Treatment topical with silver nanoparticles and Stryphnodendron Adstringens (Mart.) Coville in cervical lesions: randomized clinical trial.

OBJECTIVE: To assess the feasibility of incorporating technology as a new alternative for treating topics on cervical lesions. METHOD: This is a randomized, double-blind, controlled clinical trial with a prospective design. During the realization of this study, 43 women were included and divided between groups A (ointment without silver nanoparticles n = 23) and B (ointment with silver nanoparticles n = 20) clinically healthy and who used the unified health system. RESULTS: There were no significant differences when comparing before and after the use of ointment for IVA test (p = 0.15), Schiller test (p = 0.15), cellular changes (p = 0.47) and microbiological analysis (p = 0.89) through cytology. After use, no adverse reaction was observed in the sample studied. CONCLUSION: Based on the results identified in this study, identified that the product is safe and does not promote adverse events. Regarding the effectiveness of the product in uterine cervical lesions, it is necessary to continue the study in phase II. Registro de Ensaios Clínicos Brasileiros: UTN: U1111-1218-2820.

Treatment topical with silver nanoparticles and Stryphnodendron Adstringens (Mart. ) Coville in cervical lesions: randomized clinical trial / Tratamento tópico com nanopartículas de prata e Stryphnodendron Adstringens (Mart. ) Coville em lesões cervicais: ensaio clínico randomizado / Tratamiento tópico con nanopartículas de plata y Stryphnodendron Adstringens (Mart. ) Coville en lesiones cervicales: ensayo clínico aleatorizado

ABSTRACT Objective: To assess the feasibility of incorporating technology as a new alternative for treating topics on cervical lesions. Method: This is a randomized, double-blind, controlled clinical trial with a prospective design. During the realization of this study, 43 women were included and divided between groups A (ointment without silver nanoparticles n = 23) and B (ointment with silver nanoparticles n = 20) clinically healthy and who used the unified health system. Results: There were no significant differences when comparing before and after the use of ointment for IVA test (p = 0.15), Schiller test (p = 0.15), cellular changes (p = 0.47) and microbiological analysis (p = 0.89) through cytology. After use, no adverse reaction was observed in the sample studied. Conclusion: Based on the results identified in this study, identified that the product is safe and does not promote adverse events. Regarding the effectiveness of the product in uterine cervical lesions, it is necessary to continue the study in phase II. Registro de Ensaios Clínicos Brasileiros: UTN: U1111-1218-2820.

RESUMO Objetivo: Avaliar a viabilidade da incorporação da tecnologia como uma nova alternativa para o tratamento de lesões cervicais. Método: Trata-se de um ensaio clínico randomizado, duplo-cego e controlado com um desenho prospectivo. Durante a realização deste estudo, foram incluídas 43 mulheres, divididas entre os grupos A (pomada sem nanopartículas de prata n = 23) e B (pomada com nanopartículas de prata n = 20), clinicamente saudáveis e usuárias do sistema único de saúde. Resultados: Não houve diferenças significativas na comparação entre antes e depois do uso da pomada para o teste IVA (p = 0,15), teste de Schiller (p = 0,15), alterações celulares (p = 0,47) e análise microbiológica (p = 0,89) por meio de citologia. Após o uso, não foi observada nenhuma reação adversa na amostra estudada. Conclusões: Com base nos resultados identificados neste estudo, identificou-se que o produto é seguro e não promove eventos adversos. Com relação à eficácia do produto em lesões cervicais uterinas, é necessária a continuidade do estudo na fase II. Registro de Ensaios Clínicos Brasileiros: UTN: U1111-1218-2820.

RESUMEN Objetivo: evaluar la viabilidad de la incorporación de la tecnología como una nueva alternativa para el tratamiento de temas sobre lesiones cervicales. Método: Se trata de un ensayo clínico aleatorizado, doble ciego, controlado y con un diseño prospectivo. Durante la realización de este estudio se incluyeron 43 mujeres divididas entre los grupos A (pomada sin nanopartículas de plata n = 23) y B (pomada con nanopartículas de plata n = 20) clínicamente sanas y usuarias del sistema unificado de salud. Resultados: No hubo diferencias significativas al comparar antes y después del uso de la pomada para la prueba de IVA (p = 0,15), la prueba de Schiller (p = 0,15), los cambios celulares (p = 0,47) y el análisis microbiológico (p = 0,89) mediante citología. Tras el uso, no se observó ninguna reacción adversa en la muestra estudiada. Conclusiones: Con base en los resultados identificados en este estudio, se identificó que el producto es seguro y no promueve eventos adversos. Con relación a la eficacia del producto en lesiones cervicales uterinas, es necesario continuar el estudio en fase II. Registro de Estudios Clínicos Brasileños: UTN: U1111-1218-2820.

Polymorphisms in Toll-like receptors genes changes the host's immune response and is associated with cervical cancer.

Polymorphisms in Toll-like receptors (TLRs) genes have been associated with cervical cancer, but some inconsistencies were found in the results. The present study aimed to investigate the role of polymorphisms in the TLRs genes in cervical cancer, through meta-analysis and bioinformatics analysis. Searches were performed in PubMed, Science Direct, Scopus and Web of science online databases until November 2020. For bioinformatics analysis, we used SNP2TFBS, Raptor-X, MUpro, Gene Expression Profiling Interactive Analysis (GEPIA). The results of meta-analysis showed that the +1196T (rs4986791 TLR4), +7764T (rs1927911 TLR4), -1486C (rs187084 TRL9) +2848A (rs352140 TRL9) alleles carriers and -2604G/G (rs10759931 TLR4), -1237C/C (rs5743836 TRL9) genotypes were associated with an increased risk for cervical cancer. The bioinformatics analysis revealed that the -1237T>C (rs5743836) and -1486T>C (rs187084) polymorphisms can affect the transcription factors binding sites (RELA, NFKB1 and THAP1) in the TLR9 gene, and the +2848G>A (rs352140) polymorphism seems to alter the structure and stability of TLR4 protein. Additionally, using GEPIA, was observed a significantly high of IL-1ß, IL-18 and TNF-α expression in cervical cancer tissues compared to normal tissues. These finds indicate that polymorphisms in the TLR4 and TLR9 genes can affect intracellular signaling and, consequently, change the patterns of the immune response, leading to an increased risk for cervical cancer.

Discovery of sulfonyl hydrazone derivative as a new selective PDE4A and PDE4D inhibitor by lead-optimization approach on the prototype LASSBio-448: In vitro and in vivo preclinical studies.

Phosphodiesterase 4 (PDE4) inhibitors have emerged as a new strategy to treat asthma and other lung inflammatory diseases. Searching for new PDE4 inhibitors, we previously reported the discover of LASSBio-448, a sulfonamide with potential to prevent and reverse pivotal pathological features of asthma. In this paper, two novel series of sulfonamide (6a-6m) and sulfonyl hydrazone (7a-7j) analogues of LASSBio-448 have been synthetized and evaluated for selective inhibitory activity toward cAMP-specific PDE4 isoforms. From these studies, we have identified 7j (LASSBio-1632) as a new anti-asthmatic lead-candidate associated with selective inhibition of PDE4A and PDE4D isoenzymes and blockade of airway hyper-reactivity (AHR) and TNF-α production in the lung tissue. In addition, it was able to relax guinea pig trachea on non-sensitized and sensitized animals and showed great TGI permeability.

Association of polymorphisms in serotonin and nitric oxide genes with clinical outcome of dengue in Brazilian northeast population.

Serotonin and nitric oxide seem to be involved in Dengue virus infection. The aim of this study was to investigate if SNPs in serotonin and nitric oxide are associated with dengue severity. A retrospective case-control study was conducted, with groups of dengue fever (DF; n = 78) and dengue hemorrhagic fever patients (DHF; n = 49). Genotyping was performed using qPCR and PCR. The power of the sample size was calculated by G*power software. The heterozygous SL for 5-HTTLPR SNP was significantly correlated with protection against progression to DHF in the codominant SS/SL/LL (OR = 0.22, 95% CI = 0.06-0.81, p = 0.011) and overdominant models SL vs SS + LL (OR = 0.19, 95% CI = 0.06-0.65, p = 0.003). For the ENOS (rs1799983) SNP, the genotype GT was positively associated with protection for development of the clinical form in DHF compared to dengue fever (OR = 0.39, 95% CI = (0.13-1.14), p = 0.0058) in codominant GG/GT/TT and overdominant model GT vs GG + TT (OR = 0.35, 95% CI = (0.12-1.02), p = 0.04). To our knowledge, this is the first study to identify the association of the serotonin and nitric oxide SNPs with dengue severity.

2-Amino-thiophene derivatives present antileishmanial activity mediated by apoptosis and immunomodulation in vitro.

This study evaluated the effects of 2-amino-thiophene derivatives on the promastigote and amastigote forms of Leishmania (Leishmania) amazonensis and their possible mechanisms of action. Initially, we evaluated the antileishmanial activity of ten 2-amino-thiophene derivatives on promastigote and axenic amastigote forms of Leishmania amazonensis and their cytotoxicity against murine macrophages and human red blood cells. Three promising compounds were selected for studies of the cell death process using flow cytometry analysis and a DNA fragmentation assay. The effects of the compounds were assessed on intramacrophagic amastigotes, and the modulation of cytokine and NO production was investigated. All thiophene derivatives showed antileishmanial activity against promastigotes and axenic amastigotes with less toxicity for murine macrophages and human red blood cells. The best values were obtained for compounds containing a lateral indole ring. Docking studies suggested that these compounds played an important role in inhibiting trypanothione reductase (TryR) activity. The selected compounds SB-200, SB-44, and SB-83 induced apoptosis in promastigotes involving phosphatidylserine externalization and DNA fragmentation in a pattern similar to that observed for the positive control. Additionally, SB-200, SB-44, and SB-83 significantly reduced the infection index of macrophages by the parasites; for compounds SB-200 and SB-83 this reduction was associated with increased TNF-α, IL-12, and NO levels. This study demonstrated the effective and selective action of 2-amino-thiophene derivatives against L. amazonensis, resulting in apoptosis-like cell death and immunomodulation in vitro. The results suggest that they are promising compounds for the development of new leishmanicidal drugs.

Novel ruthenium complexes as potential drugs for Chagas's disease: enzyme inhibition and in vitro/in vivo trypanocidal activity.

BACKGROUND AND PURPOSE: The discovery of the pharmacological functions of nitric oxide has led to the development of NO donor compounds as therapeutic agents. A new generation of ruthenium NO donors, cis-[Ru(NO)(bpy)(2)L]X(n), has been developed, and our aim was to show that these complexes are able to lyse Trypanosoma cruzi in vitro and in vivo. EXPERIMENTAL APPROACH: NO donors were incubated with T. cruzi and their anti-T. cruzi activities evaluated as the percentage of lysed parasites compared to the negative control. In vivo, trypanocidal activity was evaluated by observing the levels of parasitaemia, survival rate and elimination of amastigotes in mouse myocardial tissue. The inhibition of GAPDH was monitored by the biochemical reduction of NAD(+) to NADH. KEY RESULTS: The NO donors cis-[Ru(NO)(bpy)(2)L]X(n) presented inhibitory effects on T. cruzi GAPDH (IC(50) ranging from 89 to 153 microM). The crystal structure of the enzyme shows that the inhibitory mechanism is compatible with S-nitrosylation of the active cysteine (cys166) site. Compounds cis-[Ru(NO)(bpy)(2)imN](PF(6))(3) and cis-[Ru(NO)(bpy)(2)SO(3)]PF(6), at a dose of 385 nmol.kg(-1), yielded survival rates of 80 and 60%, respectively, in infected mice, and eradicated any amastigotes from their myocardial tissue. CONCLUSIONS AND IMPLICATIONS: The ruthenium compounds exhibited potent in vitro and in vivo trypanocidal activities at doses up to 1000-fold lower than the clinical dose for benznidazole. Furthermore, one mechanism of action of these compounds is via the S-nitrosylation of Cys166 of T. cruzi GAPDH. Thus, these compounds show huge potential as candidates for the development of new drugs for the treatment of Chagas's disease.