ABSTRACT
Human biomonitoring of toxic and essential trace elements is critically important for public health protection. Amazonian riverine communities exhibit distinctive dietary patterns, heavily reliant on locally sourced fish, fruits, and vegetables. These habits may result in unique exposure profiles compared to urban populations. However, comprehensive assessments of their exposure to toxic and essential metals are lacking, representing a critical gap in understanding the health risks faced by these communities. This study aimed to establish baseline levels of 21 metals and metalloids in human blood and explore the influence of sociodemographic factors, dietary habits, and lifestyle choices as potential sources of exposure to these elements. A cross-sectional biomonitoring investigation was conducted with 1,024 individuals from 13 communities in the Tapajós and Amazon Basins (Pará, Brazil). Most of the elements in study was determined for the first time in the region. Blood samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). The levels of all elements were summarized by quantiles and compared with cutoff values from other Brazilian populations. Multiple linear regression was used to assess possible associations between element concentrations and sociodemographic characteristics, dietary habits, and lifestyle choices. High detection rates (64% to 100%) were observed, indicating the widespread presence of these elements. Elevated blood concentrations were found for mercury (median 21.1 µg.L-1, interquartile range: 12-34µg.L-1), selenium (median 166 µg.L-1, interquartile range: 137-208 µg.L-1), and lead (median 34µg.L-1, interquartile range: 20.8-64 µg.L-1). Regression analysis revealed a positive association between mercury levels and fish consumption, while manioc flour intake showed no relationship to lead levels. In conclusion, our findings emphasize the need for continued monitoring and public policy development for these vulnerable populations. Further studies should assess long-term trends and investigate the health implications of prolonged exposure to diverse chemicals in Amazonian riverside communities.
ABSTRACT
l-asparaginases play a crucial role in the treatment of acute lymphoblastic leukemia (ALL), a type of cancer that mostly affects children and teenagers. However, it is common for these molecules to cause adverse reactions during treatment. These downsides ignite the search for novel asparaginases to mitigate these problems. Thus, this work aimed to produce and characterize a recombinant asparaginase from Phaseolus vulgaris (Asp-P). In this study, Asp-P was expressed in Escherichia coli with high yields and optimum activity at 40 °C, pH 9.0. The enzyme Km and Vmax values were 7.05 mM and 1027 U/mg, respectively. Asp-P is specific for l-asparagine, showing no activity against l-glutamine and other amino acids. The enzyme showed a higher cytotoxic effect against Raji than K562 cell lines, but only at high concentrations. In silico analysis indicated that Asp-P has lower immunogenicity than a commercial enzyme. Asp-P induced biofilm formation by Candida sp. due to sublethal dose, showing an underexplored potential of asparaginases. The absence of glutaminase activity, lower immunogenicity and optimal activity similar to physiological temperature conditions are characteristics that indicate Asp-P as a potential new commercial enzyme in the treatment of ALL and its underexplored application in the treatment of other diseases.
Subject(s)
Asparaginase , Phaseolus , Recombinant Proteins , Asparaginase/chemistry , Asparaginase/pharmacology , Asparaginase/genetics , Asparaginase/immunology , Phaseolus/chemistry , Humans , Kinetics , Recombinant Proteins/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Leukemia/drug therapy , K562 Cells , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Biofilms/drug effects , Hydrogen-Ion Concentration , TemperatureABSTRACT
BACKGROUND: The Covid-19 pandemic has caused immense pressure on Intensive Care Units (ICU). In patients with severe ARDS due to Covid-19, respiratory mechanics are important for determining the severity of lung damage. Lung auscultation could not be used during the pandemic despite its merit. The main objective of this study was to investigate associations between lung auscultatory sound features and lung mechanical properties, length of stay (LOS) and survival, in adults with severe Covid-19 ARDS. METHODS: Consecutive patients admitted to a large ICU between 2020 and 2021 (n = 173) were included. Digital stethoscopes obtained auscultatory sounds and stored them in an on-line database for replay and further processing using advanced AI techniques. Correlation and regression analysis explored relationships between digital auscultation findings and lung mechanics or the ICU outcome. The resulting annotated lung sounds database is also publicly available as supplementary material. RESULTS: The presence of squawks was associated with the ICU LOS, outcome and 90-day mortality. Other features (age, SOFA score & oxygenation index upon admission, minimum crackle entropy) had significant impact on outcome. Additional features affecting the 90-d survival were age and mean crackle entropy. Multivariate logistic regression showed that survival was affected by age, baseline SOFA, baseline oxygenation index and minimum crackle entropy. CONCLUSIONS: Respiratory mechanics were associated with various adventitious sounds, whereas the lung sound analytics and the presence of certain adventitious sounds correlated with the ICU outcome and the 90-d survival. Spectral features of crackles sounds can serve as prognostic factors for survival, highlighting the importance of digital auscultation.
ABSTRACT
Mercury is a naturally occurring metal found in various inorganic and organic forms within the environment. Due to its high toxicity, there is global concern regarding human exposure to this element. The combination of high-performance liquid chromatography and inductively coupled plasma mass spectrometry (HPLC-ICP-MS) is commonly used to analyze the different forms of mercury in a sample due to its high sensitivity and ability to selectively detect mercury. However, the traditional HPLC-ICP-MS methods are often criticized for their lengthy analysis times. In this study, we have refined the conventional approach by transitioning to ultra-high performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (UHPLC-ICP-MS). This modification has resulted in significant reductions in runtime as well as reagent and argon usage, thereby offering a more rapid, environmentally friendly, and cost-effective method. We successfully adapted an HPLC-ICP-MS method to UHPLC-ICP-MS, achieving the analysis of Hg2+ and MeHg+ within 1 min with a mobile phase consumption of only 0.5 mL and a sample volume of 5.0 µL; this is a major advance compared to HPLC analysis with run times generally between 5 and 10 min. The method's performance was assessed by analyzing muscle and liver tissue samples (serving as reference material) from fish, demonstrating the versatility of the method in relation to different complex matrices.
ABSTRACT
Tumor cells may develop alterations in glycosylation patterns during the initial phase of carcinogenesis. These alterations may be important therapeutic targets for lectins with antitumor action. This work aimed to evaluate the in vitro cytotoxicity of VML on tumor and non-tumor cells (concentration of 25 µg/mL and then microdiluted) and evaluate its in vivo toxicity at different concentrations (1.8, 3.5 and 7.0 µg/mL), using Drosophila melanogaster. Toxicity in D. melanogaster evaluated mortality rate, as well as oxidative stress markers (TBARS, iron levels, nitric oxide levels, protein and non-protein thiols). The cytotoxicity assay showed that VML had cytotoxic effect on leukemic lines HL-60 (IC50 = 3.5 µg/mL), KG1 (IC50 = 18.6 µg/mL) and K562 (102.0 µg/mL). In the toxicity assay, VML showed no reduction in survival at concentrations of 3.5 and 7.0 µg/mL and did not alter oxidative stress markers at any concentrations tested. Cytotoxicity of VML from HL-60, KG1 and K562 cells could arise from the interaction between the lectin and specific carbohydrates of tumor cells. In contrast, effective concentrations of VML against no-tumor cells human keratinocyte - HaCat and in the D. melanogaster model did not show toxicity, suggesting that VML is a promising molecule in vivo studies involving leukemic cells.
Subject(s)
Drosophila melanogaster , Lectins , Animals , Humans , Cell Line, Tumor , Cell Proliferation/drug effects , Drosophila melanogaster/drug effects , HL-60 Cells , Lectins/pharmacology , Lectins/toxicity , Oxidative Stress/drug effectsABSTRACT
Optimizing early breast cancer (BC) detection requires effective risk assessment tools. This retrospective study from Brazil showcases the efficacy of machine learning in discerning complex patterns within routine blood tests, presenting a globally accessible and cost-effective approach for risk evaluation. We analyzed complete blood count (CBC) tests from 396,848 women aged 40-70, who underwent breast imaging or biopsies within six months after their CBC test. Of these, 2861 (0.72%) were identified as cases: 1882 with BC confirmed by anatomopathological tests, and 979 with highly suspicious imaging (BI-RADS 5). The remaining 393,987 participants (99.28%), with BI-RADS 1 or 2 results, were classified as controls. The database was divided into modeling (including training and validation) and testing sets based on diagnostic certainty. The testing set comprised cases confirmed by anatomopathology and controls cancer-free for 4.5-6.5 years post-CBC. Our ridge regression model, incorporating neutrophil-lymphocyte ratio, red blood cells, and age, achieved an AUC of 0.64 (95% CI 0.64-0.65). We also demonstrate that these results are slightly better than those from a boosting machine learning model, LightGBM, plus having the benefit of being fully interpretable. Using the probabilistic output from this model, we divided the study population into four risk groups: high, moderate, average, and low risk, which obtained relative ratios of BC of 1.99, 1.32, 1.02, and 0.42, respectively. The aim of this stratification was to streamline prioritization, potentially improving the early detection of breast cancer, particularly in resource-limited environments. As a risk stratification tool, this model offers the potential for personalized breast cancer screening by prioritizing women based on their individual risk, thereby indicating a shift from a broad population strategy.
Subject(s)
Breast Neoplasms , Machine Learning , Humans , Breast Neoplasms/blood , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Female , Middle Aged , Retrospective Studies , Adult , Aged , Blood Cell Count/methods , Risk Assessment/methods , Early Detection of Cancer/methods , Brazil/epidemiologyABSTRACT
Congenital heart disease (CHD) affects eight to ten out of every 1,000 births, resulting in approximately 23,057 new cases in Brazil in 2022. About one in four children with CHD requires surgery or other procedures in the first year of life, and it is expected that approximately 81% of these children with CHD will survive until at least 35 years of age. Professionals choosing to specialize in CHD surgery face numerous challenges, not only related to mastering surgical techniques and the complexity of the diseases but also to the lack of recognition by medical societies as a separate subspecialty. Furthermore, families face difficulties when access to services capable of providing treatment for these children. To address these challenges, it is essential to have specialized hospitals, qualified professionals, updated technologies, sustainable industry, appropriate financing, quality assessment systems, and knowledge generation. The path to excellence involves specialization across all involved parties. As we reflect on the importance of Pediatric Cardiovascular Surgery and Congenital Heart Diseases establishing themselves as a subspecialty of Cardiovascular Surgery, it is essential to look beyond our borders to countries like the United States of America and United Kingdom, where this evolution is already a reality. This autonomy has led to significant advancements in research, education, and patient care outcomes, establishing a care model. By following this path in Brazil, we not only align our practice with the highest international standards but also demonstrate our maturity and the ability to meet the specific needs of patients with CHD and those with acquired childhood heart disease.
Subject(s)
Heart Defects, Congenital , Humans , Brazil , Heart Defects, Congenital/surgery , Cardiac Surgical Procedures , Child , Specialties, Surgical/organization & administrationABSTRACT
Impaired respiratory variation of right atrial pressure (RAP) in severe pulmonary hypertension (PH) suggests difficulty tolerating increased preload during inspiration. Our study explores whether this impairment links to specific factors: right ventricular (RV) diastolic function, elevated RV afterload, systolic RV function, or RV-pulmonary arterial (PA) coupling. We retrospectively evaluated respiratory RAP variation in all participants enrolled in the EXERTION study. Impaired respiratory variation was defined as end-expiratory RAP - end-inspiratory RAP ≤ 2 mm Hg. RV function and afterload were evaluated using conductance catheterization. Impaired diastolic RV function was defined as end-diastolic elastance (Eed) ≥ median (0.19 mm Hg/mL). Seventy-five patients were included; PH was diagnosed in 57 patients and invasively excluded in 18 patients. Of the 75 patients, 31 (41%) had impaired RAP variation, which was linked with impaired RV systolic function and RV-PA coupling and increased tricuspid regurgitation and Eed as compared to patients with preserved RAP variation. In backward regression, RAP variation associated only with Eed. RAP variation but not simple RAP identified impaired diastolic RV function (area under the receiver operating characteristic curve [95% confidence interval]: 0.712 [0.592, 0.832] and 0.496 [0.358, 0.634], respectively). During exercise, patients with impaired RAP variation experienced greater RV dilatation and reduced diastolic reserve and cardiac output/index compared with patients with preserved RAP variation. Preserved RAP variation was associated with a better prognosis than impaired RAP variation based on the 2022 European Society of Cardiology/European Respiratory Society risk score (chi-square P = 0.025) and survival free from clinical worsening (91% vs 71% at 1 year and 79% vs 50% at 2 years [log-rank P = 0.020]; hazard ratio: 0.397 [95% confidence interval: 0.178, 0.884]). Subgroup analyses in patients with group 1 and group 4 PH demonstrated consistent findings with those observed in the overall study cohort. Respiratory RAP variations reflect RV diastolic function, are independent of RV-PA coupling or tricuspid regurgitation, are associated with exercise-induced haemodynamic changes, and are prognostic in PH.Trial registration. NCT04663217.
Subject(s)
Atrial Pressure , Hypertension, Pulmonary , Aged , Female , Humans , Male , Middle Aged , Hypertension, Pulmonary/physiopathology , Retrospective Studies , Ventricular Function, Right/physiologyABSTRACT
AIMS: Hepatic T1-time derived from cardiac magnetic resonance imaging (cMRI) reflects venous congestion and may provide a simple alternative to invasive end-diastolic elastance (Eed) for assessment of right ventricular (RV) diastolic function. We investigated the association of native hepatic T1-time with single-beat Eed and the value of hepatic T1-time for longitudinal monitoring in pulmonary hypertension (PH). METHODS AND RESULTS: We retrospectively enrolled 85 patients with suspected PH (59% female; 78 with PH diagnosed; 7 with PH excluded) who underwent standard right heart catheterization and cMRI within 24 h between 2015 and 2020. Hepatic T1-time showed moderate to strong correlations (rho >0.3, P ≤ 0.002) with pulmonary vascular resistance, native myocardial T1-time, Eed, RV size and function, brain natriuretic peptide (BNP) level, and 6-min walk distance, and a significant association with functional class (Kruskal-Wallis P < 0.001). Eed, myocardial T1-time, and BNP were independently linked to hepatic T1-time in multivariable regression. Hepatic T1-time > 598 ms predicted elevated Eed with 72.9% sensitivity and 82.1% specificity. Hepatic T1-time was superior to Eed in predicting clinical worsening. In 16 patients with follow-up assessments, those with decreasing hepatic T1-time (7 patients) showed significant hemodynamic improvements, whereas those with increasing hepatic T1-time (9 patients) did not. In a second retrospective cohort of 27 patients with chronic thromboembolic PH undergoing balloon pulmonary angioplasty, hepatic T1-time decreased significantly and hemodynamics improved after the procedure. CONCLUSIONS: Hepatic T1-time predicts RV diastolic dysfunction and prognosis, and may be useful for monitoring disease progression and treatment response in PH.
Subject(s)
Disease Progression , Hypertension, Pulmonary , Humans , Female , Male , Retrospective Studies , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/therapy , Middle Aged , Predictive Value of Tests , Magnetic Resonance Imaging, Cine/methods , Ventricular Dysfunction, Right/physiopathology , Ventricular Dysfunction, Right/diagnostic imaging , Aged , Adult , Liver/diagnostic imaging , Liver/physiopathology , Treatment Outcome , DiastoleABSTRACT
In Brazil, the favorable weather conditions and abundant land contribute to the thriving agricultural production. Brazilian crops extensively employ pesticides due to their high efficacy, cost-effectiveness, and permissive regulatory framework. However, pesticide use also endangers water resources, animal organisms, and human health. Due to the lack of data on pesticide use in the Amazonas forest-based Brazil, the present study aimed to assess the levels of twenty-one current-use pesticides (CUPs) from five different classes in river waters collected from urban and riverside areas in this region. Moreover, the non-carcinogenic risks associated with water consumption were also characterized. Thirteen CUPs were detected in concentrations above the limit of detection (LOD) in at least one of the water samples, and most pesticides were detected in riverside areas. In contrast, only 18% of the analyzed samples were considered "clean," with only one compound detected. Fenitrothion showed the highest concentration, with a mean value of 4.86 ng/mL (0.30-14.3 ng/mL). Up to 33% of the samples showed levels of fipronil above the LOD, an issue of environmental and human health concern, mainly because of the adverse effects observed in honeybees. Despite this, the human health risk assessment showed a target hazard quotient below one (HQ < 1) in adults for all substances, suggesting that pesticide exposure through water consumption should not mean risk for the riverside populations. Taking into account the large extension of Brazil, as well as its different agricultural practices throughout the country, it would be of great importance to conduct extensive research in other areas. It would help to gain knowledge in this field and to promote eco-friendly alternatives to mitigate pesticide use and, consequently, to reduce their potential adverse effects on human health and the ecosystems.
Subject(s)
Environmental Monitoring , Pesticides , Rivers , Water Pollutants, Chemical , Brazil , Risk Assessment , Pesticides/analysis , Water Pollutants, Chemical/analysis , Rivers/chemistry , Humans , Environmental Monitoring/methods , CitiesABSTRACT
Three-dimensional (3D) echocardiography-derived right ventricular (RV) ejection fraction (EF) and global longitudinal strain (GLS) are valuable RV functional markers; nevertheless, they are substantially load-dependent. Global myocardial work index (GMWI) is a novel parameter calculated by the area of the RV pressure-strain loop. By adjusting myocardial deformation to instantaneous pressure, it may reflect contractility. To test this hypothesis, we enrolled 60 patients who underwent RV pressure-conductance catheterization to determine load-independent markers of RV contractility and ventriculo-arterial coupling. Detailed 3D echocardiography was also performed, and we calculated RV EF, RV GLS, and using the RV pressure trace curve, RV GWMI. While neither RV EF nor GLS correlated with Ees, GMWI strongly correlated with Ees. In contrast, RV EF and GLS showed a relationship with Ees/Ea. By dividing the population based on their Reveal Lite 2 risk classification, different characteristics were seen among the subgroups. RV GMWI may emerge as a useful clinical tool for risk stratification and follow-up in patients with RV dysfunction.
Subject(s)
Echocardiography, Three-Dimensional , Myocardial Contraction , Stroke Volume , Ventricular Function, Right , Humans , Male , Female , Myocardial Contraction/physiology , Middle Aged , Ventricular Function, Right/physiology , Echocardiography, Three-Dimensional/methods , Stroke Volume/physiology , Ventricular Dysfunction, Right/physiopathology , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Pressure/physiology , Heart Ventricles/physiopathology , Heart Ventricles/diagnostic imaging , Cardiac Catheterization , Aged , AdultABSTRACT
Recently, a classification with four types of septal longitudinal strain patterns was described using echocardiography, suggesting a pathophysiological continuum of left bundle branch block (LBBB)-induced left ventricle (LV) remodeling. The aim of this study was to assess the feasibility of classifying these strain patterns using cardiovascular magnetic resonance (CMR), and to evaluate their association with LV remodeling and myocardial scar. Single center registry included LBBB patients with septal flash (SF) referred to CMR to assess the cause of LV systolic dysfunction. Semi-automated feature-tracking cardiac resonance (FT-CMR) was used to quantify myocardial strain and detect the four strain patterns. A total of 115 patients were studied (age 66 ± 11 years, 57% men, 28% with ischemic heart disease). In longitudinal strain analysis, 23 patients (20%) were classified in stage LBBB-1, 37 (32.1%) in LBBB-2, 25 (21.7%) in LBBB-3, and 30 (26%) in LBBB-4. Patients at higher stages had more prominent septal flash, higher LV volumes, lower LV ejection fraction, and lower absolute strain values (p < 0.05 for all). Late gadolinium enhancement (LGE) was found in 55% of the patients (n = 63). No differences were found between the strain patterns regarding the presence, distribution or location of LGE. Among patients with LBBB, there was a good association between strain patterns assessed by FT-CMR analysis and the degree of LV remodeling and LV dysfunction. This association seems to be independent from the presence and distribution of LGE.
Subject(s)
Bundle-Branch Block , Feasibility Studies , Magnetic Resonance Imaging, Cine , Predictive Value of Tests , Registries , Ventricular Function, Left , Ventricular Remodeling , Humans , Male , Female , Bundle-Branch Block/physiopathology , Bundle-Branch Block/diagnostic imaging , Aged , Middle Aged , Myocardial Contraction , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/diagnostic imaging , Stroke Volume , Reproducibility of Results , Biomechanical Phenomena , Image Interpretation, Computer-Assisted , Fibrosis , Retrospective StudiesABSTRACT
BACKGROUND: Pulmonary hypertension (PH) can lead to congestive hepatopathy, known as cardiohepatic syndrome (CHS). Hepatic congestion is associated with increased liver stiffness, which can be quantified using shear wave elastography. We aimed to investigate whether hepatic shear wave elastography detects patients at risk in the early stages of PH. METHODS: Sixty-three prospectively enrolled patients undergoing right heart catheterization (52 diagnosed with PH and 11 with invasive exclusion of PH) and 52 healthy volunteers underwent assessments including echocardiography and hepatic shear wave elastography. CHS was defined as increased levels of ≥2 of the following: gamma-glutamyl transferase, alkaline phosphatase, and bilirubin. Liver stiffness was defined as normal (≤5.0 kPa) or high (>5.0 kPa). RESULTS: Compared with normal liver stiffness, high liver stiffness was associated with impaired right ventricular (RV) and right atrial (RA) function (median [interquartile range] RV ejection fraction: 54 [49; 57]% vs 45 [34; 51]%, p < 0.001; RA reservoir strain: 49 [41; 54]% vs 33 [22; 41]%, p < 0.001), more severe tricuspid insufficiency (p < 0.001), and higher prevalence of hepatovenous backflow (2% vs 29%, p < 0.001) and CHS (2% vs 10%, p = 0.038). In the patient subgroup with precapillary PH (n = 48), CHS and high liver stiffness were associated with increased European Society of Cardiology/European Respiratory Society 2022 risk scores (p = 0.003). CONCLUSIONS: Shear wave liver elastography yields important information regarding right heart function and may complement risk assessment in patients with (suspected) PH.
Subject(s)
Elasticity Imaging Techniques , Hypertension, Pulmonary , Liver , Ventricular Dysfunction, Right , Humans , Female , Male , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/etiology , Middle Aged , Elasticity Imaging Techniques/methods , Prospective Studies , Prognosis , Ventricular Dysfunction, Right/physiopathology , Ventricular Dysfunction, Right/etiology , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Dysfunction, Right/diagnosis , Liver/diagnostic imaging , Liver/physiopathology , Syndrome , Cardiac Catheterization , Adult , Liver Diseases/physiopathology , Liver Diseases/complications , EchocardiographyABSTRACT
Background: Leishmaniasis, caused by the protozoan Leishmania sp., infects phagocyte cells present in lymphatic organs. This study demonstrates the influence of nanostructured lipid carrier-loaded hydroxymethylnitrofurazone (NLC-NFOH) on lymphatic uptake using a chylomicron-blocking flow model in rats. Method: Lymphatic uptake of NFOH was assessed 1 h after oral administration of dimethyl sulfoxide with NFOH or NLC-NFOH with and without cycloheximide pretreatment. Result: Dimethyl sulfoxide with NFOH and NLC-NFOH showed NFOH serum concentrations of 0.0316 and 0.0291 µg/ml, respectively. After chylomicron blocking, NFOH was not detected. Conclusion: Despite log P below 5, NFOH was successfully taken up by the lymphatic system. Long-chain fatty acids and particle size might be main factors in these findings. NLC-NFOH is a promising and convenient platform for treating leishmaniasis via oral administration.
Subject(s)
Leishmaniasis , Nanostructures , Nitrofurazone/analogs & derivatives , Rats , Animals , Dimethyl Sulfoxide , Chylomicrons , Administration, Oral , Drug Carriers , Particle SizeABSTRACT
Galectins, which correspond to a group of proteins capable of recognizing and reversibly binding to ß-galactoside carbohydrates, have been the subject of innovation and development of technological products. Galectins play biological roles, such as cell proliferation and apoptosis, and some studies showed differences in the concentrations of galectins dispersed in serum of patients with cancer. For this reason, different studies have evaluated the biotechnological potential of these proteins as biomarkers for the prognosis and/or diagnosis of physiological disorders. Thus, this review discusses recent technological advancements in targeting galectins for the treatment of cancer and using galectins for cancer prognosis and diagnosis. Data mining was performed using the search descriptors "Galectin 9* and cancer*" and the ESPACENET and Cortellis Drug Discovery Intelligence (CDDI) databases. PRISMA guidelines were followed as a basis for literature review which aimed to conduct a systematic study of galectin-9 patents related to cancer prognosis, diagnosis and treatment. Results showed the importance of galectin-9 protein patents in furthering biomedical advancements in the global fight against cancer.
Subject(s)
Galectins , Neoplasms , Humans , Galectins/metabolism , Neoplasms/diagnosis , Neoplasms/drug therapy , CarbohydratesABSTRACT
INTRODUCTION: Trypsin inhibitors (TIs) have the ability to competitively or non-competitively bind to trypsin and inhibit its action. These inhibitors are commonly found in plants and are used in protease inhibition studies involved in biochemical pathways of pharmacological interest. OBJECTIVES: This work aimed to purify a trypsin inhibitor from Bauhinia pulchella seeds (BpuTI), describing its kinetic mechanism and anticoagulant effect. METHODS: Affinity chromatography, protein assay, and SDS-PAGE were used to purify the inhibitor. Mass spectrometry, inhibition assays, and enzyme kinetics were used to characterize the inhibitor. In vitro assays were performed to verify its ability to prolong blood clotting time. RESULTS: Affinity chromatography on a Trypsin-Sepharose 4B column gave a yield of 43.1. BpuTI has an apparent molecular mass of 20 kDa with glycosylation (1.15%). Protein identification was determined by MS/MS, and BpuTI showed similarity to several Kunitz-type trypsin inhibitors. BpuTI inhibited bovine trypsin as an uncompetitive inhibitor with IC50 (3 x 10-6 M) and Ki (1.05 x 10-6 M). Additionally, BpuTI showed high stability to temperature and pH variations, maintaining its activity up to 100ºC and in extreme pH ranges. However, the inhibitor was susceptible to reducing agents, such as DTT, which completely abolished its activity. BpuTI showed an anticoagulant effect in vitro at a concentration of 33 µM, prolonging clotting time by 2.6 times. CONCLUSION: Our results suggest that BpuTI can be a biological tool to be used in blood clotting studies.
Subject(s)
Bauhinia , Trypsin Inhibitors , Animals , Cattle , Trypsin Inhibitors/pharmacology , Trypsin Inhibitors/chemistry , Bauhinia/metabolism , Trypsin/analysis , Trypsin/chemistry , Trypsin/metabolism , Tandem Mass Spectrometry , Seeds/chemistry , Anticoagulants/pharmacology , Anticoagulants/analysis , Anticoagulants/chemistryABSTRACT
ABSTRACT Congenital heart disease (CHD) affects eight to ten out of every 1,000 births, resulting in approximately 23,057 new cases in Brazil in 2022. About one in four children with CHD requires surgery or other procedures in the first year of life, and it is expected that approximately 81% of these children with CHD will survive until at least 35 years of age. Professionals choosing to specialize in CHD surgery face numerous challenges, not only related to mastering surgical techniques and the complexity of the diseases but also to the lack of recognition by medical societies as a separate subspecialty. Furthermore, families face difficulties when access to services capable of providing treatment for these children. To address these challenges, it is essential to have specialized hospitals, qualified professionals, updated technologies, sustainable industry, appropriate financing, quality assessment systems, and knowledge generation. The path to excellence involves specialization across all involved parties. As we reflect on the importance of Pediatric Cardiovascular Surgery and Congenital Heart Diseases establishing themselves as a subspecialty of Cardiovascular Surgery, it is essential to look beyond our borders to countries like the United States of America and United Kingdom, where this evolution is already a reality. This autonomy has led to significant advancements in research, education, and patient care outcomes, establishing a care model. By following this path in Brazil, we not only align our practice with the highest international standards but also demonstrate our maturity and the ability to meet the specific needs of patients with CHD and those with acquired childhood heart disease.
ABSTRACT
There is growing concern about the relationship between screen use by young children and negative effects on their development, as children with developmental and socioemotional impairments tend to have difficulties in their relationships and increased academic problems. The aim of our study was to analyse the relationship between the use of multimedia devices and paediatric symptoms in children below 5 years old. Data from 534 Portuguese parents of children aged from 18 to 57 months were collected via a self-report questionnaire. Children's daily exposure to multimedia devices was nearly 2 h per day. Paediatric symptoms were positively associated with watching television and screen time and negatively associated with parents' working hours. Touchscreen use was more frequent among girls and older children. Parents' working hours comprised the most significant predictor of paediatric symptoms. Our findings reinforce past findings on the adverse links between the use of multimedia devices and paediatric symptoms and also highlight the influence of other variables like the child's age and gender, as well as parental factors. The need to both create a more comprehensive framework regarding the long-term effects of multimedia device use and delineate effective strategies for prevention and intervention with parents and children is discussed.
ABSTRACT
Infant formula intake is recommended to ensure comprehensive nutritional and caloric fulfillment when exclusive breastfeeding is not possible. However, similarly to breast milk, infant formulas may also contain pollutants capable of inducing endocrine-disrupting and neurotoxic effects. Thus, considering the sensitivity of their developing physiological systems and that infants have heightened susceptibility to environmental influences, this study was aimed at assessing the contents of essential elements, and inorganic and organic pollutants in infant formulas marketed in Brazil. Additionally, health risk assessments for selected contaminants were also performed. Measured contents of essential elements (Ca, Fe, Mg, Mn, Cu, Se, and Zn) were congruent with label information. Nevertheless, some toxic elements (Pb, Cd, As, Ni, and Al) were also detected. Notably, in the upper-bound scenario, Pb and Cd surpassed established threshold values when comparing the estimated daily intake (EDI) and tolerable daily intake (TDI - 3.57 and 0.36 µg/kg bw, respectively). Bisphenol P (BPP) and benzyl butyl phthalate (BBP) were frequently detected (84 % detection rate both) with elevated contents (BPP median = 4.28 ng/g and BBP median = 0.24 ng/g). Furthermore, a positive correlation (0.41) was observed between BPP and BBP, implying a potential co-occurrence within packaging materials. Methyl-paraben also correlated positively with BBP (0.57), showing a detection rate of 53 %. The cumulative PBDE contents ranged from 0.33 to 1.62 ng/g, with BDE-154 and BDE-47 the dominant congeners. When comparing EDI values with TDIs, all organic pollutants remained below the thresholds across all exposure scenarios. Moreover, non-carcinogenic risks were below the threshold (HQ > 1) when dividing the EDIs by the respective reference doses for chronic exposure. While the current findings may suggest that infant formula intake poses no immediate risk in terms of the evaluated chemicals, it remains imperative to conduct further research to safeguard the health of infants considering other chemicals, as well as their potential cumulative effects.