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The prognosis and treatment outcomes of heart failure (HF) patients rely heavily on disease etiology, yet the majority of underlying signaling mechanisms are complex and not fully elucidated. Phosphorylation is a major point of protein regulation with rapid and profound effects on the function and activity of protein networks. Currently, there is a lack of comprehensive proteomic and phosphoproteomic studies examining cardiac tissue from HF patients with either dilated dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM). Here, we used a combined proteomic and phosphoproteomic approach to identify and quantify more than 5,000 total proteins with greater than 13,000 corresponding phosphorylation sites across explanted left ventricle (LV) tissue samples, including HF patients with DCM vs. nonfailing controls (NFC), and left ventricular infarct vs. noninfarct, and periinfarct vs. noninfarct regions of HF patients with ICM. Each pair-wise comparison revealed unique global proteomic and phosphoproteomic profiles with both shared and etiology-specific perturbations. With this approach, we identified a DCM-associated hyperphosphorylation cluster in the cardiomyocyte intercalated disc (ICD) protein, αT-catenin (CTNNA3). We demonstrate using both ex vivo isolated cardiomyocytes and in vivo using an AAV9-mediated overexpression mouse model, that CTNNA3 phosphorylation at these residues plays a key role in maintaining protein localization at the cardiomyocyte ICD to regulate conductance and cell-cell adhesion. Collectively, this integrative proteomic/phosphoproteomic approach identifies region- and etiology-associated signaling pathways in human HF and describes a role for CTNNA3 phosphorylation in the pathophysiology of DCM.
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Cardiomiopatía Dilatada , Insuficiencia Cardíaca , Animales , Ratones , Humanos , Cardiomiopatía Dilatada/metabolismo , Ventrículos Cardíacos/metabolismo , Fosforilación , Proteómica , Miocardio/metabolismo , Insuficiencia Cardíaca/metabolismo , alfa Catenina/metabolismoRESUMEN
AIMS: To evaluate the long-term safety and efficacy of enavogliflozin monotherapy (0.3 mg/day) in individuals with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Following a 24-week randomized, double-blind treatment period with enavogliflozin 0.3 mg/day (n = 77) or placebo (n = 69), consenting participants received enavogliflozin 0.3 mg/day for an additional 28 weeks during an open-label extension (OLE) period. The safety and efficacy of enavogliflozin were assessed at Week 52. RESULTS: A total of 37 participants continued enavogliflozin (maintenance group), and 26 participants switched from placebo to enavogliflozin (switch group). No additional adverse drug reactions related to enavogliflozin were observed during the OLE period. At Week 52, glycated haemoglobin (HbA1c) and fasting plasma glucose were significantly lower than at the baseline, by 0.9% and 24.9 mg/dL, respectively, in the maintenance group (p < 0.0001 for both), and by 0.7% and 18.0 mg/dL, respectively, in the switch group (p < 0.0001 and p = 0.002). The proportions of participants reaching HbA1c 7.0% (53 mmol/mol) at Week 52 were 69.4% in the maintenance group and 65.4% in the switch group. A significant increase in urine glucose-to-creatinine ratio was observed at Week 52, by 84.9 g/g and 67.1 g/g in the maintenance and switch groups, respectively (p < 0.0001 for both). Body weight in both groups decreased significantly (p < 0.0001) from baseline to Week 52, by 3.5 kg and 3.8 kg in the maintenance and switch groups, respectively. CONCLUSIONS: Enavogliflozin 0.3 mg monotherapy provides long-term glycaemic control in T2DM and is safe and well tolerated during a 52-week treatment period.
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SHORT: and ultra-short chain perfluoroalkyl substances (S- and US-PFAS) are alternatives for the long-chain PFAS which have been more regulated over time. They are highly mobile in the environment and can easily reach drinking water sources which can become an important human exposure route. Furthermore, there have been growing concerns about the presence of PFAS in Flanders. Because of this, human exposure to S- and US-PFAS through Flemish drinking water was evaluated in this study. For this purpose, the presence of 2 S-PFAS (PFBS and PFBA) and 5 US-PFAS (PFPrS, PFEtS, TFMS, PFPrA and TFA) was investigated in 47 tap water samples, collected from different Flemish provinces, and 16 bottled waters purchased in Flanders. Out of the 7 target PFAS, 4 (PFBA, PFBS, PFPrS and PFEtS) were detected at concentrations above LOQ in tap water. In bottled water, only TFMS was present above its LOQ. PFAS concentrations in all analyzed water samples ranged from <0.7 to 7.3 ng/L for PFBS, <0.03-15.0 ng/L for TFMS and <0.9-12.0 ng/L for PFBA. PFPrS was only detected once above its LOQ, at 0.6 ng/L. No value could be reported for PFPrA due to high procedural blanks resulting in a high LOQ, nor for TFA due to high matrix effect. No significant differences in PFAS concentrations were seen in tap water among different drinking water companies, provinces, nor between the two types of analyzed bottled water (natural mineral water vs spring water). The use of a commercial carbon filter significantly reduced the median concentrations of the studied compounds in tap water. Finally, it was estimated that the presence of S- and US-PFAS in Flemish drinking water does not pose an immediate threat to human health, as concentrations were at least two orders of magnitude below the available guidance values.
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BACKGROUND: Despite the widespread use of botulinum toxin (BTX) injection for the treatment of masseter muscle hypertrophy (MMH), there is no standard treatment option. OBJECTIVE: We report the efficacy and safety for BTX in MMH over a period of 48 weeks. METHODS: In double-blinded, placebo-controlled phase 3 trials, 180 patients (randomized 1:1) received treatment with placebo (normal saline) or prabotulinumtoxinA (48 units). Masseter muscle thickness (at maximal clenching and resting positions), 3D imaging analysis, and masseter muscle hypertrophy scale grades were analyzed at each time point. After the 24-week CORE study, all patients who met the same criteria of the CORE study at week 24 ( n = 114) received only prabotulinumtoxinA, regardless of previous treatment, for an additional 24 weeks (48 weeks in total) for the open-label extension study. RESULTS: The largest differences in mean and percent changes from baseline in masseter muscle thickness were observed at 12 weeks, and there were significant differences between the 2 groups at all time points (all p < .001). The effect was independent of the number of injections. No serious adverse event was observed. CONCLUSION: PrabotulinumtoxinA could effectively ameliorate MMH without major complications.
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Toxinas Botulínicas Tipo A , Hipertrofia , Músculo Masetero , Humanos , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/efectos adversos , Método Doble Ciego , Hipertrofia/tratamiento farmacológico , Músculo Masetero/efectos de los fármacos , Músculo Masetero/patología , Músculo Masetero/anomalías , Femenino , Persona de Mediana Edad , Adulto , Masculino , Resultado del Tratamiento , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/efectos adversos , Inyecciones IntramuscularesRESUMEN
The gut microbial and metabolic characteristics of intestinal Behçet's disease (BD), a condition sharing many clinical similarities with ulcerative colitis (UC) and Crohn's disease (CD), are largely unexplored. This study investigated the gut microbial and metabolic characteristics of intestinal BD as well as potential biomarkers, comparing them with those in UC, CD, and healthy controls. Colon tissue and stool samples from 100 patients (35 UC, 30 CD, and 35 intestinal BD) and 41 healthy volunteers were analyzed using 16S ribosomal RNA sequencing to assess microbial diversity, taxonomic composition, and functional profiling. Plasma metabolomic analyses were performed using gas chromatography and ultra-performance liquid chromatography-mass spectrometry. Results indicated reduced microbial diversity in CD but not in intestinal BD, with intestinal BD showing fewer changes compared to controls yet distinct taxonomic features from UC, CD, and controls. Common alterations across all diseases included a reduction in beneficial bacteria producing short-chain fatty acids. Intestinal BD-specific changes featured a decreased abundance of Bacteroides fragilis. Metabolomic profiles in intestinal BD were similar to those in CD but distinct from those in UC, displaying significant changes in energy metabolism and genetic information processing. This integrative analysis revealed both shared and unique profiles in intestinal BD compared with UC, CD, and controls, advancing our understanding of the distinctive features of these diseases.
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Síndrome de Behçet , Microbioma Gastrointestinal , Metaboloma , Humanos , Síndrome de Behçet/microbiología , Síndrome de Behçet/metabolismo , Masculino , Femenino , Adulto , Persona de Mediana Edad , ARN Ribosómico 16S/genética , Enfermedad de Crohn/microbiología , Enfermedad de Crohn/metabolismo , Metabolómica/métodos , Enfermedades Inflamatorias del Intestino/microbiología , Enfermedades Inflamatorias del Intestino/metabolismo , Biomarcadores , Heces/microbiología , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/metabolismo , Estudios de Casos y ControlesRESUMEN
OBJECTIVES: This study aimed to determine the overall oral health statuses of patients with fixed orthodontic appliance and clear aligner, as well as their oral hygiene management behaviours and satisfaction. METHODS: We selected 40 participants (20 each with fixed orthodontic devices and clear aligners) who visited a dental clinic. We conducted a survey to determine the oral hygiene management behaviours of the subjects and their satisfaction with their orthodontic treatment. Three measurements were also conducted at 4-week intervals to determine the oral health statuses of the subjects. RESULTS: The Löe and Silness gingival index of patients with fixed orthodontic appliances indicated moderate gingivitis (1.1 ± 0.3), and those with clear aligners had mild gingivitis (0.6 ± 0.4) (p < 0.001). The modified O'Leary index also indicated that the degree of dental plaque deposition in the oral cavity was lower in patients treated with a clear aligner (43.0 ± 18.2 points) than in those treated with a fixed orthodontic (28.1 ± 10.9 points) (p = 0.004). Regarding oral hygiene management, the fixed orthodontic group received scaling more frequently (p = 0.006), received more oral health education (p < 0.001) and had a longer brushing time (p = 0.008) than the clear aligner group. No significant difference was observed in satisfaction between the fixed orthodontic appliance and the clear aligner. CONCLUSIONS: Regarding the oral health status by orthodontic appliance type, the clear aligner group had the advantages of reduction in dental plaque attachment and gingival health. The fixed orthodontic group exhibited better oral hygiene management behaviours. Satisfaction with orthodontic treatment was found to be similar for the two device types.
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BACKGROUND: In Canada, Ontario Health Teams (OHTs) are a new model for integrated healthcare. Core to OHTs are family physicians (FPs) and their ability to collaborate with other FPs and healthcare providers. Whereas the factors for intra-organizational collaboration have been well-studied, inter-organizational collaboration between FPs and other healthcare organizations as an integrated care network, are less understood. This paper aims to explore the structural factors, processes, and theoretical frameworks that support FPs' collaboration for integrated healthcare. METHODS: A scoping review was undertaken based on Joanna Briggs Institute (JBI) methodology for scoping review and using the Preferred Reporting Items for Systematic Review and Meta-Analysis for Scoping Review (PRISMA_ScR) checklist. A search for academic and relevant grey literature published between 2000-2021 was conducted across databases (MEDLINE, EMBASE, EBSCOhost).Thematic analysis was used to identify the key findings of the selected studies. RESULTS: Thirty-two studies were included as eligible for this review. Three structural components were identified as critical to FPs' successful participation in inter-organizational partnerships: (1) shared vision/values, (2) leadership by FPs, and (3) defined decision-making procedures. Also, three processes were identified: (1) effective communication, (2) a collective sense of motivation for change, and (3) relationships built on trust. Three theoretical frameworks provided insight into collaborative initiatives: (1) Social Identity Approach, (2) framework of interprofessional collaboration, and (3) competing values framework. CONCLUSION: FPs hold unique positions in healthcare and this review is the first to synthesize the best evidence for building collaborations between FPs and other healthcare sectors. These findings will inform collaboration strategies for healthcare integration, including with OHTs.
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Atención a la Salud , Médicos de Familia , Humanos , Instituciones de Salud , Ontario , Grupos de PoblaciónRESUMEN
The provision of distance education has increased rapidly over the past few years owing to the COVID-19 pandemic. The core of gross anatomy distance education is three-dimensional (3D) visualization of anatomical structures, and the use of simple 3D visualization tools has increased as distance education has become more popular. The purpose of this study was to establish a more effective operation plan in dental hygiene by investigating learners' opinions about distance education of gross anatomy and 3D visualization tools, and by comparing and analyzing their academic achievements. The study involved 250 students and comprised an analysis of 120 students who took a head and neck anatomy class at the Department of Dental Hygiene at D University via distance learning during 2020-2022, and 130 graduates who had completed the class via face-to-face learning during 2015-2017. An online survey of 120 of the enrolled students comprised 10 questions asking for opinions on the head and neck anatomy distance learning classes, five questions on the 3D visualization tool, and five on general characteristics. Overall, the learners had positive perceptions of distance education for head and neck anatomy and the 3D visualization tool. Among the education methods compared, they generally preferred blended learning (n = 47, 39.2%). There was a significant preference for the distance learning method of asynchronous classes (n = 86, 94.5%). Analysis of academic achievements according to whether or not distance education was conducted revealed a significantly higher score in the face-to-face class group (P < 0.05). A blended learning method can be effective in increasing learner satisfaction and improving academic achievement in gross anatomy classes on dental hygiene. It is suggested that theoretical material should be learned through asynchronous content and knowledge expanded through small-group activities during face-to-face learning. This will help establish a standard model for teaching of gross anatomy in dental hygiene in the postpandemic era.
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Éxito Académico , Anatomía , COVID-19 , Humanos , Higiene Bucal , Pandemias/prevención & control , Estudiantes , Anatomía/educaciónRESUMEN
Lactobacilli have been widely used as probiotics because of their benefits for intestinal health and physiological functions. Among a variety of Lactobacillus genera, Limosilactobacillus reuteri has been studied for its ability to exert anti-inflammatory functions and its role in controlling metabolic disorders, as well as the production of the antimicrobial compound reuterin. However, the effects and mechanisms of L. reuteri on enhancing immune responses in the immunosuppressed states have been relatively understudied. In this study, we isolated an immunomodulatory strain, namely, L. reuteri KBL346 (KBL346), from a fecal sample of a 3-month-old infant in Korea. We evaluated the immunostimulatory activity and hematopoietic function of KBL346 in macrophages and cyclophosphamide (CPA)-induced immunosuppressed mice. KBL346 increased the phagocytic activity against Candida albicans MYA-4788 in macrophages, and as biomarkers for this, increased secretions of nitric oxide (NO) and prostaglandin E2 (PGE2) were confirmed. Also, the secretions of innate cytokines (TNF-α, IL-1ß, and IL-6) were increased. In CPA-induced immunosuppressed mice, KBL346 at a dosage of 1010 CFU/kg protected against spleen injury and suppressed levels of immune-associated parameters, including NK cell activity, T and B lymphocyte proliferation, CD4+ and CD8+ T cell abundance, cytokines, and immunoglobulins in vivo. The effects were comparable or superior to those in the Korean red ginseng positive control group. Furthermore, the safety assessment of KBL346 as a probiotic was conducted by evaluating its antibiotic resistance, hemolytic activity, cytotoxicity, and metabolic characteristics. This study demonstrated the efficacy and safety of KBL346, which could potentially be used as a supplement to enhance the immune system.
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Limosilactobacillus reuteri , Humanos , Lactante , Animales , Ratones , Huésped Inmunocomprometido , Lactobacillus , Activación de Linfocitos , Ciclofosfamida , Citocinas , DinoprostonaRESUMEN
Phloroglucinol is a class of polyphenolic compounds containing aromatic phenyl rings and is known to have various pharmacological activities. Recently, we reported that this compound isolated from Ecklonia cava, a brown alga belonging to the family Laminariaceae, has potent antioxidant activity in human dermal keratinocytes. In this study, we evaluated whether phloroglucinol could protect against hydrogen peroxide (H2O2)-induced oxidative damage in murine-derived C2C12 myoblasts. Our results revealed that phloroglucinol suppressed H2O2-induced cytotoxicity and DNA damage while blocking the production of reactive oxygen species. We also found that phloroglucinol protected cells from the induction of apoptosis associated with mitochondrial impairment caused by H2O2 treatment. Furthermore, phloroglucinol enhanced the phosphorylation of nuclear factor-erythroid-2 related factor 2 (Nrf2) as well as the expression and activity of heme oxygenase-1 (HO-1). However, such anti-apoptotic and cytoprotective effects of phloroglucinol were greatly abolished by the HO-1 inhibitor, suggesting that phloroglucinol could increase the Nrf2-mediated activity of HO-1 to protect C2C12 myoblasts from oxidative stress. Taken together, our results indicate that phloroglucinol has a strong antioxidant activity as an Nrf2 activator and may have therapeutic benefits for oxidative-stress-mediated muscle disease.
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Antioxidantes , Estrés Oxidativo , Phaeophyceae , Floroglucinol , Animales , Humanos , Ratones , Antioxidantes/farmacología , Apoptosis , Línea Celular , Hemo-Oxigenasa 1/metabolismo , Peróxido de Hidrógeno/metabolismo , Mioblastos/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Phaeophyceae/metabolismo , Floroglucinol/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
This phenotype-genotype study aimed to investigate the extent of audioprofile variability related to cochlin major domains and to identify potential ethnic-specific differences associated with COCH-related hearing loss. Eight Korean families (26 cases) were diagnosed with COCH-related hearing loss by exome sequencing. Audiometric test results were combined with those from nine published East Asian families (20 cases) and compared with those from 38 European-descent families (277 cases). Audioprofiles were created by grouping audiometric test results into age ranges by age at testing and then averaging hearing loss thresholds by frequency within age ranges. The functional impact of the identified variants was assessed in vitro by examining the intracellular trafficking, secretion, and cleavage of cochlin. In both East Asian and European-descent families segregating COCH-related hearing loss, deafness-associated variants in non-LCCL domains of cochlin were associated with hearing loss that was more severe earlier in life than hearing loss caused by variants in the LCCL domain. Consistent with this phenotypic difference, functional studies demonstrated distinct pathogenic mechanisms for COCH variants in a domain-dependent manner; specifically, a cytotoxic effect was observed for the p.Phe230Leu variant, which is located in the vWFA1 domain. No ethnic-specific differences in hearing loss progression were observed, except for those attributable to an overrepresentation of presymptomatic cases in the European-descent cohort.
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Sordera , Pérdida Auditiva Sensorineural , Pérdida Auditiva , Humanos , Sordera/genética , Proteínas de la Matriz Extracelular/genética , Genotipo , Pérdida Auditiva/genética , Pérdida Auditiva Sensorineural/genética , Mutación , Linaje , FenotipoRESUMEN
Ski-slope hearing loss (HL), which refers to increased auditory threshold at high frequencies, is common in adults. However, genetic contributions to this post-lingual HL remain largely unknown. Here, we prospectively investigated deafness-associated and novel candidate genes causing ski-slope HL. We analyzed 192 families with post-lingual HL via gene panel and/or exome sequencing. With an overall molecular diagnostic rate of 35.4% (68/192) in post-lingual HL, ski-slope HL showed a lower diagnostic rate (30.7%) compared with other conditions (40.7%). In patients who showed HL onset before the age of 40, genetic diagnostic probability was significantly lower for ski-slope HL than for other conditions. Further analysis of 51 genetically undiagnosed patients in the ski-slope HL group identified three variants in delta-like ligand 1 (DLL1), a Notch ligand, which presented in vitro gain-of-function effects on Notch downstream signaling. In conclusion, genetic diagnostic rates in post-lingual HL varied according to audiogram patterns with age-of-onset as a confounding factor. DLL1 was identified as a candidate gene causing ski-slope HL.
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Pérdida Auditiva Sensorineural , Pérdida Auditiva , Adulto , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/genética , Pérdida Auditiva Sensorineural/genética , Pruebas Auditivas , Humanos , Ligandos , Patología Molecular , Linaje , Secuenciación del ExomaRESUMEN
BACKGROUND: Probiotic starters can improve the flavor profile, texture, and health-promoting properties of fermented foods. Tetragenococcus halophilus is a halophilic lactic acid bacterium that is a candidate starter for high-salt fermented foods. However, the species is known to produce biogenic amines, which are associated with neurotoxicity. Here, we report a probiotic starter strain of T. halophilus, EFEL7002, that is suitable for use in high-salt fermentation. RESULTS: EFEL7002 was isolated from Korean meju (fermented soybean) and identified as T. halophilus, with 99.85% similarity. The strain is safe for use in food as it is a non-hemolytic and non-biogenic amine producer. EFEL7002 is tolerant to gastrointestinal conditions and can adhere to Caco-2 cells. This strain showed antioxidant, anti-inflammatory, and protective effects against the human gut epithelial barrier. EFEL7002 grew well in media containing 0-18% NaCl showing maximum cell densities in 6% or 12% NaCl. CONCLUSIONS: T. halophilus EFEL7002 can be used as a health-promoting probiotic starter culture for various salty fermented foods.
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Probióticos , Cloruro de Sodio , Aminas Biogénicas/análisis , Células CACO-2 , Enterococcaceae , Fermentación , Microbiología de Alimentos , Humanos , República de Corea , Glycine maxRESUMEN
RATIONALE: In young adults, the role of mildly abnormal lipid levels and lipid variability in the risk of atherosclerotic cardiovascular diseases remains uncertain. OBJECTIVE: To investigate the association of these abnormalities in lipid profiles with the risk of myocardial infarction (MI) and stroke in young population. METHODS AND RESULTS: From the Korean National Health Insurance Service, a nationwide population-based cohort of 1 934 324 statin-naive adults aged 20 to 39 years, with ≥3 lipid profile measurements and without a history of MI and stroke, were followed-up until the date of MI or stroke, or December 31, 2017. The primary measure of lipid variability was variability independent of the mean. Higher baseline total cholesterol, LDL-C (low-density lipoprotein-cholesterol), and triglycerides and lower HDL-C (high-density lipoprotein-cholesterol) levels were significantly associated with increased MI risk; respective adjusted hazard ratios and 95% CIs comparing the highest versus lowest quartiles were 1.35 (1.20-1.53) for total cholesterol, 1.41 (1.25-1.60) for LDL-C, 1.28 (1.11-1.47) for triglycerides, and 0.82 (0.72-0.94) for HDL-C. Adjusted analyses for deciles of lipid profiles showed that MI risk was significantly elevated among participants with total cholesterol ≥223.4 mg/dL, LDL-C ≥139.5 mg/dL, HDL-C ≤41.8 mg/dL, and triglycerides ≥200.1 mg/dL. The associations between lipid levels and stroke risk were less prominent. Multivariable-adjusted restricted cubic spline analysis demonstrated that the increase in MI risk was not exclusively driven by extreme values of lipid profiles. Similar results were obtained on sensitivity analyses of baseline lipid levels. However, associations between lipid variability and the risk of MI and stroke varied depending on the measure of lipid variability used. CONCLUSIONS: Mildly abnormal baseline lipid levels were associated with an increased future risk of atherosclerotic cardiovascular disease events, particularly MI, whereas measures of lipid variability were not. Therefore, in young adults, achieving optimal lipid levels could be valuable in the prevention of atherosclerotic cardiovascular disease.
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HDL-Colesterol/sangre , Colesterol/sangre , Infarto del Miocardio/sangre , Accidente Cerebrovascular/sangre , Triglicéridos/sangre , Adulto , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Análisis Multivariante , Infarto del Miocardio/diagnóstico , Análisis de Regresión , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Adulto JovenRESUMEN
The increasing human exposure to contaminants of emerging concern (CECs) cannot be fully assessed by targeted biomonitoring methods alone as these are limited to a subset of known analytes. On the contrary, suspect screening approaches based on liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) allow the simultaneous detection of a high number of CECs and/or their (predicted) metabolites leading to a more comprehensive assessment of possible human exposure to these compounds. Within this study, 83 urine samples of Flemish adolescents (47 males, 36 females) collected in the frame of the 4th cycle of the Flemish Environment and Health Study (FLEHS IV) were selected with the aim of including a high and a low exposure group based on the overall exposure of 45 known contaminants. Samples were analyzed using a previously developed method involving a suspect screening approach to annotate CECs and their metabolites. The applied suspect list contained a total of >12,500 CECs and their known and predicted metabolites resulting from metabolization reactions, such as hydroxylation, glucuronidation and methylation. In total, 63 compounds were annotated at a confidence level of 3 or better, with most of the detected compounds not included in current biomonitoring programs. 5 out of the 63 compounds could be assigned with confidence level 2. Five compounds could unequivocally be identified (confidence level 1) through the comparison with reference standards. Personal care products were the main detected compound class (42% of detected compounds). Additionally, a detailed literature search indicated potential toxic effects for several of the detected CECs. Lastly, in the urine samples, a significantly higher number (p < 0.05) of compounds was detected in the high exposure group as opposed to the low exposure group. This difference could only be observed between high and low exposure load samples of female participants (p < 0.01).
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Monitoreo Biológico , Monitoreo del Ambiente , Adolescente , Cromatografía Liquida/métodos , Monitoreo del Ambiente/métodos , Femenino , Humanos , Masculino , Espectrometría de MasasRESUMEN
This study aimed to evaluate the effect of a horse-riding simulator (HRS) with virtual reality (VR) on gross motor function, balance control, and body composition in children with spastic cerebral palsy (CP). Seventeen preschool and school-aged children with spastic CP were included; 10 children in the intervention group (HRS group) received 30 min of HRS with VR training twice a week for a total of 16 sessions in addition to conventional physiotherapy. Seven children in the control group were instructed to perform home-based aerobic exercises twice a week for 8 weeks in addition to conventional physiotherapy. Gross motor function measure (GMFM) and body composition were evaluated before the first session and after the last session. Before and after the 2-month intervention, Pediatric Balance Scale and Timed Up and Go test were evaluated for the HRS group. GMFM scores and body composition changed significantly in the HRS group (p < 0.05). However, no significant differences were observed in the control group. Changes in the GMFM total scores, GMFM dimension D scores, and skeletal muscle mass significantly differed between the HRS and control groups (p < 0.05). HRS with VR may be an effective adjunctive therapeutic approach for the rehabilitation of children with CP.
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Parálisis Cerebral , Realidad Virtual , Animales , Composición Corporal , Niño , Preescolar , Caballos , Humanos , Destreza Motora , Equilibrio Postural/fisiología , Estudios de Tiempo y MovimientoRESUMEN
The present study investigated the effects of relative humidity (RH) on the laying performance, egg quality, and stress indicators of laying hens raised at high ambient temperatures. A total of 180 Hy-Line Brown laying hens (68-wk-old) were randomly allotted to one of the following three RH conditions for 12 h a day (9:00 a.m.-9:00 p.m.) over four weeks: low RH (LRH; 25% RH), moderate RH (MRH; 50% RH), and high RH (HRH; 75% RH); ambient temperature was 30 °C under all treatments. None of the RH treatments affected hen-day egg production, egg weight, or egg mass (P > 0.05). However, feed intake was lower in the HRH group than in the LRH group (P < 0.05). Plasma corticosterone (CORT) concentration on day 21, yolk CORT concentration on day 3, and albumen CORT concentration on day 7 following RH exposure were higher in the HRH group than in the LRH group (P < 0.05). Moreover, plasma HDL-cholesterol concentration on day 14 was higher in the HRH group than in the LRH group (P < 0.05). On days 3 and 14, the Haugh unit decreased (P < 0.05) in the LRH group compared with that in the MRH and HRH groups. The HRH-exposed laying hens showed the lowest (P < 0.05) eggshell thickness on day 14. The absolute weights of eggshell, yolk, and albumen decreased in the HRH group compared with those in the MRH and LRH groups. Overall, high RH lowered feed intake and egg quality except for the Haugh unit, and induced stress response as manifested by elevated plasma, yolk, and albumen CORT concentrations. To our best knowledge, the present study is the first to demonstrate the role of RH in triggering temperature stress responses in laying hens.
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Pollos/fisiología , Huevos/análisis , Respuesta al Choque Térmico/fisiología , Humedad , Alimentación Animal/análisis , Animales , Corticosterona/sangre , Dieta/veterinaria , Ingestión de Alimentos , Cáscara de Huevo/fisiología , Femenino , CalorRESUMEN
Chinese cabbage (Brassica rapa L.) leaves are purple in color due to anthocyanin accumulation and have nutritional and aesthetic value, as well as antioxidant properties. Here, we identified the R3 MYB transcription factor BrMYBL2.1 as a key negative regulator of anthocyanin biosynthesis. A Chinese cabbage cultivar with green leaves harbored a functional BrMYBL2.1 protein, designated BrMYBL2.1-G, with transcriptional repressor activity of anthocyanin biosynthetic genes. By contrast, BrMYBL2.1 from a Chinese cabbage cultivar with purple leaves carried a poly(A) insertion in the third exon of the gene, resulting in the insertion of multiple lysine residues in the predicted protein, designated BrMYBL2.1-P. Although both BrMYBL2.1 variants localized to the nucleus, only BrMYBL2.1-G interacted with its cognate partner BrTT8. Transient infiltration assays in tobacco leaves revealed that BrMYBL2.1-G, but not BrMYBL2.1-P, actively represses pigment accumulation by inhibiting the transcription of anthocyanin biosynthetic genes. Transient promoter activation assay in Arabidopsis protoplasts verified that BrMYBL2.1-G, but not BrMYBL2.1-P, can repress transcriptional activation of BrCHS and BrDFR, which was activated by co-expression with BrPAP1 and BrTT8. We determined that BrMYBL2.1-P may be more prone to degradation than BrMYBL2.1-G via ubiquitination. Taken together, these results demonstrate that BrMYBL2.1-G blocks the activity of the MBW complex and thus represses anthocyanin biosynthesis, whereas the variant BrMYBL2.1-P from purple Chinese cabbage cannot, thus leading to higher anthocyanin accumulation.
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Arabidopsis , Brassica rapa , Brassica , Antocianinas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Brassica/metabolismo , Brassica rapa/genética , Brassica rapa/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
MBW complexes, consisting of MYB, basic helix-loop-helix (bHLH), and WD40 proteins, regulate multiple traits in plants, including anthocyanin and proanthocyanidin (PA) biosynthesis and the determination of epidermal cell fate. Here, a WD40 gene from Raphanus sativus, designated TRANSPARENT TESTA GLABRA 1 (RsTTG1), was cloned and functionally characterized. Heterologous expression of RsTTG1 in the Arabidopsis thaliana mutant ttg1-22 background restored accumulation of anthocyanin and PA in the mutant and rescued trichome development. In radish, RsTTG1 was abundantly expressed in all root and leaf tissues, independently of anthocyanin accumulation, while its MBW partners RsMYB1 and TRANSPARENT TESTA 8 (RsTT8) were expressed at higher levels in pigment-accumulating tissues. In yeast two-hybrid analysis, the full-length RsTTG1 protein interacted with RsTT8. Moreover, transient protoplast co-expression assays demonstrated that RsTTG1, which localized to both the cytoplasm and nucleus, moves from the cytoplasm to the nucleus in the presence of RsTT8. When co-expressed with RsMYB1 and RsTT8, RsTTG1 stably activated the promoters of the anthocyanin biosynthesis genes CHALCONE SYNTHASE (RsCHS) and DIHYDROFLAVONOL 4-REDUCTASE (RsDFR). Transient expression of RsTTG1 in tobacco leaves exhibited an increase in anthocyanin accumulation due to activation of the expression of anthocyanin biosynthesis genes when simultaneously expressed with RsMYB1 and RsTT8. These results indicate that RsTTG1 is a vital regulator of pigmentation and trichome development as a functional homolog of AtTTG1.
Asunto(s)
Arabidopsis , Proantocianidinas , Raphanus , Antocianinas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Regulación de la Expresión Génica de las Plantas , Oxidorreductasas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proantocianidinas/metabolismo , Raphanus/genética , Raphanus/metabolismoRESUMEN
Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters. Several studies have suggested that GABA supplements can reduce blood pressure and modulate the renal immune system in vitro and in vivo. In the present study, we investigated the effect of GABA-enriched salt as an alternative to traditional salt on aggravated renal injury by high salt intake in cisplatin-induced nephrotoxicity mice. High salt intake accelerated the increase of biomarkers, such as blood urea nitrogen and serum creatinine levels for renal injury in cisplatin-induced nephrotoxicity mice. However, oral administration of GABA-contained salt notably suppressed serum BUN and creatinine levels. The efficacy of GABA salt was superior to lacto GABA salt and postbiotics GABA salt. Furthermore, GABA-enriched salt markedly restored histological symptoms of nephrotoxicity including renal hypertrophy, tubular dilation, hemorrhage, and collagen deposition aggravated by salt over-loading in cisplatin-exposed mice. Among them, GABA salt showed a higher protective effect against cisplatin-induced renal histological changes than lacto GABA salt and postbiotics GABA salt. In addition, administration of high salt significantly enhanced expression levels of apoptosis and inflammatory mediators in cisplatin-induced nephrotoxicity mice, while GABA-enriched salt greatly down-regulated the expression of these mediators. Taken together, these results demonstrate the protective effect of GABA against damage caused by high salt intake in cisplatin-induced renal toxicity. Its mechanism may be due to the suppression of hematological and biochemical toxicity, apoptosis, and inflammation. In conclusion, although the protective efficacy of GABA salt on renal injury is different depending on the sterilization and filtration process after fermentation with L. brevis BJ20 and L. plantarum BJ21, our findings suggest that GABA-enriched salt has a beneficial effect against immoderate high salt intake-mediated kidney injury in patients with cisplatin-induced nephrotoxicity.