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1.
Biologicals ; 85: 101740, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38217963

ABSTRACT

Whooping cough is a disease caused by Bordetella pertussis, whose morbidity has increased, motivating the improvement of current vaccines. Reverse vaccinology is a strategy that helps identify proteins with good characteristics fast and with fewer resources. In this work, we applied reverse vaccinology to study the B. pertussis proteome and pangenome with several in-silico tools. We analyzed the B. pertussis Tohama I proteome with NERVE software and compared 234 proteins with B. parapertussis, B. bronchiseptica, and B. holmessi. VaxiJen was used to calculate an antigenicity value; our threshold was 0.6, selecting 84 proteins. The candidates were depurated and grouped in eight family proteins to select representative candidates, according to bibliographic information and their immunological response predicted with ABCpred, Bcepred, IgPred, and C-ImmSim. Additionally, a pangenome study was conducted with 603 B. pertussis strains and PanRV software, identifying 3421 core proteins that were analyzed to select the best candidates. Finally, we selected 15 proteins from the proteome study and seven proteins from the pangenome analysis as good vaccine candidates.


Subject(s)
Bordetella parapertussis , Whooping Cough , Humans , Bordetella pertussis/genetics , Whooping Cough/prevention & control , Proteome/metabolism , Vaccinology , Bordetella parapertussis/metabolism , Pertussis Vaccine
2.
Molecules ; 29(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38731445

ABSTRACT

Reducing high concentrations of pollutants such as heavy metals, pesticides, drugs, and dyes from water is an emerging necessity. We evaluated the use of Luffa cylindrica (Lc) as a natural non-conventional adsorbent to remove azo dye mixture (ADM) from water. The capacity of Lc at three different doses (2.5, 5.0, and 10.0 g/L) was evaluated using three concentrations of azo dyes (0.125, 0.250, and 0.500 g/L). The removal percent (R%), maximum adsorption capacity (Qm), isotherm and kinetics adsorption models, and pH influence were evaluated, and Fourier-transform infrared spectroscopy and scanning electron microscopy were performed. The maximum R% was 70.8% for 10.0 g L-1Lc and 0.125 g L-1 ADM. The Qm of Lc was 161.29 mg g-1. Adsorption by Lc obeys a Langmuir isotherm and occurs through the pseudo-second-order kinetic model. Statistical analysis showed that the adsorbent dose, the azo dye concentration, and contact time significantly influenced R% and the adsorption capacity. These findings indicate that Lc could be used as a natural non-conventional adsorbent to reduce ADM in water, and it has a potential application in the pretreatment of wastewaters.


Subject(s)
Azo Compounds , Coloring Agents , Luffa , Water Pollutants, Chemical , Water Purification , Luffa/chemistry , Azo Compounds/chemistry , Azo Compounds/isolation & purification , Adsorption , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/isolation & purification , Water Purification/methods , Kinetics , Coloring Agents/chemistry , Hydrogen-Ion Concentration , Spectroscopy, Fourier Transform Infrared , Water/chemistry
3.
Microb Pathog ; 176: 106005, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36717005

ABSTRACT

The Gram-negative bacteria Brucella abortus is a major cause of brucellosis in animals and humans. The host innate immune response to B. abortus is mainly associated with phagocytic cells such as dendritic cells, neutrophils, and macrophages. However, as mast cells naturally reside in the main bacterial entry sites they may be involved in bacterial recognition. At present, little is known about the role of mast cells during B. abortus infection. The role of the innate immune receptors TLR2 and TLR4 in activation of mast cells by B. abortus (strain RB51) infection was analyzed in this study. The results showed that B. abortus did not induce mast cell degranulation, but did induce the synthesis of the cytokines IL-1ß, IL-6, TNF-α, CCL3, CCL4, and CCL5. Furthermore, B. abortus stimulated key cell signaling molecules involved in mast cell activation such as p38 and NF-κB. Blockade of the receptors TLR2 and TLR4 decreased TNF-α and IL-6 release by mast cells in response to B. abortus. Taken together, our results demonstrate that mast cells are activated by B. abortus and may play a role in inducing an inflammatory response during the initial phase of the infection.


Subject(s)
Brucella abortus , Brucellosis , Humans , Animals , Toll-Like Receptor 2 , Toll-Like Receptor 4 , Mast Cells , Tumor Necrosis Factor-alpha , Interleukin-6
4.
Int J Health Plann Manage ; 38(3): 628-642, 2023 May.
Article in English | MEDLINE | ID: mdl-36540043

ABSTRACT

BACKGROUND: The influence of the work environment on missed care and service quality has been well documented. However, available evidence concerning this relationship comes mostly from developed countries. Few studies have been conducted in low- or middle-income countries. We assessed the relationship between the work environment and missed nursing care in highly specialised hospitals in Mexico. METHODS: We conducted an observational cross-sectional study with data collected from January 2019 to February 2020 in 11 highly specialised hospitals (n = 510 nurses). We estimated missed nursing care utilising the MISSCARE questionnaire and used the Practice Environment Scale-Nursing Work Index instrument to assess the work environment. After describing the main attributes of the study sample according to the type of work environment, we constructed five adjusted fractional regression models, the first concerning the overall index of missed care, and the others pertaining to its various dimensions. RESULTS: The sample analysed was balanced as regards adjustment variables according to the type of work environment. The adjusted estimates confirmed an inverse relationship between the missed care index and enjoying an enhanced, or favourable, work environment. Overall, the difference was 9 percentage points (pp); however, by dimension of missed care, the major differences between enhanced and attenuated, or unfavourable, work environments were registered for basic care, followed by patient education and discharge planning (4pp) and individual needs (8pp). CONCLUSIONS: The work environment determines the frequency of missed nursing care, both overall and by dimension. Nursing managers need to create short- and mid-term strategies favouring positive work environments in order to improve working conditions for nursing professionals.


Subject(s)
Nurse Administrators , Nursing Care , Nursing Staff, Hospital , Humans , Cross-Sectional Studies , Mexico , Surveys and Questionnaires , Hospitals
5.
Molecules ; 27(6)2022 Mar 08.
Article in English | MEDLINE | ID: mdl-35335119

ABSTRACT

Prostate and bladder cancers are commonly diagnosed malignancies in men. Several nitric oxide donor compounds with strong antitumor activity have been reported. Thus, continuing with our efforts to explore the chemical space around bioactive furoxan moiety, multicomponent reactions were employed for the rapid generation of molecular diversity and complexity. We herein report the use of Ugi and Groebke-Blackburn-Bienaymé multicomponent reactions under efficient, safe, and environmentally friendly conditions to synthesize a small collection of nitric-oxide-releasing molecules. The in vitro antiproliferative activity of the synthesized compounds was measured against two different human cancer cell lines, LNCaP (prostate) and T24 (bladder). Almost all compounds displayed antiproliferative activity against both cancer cell lines, providing lead compounds with nanomolar GI50 values against the cancer bladder cell line with selectivity indices higher than 10.


Subject(s)
Neoplasms , Nitric Oxide Donors , Humans , Nitric Oxide/metabolism , Oxadiazoles
6.
Stroke ; 50(7): 1797-1804, 2019 07.
Article in English | MEDLINE | ID: mdl-31159701

ABSTRACT

Background and Purpose- After large-vessel intracranial occlusion, the fate of the ischemic penumbra, and ultimately final infarct volume, largely depends on tissue perfusion. In this study, we evaluated whether blood pressure reduction and sustained relative hypotension during endovascular thrombectomy are associated with infarct progression and functional outcome. Methods- We identified consecutive patients with large-vessel intracranial occlusion ischemic stroke who underwent mechanical thrombectomy at 2 comprehensive stroke centers. Intraprocedural mean arterial pressure (MAP) was monitored throughout the procedure. ΔMAP was calculated as the difference between admission MAP and lowest MAP during endovascular thrombectomy until recanalization. Sustained hypotension was measured as the area between admission MAP and continuous measurements of intraprocedural MAP (aMAP). Final infarct volume was measured using magnetic resonance imaging at 24 hours, and functional outcome was assessed using the modified Rankin Scale at discharge and 90 days. Associations with outcome were analyzed using linear and ordinal multivariable logistic regression. Results- Three hundred ninety patients (mean age 71±14 years, mean National Institutes of Health Stroke Scale score of 17) were included in the study; of these, 280 (72%) achieved Thrombolysis in Cerebral Infarction 2B/3 reperfusion. Eighty-seven percent of patients experienced MAP reductions during endovascular thrombectomy (mean 31±20 mm Hg). ΔMAP was associated with greater infarct growth ( P=0.036) and final infarct volume ( P=0.035). Mean ΔMAP among patients with favorable outcomes (modified Rankin Scale score, 0-2) was 20±21 mm Hg compared with 30±24 mm Hg among patients with poor outcome ( P=0.002). In the multivariable analysis, ΔMAP was independently associated with higher (worse) modified Rankin Scale scores at discharge (adjusted odds ratio per 10 mm Hg, 1.17; 95% CI, 1.04-1.32; P=0.009) and at 90 days (adjusted odds ratio per 10 mm Hg, 1.22; 95% CI, 1.07-1.38; P=0.003). The association between aMAP and outcome was also significant at discharge ( P=0.002) and 90 days ( P=0.001). Conclusions- Blood pressure reduction before recanalization is associated with larger infarct volumes and worse functional outcomes for patients affected by large-vessel intracranial occlusion stroke. These results underscore the importance of BP management during endovascular thrombectomy and highlight the need for further investigation of blood pressure management after large-vessel intracranial occlusion stroke.


Subject(s)
Blood Pressure , Cerebral Infarction/therapy , Stroke/therapy , Thrombectomy/methods , Aged , Aged, 80 and over , Arterial Pressure , Brain Ischemia/diagnostic imaging , Brain Ischemia/physiopathology , Brain Ischemia/therapy , Cerebral Infarction/diagnostic imaging , Cerebral Infarction/physiopathology , Disease Progression , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Recovery of Function , Retrospective Studies , Stroke/diagnostic imaging , Stroke/physiopathology , Treatment Outcome
7.
Anticancer Drugs ; 30(4): 330-338, 2019 04.
Article in English | MEDLINE | ID: mdl-30489292

ABSTRACT

We determined the antiproliferative and nitric oxide (NO)-releasing activity of furoxans and tocopherol analogs-furoxan hybrids by tandem Griess/resazurin/sulforhodamin B assays in HeLa, 253J, T24, and HepG2 cancer cells. In addition, to investigate the NO implications in the inhibition of cell growth, cells were pretreated with the NO scavenger hemoglobin and the genotoxic damage was determined. The compounds 1 and 3 emerged as good anticancer agents for bladder cancer treatment. The NO-releasing activity of these compounds appears to be necessary to obtain the antiproliferative effect. Although compound 1 exerted a DNA damage mechanism of action, compound 3 seemed to act in a different way. The low toxicity levels against normal cell line HaCaT point them out as a very promising scaffold for the further design of new anticancer agents.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Proliferation , DNA Damage/drug effects , Neoplasms/drug therapy , Oxadiazoles/chemistry , Tocopherols/chemistry , Apoptosis , Drug Screening Assays, Antitumor , Humans , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Nitric Oxide/metabolism , Tumor Cells, Cultured
8.
Nurs Res ; 68(6): 453-463, 2019.
Article in English | MEDLINE | ID: mdl-31693551

ABSTRACT

BACKGROUND: Evidence suggests that behavioral, social, and environmental factors may modify the effects of life stress on health and performance of new nurses as they transition to hospitals. OBJECTIVES: The aim of this study was to describe the methods of a project designed to investigate the role of social, behavioral, and environmental factors in modifying the adverse effects of stress on new nurses and to discuss demographic, health, and life stress characteristics of the cohort at baseline. METHODS: A prospective cohort design was used to conduct a comprehensive assessment of health endpoints, life stress, behaviors, personal traits, social factors, indicators of engagement and performance, and environmental exposures in nursing students. Adjusted odds ratios and analyses of covariance were used to examine associations between these factors at baseline. RESULTS: Health indicators in the cohort were comparable or better than in the broader United States population, and lifetime stress exposure was lower than among students from other majors. Exposure to more lifetime stressors was associated with greater risk for various health conditions, including hypertension, diabetes, and depression. Conversely, better social, environmental, behavioral, and personal profiles were associated with protective effects for the same health conditions. DISCUSSION: These data comprehensively summarize the lives of predominately Hispanic nursing students and highlight risk and resilience factors associated with their health and well-being. The findings are timely, as the nursing field diversifies in preparation to care for a diverse and aging population. Comprehensively assessing stress-health relationships among student nurses ought to inform the policies, practices, and curricula of nursing schools to better prepare nurses to thrive in the often-strenuous healthcare environment.


Subject(s)
Stress, Psychological/epidemiology , Students, Nursing/psychology , Adolescent , Adult , Cohort Studies , Female , Health Behavior , Health Status , Humans , Life Style , Male , Middle Aged , Socioeconomic Factors , United States , Young Adult
9.
Molecules ; 20(7): 11793-807, 2015 Jun 26.
Article in English | MEDLINE | ID: mdl-26132905

ABSTRACT

Parasitic flatworms cause serious infectious diseases that affect humans and livestock in vast regions of the world, yet there are few effective drugs to treat them. Thioredoxin glutathione reductase (TGR) is an essential enzyme for redox homeostasis in flatworm parasites and a promising pharmacological target. We purified to homogeneity and characterized the TGR from the tapeworm Mesocestoides vogae (syn. M. corti). This purification revealed absence of conventional TR and GR. The glutathione reductase activity of the purified TGR exhibits a hysteretic behavior typical of flatworm TGRs. Consistently, M. vogae genome analysis revealed the presence of a selenocysteine-containing TGR and absence of conventional TR and GR. M. vogae thioredoxin and glutathione reductase activities were inhibited by 3,4-bis(phenylsulfonyl)-1,2,5-oxadiazole N2-oxide (VL16E), an oxadiazole N-oxide previously identified as an inhibitor of fluke and tapeworm TGRs. Finally, we show that mice experimentally infected with M. vogae tetrathyridia and treated with either praziquantel, the reference drug for flatworm infections, or VL16E exhibited a 28% reduction of intraperitoneal larvae numbers compared to vehicle treated mice. Our results show that oxadiazole N-oxide is a promising chemotype in vivo and highlights the convenience of M. vogae as a model for rapid assessment of tapeworm infections in vivo.


Subject(s)
Cestoda/drug effects , Cestode Infections/parasitology , Multienzyme Complexes/metabolism , NADH, NADPH Oxidoreductases/metabolism , Oxadiazoles/pharmacology , Amino Acid Sequence , Animals , Cestoda/metabolism , Mesocestoides , Mice , Molecular Sequence Data , Multienzyme Complexes/chemistry , NADH, NADPH Oxidoreductases/chemistry , Sequence Homology, Amino Acid
10.
Rev Med Chil ; 143(5): 627-36, 2015 May.
Article in Spanish | MEDLINE | ID: mdl-26203576

ABSTRACT

Insulin resistance is a prevalent condition commonly associated with unhealthy lifestyles. It affects several metabolic pathways, increasing risk of abnormalities at different organ levels. Thus, diverse medical specialties should be involved in its diagnosis and treatment. With the purpose of unifying criteria about this condition, a scientific-based consensus was elaborated. A questionnaire including the most important topics such as cardio-metabolic risk, non-alcoholic fatty liver disease and polycystic ovary syndrome, was designed and sent to national experts. When no agreement among them was achieved, the Delphi methodology was applied. The main conclusions reached are that clinical findings are critical for the diagnosis of insulin resistance, not being necessary blood testing. Acquisition of a healthy lifestyle is the most important therapeutic tool. Insulin-sensitizing drugs should be prescribed to individuals at high risk of disease according to clinically validated outcomes. There are specific recommendations for pregnant women, children, adolescents and older people.


Subject(s)
Insulin Resistance/physiology , Chile , Delphi Technique , Female , Humans , Hypoglycemic Agents/therapeutic use , Life Style , Metformin/therapeutic use , Overweight/complications , Polycystic Ovary Syndrome/complications , Risk Factors , Societies, Medical/standards
11.
Endocrinol Diabetes Nutr (Engl Ed) ; 71(2): 44-52, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38493012

ABSTRACT

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is related to glomerular filtration rate (GFR) impairment, which is one of the main causes of chronic kidney disease. The objective of this study was to identify the risk factors related to GFR in Mexican adults with T2DM, using a validated multiple linear regression model (MLRM), with emphasis in body adiposity, glycemic control, duration of the diabetes and other relevant risk factors. MATERIALS AND METHODS: A cross-sectional, analytical, and observational study was carried out in 252 adults with a previous diagnosis of T2DM. Body mass index (BMI) and waist circumference (WC) were determined and a fasting blood sample was collected for glucose, creatinine and HbA1c determinations. GFR was calculated with the Cockcroft-Gault equation adjusted for body surface area. Four MLRM were performed to determine the factors related to the GFR; it was evaluated whether these models complied with the statistical assumptions of the linear regression model. RESULTS: The average age of the participants was 60 ±â€¯12 years, 62.3% of them were women. GFR correlated with BMI and WC; age and duration of the diabetes were associated inversely. Model 4 of the MLRM reported a coefficient of determination of 53.5% where the variables BMI (ß = 1.31), male sex (ß = -6.01), duration of T2DM (ß = -0.57), arterial hypertension (ß = -6.53) and age (ß = -1.45) were simultaneously and significantly related to the GFR. CONCLUSIONS: Older age, male sex, longer duration of T2DM and the presence of arterial hypertension were associated with a decrease in the GFR; BMI and WC were directly associated. No effect of glucose and HbA1c on GFR was observed.


Subject(s)
Diabetes Mellitus, Type 2 , Hypertension , Adult , Humans , Male , Female , Middle Aged , Aged , Diabetes Mellitus, Type 2/complications , Glomerular Filtration Rate , Glycated Hemoglobin , Cross-Sectional Studies , Risk Factors , Hypertension/epidemiology , Hypertension/complications , Glucose
12.
mSphere ; 9(5): e0016224, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38606973

ABSTRACT

Acinetobacter junii is an opportunistic human and animal pathogen severely understudied. Here, we conducted the largest genomic epidemiological study on this pathogen to date. Our data show that this bacterium has spread globally. Also, we found that some human and non-human isolates are not well differentiated from one another, implying transmission between clinical and non-clinical, non-human settings. Remarkably, human but also some non-human isolates have clinically important antibiotic resistance genes, and some of these genes are located in plasmids. Given these results, we put forward that A. junii should be considered an emerging One Health problem. In this regard, future molecular epidemiological studies about this species will go beyond human isolates and will consider animal-, plant-, and water-associated environments. IMPORTANCE: Acinetobacter baumannii is the most well-known species from the genus Acinetobacter. However, other much less studied Acinetobacter species could be important opportunistic pathogens of animals, plants and humans. Here, we conducted the largest genomic epidemiological study of A. junii, which has been described as a source not only of human but also of animal infections. Our analyses show that this bacterium has spread globally and that, in some instances, human and non-human isolates are not well differentiated. Remarkably, some non-human isolates have important antibiotic resistance genes against important antibiotics used in human medicine. Based on our results, we propose that this pathogen must be considered an issue not only for humans but also for veterinary medicine.


Subject(s)
Acinetobacter Infections , Acinetobacter , Acinetobacter Infections/microbiology , Acinetobacter Infections/epidemiology , Humans , Acinetobacter/genetics , Acinetobacter/drug effects , Acinetobacter/classification , Acinetobacter/isolation & purification , Acinetobacter/pathogenicity , Animals , One Health , Genome, Bacterial , Anti-Bacterial Agents/pharmacology , Molecular Epidemiology , Communicable Diseases, Emerging/microbiology , Communicable Diseases, Emerging/epidemiology , Drug Resistance, Bacterial/genetics , Plasmids/genetics , Genomics
13.
Food Nutr Bull ; 34(2): 215-21, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23964394

ABSTRACT

BACKGROUND: Type 2 diabetes is highly prevalent in populations having high rates of overweight and obesity. It is a chronic condition responsible for long-term severe dysfunction of several organs, including the kidneys, heart, blood vessels, and eyes. Although there are a number of pharmacologic products in the market to treat insulin resistance and impaired insulin secretion--the most prominent features of this disease--interventions directed at preserving the integrity and function of beta-cells in the long term are less available. The use of some nutrients with important cellular protective roles that may lead to a preservation of beta-cells has not been fully tested; among these, zinc may be an interesting candidate. OBJECTIVE: To assess the potential of zinc supplementation as coadjuvant to diabetes therapy. METHODS: This article reviews the available information on the use of zinc as part of diabetes therapy. RESULTS: Cellular and animal models provide information on the insulin mimetic action of zinc, as well as its role as a regulator of oxidative stress, inflammation, apoptosis, and insulin secretion. Zinc supplementation studies in humans are limited, although some positive effects have been reported; mainly, a modest but significant reduction in fasting glucose and a trend to decreased glycated hemoglobin (HbA1c). CONCLUSIONS: Zinc supplementation may have beneficial effects on glycemic control. Nevertheless, among the studies considered, the vast majority lasted for 6 months or less, suggesting the importance of conducting long-duration studies given the characteristics of type 2 diabetes as a chronic disease.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Zinc/therapeutic use , Animals , Apoptosis , Blood Glucose/analysis , Diabetes Mellitus, Type 2/complications , Dietary Supplements , Humans , Inflammation , Insulin/metabolism , Insulin Resistance , Insulin Secretion , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/physiology , Oxidative Stress , Zinc/administration & dosage , Zinc/physiology
15.
Ultrasound J ; 15(1): 42, 2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37815637

ABSTRACT

INTRODUCTION: Ultrasound is the current standard for central venous access due to its advantages in efficiency and safety. In-plane and out-of-plane visualization techniques are commonly used, but there is no clear evidence showing an advantage of one technique over the other. The objective of this study was to compare the success and time required for biplane visualization vs. in-plane and out-of-plane techniques in simulated models. METHODOLOGY: Ten emergency medicine specialists participated in 60 simulated events, with randomization of the visualization technique for each event. Each event required intravenous cannulation of a simulated model for jugular venous access, with a maximum of three attempts allowed. The number of attempts required for each event, success of puncture and venous cannulation, frequency of redirection and puncture of the posterior wall, time required to obtain an optimal window, visualize the needle inside the vessel, and passage of the guidewire were recorded. The success ratios and times required for each visualization technique (biplane, in-plane, and out-of-plane) were compared. RESULTS: Cannulation success rate was 100% for all three techniques. Success on the first attempt was 95% for biplane visualization vs. 100% for in-plane and out-of-plane. The median total time for the procedure was higher for biplane visualization (29.9 s) compared to in-plane (25.2 s) and out-of-plane (29 s), but this difference was not statistically significant (p = 0.999). There were no significant differences in cannulation success, needle redirection, or posterior wall puncture frequency between biplane visualization and in-plane and out-of-plane techniques. CONCLUSIONS: This study suggests that biplane visualization with the use of pocket ultrasound for internal jugular cannulation in simulated models did not demonstrate significant differences when compared with in-plane and out-of-plane visualization techniques. Further research with larger sample sizes may be needed to confirm these results.

16.
Biomedicines ; 11(1)2023 Jan 12.
Article in English | MEDLINE | ID: mdl-36672707

ABSTRACT

Bladder cancer is a worldwide problem and improved therapies are urgently needed. In the search for newer strong antitumor compounds, herein, we present the study of three nitric oxide-releasing compounds and evaluate them as possible therapies for this malignancy. Bladder cancer cell lines T24 and 253J were used to evaluate the antiproliferative, antimigratory, and genotoxic effects of compounds. Moreover, we determined the NF-κB pathway inhibition, and finally, the survivin downregulation exerted by our molecules. The results revealed that compounds 1 and 3 exerted a high antiproliferative activity against bladder cancer cells through DNA damage and survivin downregulation. In addition, compound 3 reduced bladder cancer cell migration. We found that nitric oxide donors are promising molecules for the development of a new therapeutic targeting the underlying mechanisms of tumorigenesis and progression of bladder cancer.

17.
Microorganisms ; 11(7)2023 Jun 24.
Article in English | MEDLINE | ID: mdl-37512820

ABSTRACT

Tuberculosis is a disease caused by Mycobacterium tuberculosis, representing the second leading cause of death by an infectious agent worldwide. The available vaccine against this disease has insufficient coverage and variable efficacy, accounting for a high number of cases worldwide. In fact, an estimated third of the world's population has a latent infection. Therefore, developing new vaccines is crucial to preventing it. In this study, the highly antigenic PE_PGRS49 and PE_PGRS56 proteins were analyzed. These proteins were used for predicting T- and B-cell epitopes and for human leukocyte antigen (HLA) protein binding efficiency. Epitopes GGAGGNGSLSS, FAGAGGQGGLGG, GIGGGTQSATGLG (PE_PGRS49), and GTGWNGGKGDTG (PE_PGRS56) were selected based on their best physicochemical, antigenic, non-allergenic, and non-toxic properties and coupled to HLA I and HLA II structures for in silico assays. A construct with an adjuvant (RS09) plus each epitope joined by GPGPG linkers was designed, and the stability of the HLA-coupled construct was further evaluated by molecular dynamics simulations. Although experimental and in vivo studies are still necessary to ensure its protective effect against the disease, this study shows that the vaccine construct is dynamically stable and potentially effective against tuberculosis.

18.
Front Pharmacol ; 14: 1193282, 2023.
Article in English | MEDLINE | ID: mdl-37426813

ABSTRACT

Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence. Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy -performed in a large and diverse chemolibrary- complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening. Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 µM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12-20 µM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7-45 µM). Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known "garbage in, garbage out" machine learning principle.

19.
Stud Health Technol Inform ; 177: 283-8, 2012.
Article in English | MEDLINE | ID: mdl-22942068

ABSTRACT

There are various techniques available to measure human physical activity (PA). Accelerometer based techniques claim to be non-invasive and easy to use. The signal magnitude area (SMA) is the most extended feature used to measure the physical activity. It is calculated by sampling and filtering an accelerometer signal of at least at 50 Hz. SMA has a proven and widely accepted linear relation with the energy expenditure. A novel magnitude called JIM, which is more efficient than SMA, is proposed in this paper. The jerk-based inactivity magnitude (JIM) is also calculated from the acceleration signal, but at a sampling rate of 1Hz, increasing the battery life of the measuring system. This magnitude gives the same information as the SMA (correlation of 95%) and is validated with a group of 39 users in free-living conditions for at least 24 hours.


Subject(s)
Acceleration , Actigraphy/methods , Algorithms , Diagnosis, Computer-Assisted/methods , Monitoring, Ambulatory/methods , Motor Activity/physiology , Signal Processing, Computer-Assisted , Humans , Reproducibility of Results , Sensitivity and Specificity
20.
Arthritis Res Ther ; 24(1): 232, 2022 10 13.
Article in English | MEDLINE | ID: mdl-36229861

ABSTRACT

OBJECTIVE: To evaluate the impact of cardiovascular risk (CVR) on the diagnostic accuracy of the ultrasonographic (US) Halo Score in patients with suspected giant cell arteritis (GCA). METHODS: Retrospective observational study of patients referred to our US fast track clinic with suspected GCA for a 2-year period. The intima-media thickness (IMT) of cranial and extra-cranial arteries and the Halo Score was determined to assess the extent of vascular inflammation. The European Society of Cardiology Guidelines on CV Disease Prevention were used to define different categories of CVR and patients were classified according to the Systemic Coronary Risk Evaluation (SCORE). The gold standard for GCA diagnosis was clinical confirmation after a 6-month follow-up. RESULTS: Of the 157 patients included, 47 (29.9%) had GCA after a 6-month follow-up. Extra-cranial artery IMT was significantly higher in patients with high/very high CVR than in those with low/moderate CVR, but only among patients without GCA. Non-GCA patients with high/very high CVR had also a significantly higher Halo Score in contrast with low/moderate CVR [9.38 (5.93) vs 6.16 (5.22); p = 0.007]. The area under the ROC curve of the Halo Score to identify GCA was 0.835 (95% CI 0.756-0.914), slightly greater in patients with low/moderate CVR (0.965 [95% CI 0.911-1]) versus patients with high/very high CVR (0.798 [95% CI 0.702-0.895]). A statistically weak positive correlation was found between the Halo Score and the SCORE (r 0.245; c = 0.002). CONCLUSIONS: Elevated CVR may influence the diagnostic accuracy of the US Halo Score for GCA. Thus, CVR should be taken into consideration in the US screening for GCA.


Subject(s)
Cardiovascular Diseases , Giant Cell Arteritis , Cardiovascular Diseases/diagnostic imaging , Carotid Intima-Media Thickness , Giant Cell Arteritis/diagnosis , Heart Disease Risk Factors , Humans , Risk Factors , Sensitivity and Specificity , Temporal Arteries/diagnostic imaging
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