RESUMEN
Pathologies of the skull and teeth are well documented for many human populations, but there are fewer studies of other primates. We contrast lesion prevalence and patterning among cercopithecoid primates and map variation onto socioecological variables. We compare craniodental lesions in six species: Nasalis larvatus (n = 54), Colobus polykomos (n = 64), Cercopithecus mitis (n = 65), Macaca fascicularis (n = 109), Theropithecus gelada (n = 13), and Papio anubis (n = 76). One of us (C.A.K.) evaluated each adult skull for multiple lesion types using standard criteria. We also tested for a relationship between lesion prevalence and cranial suture fusion (age proxy). We used nonparametric tests for sex and species differences as well as pathology co-occurrence in SPSS. Socioecological data come from previous studies. Sex differences in lesion prevalence were only detected in P. anubis. Within taxa, some lesion types co-occurred. In Macaca, the presence of caries was associated with several other lesion types. Pulp cavity exposure co-occurred with TMJ osteoarthritis in multiple taxa. Among taxa, male P. anubis had higher lesion prevalences, particularly related to the anterior dentition and facial trauma. Because we did not detect a relationship between suture fusion and lesion prevalence, we propose that craniodental lesions may also be influenced by socioecological variables such as group composition and ratio of fruit to leaves in the diet. Our findings suggest that pain from pulp cavity exposure and related dental infections may alter chewing biomechanics and contribute to onset of TMJ osteoarthritis in nonhuman primates, as seen in humans. Further, we suggest that higher lesion prevalence in male baboons is likely related to male-male competition. Skeletal lesion analysis provides useful insight into primate socioecology, particularly for rare or difficult-to-observe phenomena, and provides additional biological context for our own species.
Asunto(s)
Cráneo , Animales , Masculino , Femenino , Cráneo/anatomía & histología , Enfermedades de los Monos/epidemiología , Enfermedades de los Monos/patología , Especificidad de la Especie , Prevalencia , Enfermedades Dentales/veterinaria , Enfermedades Dentales/epidemiología , Enfermedades Dentales/patología , Factores Sexuales , Suturas Craneales/anatomía & histologíaRESUMEN
Type 1 Gaucher disease (GD1) is a rare, autosomal recessive disorder caused by glucocerebrosidase deficiency. Skeletal manifestations represent one of the most debilitating and potentially irreversible complications of GD1. Although imaging studies are the gold standard, early diagnostic/prognostic tools, such as molecular biomarkers, are needed for the rapid management of skeletal complications. This study aimed to identify potential protein biomarkers capable of predicting the early diagnosis of bone skeletal complications in GD1 patients using artificial intelligence. An in silico study was performed using the novel Therapeutic Performance Mapping System methodology to construct mathematical models of GD1-associated complications at the protein level. Pathophysiological characterization was performed before modeling, and a data science strategy was applied to the predicted protein activity for each protein in the models to identify classifiers. Statistical criteria were used to prioritize the most promising candidates, and 18 candidates were identified. Among them, PDGFB, IL1R2, PTH and CCL3 (MIP-1α) were highlighted due to their ease of measurement in blood. This study proposes a validated novel tool to discover new protein biomarkers to support clinician decision-making in an area where medical needs have not yet been met. However, confirming the results using in vitro and/or in vivo studies is necessary.
Asunto(s)
Biomarcadores , Quimiocina CCL3 , Enfermedad de Gaucher , Aprendizaje Automático , Enfermedad de Gaucher/metabolismo , Enfermedad de Gaucher/diagnóstico , Enfermedad de Gaucher/complicaciones , Humanos , Biomarcadores/sangre , Quimiocina CCL3/sangre , Quimiocina CCL3/metabolismo , Enfermedades Óseas/etiología , Enfermedades Óseas/diagnósticoRESUMEN
Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is one of the most important neglected diseases in Latin America. The limited use of the current nitro-derivative-based chemotherapy highlights the need for alternative drugs and the identification of their molecular targets. In this study, we investigated the trypanocidal effect of the sesquiterpene lactone dehydroleucodine (DhL) and its derivatives, focusing on the antioxidative defense of the parasites. DhL and two derivatives, at lesser extent, displayed antiproliferative effect on the parasites. This effect was blocked by the reducing agent glutathione (GSH). Treated parasites exhibited increased intracellular ROS concentration and trypanothione synthetase activity, accompanied by mitochondrial swelling. Although molecular dynamics studies predicted that GSH would not interact with DhL, 1H-NMR analysis confirmed that GSH could protect parasites by interacting with the lactone. When parasites overexpressing mitochondrial tryparedoxin peroxidase were incubated with DhL, its effect was attenuated. Overexpression of cytosolic tryparedoxin peroxidase also provided some protection against DhL. These findings suggest that DhL induces oxidative imbalance in T. cruzi, offering new insights into potential drug targets against this parasite.
Asunto(s)
Lactonas , Especies Reactivas de Oxígeno , Sesquiterpenos , Trypanosoma cruzi , Trypanosoma cruzi/efectos de los fármacos , Trypanosoma cruzi/metabolismo , Sesquiterpenos/farmacología , Lactonas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Tripanocidas/farmacología , Glutatión/metabolismo , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/parasitología , Proteínas Protozoarias/metabolismo , Animales , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Amida SintasasRESUMEN
There is scarce evidence on sociodemographic and lifestyle characteristics that may explain adherence to different dietary patterns (DPs) during pregnancy. Our aims were to identify dietary patterns in a sample of pregnant Mexican women and to describe their association with selected sociodemographic and lifestyle characteristics. This is a secondary cross-sectional analysis of 252 mothers of children that participated as controls in a hospital-based case-control study of childhood leukemia. We obtained parents' information about selected sociodemographic characteristics, as well as alcohol and tobacco consumption. We also obtained dietary information during pregnancy. We identified DPs using cluster and factor analyses and we estimated their association with characteristics of interest. We identified two DPs using cluster analysis, which we called "Prudent" and "Non healthy", as well as three DPs through factor analysis, namely "Prudent", "Processed foods and fish", and "Chicken and vegetables". Characteristics associated with greater adherence to "Prudent" patterns were maternal education, older paternal age, not smoking, and being a government employee and/or uncovered population. Likewise, the "Processed foods and fish" pattern was associated with greater maternal and paternal education, as well as those with less household overcrowding. We did not identify sociodemographic variables related to the "Chicken and Vegetables" pattern. Our results may be useful to identify target populations that may benefit from interventions aimed to improve individual dietary decisions during pregnancy.
Asunto(s)
Dieta , Estilo de Vida , Humanos , Femenino , México , Embarazo , Adulto , Estudios Transversales , Dieta/estadística & datos numéricos , Factores Socioeconómicos , Conducta Alimentaria , Factores Sociodemográficos , Estudios de Casos y Controles , Adulto Joven , Fenómenos Fisiologicos Nutricionales Maternos , Patrones DietéticosRESUMEN
Esophageal varices (EVs), a significant complication of cirrhosis, present a considerable challenge in clinical practice due to their high risk of bleeding and associated morbidity and mortality. This manuscript explores the transformative role of artificial intelligence (AI) in the management of EV, particularly in enhancing diagnostic accuracy and predicting bleeding risks. It underscores the potential of AI in offering noninvasive, efficient alternatives to traditional diagnostic methods such as esophagogastroduodenoscopy (EGD). The complexity of EV management is highlighted, necessitating a multidisciplinary approach that includes pharmacological therapy, endoscopic interventions, and, in some cases, surgical options tailored to individual patient profiles. Additionally, the paper emphasizes the importance of integrating AI into medical education and practice, preparing healthcare professionals for the evolving landscape of medical technology. It projects a future where AI significantly influences the management of gastrointestinal bleeding, improving clinical decision-making, patient outcomes, and overall healthcare efficiency. The study advocates for a patient-centered approach in healthcare, balancing the incorporation of innovative technologies with ethical principles and the diverse needs of patients to optimize treatment efficacy and enhance healthcare accessibility.
RESUMEN
Chagas disease, caused by the protozoan Trypanosoma cruzi, affects 6-7 million people worldwide. The dichloromethane extract obtained from the aerial parts of Gymnocoronis spilanthoides var subcordata showed trypanocidal activity in vitro. The fractionation of the dewaxed organic extract via column chromatography led to the isolation of three diterpenoids: ent-9α,11α-dihydroxy-15-oxo-kaur-16-en-19-oic acid or adenostemmoic acid B, (16R)-ent-11α-hydroxy-15-oxokauran-19-oic acid and ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid. These compounds showed IC50 values of 10.6, 15.9 and 4.8 µM against T. cruzi epimastigotes, respectively. When tested against amastigotes, the diterpenoids afforded IC50 values of 6.1, 19.5 and 60.6 µM, respectively. The cytotoxicity of the compounds was tested on mammalian cells using an MTT assay, resulting in CC50s of 321.8, 23.3 and 14.8 µM, respectively. The effect of adenostemmoic acid B on T. cruzi was examined at the ultrastructural level using transmission microscopy. Treatment with 20 µM for 48 h stimulated the formation of abnormal cytosolic membranous structures in the parasite. This compound also showed an anti-inflammatory effect in murine macrophages stimulated with LPS and other TLR agonists. Treatment of macrophages with adenostemmoic acid B was able to reduce TNF secretion and nitric oxide production, while increasing IL-10 production. The combination of adenostemmoic acid B with benznidazole resulted in greater inhibition of NF-kB and a decrease in nitrite concentration. The administration of adenostemmoic acid B to mice infected with trypomastigotes of T. cruzi at the dose of 1 mg/kg/day for five days produced a significant decrease in parasitemia levels and weight loss. Treatment with the association with benznidazole increased the survival time of the animals. In view of these results, adenostemmoic acid B could be considered a promising candidate for further studies in the search for new treatments for Chagas disease.
RESUMEN
While direct at-the-breast feeding is biologically optimal, Neonatal Intensive Care Unit (NICU) admission due to infant immaturity or illness often necessitates the expression and storage of parent's milk. The provision of freshly expressed (never stored) parent's own milk to preterm infants is not widely prioritized, and this article provides an exploration of NICU practices and their implications for feeding premature or ill infants with parent's own milk. In this article, we discuss the potential biological benefits of fresh parent's own milk, highlighting its dynamic components and the changes incurred during storage. Research suggests that fresh milk may offer health advantages over stored milk. The authors advocate for further research, emphasizing the need for standardized definitions. Research is needed on the biological impact of fresh milk, both short- and long-term, as well as defining and understanding healthcare economics when using fresh milk.
Asunto(s)
Recien Nacido Prematuro , Leche Humana , Lactante , Femenino , Recién Nacido , Humanos , Lactancia Materna , Unidades de Cuidado Intensivo Neonatal , PadresRESUMEN
BACKGROUND: Raw, never stored or pasteurized mother's own milk (MOM) is not always available to feed preterm infants; however, storage and pasteurization of MOM diminishes some bioactive components. It can be difficult to feed raw MOM to preterm infants due to transportation and storage of small volumes that might be pumped away from the infant, and a concern that they might harbor bacteria. However, the higher availability of bioactive components in raw MOM may provide benefits to preterm infants compared to frozen or pasteurized MOM. RESEARCH AIM: To systematically review and summarize the results of studies on feeding raw MOM versus frozen or pasteurized MOM to preterm infants born at less than 37 weeks of gestation. METHODS: Four databases were searched (Cochrane, Embase, Ovid MEDLINE, and Web of Science) for this systematic review. Of 542 studies identified, nine met inclusion criteria and were critically evaluated using the quality assessment tool for quantitative studies by the Effective Public Health Practice Project. Studies were organized using the Breastfeeding Challenges Facing Preterm Mother-Infant Dyads theoretical framework. RESULTS: Included studies evaluated the outcomes of preterm infants fed raw versus pasteurized MOM (n = 7, 77.8%) or raw versus frozen MOM (n = 2, 22.2%). Researchers found that raw MOM did not increase infant infections and may have improved health and growth outcomes for study participants. CONCLUSION: There is laboratory evidence supporting the safety and efficacy of the use of raw MOM for preterm infants. A raw MOM diet is recommended for preterm infants by professional organizations. Despite this, it may not be universally prioritized and could require purposeful implementation by each institution. Further research is needed to pursue the potential benefits of a raw MOM diet for preterm infants.
Asunto(s)
Recien Nacido Prematuro , Leche Humana , Pasteurización , Humanos , Recien Nacido Prematuro/crecimiento & desarrollo , Recién Nacido , Pasteurización/métodos , Pasteurización/normas , Femenino , Fenómenos Fisiológicos Nutricionales del Lactante , Lactancia Materna/métodos , Dieta/métodos , Dieta/normasRESUMEN
This research was designed to investigate the metabolite profiling, phenolics, and flavonoids content as well as the potential nematicidal properties of decoction (ZpDe), orange-yellow resin (ZpRe) and essential oil (ZpEO) from Argentinean medicinal plant Zuccagnia punctata Cav. Additionally, the antioxidant and antibacterial properties of ZpDe and ZpEO were determined. Metabolite profiling was obtained by an ultrahigh-resolution liquid chromatography MS analysis (UHPLC-ESI-QTOF/OT-MS-MS) and GCMS. The nematicidal activity was assayed by a standardized method against Meloidogyne incognita. The antioxidant properties were screened by four methods: (2,2-diphenyl-1-picrylhydrazyl assay (DPPH), Trolox equivalent antioxidant activity assay (TEAC), ferric-reducing antioxidant power assay (FRAP), and lipid peroxidation in erythrocytes (ILP). The antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) rules. The ZpDe, ZpRe and ZpEO displayed a strong nematicidal activity with an LC50 of 0.208, 0.017 and 0.142 mg/mL, respectively. On the other hand, the ZpDe showed a strong DPPH scavenging activity (IC50 = 28.54 µg/mL); ILP of 87.75% at 250 µg ZpDe/mL and moderated antimicrobial activity. The ZpEO showed promising activity against a panel of yeasts Candida albicans and non-albicans (ATCC and clinically isolated) with MIC values from 750 to 1500 µg/mL. The ZpDe showed a content of phenolics and flavonoid compounds of 241 mg GAE/g and 10 mg EQ/g, respectively. Fifty phenolic compounds were identified in ZpDe by ultrahigh-resolution liquid chromatography (UHPLC-PDA- Q-TOF-MS) analysis, while forty-six phenolic compounds were identified in ZpRe by UHPLC-ESI-Q-OT-MS-MS and twenty-nine in ZpEO using a GC-MS analysis, updating the knowledge on the chemical profile of this species. The results support and standardize this medicinal plant mainly as a potential environmentally friendly and sustainable bionematicide for the control of Argentinean horticultural crops including tomatoes and peppers and as a source of antimicrobial and antioxidant compounds which could be further explored and exploited for potential applications.
RESUMEN
Background: Childhood cancer is the leading cause of disease-related mortality among children aged 5-14 years in Mexico, with acute leukemia being the most common cancer among infants. Examining the overall dietary patterns allows for a comprehensive assessment of food and nutrient consumption, providing a more predictive measure of disease risk than individual foods or nutrients. This study aims to evaluate the association between maternal dietary patterns during pregnancy and the risk of acute leukemia in Mexican infants. Methods: A hospital-based case-control study was conducted, comparing 109 confirmed acute leukemia cases with 152 age-matched controls. All participants (≤24 months) were identified at hospitals in Mexico City between 2010 and 2019. Data on a posteriori dietary patterns and other relevant variables were collected through structured interviews and dietary questionnaires. Multivariate logistic regression was employed to estimate the association between maternal dietary patterns during pregnancy and the risk of acute leukemia in infants. Results: The "Balanced & Vegetable-Rich" pattern, characterized by a balanced consumption of various food groups and higher vegetable intake, exhibited a negative association with acute leukemia when compared to the "High Dairy & Cereals" Pattern (adjusted odds ratio [OR] = 0.51; 95% confidence interval [CI]: 0.29, 0.90). We observed that mothers who gave birth to girls and adhered to a healthy dietary pattern during pregnancy exhibited significantly lower odds of their children developing AL compared to those who gave birth to boys [OR = 0.32 (95% CI 0.11, 0.97)]. Our results underscore the significance of maternal nutrition as a modifiable factor in disease prevention and the importance of prenatal health education.
RESUMEN
Introduction: Maternal dietary consumption during pregnancy has been inconclusively associated with acute leukemia (AL) in infants, probably because epidemiological evidence has emerged mainly from the analysis of one-by-one nutrient, which is not a real-life scenario. Our objective was to evaluate the association between AL in Mexican children under 2 years of age and their mothers' nutrients concomitant intake during pregnancy, as well as to explore whether there are differences between girls and boys. Methods: We conducted a study of 110 cases of AL and 252 hospital-based controls in the Mexico City Metropolitan area from 2010 to 2019. We obtained information on maternal intake of 32 nutrients by a food frequency questionnaire and used weighted quantile sum regression to identify nutrient concomitant intakes. Results: We found a concomitant intake of nutrients negatively associated with AL (OR 0.17; CI95% 0.03,0.88) only among girls; and we did not find a nutrient concomitant intake positively associated with AL. Discussion: This is the first study that suggests nutrients that have been individually associated with AL are not necessarily the same in the presence of other nutrients (concomitant intake); as well as that maternal diet might reduce AL risk only in girls.
RESUMEN
Metachromatic leukodystrophy (MLD) is a rare, autosomal recessive lysosomal storage disease. Deficient activity of arylsulfatase A causes sulfatides to accumulate in cells of different tissues, including those in the central and peripheral nervous systems, leading to progressive demyelination and neurodegeneration. Although there is some association between specific arylsulfatase A alleles and disease severity, genotype-phenotype correlations are not fully understood. We aimed to identify biomarker candidates of early tissue damage in MLD using a modeling approach based on systems biology. A review of the literature was performed in an initial disease characterization step, allowing identification of pathophysiological processes involved in MLD and proteins relating to these processes. Three mathematical models were generated to simulate different stages of MLD at the molecular level: an early pro-inflammatory stage model (including only processes considered to be active in the early stages of disease), a pre-demyelination stage model (including additional processes that are active after some disease progression), and a demyelination stage model (in which all pathophysiological processes are active). The models evaluated 3457 proteins of interest, individually and by pairs through data mining techniques, applying five filters to prioritize biomarkers that could differentiate between the models. Sixteen potential biomarkers were identified, including effectors relating to mitochondrial dysfunction, remyelination, and neurodegeneration. The findings were corroborated in a gene expression data set from T lymphocytes of patients with MLD; all candidates formed combinations that were able to distinguish patients with MLD from controls, and all but one candidate distinguished late-infantile MLD from juvenile MLD as part of a combinatorial biomarker pair. In particular, pro-neuregulin-1 appeared as differential on all comparisons (patients with MLD vs controls and within clinical subtypes); casein kinase II subunit alpha was detected as a potential individual marker within clinical subtypes. These findings provide a panel of biomarker candidates suitable for experimental validation and highlight the utility of mathematical models to identify biomarker candidates of early tissue damage in MLD with a high degree of accuracy and sensitivity.
RESUMEN
Gigantomastia is a rare entity characterized by diffuse and excessive breast enlargement. It mainly occurs during puberty and pregnancy as a consequence of hormonal fluctuations. We report an unusual case of gigantomastia in a 29-year-old woman with a history of personal and familiar autoimmune phenomena. She had autoimmune thyroiditis and several positive autoantibodies, and developed 3 crises of the disease, 1 related to pregnancy (possibly hormone-mediated), and 2 unrelated to pregnancy in which an autoimmune role is raised based in clinical, histological and laboratory findings. Immunological aspects that may be involved in this presentation of the disease are discussed.
Asunto(s)
Autoinmunidad , Enfermedad de Hashimoto , Femenino , Embarazo , Humanos , Adulto , Mama/patología , Hipertrofia/patologíaRESUMEN
Since 1942, health care personnel have administered antibiotics in the United States to prevent and treat a variety of infections, including surgical site infections. Bacteria can mutate and develop resistance after frequent and repeated antibiotic exposure, thus limiting the antibiotic's effectiveness. Because antibiotic resistance can be passed from one bacterium to another, antibiotics are the only class of medications where use in one patient may negatively affect clinical outcomes in another. Antibiotic stewardship (AS) focuses on appropriate antibiotic selection, dosing, route, and duration of therapy; it seeks to minimize unplanned consequences, such as resistance and toxicity. Although there is a lack of literature on AS specific to perioperative nurses, general nursing practice includes AS activities (eg, assessing patient allergies, adhering to antibiotic administration recommendations). Perioperative nurses should participate in AS activities and use evidence-based strategies to communicate effectively with health care team members when advocating for appropriate antibiotic use.
Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos , Enfermeras y Enfermeros , Humanos , Antibacterianos/uso terapéutico , Farmacorresistencia Microbiana , Personal de SaludRESUMEN
Stevia species (Asteraceae) have been a rich source of terpenoid compounds, mainly sesquiterpene lactones, several of which show antiprotozoal activity. In the search for new trypanocidal compounds, S. satureiifolia var. satureiifolia and S. alpina were studied. Two sesquiterpene lactones, santhemoidin C and 2-oxo-8-deoxyligustrin, respectively, were isolated. These compounds were assessed in vitro against Trypanosoma cruzi stages, showing IC50 values of 11.80 and 4.98 on epimastigotes, 56.08 and 26.19 on trypomastigotes and 4.88 and 20.20 µM on amastigotes, respectively. Cytotoxicity was evaluated on Vero cells by the MTT assay. The effect of the compounds on trypanothyone reductase (TcTR), Trans-sialidase (TcTS) and the prolyl oligopeptidase of 80 kDa (Tc80) as potential molecular targets of T. cruzi was investigated. Santhemoidin C inhibited oligopeptidase activity when tested against recombinant Tc80 using a fluorometric assay, reaching an IC50 of 34.9 µM. Molecular docking was performed to study the interaction between santhemoidin C and the Tc80 protein, reaching high docking energy levels. Plasma membrane shedding and cytoplasmic vacuoles, resembling autophagosomes, were detected by transmission microscopy in parasites treated with santhemoidin C. Based on these results, santhemoidin C represents a promising candidate for further studies in the search for new molecules for the development of trypanocidal drugs.
RESUMEN
Azara dentata Ruiz & Pav. is a small Chilean native plant from Patagonia, a producer of small white reddish berries. For the first time, the proximal analysis of the fruits, phenolic fingerprinting, the antioxidant activity, and the enzymatic inhibition and relaxation effects in rat aorta induced by the ethanolic extract of these fruits were investigated. The proximal composition and the mineral (Ca: 2434 ± 40 mg/kg; Mg: 702 ± 13 mg/kg; Fe: 117.1 ± 1.6 mg/kg; Zn: 16.1 ± 0.4 mg/kg) and heavy metal (As: 121 ± 11 µg/kg; Cd: 152 ± 5 µg/kg; Hg: 7.7 ± 1.3 µg/kg; Pb 294 ± 4 µg/kg) contents were analyzed. Anthocyanins, flavonoids, phenolic acids, and coumarins were identified using UHPLC-PDA-QTOF-MS. The ethanolic extracts showed a total phenolic content of 23.50 ± 0.93 mg GAE/g extract. In addition, the antioxidant activity was assessed using both DPPH and TEAC (28.64 ± 1.87 and 34.72 ± 2.33 mg Trolox/g of dry fruit, respectively), FRAP (25.32 ± 0.23 mg Trolox equivalent/g dry fruit), and ORAC (64.95 ± 1.23 mg Trolox equivalents/g dry fruit). The inhibition of enzymatic activities (acetylcholinesterase IC50: 2.87 + 0.23 µg extract/mL, butyrylcholinesterase IC50: 6.73 + 0.07 µg extract/mL, amylase IC50: 5.6 ± 0.0 µg extract/mL, lipase IC50: 30.8 ± 0.0 µg extract/mL, and tyrosinase IC50: 9.25 ± 0.15 µg extract/mL) was also assessed. The extract showed 50-60% relaxation in rat aorta (intact), mediated thorough the release of endothelial nitric oxide. Our results suggest that A. dentata is a good source of compounds with the capacity to inhibit important enzymes, can be hypotensive, and can thus have good potentiality as supplements in the amelioration of neurodegenerative diseases and could also have potential to be used to develop new functional foods. The study highlights the benefits of these neglected small fruits and could boost their consumption.
RESUMEN
BACKGROUND: Chronic spontaneous urticaria (CSU) is a rare, heterogeneous, severely debilitating, and often poorly controlled skin disease resulting in an itchy eruption that can be persistent. Antihistamines and omalizumab, an anti-IgE mAb, are the only licensed therapies. Although CSU pathogenesis is not yet fully understood, mast cell activation through the IgE:high-affinity IgE receptor (FcεRI) axis appears central to the disease process. OBJECTIVE: We sought to model CSU pathophysiology and identify in silico the mechanism of action of different CSU therapeutic strategies currently in use or under development. METHODS: Therapeutic performance mapping system technology, based on systems biology and machine learning, was used to create a CSU interactome validated with gene expression data from patients with CSU and a CSU model that was used to evaluate CSU pathophysiology and the mechanism of action of different therapeutic strategies. RESULTS: Our models reflect the known role of mast cell activation as a central process of CSU pathophysiology, as well as recognized roles for different therapeutic strategies in this and other innate and adaptive immune processes. They also allow determining similarities and differences between them; anti-IgE and Bruton tyrosine kinase inhibitors play a more direct role in mast cell biology through abrogation of FcεRI signaling activity, whereas anti-interleukins and anti-Siglec-8 have a role in adaptive immunity modulation. CONCLUSION: In silico CSU models reproduced known CSU and therapeutic strategies features. Our results could help advance understanding of therapeutic mechanisms of action and further advance treatment research by patient profile.
Asunto(s)
Antialérgicos , Urticaria Crónica , Urticaria , Humanos , Inmunoglobulina E , Urticaria/tratamiento farmacológico , Urticaria/genética , Biología de Sistemas , Urticaria Crónica/tratamiento farmacológico , Receptores de IgE , Omalizumab/uso terapéutico , Inmunosupresores/uso terapéutico , Enfermedad Crónica , Antialérgicos/farmacología , Antialérgicos/uso terapéuticoRESUMEN
Objetivo: Evaluar el efecto de la ivermectina sobre Demodex folliculorum in vitro. Materiales y métodos: Bajo microscopio de luz se evaluó el movimiento y anatomía de los parásitos durante 90 minutos. En una lámina portaobjetos no se aplicó nada y sirvió como control. En las otras láminas se aplicó ivermectina al 0.6 y 1%, respectivamente. Resultados: Los parásitos en la placa de control no presentaron cambios en su movilidad ni en su estructura anatómica. Los parásitos a los que se les aplicó ivermectina en concentraciones de 0.6% presentaron alteraciones de movilidad y estructura después del minuto 30 y aquellos sometidos a la concentración al 1% presentaron alteraciones de movilidad y estructura después del minuto 15. Conclusiones: Nuestro estudio demuestra que la ivermectina al 0.6 y 1% afecta la estructura y función de Demodex folliculorum in vitro.
Objective: To evaluate the effect of Ivermectin on Demodex folliculorum in vitro. Materials and methods: Under a light microscope, the movement and anatomy of parasites was evaluated during 90 minutes. On one plate nothing was applied and served as a control. In the other two plates, ivermectin was applied at 0.6% and 1%, respectively. Results: The parasites on the control plate showed no changes in their mobility or anatomical structure. The parasites to which ivermectin was applied in concentrations of 0.6% presented alterations of mobility and structure after the 30th minute and those subjected to the 1% concentration presented alterations of mobility and structure after the 15th minute. Conclusions: Our study shows that ivermectin at 0.6 and 1% affects the structure and function of Demodex folliculorum in vitro.
Asunto(s)
HumanosRESUMEN
Recently, we reported the chemical profile and the hypocholesterolemic effects of a decoction of Tessaria absinthioides (Hook. & Arn.) DC. (Asteraceae). In this study, we evaluated a methanolic extract (METa) instead. Metabolite profiling was conducted using ultra-high-resolution liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS), identifying thirty compounds, including flavonoids, phenolic acids, fatty acids, and phorbolesters. Antioxidant properties were assessed through 2,2-diphenyl-1-picrylhydrazyl (DPPH), Trolox equivalent antioxidant activity (TEAC), ferric-reducing antioxidant power (FRAP), and inhibition of lipid peroxidation in erythrocytes (ILP) assays, exhibiting robust antioxidant activity. The in vivo impact of METa on serum lipid parameters and liver X receptors (LXRs) was evaluated in a hypercholesterolemic animal model. After 14 days on a high-fat diet, male rats received either a vehicle (V) or METa100, METa200 or METa500 (100; 200 and 500 mg METa/kg animal, respectively) for an additional two weeks. METa500 reduced total cholesterol levels (17.62%; p < 0.05) and all doses increased high-density lipoprotein cholesterol levels (METa100: 86.27%; METa200: 48.37%, and METa500: 29.42%; p < 0.0001). However, METa did not alter LXRs expression. The observed antioxidant and hypocholesterolemic properties of METa may be linked to the presence of six di-caffeoylquinic acids. These findings underscore T. absinthioides as a potential candidate for the treatment of metabolic disease.
RESUMEN
NK cells have unique attributes to react towards cells undergoing malignant transformation or viral infection. This reactivity is regulated by activating or inhibitory germline encoded receptors. An impaired NK cell function may result from an aberrant expression of such receptors, a condition often seen in patients with hematological cancers. Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer worldwide and NK cells have emerged as crucial targets for developing immunotherapies. However, there are important gaps concerning the phenotype and behavior of NK cells during emergence of ALL. In this study we analyze the phenotype and function of NK cells from peripheral blood in pediatric patients with ALL at diagnosis. Our results showed that NK cells exhibited an altered phenotype highlighted by a significant reduction in the overall expression and percent representation of activating receptors compared to age-matched controls. No significant differences were found for the expression of inhibitory receptors. Moreover, NK cells with a concurrent reduced expression in various activating receptors, was the dominant phenotype among patients. An alteration in the relative frequencies of NK cells expressing NKG2A and CD57 within the mature NK cell pool was also observed. In addition, NK cells from patients displayed a significant reduction in the ability to sustain antibody-dependent cellular cytotoxicity (ADCC). Finally, an aberrant expression of activating receptors is associated with the phenomenon of leukemia during childhood.