg, F1 reduced articular edema and the spleen index. In addition, it modulated spleen and joint cytokine levels and decreased pain. According to a GC-MS analysis, the main components of F1 are fatty-acid derivatives: palmitic acid methyl ester, palmitic acid ethyl ester, octadecenoic acid methyl ester, linoleic acid ethyl ester, and oleic acid ethyl ester.
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Agave , Ratones , Animales , Antiinflamatorios/uso terapéutico , Extractos Vegetales/uso terapéutico , Ácidos Grasos/uso terapéutico , Edema/inducido químicamente , Edema/tratamiento farmacológico , Carragenina/efectos adversos , Dolor/tratamiento farmacológico , Ésteres , FitoterapiaRESUMEN
In this study, conditions for the ultrasound-assisted extraction (UAE) of soluble polyphenols from Psidium cattleianum (PC) leaves were optimized using response surface methodology (RSM) by assessing the effect of extraction time (XET = 2, 4, and 6 min), sonication amplitude (XSA = 60, 80, and 100%), and pulse cycle (XPC = 0.4, 0.7, and 1 s). Furthermore, the optimized UAE conditions were compared with a conventional aqueous-organic extraction (AOE) method for extracting total phenolics; moreover, a phenolic profile using HPLC and antioxidant activity (DPPH, ABTS, and FRAP) were also compared. According to the RSM, the best conditions for UAE to extract the highest soluble polyphenol content and yield (158.18 mg/g dry matter [DM] and 15.81%) include a 100% sonication amplitude for 4 min at 0.6 s of pulse cycle. The optimal UAE conditions exhibited an effectiveness of 1.71 times in comparison to the AOE method for extracting total phenolics, in 96.66% less time; moreover, PC leaf extracts by UAE showed higher antioxidant values than AOE. Additionally, gallic, protocateic, chlorogenic, caffeic, coumaric, trans-cinnamic, 4-hydroxybenzoic, and syringic acids, as well as kaempferol were identified in PC leaves under UAE. PC leaf extracts are widely used for therapeutic and other industrial purposes; thus, the UAE proves to be a useful technology with which to improve the yield extraction of PC leaf phytochemicals.
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Psidium , Antioxidantes , Fenoles/química , Extractos Vegetales/química , PolifenolesRESUMEN
The objective of this work was to find the optimal conditions by thermosonication-assisted extraction (TSAE) of the total acetogenin content (TAC) and yield from A. muricata seeds, assessing the effect of the temperature (40, 50, and 60 °C), sonication amplitude (80, 90, and 100%), and pulse-cycle (0.5, 0.7, and 1 s). In addition, optimal TSAE conditions of acetogenins (ACGs) were compared with extraction by ultrasound at 25 °C and the soxhlet method measuring TAC and antioxidant capacity. Moreover, solubility and identification of isolated ACGs were performed. Furthermore, the antifungal activity of ACGs crude extract and isolated ACGs was evaluated. Optimal TSAE conditions to extract the highest TAC (35.89 mg/g) and yield (3.6%) were 50 °C, 100% amplitude, and 0.5 s pulse-cycle. TSAE was 2.17-fold and 15.60-fold more effective than ultrasound at 25 °C and the Soxhlet method to extract ACGs with antioxidant capacity. Isolated ACGs were mostly soluble in acetone and methanol. Seven ACGs were identified, and pseudoannonacin was the most abundant. The inhibition of Candida albicans, Candida krusei, and Candida tropicalis was higher from isolated ACGs than crude extract. TSAE was effective to increase the yield in the ACGs extraction from A. muricata seeds and these ACGs have important antifungal activity.
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Annona , Acetogeninas/farmacología , Acetona , Antifúngicos/farmacología , Antioxidantes/farmacología , Metanol , Extractos Vegetales/farmacología , SemillasRESUMEN
The aim was to evaluate the pre-weaning productive performance and growth curve of Dorper*Katahdin (DPr; n = 46), Kathadin*Kathadin (KTn; n = 204) and Romanov*Kathadin (RMv; n = 40) of commercial crossed lambs from central Mexico. We considered 1450 data from 290 crossbred lambs. The variables contemplated in this study were cross (CR), lambing type (LT), sex, birth weight (BW), weaning weight (WW), test days (TD), and daily weight gain (DWG). Correlation analysis and adjustment of growth curve were performed. Differences in CR and sex were found only in BW (p < 0.05). No differences in DWG, WW, and TD (p > 0.05) by CR and sex were found. Single lambing had the highest (p < 0.05) BW, WW, and DWG. Phenotypic correlations differ among crosses. Lambs crossed with DPr presented the highest values in parameters a and b and the lowest in c. The productive behavior of DPr, KTn, and RMv cross with KTn lambs in central Mexico is similar in the pre-weaning period; however, the growth curve and parameters that characterize it suggest that DPr lambs show a tendency to enhance productive behavior in this period.
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Oveja Doméstica , Aumento de Peso , Animales , Peso al Nacer , México , Ovinos , DesteteRESUMEN
It is essential to quantify the impacts of the COVID-19 pandemic on cancer screening, including for vulnerable sub-populations, to inform the development of evidence-based, targeted pandemic recovery strategies. We undertook a population-based retrospective observational study in Ontario, Canada to assess the impact of the pandemic on organized cancer screening and diagnostic services, and assess whether patterns of cancer screening service use and diagnostic delay differ across population sub-groups during the pandemic. Provincial health databases were used to identify age-eligible individuals who participated in one or more of Ontario's breast, cervical, colorectal, and lung cancer screening programs from January 1, 2019-December 31, 2020. Ontario's screening programs delivered 951,000 (-41%) fewer screening tests in 2020 than in 2019 and volumes for most programs remained more than 20% below historical levels by the end of 2020. A smaller percentage of cervical screening participants were older (50-59 and 60-69 years) during the pandemic when compared with 2019. Individuals in the oldest age groups and in lower-income neighborhoods were significantly more likely to experience diagnostic delay following an abnormal breast, cervical, or colorectal cancer screening test during the pandemic, and individuals with a high probability of living on a First Nation reserve were significantly more likely to experience diagnostic delay following an abnormal fecal test. Ongoing monitoring and management of backlogs must continue. Further evaluation is required to identify populations for whom access to cancer screening and diagnostic care has been disproportionately impacted and quantify impacts of these service disruptions on cancer incidence, stage, and mortality. This information is critical to pandemic recovery efforts that are aimed at achieving equitable and timely access to cancer screening-related care.
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COVID-19 , Neoplasias Pulmonares , Neoplasias del Cuello Uterino , Cuidados Posteriores , Diagnóstico Tardío , Detección Precoz del Cáncer , Femenino , Humanos , Ontario , Pandemias , SARS-CoV-2RESUMEN
A fast PCR-assisted impedimetric biosensor was developed for the selective detection of the clbN gene from the polyketide synthase (pks) genomic island in real Escherichia coli samples. This genomic island is responsible for the production of colibactin, a harmful genotoxin that has been associated with colorectal cancer. The experimental protocol consisted of immobilizing the designated forward primer onto an Au electrode surface to create the sensing probe, followed by PCR temperature cycling in blank, positive, and negative DNA controls. Target DNA identification was possible by monitoring changes in the system's charge transfer resistance values (Rct) before and after PCR treatment through electrochemical impedance spectroscopy (EIS) analysis. Custom-made, flexible gold electrodes were fabricated using chemical etching optical lithography. A PCR cycle study determined the optimum conditions to be at 6 cycles providing fast results while maintaining a good sensitivity. EIS data for the DNA recognition process demonstrated the successful distinction between target interaction resulting in an increase in resistance to charge transfer (Rct) percentage change of 176% for the positive DNA control vs. 21% and 20% for the negative and non-DNA-containing controls, respectively. Results showed effective fabrication of a fast, PCR-based electrochemical biosensor for the detection of pks genomic island with a calculated limit of detection of 17 ng/µL.
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Técnicas Biosensibles/métodos , Espectroscopía Dieléctrica/métodos , Escherichia coli/genética , Genoma Bacteriano , Péptidos/genética , Sintasas Poliquetidas/genética , Reacción en Cadena de la Polimerasa/métodos , Límite de Detección , PolicétidosRESUMEN
Diverse researchers have considered by-products of food and agricultural processing industries as a source of antioxidants. Tamarind (Tamarindus indica) is a leguminous tree, native from tropical Africa bearing edible fruit. The fruit is composed of 30% pulp, 40% seed, and 30% pericarp. Currently, tamarind pericarp is a waste from tamarind processing (approximately 54,400 tons of pericarp in 2012 worldwide) and is contributing to environmental contamination. This research aimed to determine the effect of maceration, microwaves, and ultrasound on the increase in the antioxidant availability in tamarind pericarp and its incorporation as a functional ingredient in cookies (5 and 10% substitution). Antioxidant content, antioxidant activity, proximate, and sensorial analysis of the cookies were conducted. The microwave method was the best pretreatment compared with sonication and maceration since it showed 1.3-fold higher amounts of phenolic compounds and 1.2-fold higher antioxidant capacity. The 10% substitution of tamarind pericarp powder in cookies, significantly increased the fiber content (four-fold) and phenolic compounds content (2.6-fold) and the product presented good acceptance in a sensorial test. Thus, tamarind pericarp powder could be considered as an antioxidant and fiber source and could be used as a functional ingredient in food products.
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OBJECTIVE: Acute myocardial infarction (AMI) initiates pathological inflammation which aggravates tissue damage and causes heart failure. Lysophosphatidic acid (LPA), produced by autotaxin (ATX), promotes inflammation and the development of atherosclerosis. The role of ATX/LPA signaling nexus in cardiac inflammation and resulting adverse cardiac remodeling is poorly understood. APPROACH AND RESULTS: We assessed autotaxin activity and LPA levels in relation to cardiac and systemic inflammation in AMI patients and C57BL/6 (WT) mice. Human and murine peripheral blood and cardiac tissue samples showed elevated levels of ATX activity, LPA, and inflammatory cells following AMI and there was strong correlation between LPA levels and circulating inflammatory cells. In a gain of function model, lipid phosphate phosphatase-3 (LPP3) specific inducible knock out (Mx1-Plpp3Δ) showed higher systemic and cardiac inflammation after AMI compared to littermate controls (Mx1-Plpp3fl/fl); and a corresponding increase in bone marrow progenitor cell count and proliferation. Moreover, in Mx1- Plpp3Δ mice, cardiac functional recovery was reduced with corresponding increases in adverse cardiac remodeling and scar size (as assessed by echocardiography and Masson's Trichrome staining). To examine the effect of ATX/LPA nexus inhibition, we treated WT mice with the specific pharmacological inhibitor, PF8380, twice a day for 7 days post AMI. Inhibition of the ATX/LPA signaling nexus resulted in significant reduction in post-AMI inflammatory response, leading to favorable cardiac functional recovery, reduced scar size and enhanced angiogenesis. CONCLUSION: ATX/LPA signaling nexus plays an important role in modulating inflammation after AMI and targeting this mechanism represents a novel therapeutic target for patients presenting with acute myocardial injury.
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Inflamación/patología , Infarto del Miocardio/enzimología , Infarto del Miocardio/fisiopatología , Miocardio/enzimología , Hidrolasas Diéster Fosfóricas/metabolismo , Remodelación Vascular , Animales , Benzoxazoles/farmacología , Recuento de Células , Movimiento Celular/efectos de los fármacos , Femenino , Eliminación de Gen , Humanos , Inflamación/genética , Interferón-alfa/metabolismo , Interferón beta/metabolismo , Lisofosfolípidos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Mielopoyesis , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/genética , Miocardio/patología , Fosfatidato Fosfatasa/metabolismo , Piperazinas/farmacología , Recuperación de la Función/efectos de los fármacos , Regulación hacia Arriba/genética , Cicatrización de HeridasRESUMEN
BACKGROUND: Outcomes after acute kidney injury (AKI) are well described, but not for those already under nephrology clinic care. This is where discussions about kidney failure risk are commonplace. We evaluated whether the established kidney failure risk equation (KFRE) should account for previous AKI episodes when used in this setting. METHODS: This observational cohort study included 7491 people referred for nephrology clinic care in British Columbia in 2003-09 followed to 2016. Predictors were previous Kidney Disease: Improving Global Outcomes-based AKI, age, sex, proteinuria, estimated glomerular filtration rate (eGFR) and renal diagnosis. Outcomes were 5-year kidney failure and death. We developed cause-specific Cox models (AKI versus no AKI) for kidney failure and death, stratified by eGFR (≥30 mL/min/1.73 m2). We also compared prediction models comparing the 5-year KFRE with two refitted models, one with and one without AKI as a predictor. RESULTS: AKI was associated with increased kidney failure (33.1% versus 26.3%) and death (23.8% versus 16.8%) (P < 0.001). In Cox models, AKI was independently associated with increased kidney failure in those with an eGFR ≥30 mL/min/1.73 m2 {hazard ratio [HR] 1.35 [95% confidence interval (CI) 1.07-1.70]}, no increase in those with eGFR <30 mL/min/1.73 m2 ([HR 1.05 95% CI 0.91-1.21)] and increased mortality in both subgroups [respective HRs 1.89 (95% CI 1.56-2.30) and 1.43 (1.16-1.75)]. Incorporating AKI into a refitted kidney failure prediction model did not improve predictions on comparison of receiver operating characteristics (P = 0.16) or decision curve analysis. The original KFRE calibrated poorly in this setting, underpredicting risk. CONCLUSIONS: AKI carries a poorer long-term prognosis among those already under nephrology care. AKI may not alter kidney failure risk predictions, but the use of prediction models without appreciating the full impact of AKI, including increased mortality, would be simplistic. People with kidney diseases have risks beyond simply kidney failure. This complexity and variability of outcomes of individuals is important.
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Lesión Renal Aguda/complicaciones , Tasa de Filtración Glomerular , Fallo Renal Crónico/etiología , Nefrología/estadística & datos numéricos , Proteinuria/fisiopatología , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/fisiopatología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Nefrología/normas , Pronóstico , Curva ROC , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Loop-mediated amplification (LAMP) is an isothermal amplification technique favored in diagnostics and point-of-care work due to its high sensitivity and ability to run in isothermal conditions. In addition, a visual readout by lateral flow strips (LFS) can be used in conjunction with LAMP, making the assay accessible at the point-of-care. However, the amplicons resulting from a LAMP reaction varied in length and shape, making them undiscernible on a double-stranded DNA intercalating dye stained gel. Standard characterization techniques also do not identify which amplicons specifically bind to the LFS, which generate the visual readout. We aimed to standardize our characterization of LAMP products during assay development by using fluorescein amidite (FAM) and biotin-tagged loop forward and backward primers during assay development. A pvuII restriction enzyme digest is applied to the LAMP products. FAM-tagged bands are directly correlated with the LFS visual readout. We applied this assay development workflow for an HPV 16 assay using both plasmid DNA and clinical samples to demonstrate proof of concept for generalized assay development work.
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Papillomavirus Humano 16/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico/métodos , Sistemas de Atención de Punto , Papillomavirus Humano 16/genética , Humanos , Prueba de Estudio Conceptual , Sensibilidad y EspecificidadRESUMEN
The soursop fruit or Annona muricata (A. muricata) fruit is recognized by its bioactive compounds and acetogenins (ACG) are among the most important. The effect of ACGs, with greater importance in health, is that they present anti-tumor activity; however, the methods of extraction of ACGs are very slow and with a high expenditure of solvents. To our knowledge, there is no report of an optimal method for the extraction of acetogenins from the Annonaceae family by ultrasound-assisted extraction (UAE); therefore, the aim was to find the best UEA conditions of acetogenins from A. muricata fruit (peel, pulp, seed, and columella) by using response surface methodology. The effect of amplitude (40%, 70%, and 100%), time (5, 10, and 15 min), and pulse-cycle (0.4, 0.7, and 1 s) of ultrasound at 24 kHz was evaluated on the total acetogenin content (TAC). Optimal extraction conditions of acetogenins (ACGs) with UEA were compared with the extraction of ACGs by maceration. The optimal UEA conditions in the A. muricata pulp and by-products were dependent on each raw material. The highest TAC was found in the seed (13.01 mg/g dry weight (DW)), followed by the peel (1.69 mg/g DW), the pulp (1.67 mg/g DW), and columella (1.52 mg/g DW). The experimental TAC correlated well with the model (Adjusted R2 with values between 0.88 and 0.97). The highest effectiveness in ACG extraction was obtained in seeds and peels using UEA compared to extraction by maceration (993% and 650%, respectively). The results showed that A. muricata by-products are an important source of ACGs and that UAE could be a viable alternative, with high potential for large-scale extraction.
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Acetogeninas/química , Annona/química , Frutas/química , Extractos Vegetales/química , Ondas UltrasónicasRESUMEN
Fermented whey-based beverages were elaborated using commercial probiotics cultures (CHR HANSEN): BCT-1®, ABT-4®, ABC where A: Lactobacillus acidophilus, B: Bifidobacterium animalis subsp. lactis, C: Lactobacillus paracasei subsp. paracasei and T: Streptococccus thermophiles. Three treatments were prepared with these probiotics cultures and a treatment without cultures added as a control. All beverage were maintained at 4 °C and evaluated during their shelf life at 0, 7, 14 and 21 days. The variables analyzed were peptide concentration, proteolysis, ACE-inhibitory activity and, peptide and aromatic amino acid profiles. Principal component analysis (PCA) was conducted to assess the relationship between these variables. All whey-based fermented beverages added with probiotics presented ACE inhibitory activity (22-100%). However, whey-based beverage without probiotics added had the highest ACE inhibitory activity (100%), and it was maintained during its shelf life. Fermented beverage with ABT-4® culture had an ACE inhibitory activity from 80 to 100% during its shelf life. Thus can be attributed to the release of peptides during processing. Meanwhile, significative correlations were observed between variables varying this depending on the treatment, both, in magnitude and in direct or inverse direction (0.684-0.986). The ACE inhibitory activity was correlated to proteolysis and peptide and aromatic amino acids profiles. And, the IC50 was observed in the range of 0.01-0.055 mg/mL.
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Age-related macular degeneration (AMD) is the leading cause of central vision loss and severe blindness among the elderly population. Recently, we reported on the association of the SGCD gene (encoding for δ-sarcoglycan) polymorphisms with AMD. However, the functional consequence of Sgcd alterations in retinal degeneration is not known. Herein, we characterized changes in the retina of the Sgcd knocked-out mouse (KO, Sgcd-/-). At baseline, we analyzed the retina structure of three-month-old wild-type (WT, Sgcd+/+) and Sgcd-/- mice by hematoxylin and eosin (H&E) staining, assessed the Sgcd-protein complex (α-, ß-, γ-, and ε-sarcoglycan, and sarcospan) by immunofluorescence (IF) and Western blot (WB), and performed electroretinography. Compared to the WT, Sgcd-/- mice are five times more likely to have retinal ruptures. Additionally, all the retinal layers are significantly thinner, more so in the inner plexiform layer (IPL). In addition, the number of nuclei in the KO versus the WT is ever so slightly increased. WT mice express Sgcd-protein partners in specific retinal layers, and as expected, KO mice have decreased or no protein expression, with a significant increase in the α subunit. At three months of age, there were no significant differences in the scotopic electroretinographic responses, regarding both a- and b-waves. According to our data, Sgcd-/- has a phenotype that is compatible with retinal degeneration.
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Degeneración Retiniana/genética , Sarcoglicanos/genética , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Retina/metabolismo , Retina/patología , Sarcoglicanos/metabolismoRESUMEN
Ultrasound-assisted extraction (UAE) is widely used; however, the efficiency of extraction depends on the raw materials. Therefore, optimization of UAE must be investigated for each type of plant material. By-products from soursop fruit have not been studied as a source of bioactive compounds. In this work, the optimization of UAE conditions (extraction time (5, 10, and 15 min), pulse cycle (0.4, 0.7, and 1 s), and sonication amplitude (40%, 70%, and 100%)) for the extraction of phenolic compounds (soluble, hydrolyzable, condensed tannins, and total polyphenols) from soursop by-products (seed, peel, and columella) and pulp was evaluated using response surface methodology. The optimal conditions for UAE to obtain the highest total polyphenol content from by-products and pulp was dependent on the raw material. Peel resulted in the highest content of total polyphenols (187.32 mg/g dry matter [DM]) followed by columella (164.14 mg/g DM), seed (36.15 mg/g DM), and pulp (33.24 mg/g DM). The yield of polyphenolic content from peel and columella obtained with UAE was higher (32â»37%) than conventional extraction for 2 h under stirring (14â»16%). The contents of gallic acid (0.36â»15.86 µg/g DM), coumaric acid (0.07â»1.37 µg/g DM), and chlorogenic acid (9.18â»32.67 µg/g DM) in the different parts of the fruit were higher in the extracts obtained by UAE compared with a conventional extraction method (0.08â»0.61, 0.05â»0.08, 3.15â»13.08 µg/g DM, respectively), although it was dependent on the raw materials. Soursop by-products can be functionally important if they are used to extract bioactive compounds by UAE; a technology with high potential for commercial extraction on a large scale.
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Annona/química , Fraccionamiento Químico , Fenoles/química , Fenoles/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Sonicación , Fraccionamiento Químico/métodos , Polifenoles/aislamiento & purificación , Solubilidad , Sonicación/métodosRESUMEN
Background: Immunosuppression (IS) is the main treatment for most types of glomerulonephritis (GN). Quantifying the cost of IS is necessary to ensure equitable access to therapies and optimal health outcomes, but the real-world cost of IS treatment for GN is largely unknown. We examined temporal changes in the population-level IS medication costs for GN over a 14-year period in a large Canadian province. Methods: We linked a provincial pathology database (containing all GN cases from 2000 to 2012) with renal and medication administrative databases to capture clinical characteristics and IS medications, with follow-up until 2013. The primary outcome (mean IS medication cost per treated patient each year) was evaluated for trends over time. Results: The cohort included 2983 GN patients followed for a mean of 5.7 years. The yearly per-patient medication cost increased 6.8-fold from $205 to $1394 (P < 0.001), with significant increases of 3.5-11.7-fold in anti-neutrophil cytoplasmic antibody (ANCA) vasculitis, focal segmental glomerulosclerosis, lupus nephritis, minimal change disease and membranous nephropathy (P ≤ 0.004), but no change in immunoglobulin A (IgA) nephropathy. The cost of mycophenolate mofetil, calcineurin inhibitors and rituximab increased significantly (P < 0.001) such that in 2000 they accounted for 17.6% of medication costs and were used by 2.2% of patients, which increased to 94.5% and 44.6%, respectively, in 2013. The costs of azathioprine, cyclophosphamide and prednisone increased only slightly or decreased. Patterns of drug use and contribution to cost varied by type of GN. Conclusions: These are the first population-level estimates of the IS treatment costs for GN, and demonstrate a striking increase due to changing practice patterns from older, cheaper medications to newer, more expensive therapies. These results provide important information to guide future health policy strategies and cost-effectiveness research in glomerular diseases.
Asunto(s)
Bases de Datos Factuales , Glomerulonefritis/economía , Inmunosupresores/economía , Inmunosupresores/uso terapéutico , Pautas de la Práctica en Medicina/normas , Adulto , Canadá/epidemiología , Femenino , Glomerulonefritis/clasificación , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSE: The purpose of this study was to determine whether the muscle appearance satisfaction scale (MASS) shows acceptable psychometric properties in Mexican bodybuilders. METHODS: A total of 258 Mexican male bodybuilders were recruited. Two self-report questionnaires, including the MASS and drive for muscularity scale (DMS), were administered. Six models of the latent structure of the MASS were evaluated, using confirmatory factor analysis with maximum likelihood, considering robust Satorra-Bentler correction to estimate the fit of the models to the data. RESULTS: Similar to the original MASS, the series of CFA confirmed that the Mexican version was well represented with the 17-item five-factor structure, which showed a good model fit [Satorra-Bentler Chi-square (109, n = 258) = 189.18, p < 0.0001; NNFI = 0.91; CFI = 0.93; IFI = 0.93; RMSEA = 0.05 (0.04, 0.07)]. Internal consistency was estimated with McDonald's omega, which was acceptable for the MASS (0.88), and their subscales (0.80 to 0.89), except for muscle checking scale (0.77). Test-retest reliability analysis showed stability of the MASS total as well as of the subscale scores over a 2-week period (intraclass correlation coefficients = 0.75-0.91). Construct validity was demonstrated by a significant positive correlation between MASS and DMS results (r = 0.75; p = 0.0001). These results were similar to those of previous studies, which demonstrate the scale's usefulness. CONCLUSIONS: Our results support the suitability of the MASS and its subscales to measure muscle dysmorphia symptoms in Mexican male bodybuilders.