ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Enzyme-Linked Immunosorbent Assay , Polyethylene Glycols , Sensitivity and Specificity , Humans , Enzyme-Linked Immunosorbent Assay/methods , Polyethylene Glycols/chemistry , Antigens, Protozoan/immunology , Leishmaniasis/diagnosis , Magnetic Iron Oxide Nanoparticles/chemistry , Antibodies, Protozoan/bloodABSTRACT
Poly(thioether-ester) (PTEe) nanoparticles obtained by thiol-ene polymerization have received attention of many researchers due to several advantages, including, biocompatibility and biodegradability. The search for new nanomaterials requires toxicity studies to assess potential toxic effects of their administration. Therefore, the aim of this study was to evaluate the in vivo acute toxicity of PTEe and poly(thioether-ester)-coated magnetic nanoparticles prepared by thiol-ene polymerization in miniemulsion. These nanoparticles presented a mean size of approximately 120 nm, spherical morphology, and negative surface charge. Doses of 40 mg/kg were administered intraperitoneally to Swiss mice and nociceptive, behavioral and biochemical parameters were investigated in five different organs. None of the nanoparticles led to any alterations in the nociceptive and behavioral responses. Biochemical alterations were observed in liver, decreasing the sulfhydryl and glutathione (GSH) levels, suggesting the dependence of the GSH metabolism in the elimination of the nanoparticles. In general, both nanoparticle types did not cause disturbances in biochemical parameters analyzed in others organs. These results suggest that both nanoparticle types did not induce acute toxicity to the different organs evaluated, reinforcing the biocompatibility of PTEe nanoparticles synthetized by thiol-ene polymerization.
Subject(s)
Nanoparticles , Sulfides , Animals , Esters , Magnetic Iron Oxide Nanoparticles , Mice , Nanoparticles/toxicity , Polymerization , Sulfhydryl Compounds , Sulfides/toxicityABSTRACT
El presente artículo tuvo como objetivo presentar un caso clínico de una paciente que buscó la clínica del SERVICIO ATM quejándose de graves chasquidos durante la masticación y dolor en los músculos masticatorios, que han comenzado poco después de sufrir un accidente de autobús. El diagnóstico fue sugestivo de desorden temporomandibulares asociado con injuria en flexión-extensión del cuello. Este tipo de lesión es secundaria a una fuerza súbita, lo que conduce a un mecanismo de aceleración-deceleración de energía transferida al cuello, que puede causar daños a los tejidos blandos y una variedad de manifestaciones clínicas. A menudo se produce después de los accidentes de tráfico y es responsable de la aparición de muchos casos de desorden temporomandibular. Los principales síntomas son graves chasquidos, sensibilidad dolorosa a la palpación de los músculos de la masticación, en la articulación temporomandibular durante la apertura de la boca, en el cuello y las estructuras adyacentes, además de dolor de cabeza. El tratamiento propuesto se instituyó el uso de férula oclusal, 24 horas al día, reduciendo el tiempo de uso de acuerdo a la regresión de los síntomas. Después de 5 meses de tratamiento, hubo regresión total del dolor y parcial del chasquido
The aim of this article is to report clinical case of a pacient that described severe "clicking sound" during the chewing and pain in the masticatory muscles, which began immediately after a motor vehicle accident. The suggestive diagnosis was temporomandibular joint disorder associated to a whiplash injury. It has been described as an acceleration-deceleration mechanism of energy transfer to the neck, which can lead to soft tissue injuries and a variety of clinical manifestations. These injuries usually occur after motor vehicle accidents and it's responsible for the occurrence of many cases of temporomandibular joint disorder. The main signs and symptoms are severe "clicking sound", pain in the masticatory muscles, temporomandibular joint pain during wide mouth opening, pain in the neck and adjacent structures and headache. The proposed treatment consisted of the use of oclusal splint, 24 hours per day. The decreasing of use was indicated accordingly to the decreasing of the symptoms. After five months, the pain was extinguished and clicking sound was partially decreased
