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1.
Front Pharmacol ; 15: 1403203, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38873424

RESUMEN

Visceral Leishmaniasis (VL) is a serious public health issue, documented in more than ninety countries, where an estimated 500,000 new cases emerge each year. Regardless of novel methodologies, advancements, and experimental interventions, therapeutic limitations, and drug resistance are still challenging. For this reason, based on previous research, we screened natural products (NP) from Nuclei of Bioassays, Ecophysiology, and Biosynthesis of Natural Products Database (NuBBEDB), Mexican Compound Database of Natural Products (BIOFACQUIM), and Peruvian Natural Products Database (PeruNPDB) databases, in addition to structural analogs of Miglitol and Acarbose, which have been suggested as treatments for VL and have shown encouraging action against parasite's N-glycan biosynthesis. Using computer-aided drug design (CADD) approaches, the potential inhibitory effect of these NP candidates was evaluated by inhibiting the Mannosyl-oligosaccharide Glucosidase Protein (MOGS) from Leishmania infantum, an enzyme essential for the protein glycosylation process, at various pH to mimic the parasite's changing environment. Also, computational analysis was used to evaluate the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profile, while molecular dynamic simulations were used to gather information on the interactions between these ligands and the protein target. Our findings indicated that Ocotillone and Subsessiline have potential antileishmanial effects at pH 5 and 7, respectively, due to their high binding affinity to MOGS and interactions in the active center. Furthermore, these compounds were non-toxic and had the potential to be administered orally. This research indicates the promising anti-leishmanial activity of Ocotillone and Subsessiline, suggesting further validation through in vitro and in vivo experiments.

2.
Diagnostics (Basel) ; 14(12)2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38928656

RESUMEN

Low-density lipoprotein cholesterol (LDL-C), which makes up about 70% of the cholesterol in the blood, is critical in the formation of arteriosclerotic plaques, increasing the risk of heart disease. LDL-C levels are estimated using Friedewald, Martin and Sampson equations, though they have limitations with high triglycerides. Our aim is to compare the effectiveness of these equations versus the ultracentrifugation technique in individuals with and without dyslipidemia and identify precision. There were 113 participants, 59 healthy controls and 54 dyslipidemic patients. Samples were collected after fasting. LDL-C was estimated using the Friedewald, Martin and Sampson equations. The purified LDL-C, ultracentrifugated and dialysized control group without dyslipidemia vs. patients with coronary artery disease (CAD) showed differences in age, HDL-C, triglycerides and glucose non-HDL-C (p = 0.001 in all). There were correlations in CGWD between ultracentrifugation and Sampson R-squared (R2) = 0.791. In the dyslipidemia control group, ultracentrifugation and Friedewald R2 = 0.911. In patients with CAD, correlation between ultracentrifugation and Sampson R2 = 0.892; Bland-Altman confirmed agreement in controls without dyslipidemia. The Martin and Sampson equations are interchangeable with ultracentrifugation. Conclusion: The role of LDL analysis using precise techniques is necessary to obtain better control of disease outcomes after the use of precise therapies and suggests verifying its importance through clinical trials.

3.
An Acad Bras Cienc ; 96(2): e20231208, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38747841

RESUMEN

The enterotoxigenic Escherichia coli (ETEC) strain is one of the most frequent causative agents of childhood diarrhea and travelers' diarrhea in low-and middle-income countries. Among the virulence factors secreted by ETEC, the exoprotein EtpA has been described as an important. In the present study, a new detection tool for enterotoxigenic E. coli bacteria using the EtpA protein was developed. Initially, antigenic sequences of the EtpA protein were selected via in silico prediction. A chimeric recombinant protein, corresponding to the selected regions, was expressed in an E. coli host, purified and used for the immunization of mice. The specific recognition of anti-EtpA IgG antibodies generated was evaluated using flow cytometry. The tests demonstrated that the antibodiesdeveloped were able to recognize the native EtpA protein. By coupling these antibodies to magnetic beads for the capture and detection of ETEC isolates, cytometric analyses showed an increase in sensitivity, specificity and the effectiveness of the method of separation and detection of these pathogens. This is the first report of the use of this methodology for ETEC separation. Future trials may indicate their potential use for isolating these and other pathogens in clinical samples, thus accelerating the diagnosis and treatment of diseases.


Asunto(s)
Anticuerpos Antibacterianos , Escherichia coli Enterotoxigénica , Proteínas de Escherichia coli , Citometría de Flujo , Escherichia coli Enterotoxigénica/inmunología , Animales , Ratones , Citometría de Flujo/métodos , Proteínas de Escherichia coli/inmunología , Anticuerpos Antibacterianos/inmunología , Sensibilidad y Especificidad , Ratones Endogámicos BALB C , Femenino , Inmunoglobulina G/inmunología
4.
Diagn Microbiol Infect Dis ; 109(3): 116326, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38692205

RESUMEN

Serodiagnosis methods have been used as platforms for diagnostic tests for many diseases. Due to magnetic nanoparticles' properties to quickly detach from an external magnetic field and particle size effects, these nanomaterials' functionalization allows the specific isolation of target analytes, enhancing accuracy parameters and reducing serodiagnosis time. Superparamagnetic iron oxide nanoparticles (MNPs) were synthesized and functionalized with polyethylene glycol (PEG) and then associated with the synthetic Leishmaniosis epitope. This nano-peptide antigen showed promising results. Regarding Tegumentary leishmaniasis diagnostic accuracy, the AUC was 0.8398 with sensibility 75% (95CI% 50.50 - 89.82) and specificity 87.50% (95CI% 71.93 - 95.03), and Visceral leishmaniasis accuracy study also present high performance, the AUC was 0.9258 with sensibility 87.50% (95CI% 63.98 - 97.78) and specificity 87.50% (95CI% 71.93 - 95.03). Our results demonstrate that the association of the antigen with MNPs accelerates and improves the diagnosis process. MNPs could be an important tool for enhancing serodiagnosis.


Asunto(s)
Ensayo de Inmunoadsorción Enzimática , Polietilenglicoles , Sensibilidad y Especificidad , Humanos , Ensayo de Inmunoadsorción Enzimática/métodos , Polietilenglicoles/química , Antígenos de Protozoos/inmunología , Leishmaniasis/diagnóstico , Nanopartículas Magnéticas de Óxido de Hierro/química , Anticuerpos Antiprotozoarios/sangre
5.
Diagn Microbiol Infect Dis ; 109(3): 116338, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38718661

RESUMEN

The diagnosis if leprosy is difficult, as it requires clinical expertise and sensitive laboratory tests. In this study, we develop a serological test for leprosy by using bioinformatics tools to identify specific B-cell epitopes from Mycobacterium leprae hypothetical proteins, which were used to construct a recombinant chimeric protein, M1. The synthetic peptides were obtained and showed good reactivity to detect leprosy patients, although the M1 chimera have showed sensitivity (Se) and specificity (Sp) values higher than 90.0% to diagnose both paucibacillary (PB) and multibacillary (MB) leprosy patients, but not those developing tegumentary or visceral leishmaniasis, tuberculosis, Chagas disease, malaria, histoplasmosis and aspergillosis, in ELISA experiments. Using sera from household contacts, values for Se and Sp were 100% and 65.3%, respectively. In conclusion, our proof-of-concept study has generated data that suggest that a new recombinant protein could be developed into a diagnostic antigen for leprosy.


Asunto(s)
Antígenos Bacterianos , Proteínas Bacterianas , Epítopos de Linfocito B , Lepra , Mycobacterium leprae , Sensibilidad y Especificidad , Humanos , Mycobacterium leprae/inmunología , Mycobacterium leprae/genética , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito B/genética , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/genética , Lepra/diagnóstico , Lepra/inmunología , Proteínas Bacterianas/inmunología , Proteínas Bacterianas/genética , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/genética , Ensayo de Inmunoadsorción Enzimática/métodos , Adulto , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Masculino , Femenino , Pruebas Serológicas/métodos , Biología Computacional/métodos , Persona de Mediana Edad , Adulto Joven , Adolescente
6.
Immunol Res ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38698191

RESUMEN

The pathological manifestation of the inflammatory process primarily stems from the heightened release of pro-inflammatory cytokines, with IL-1ß standing out as a pivotal cytokine. The excessive presence of IL-1ß disrupts immune signaling, thereby assuming a pathogenic and exacerbating role in the pathophysiology of numerous inflammatory diseases. Regulating IL-1ß levels becomes crucial, and the IL-1Ra molecule serves this purpose by binding to the IL-1R1 receptor, thereby impeding the binding of IL-1ß. Several pharmaceuticals have entered the market, aiming to neutralize IL-1ß's biological function through diverse mechanisms. However, the existing IL-1ß inhibitors are recombinant proteins, characterized by a high production cost and limited stability. Therefore, this study aimed to predict a peptide, named DAP1-2, based on the IL-1Ra molecule. DAP1-2 was designed to attenuate responses triggered by IL-1ß by blocking the IL-1R1 receptor. The selection of amino acids from the IL-1Ra molecule (PDB: I1RA) that interact with the three domains of the IL-1R1 receptor was performed using Swiss PDB Viewer. After prediction, chemical synthesis was made using the Fmoc-Synthesis technique. The efficacy of DAP1-2 was assessed using RAW 264.7 cells, which were exposed to LPS (5 µg/mL) for 24 h to induce IL-1ß expression and treated with the peptides in different concentrations. IL-1ß levels were assessed using ELISA, and the gene expression of IL-1ß was measured by RT-qPCR, additionally to the viability test. Results revealed a significant reduction in IL-1ß levels and gene expression in cells stimulated by LPS and treated with DAP1-2 in different concentrations. Furthermore, the MTT assay confirmed the nontoxic nature of the peptides on the cell lineage. This alternative approach shows promise as an IL-1 inhibitor, due to the stability, ease of production, and cost-effectiveness provided by the use of synthetic peptides.

7.
Tuberculosis (Edinb) ; 147: 102505, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38583359

RESUMEN

Leprosy diagnosis is difficult due to the clinical similarity with other infectious diseases, and laboratory tests presents problems related to sensitivity and/or specificity. In this study, we used bioinformatics to assess Mycobacterium leprae proteins and formulated a chimeric protein that was tested as a diagnostic marker for the disease. The amino acid sequences from ML0008, ML0126, ML0308, ML1057, ML2028, ML2038, ML2498 proteins were evaluated, and the B-cell epitopes QASVAYPATSYADFRAHNHWWNGP, SLQRSISPNSYNTARVDP and QLLGQTADVAGAAKSGPVQPMGDRGSVSPVGQ were considered M. leprae-specific and used to construct the gene encoding the recombinant antigen. The gene was constructed, the recombinant protein was expressed, purified and tested in ELISA using 252 sera, which contained samples from multibacillary (MB) or paucibacillary (PB) leprosy patients, from their household contacts and healthy individuals, as well as from patients with Chagas disease, visceral and tegumentary leishmaniases (VL/TL), malaria, tuberculosis, and HIV. Sensitivity (Se) and specificity (Sp) for MB and PB samples compared to sera from both healthy subjects and individuals with cross-reactive diseases were 100%. The Se value for MB and PB samples compared to sera from household contacts was 100%, but Sp was 64%. In conclusion, data suggest that this protein could be considered in future studies for leprosy diagnosis.


Asunto(s)
Antígenos Bacterianos , Proteínas Bacterianas , Ensayo de Inmunoadsorción Enzimática , Epítopos de Linfocito B , Lepra Multibacilar , Lepra Paucibacilar , Mycobacterium leprae , Pruebas Serológicas , Mycobacterium leprae/inmunología , Mycobacterium leprae/genética , Humanos , Epítopos de Linfocito B/inmunología , Pruebas Serológicas/métodos , Ensayo de Inmunoadsorción Enzimática/métodos , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/genética , Lepra Paucibacilar/diagnóstico , Lepra Paucibacilar/inmunología , Proteínas Bacterianas/inmunología , Proteínas Bacterianas/genética , Lepra Multibacilar/diagnóstico , Lepra Multibacilar/inmunología , Anticuerpos Antibacterianos/sangre , Proteínas Recombinantes de Fusión/inmunología , Valor Predictivo de las Pruebas , Femenino , Masculino , Sensibilidad y Especificidad , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética
8.
Toxicon ; 243: 107717, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38614245

RESUMEN

Cancer-related pain is considered one of the most prevalent symptoms for those affected by cancer, significantly influencing quality of life and treatment outcomes. Morphine is currently employed for analgesic treatment in this case, however, chronic use of this opioid is limited by the development of analgesic tolerance and adverse effects, such as digestive and neurological disorders. Alternative therapies, such as ion channel blockade, are explored. The toxin Phα1ß has demonstrated efficacy in blocking calcium channels, making it a potential candidate for alleviating cancer-related pain. This study aims to assess the antinociceptive effects resulting from intravenous administration of the recombinant form of Phα1ß (r-Phα1ß) in an experimental model of cancer-related pain in mice, tolerant or not to morphine. The model of cancer-induced pain was used to evaluate these effects, with the injection of B16F10 cells, followed by the administration of the r-Phα1ß, and evaluation of the mechanical threshold by the von Frey test. Also, adverse effects were assessed using a score scale, the rotarod, and open field tests. Results indicate that the administration of r-Phα1ß provoked antinociception in animals with cancer-induced mechanical hyperalgesia, with or without morphine tolerance. Previous administration of r-Phα1ß was able to recover the analgesic activity of morphine in animals tolerant to this opioid. r-Phα1ß was proved safe for these parameters, as no adverse effects related to motor and behavioral activity were observed following intravenous administration. This study suggests that the concomitant use of morphine and r-Phα1ß could be a viable strategy for pain modulation in cancer patients.


Asunto(s)
Administración Intravenosa , Dolor en Cáncer , Tolerancia a Medicamentos , Morfina , Animales , Morfina/administración & dosificación , Morfina/uso terapéutico , Morfina/farmacología , Dolor en Cáncer/tratamiento farmacológico , Ratones , Analgésicos/uso terapéutico , Analgésicos/farmacología , Venenos de Araña , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/administración & dosificación , Masculino , Proteínas Recombinantes/uso terapéutico , Modelos Animales de Enfermedad , Hiperalgesia/tratamiento farmacológico
9.
Trop Med Infect Dis ; 9(2)2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38393130

RESUMEN

Visceral Leishmaniasis (VL) has a high death rate, with 500,000 new cases and 50,000 deaths occurring annually. Despite the development of novel strategies and technologies, there is no adequate treatment for the disease. Therefore, the purpose of this study is to find structural analogs of natural products as potential novel drugs to treat VL. We selected structural analogs from natural products that have shown antileishmanial activities, and that may impede the purine salvage pathway using computer-aided drug-design (CADD) approaches. For these, we started with the vastly studied target in the pathway, the adenine phosphoribosyl transferase (APRT) protein, which alone is non-essential for the survival of the parasite. Keeping this in mind, we search for a substance that can bind to multiple targets throughout the pathway. Computational techniques were used to study the purine salvage pathway from Leishmania infantum, and molecular dynamic simulations were used to gather information on the interactions between ligands and proteins. Because of its low homology to human proteins and its essential role in the purine salvage pathway proteins network interaction, the findings further highlight the significance of adenylosuccinate lyase protein (ADL) as a therapeutic target. An analog of the alkaloid Skimmianine, N,N-diethyl-4-methoxy-1-benzofuran-6-carboxamide, demonstrated a good binding affinity to APRT and ADL targets, no expected toxicity, and potential for oral route administration. This study indicates that the compound may have antileishmanial activity, which was granted in vitro and in vivo experiments to settle this finding in the future.

10.
Front Vet Sci ; 11: 1248811, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38414656

RESUMEN

Current vaccination protocols raise concerns about the efficacy of immunization. There is evidence that changes in the gut microbiota can impact immune response. The formation of the gut microbiota in newborns plays a crucial role in immunity. Probiotic bacteria and prebiotics present important health-promoting and immunomodulatory properties. Thus, we hypothesize that pro and prebiotic supplementation can improve the efficacy of vaccination in newborns. In this protocol, newborn mice were used and treated with a single-dose rabies vaccine combined with Nuxcell Neo® (2 g/animal/week) for 3 weeks. Samples were collected on days 7, 14, and 21 after vaccination for analysis of cytokines and concentration of circulating antibodies. Our results show an increased concentration of antibodies in animals vaccinated against rabies and simultaneously treated with Nuxcell Neo® on days 14 and 21 when compared to the group receiving only the vaccine. In the cytokine levels analysis, it was possible to observe that there weren't relevant and significant changes between the groups, which demonstrates that the health of the animal remains stable. The results of our study confirm the promising impact of the use of Nuxcell Neo® on the immune response after vaccination.

11.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38338740

RESUMEN

Some parasites are known to influence brain proteins or induce changes in the functioning of the nervous system. In this study, our objective is to demonstrate how the two-dimensional gel technique is valuable for detecting differences in protein expression and providing detailed information on changes in the brain proteome during a parasitic infection. Subsequently, we seek to understand how the parasitic infection affects the protein composition in the brain and how this may be related to changes in brain function. By analyzing de novo-expressed proteins at 2, 4, and 8 weeks post-infection compared to the brains of the control mice, we observed that proteins expressed at 2 weeks are primarily associated with neuroprotection or the initial response of the mouse brain to the infection. At 8 weeks, parasitic infection can induce oxidative stress in the brain, potentially activating signaling pathways related to the response to cellular damage. Proteins expressed at 8 weeks exhibit a pattern indicating that, as the host fails to balance the Neuro-Immuno-Endocrine network of the organism, the brain begins to undergo an apoptotic process and consequently experiences brain damage.


Asunto(s)
Parásitos , Enfermedades Parasitarias , Taenia , Animales , Ratones , Encéfalo , Ratones Endogámicos BALB C
12.
Inflammation ; 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38236386

RESUMEN

Chronic hyperglycemia caused by diabetes mellitus (DM) slows down the healing process due to prolonged inflammation which impedes the regeneration progression. Photobiomodulation (PBM) is considered a non-pharmacological intervention and has anti-inflammatory and biostimulatory effects that accelerate the healing process. Currently found IL-1ß inhibitors are difficult to implement due to their cytotoxic potential, excessive amounts, and invasive administration, and therefore, the application of this peptide in diabetic wounds represents a promising intervention to help resolve the inflammatory response. This study aimed to investigate the effect of an IL-1ß inhibitor molecule associated with PBM irradiation in a model of epithelial injury in diabetic mice. After the induction of the DM model with streptozotocin (STZ), the skin lesion model was implemented through surgical excision. Sixty C57BL/6 mice divided into five experimental groups (n = 12) were used: excisional wound (EW), DM + EW, DM + EW + DAP 1-2 (inhibitor peptide), DM + EW + PBM, and DM + EW + PBM + DAP 1-2. Treatment started 12 h after wound induction and was performed daily for 5 days. Twenty-four hours after the last application, the animals were euthanized and the outer edge of the wound was removed. The results obtained demonstrate that the DM + EW + PBM + DAP 1-2 group caused a reduction in the levels of pro-inflammatory cytokines, an increase in anti-inflammatory cytokines, and an increase in TGF-ß and maintenance of the cellular redox state with a consequent reduction in levels of inflammatory infiltrate and concomitant stimulation of type III collagen gene expression, as well as a decrease in the size of the wound in square centimeter 6 days after the injury. Only the combination of therapies was able to favor the process of tissue regeneration due to the development of an approach capable of acting at different stages of the regenerative process, through the mechanisms of action of interventions on the inflammatory process by avoiding its stagnation and stimulating progression of regeneration.

13.
Mol Neurobiol ; 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38296901

RESUMEN

Obesity causes inflammation in the adipose tissue and can affect the central nervous system, leading to oxidative stress and mitochondrial dysfunction. Therefore, it becomes necessary to seek new therapeutic alternatives. Gold nanoparticles (GNPs) could take carnitine to the adipose tissue, thus increasing fatty acid oxidation, reducing inflammation, and, consequently, restoring brain homeostasis. The objective of this study was to investigate the effects of GNPs associated with carnitine on the neurochemical parameters of obesity-induced mice. Eighty male Swiss mice that received a normal lipid diet (control group) or a high-fat diet (obese group) for 10 weeks were used. At the end of the sixth week, the groups were divided for daily treatment with saline, GNPs (70 µg/kg), carnitine (500 mg/kg), or GNPs associated with carnitine, respectively. Body weight was monitored weekly. At the end of the tenth week, the animals were euthanized and the mesenteric fat removed and weighed; the brain structures were separated for biochemical analysis. It was found that obesity caused oxidative damage and mitochondrial dysfunction in brain structures. Treatment with GNPs isolated reduced oxidative stress in the hippocampus. Carnitine isolated decreased the accumulation of mesenteric fat and oxidative stress in the hippocampus. The combination of treatments reduced the accumulation of mesenteric fat and mitochondrial dysfunction in the striatum. Therefore, these treatments in isolation, become a promising option for the treatment of obesity.

14.
J Thorac Oncol ; 19(1): 94-105, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37595684

RESUMEN

INTRODUCTION: With global adoption of computed tomography (CT) lung cancer screening, there is increasing interest to use artificial intelligence (AI) deep learning methods to improve the clinical management process. To enable AI research using an open-source, cloud-based, globally distributed, screening CT imaging data set and computational environment that are compliant with the most stringent international privacy regulations that also protect the intellectual properties of researchers, the International Association for the Study of Lung Cancer sponsored development of the Early Lung Imaging Confederation (ELIC) resource in 2018. The objective of this report is to describe the updated capabilities of ELIC and illustrate how this resource can be used for clinically relevant AI research. METHODS: In this second phase of the initiative, metadata and screening CT scans from two time points were collected from 100 screening participants in seven countries. An automated deep learning AI lung segmentation algorithm, automated quantitative emphysema metrics, and a quantitative lung nodule volume measurement algorithm were run on these scans. RESULTS: A total of 1394 CTs were collected from 697 participants. The LAV950 quantitative emphysema metric was found to be potentially useful in distinguishing lung cancer from benign cases using a combined slice thickness more than or equal to 2.5 mm. Lung nodule volume change measurements had better sensitivity and specificity for classifying malignant from benign lung nodules when applied to solid lung nodules from high-quality CT scans. CONCLUSIONS: These initial experiments revealed that ELIC can support deep learning AI and quantitative imaging analyses on diverse and globally distributed cloud-based data sets.


Asunto(s)
Aprendizaje Profundo , Enfisema , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Inteligencia Artificial , Detección Precoz del Cáncer , Pulmón/patología , Enfisema/patología
15.
Neurochem Res ; 49(3): 758-770, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38104040

RESUMEN

Maple Syrup Urine Disease (MSUD) is a metabolic disease characterized by the accumulation of branched-chain amino acids (BCAA) in different tissues due to a deficit in the branched-chain alpha-ketoacid dehydrogenase complex. The most common symptoms are poor feeding, psychomotor delay, and neurological damage. However, dietary therapy is not effective. Studies have demonstrated that memantine improves neurological damage in neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Therefore, we hypothesize that memantine, an NMDA receptor antagonist can ameliorate the effects elicited by BCAA in an MSUD animal model. For this, we organized the rats into four groups: control group (1), MSUD group (2), memantine group (3), and MSUD + memantine group (4). Animals were exposed to the MSUD model by the administration of BCAA (15.8 µL/g) (groups 2 and 4) or saline solution (0.9%) (groups 1 and 3) and treated with water or memantine (5 mg/kg) (groups 3 and 4). Our results showed that BCAA administration induced memory alterations, and changes in the levels of acetylcholine in the cerebral cortex. Furthermore, induction of oxidative damage and alterations in antioxidant enzyme activities along with an increase in pro-inflammatory cytokines were verified in the cerebral cortex. Thus, memantine treatment prevented the alterations in memory, acetylcholinesterase activity, 2',7'-Dichlorofluorescein oxidation, thiobarbituric acid reactive substances levels, sulfhydryl content, and inflammation. These findings suggest that memantine can improve the pathomechanisms observed in the MSUD model, and may improve oxidative stress, inflammation, and behavior alterations.


Asunto(s)
Enfermedad de la Orina de Jarabe de Arce , Ratas , Animales , Enfermedad de la Orina de Jarabe de Arce/tratamiento farmacológico , Enfermedad de la Orina de Jarabe de Arce/metabolismo , Memantina/farmacología , Memantina/uso terapéutico , Acetilcolinesterasa , Modelos Animales de Enfermedad , Aminoácidos de Cadena Ramificada , Antioxidantes/farmacología , Inflamación
16.
J Drug Target ; 32(2): 172-185, 2024 12.
Artículo en Inglés | MEDLINE | ID: mdl-38155427

RESUMEN

Introduction: The search for fast and efficient treatment for dermonecrotic lesions caused by the venom of the spider from the Loxosceles simillis, is a demand in health. Prednisolone is one of the most used drugs, however it has side effects. In this context, addictionally gold nanoparticles (GNPs) have anti-inflammatory, antioxidant, and antibacterial properties. The use of photobiomodulation has show to be efficient in the process of tissue repair. Therefore, the purpose of this study was to investigate the anti-inflammatory effect of photobiomodulation and GNPs associated or not with a low concentration of prednisolone in animal models of dermonecrotic lesion.Methodology: For this, rabbits with venon-induced dermonecrotic lesion were subjected to topical treatment with prednisolone + laser or GNPs + laser or Pred-GNPs + laser. The area of edema, necrosis and erythema were measured. On the last day of treatment, the animals were euthanized to remove the organs for histopathological and biochemical analysis.Results: All treatments combinations were effective in promoting the reduction of necrotic tissue and erythema.Conclusion: With this results, we suggest that the use of laser and nanoparticles, associated or not with prednisolone, should be considered for the treatment of dermonecrotic injury.


Asunto(s)
Terapia por Luz de Baja Intensidad , Nanopartículas del Metal , Venenos de Araña , Animales , Conejos , Hidrolasas Diéster Fosfóricas/química , Oro , Venenos de Araña/química , Eritema , Prednisolona/farmacología , Prednisolona/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico
17.
Quant Imaging Med Surg ; 13(9): 6193-6204, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37711774

RESUMEN

Background: A calibration phantom-based method has been developed for predicting small lung nodule volume measurement bias and precision that is specific to a particular computed tomography (CT) scanner and acquisition protocol. Methods: The approach involves CT scanning a simple reference object with a specific acquisition protocol, analyzing the scan to estimate the fundamental imaging properties of the CT acquisition system, generating numerous simulated images of a target geometry using the fundamental imaging properties, measuring the simulated images with a standard nodule volume segmentation algorithm, and calculating bias and precision performance statistics from the resulting volume measurements. We evaluated the ability of this approach to predict volume measurement bias and precision of Teflon spheres (diameters =4.76, 6.36, and 7.94 mm) placed within an anthropomorphic chest phantom when using 3M Scotch Magic™ tape as the reference object. CT scanning of the spheres was performed with 0.625, 1.25, and 2.5 mm slice thickness and spacing. Results: The study demonstrated good agreement between predicted volumetric performance and observed volume measurement performance for both volumetric measurement bias and precision. The predicted and observed volume mean for all slice thicknesses was found to be 28% and 13% lower on average than the manufactured sphere volume, respectively. When restricted to 0.625 and 1.25 mm slice thickness scans, which are recommended for small lung nodule volume measurement, we found that the difference between predicted and observed volume coefficient of variation was less than 1.0 %. The approach also showed a resilience to varying CT image acquisition protocols, a critical capability when deploying in a real-world clinical setting. Conclusions: This is the first report of a calibration phantom-based method's ability to predict both small lung nodule volume measurement bias and precision. Volume measurement bias and precision for small lung nodules can be predicted using simple low-cost reference objects to estimate fundamental CT image characteristics and modeling and simulation techniques. The approach demonstrates an improved method for predicting task specific, clinically relevant measurement performance using advanced and fully automated image analysis techniques and low-cost reference objects.

18.
Viruses ; 15(9)2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37766284

RESUMEN

The impact of the COVID-19 pandemic caused by the SARS-CoV-2 virus underscored the crucial role of laboratorial tests as a strategy to control the disease, mainly to indicate the presence of specific antibodies in human samples from infected patients. Therefore, suitable recombinant antigens are relevant for the development of reliable tests, and so far, single recombinant proteins have been used. In this context, B-cell epitopes-based chimeric proteins can be an alternative to obtain tests with high accuracy through easier and cheaper production. The present study used bioinformatics tools to select specific B-cell epitopes from the spike (S) and the nucleocapsid (N) proteins from the SARS-CoV-2 virus, aiming to produce a novel recombinant chimeric antigen (N4S11-SC2). Eleven S and four N-derived B-cell epitopes were predicted and used to construct the N4S11-SC2 protein, which was analyzed in a recombinant format against serum and urine samples, by means of an in house-ELISA. Specific antibodies were detected in the serum and urine samples of COVID-19 patients, which were previously confirmed by qRT-PCR. Results showed that N4S11-SC2 presented 83.7% sensitivity and 100% specificity when using sera samples, and 91.1% sensitivity and 100% specificity using urine samples. Comparable findings were achieved with paired urine samples when compared to N and S recombinant proteins expressed in prokaryotic systems. However, better results were reached for N4S11-SC2 in comparison to the S recombinant protein when using paired serum samples. Anti-N4S11-SC2 antibodies were not clearly identified in Janssen Ad26.COV2.S COVID-19-vaccinated subjects, using serum or paired urine samples. In conclusion, this study presents a new chimeric recombinant antigen expressed in a prokaryotic system that could be considered as an alternative diagnostic marker for the SARS-CoV-2 infection, with the potential benefits to be used on serum or urine from infected patients.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Epítopos de Linfocito B , Ad26COVS1 , Pandemias , COVID-19/diagnóstico , Proteínas Recombinantes/genética , Proteínas Recombinantes de Fusión/genética
19.
Antioxidants (Basel) ; 12(8)2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37627569

RESUMEN

This study aimed to evaluate and compare the effects of treatment with gold nanoparticles (GNPs) reduced with Curcumin (Curcuma longa L.) or Açai (Euterpe oleracea) to a standard commercial treatment of the pharmacological type (Omcilon®) and an electrophysical agent (photobiomodulation) in the palatal wounds of rats. As for the in vitro assay, a cell viability test was performed to assess the toxicity of the synthesized nanoparticles. In vivo assay: 60 Wistar rats were divided into five groups (n = 12): I. Palatal Wound (PW); II. PW + Photobiomodulation (PBM); III. PW + Omcilon®; IV. PW + GNPs-Cur (0.025 mg/mL); V. PW + GNPs-Açai (0.025 mg/mL). Animals were first anesthetized, and circular lesions in the palatine mucosa were induced using a 4 mm-diameter punch. The first treatment session started 24 h after the injury and occurred daily for 5 days. The animals were euthanized, and the palatal mucosa tissue was removed for histological, biochemical, and molecular analysis. GNPs-Açai were able to significantly reduce pro-inflammatory cytokines and increase anti-inflammatory ones, reduce oxidant markers, and reduce inflammatory infiltrate while increasing the collagen area and contraction rate of the wound, along with an improved visual qualification. The present study demonstrated that the proposed therapies of GNPs synthesized greenly, thus associating their effects with those of plants, favor the tissue repair process in palatal wounds.

20.
Int J Biol Macromol ; 246: 125588, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37399872

RESUMEN

In the Americas and specially in Brazil, the Loxosceles intermedia, Loxosceles gaucho and Loxosceles laeta are the three most medically relevant brown spider species, and whose bites can lead to the condition known as loxoscelism. Here, we report the development of a tool capable of identifying a common epitope amongst Loxosceles sp. venom's toxins. A murine monoclonal antibody (LmAb12) and its recombinant fragments (scFv12P and diabody12P) have been produced and characterized. This antibody and its recombinant constructs were able to recognize proteins of Loxosceles spider venoms with specificity. The scFv12P variant was also able to detect low concentrations of Loxosceles venom in a competitive ELISA assay, displaying potential as a venom identification tool. The primary antigenic target of LmAb12 is a knottin, a venom neurotoxin, that has a shared identity of 100 % between the L. intermedia and L. gaucho species and high similarity to L. laeta. Furthermore, we observed LmAb12 was able to partially inhibit in vitro hemolysis, a cellular event typically induced by the Loxosceles sp. venoms. Such behavior might be due to LmAb12 cross-reactivity between the antigenic target of LmAb12 and the venom's dermonecrotic toxins, the PLDs, or even the existence of synergism between these two toxins.


Asunto(s)
Venenos de Araña , Arañas , Animales , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Antígenos/química , Antivenenos/química , Reacciones Cruzadas , Miniproteínas Nodales de Cistina/química , Fosfolipasa D/química , Venenos de Araña/química , Arañas/química , Epítopos/química
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