RESUMO
Silver nanoparticles (Ag-NPs), silver oxide nanoparticles (AgO-NPs), and zinc oxide nanoparticles (ZnO-NPs) have healing, antibacterial, and antioxidant properties. Furthermore, Ag-NPs and ZnO-NPs also have anti-inflammatory properties. In this study, we synthesized a nanocomposite using Ag-ZnO and AgO-NPs (Ag-ZnO/AgO NPs). The structural and morphological properties of nanocrystals and nanocomposite were investigated by X-ray diffraction and scanning electronics microscopic. The wurtzite crystalline structure of Ag-ZnO and two morphologies for the nanocomposite (nanorods and nanoplatelets) were determined. Topical treatment with 1% Ag-ZnO/AgO NPs was compared to untreated wounds (control group). Wounds were induced in the dorsal region of BALB/c mice and evaluated after 3, 7, 14, and 21 days of treatment. The nanocomposite demonstrated anti-inflammatory and antioxidant capacities. In addition, wounds treated with Ag-ZnO/AgO NPs showed accelerated closure, non-cytotoxicity, especially on keratinocytes and collagen deposition, and increased metalloproteinases 2 and 9 activity. The nanocomposite improved healing by reducing the inflammatory process, protecting tissues from damage caused by free radicals, and increasing collagen deposition in the extracellular matrix. These characteristics contributed to the accelerated wound closure process. Thus, Ag-ZnO/AgO NPs show potential for can be a strategy for topical use in formulations of new drugs to treat wounds.
Assuntos
Nanopartículas Metálicas , Nanocompostos , Óxido de Zinco , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Nanopartículas Metálicas/química , Camundongos , Nanocompostos/química , Óxidos , Prata/farmacologia , Compostos de Prata , Cicatrização , Óxido de Zinco/química , Óxido de Zinco/farmacologiaRESUMO
The species Annona nutans (R. E. Fries) is a plant found in Bolivia, Paraguay, Argentina and the Brazilian cerrado. Considering the anti-inflammatory and antinociceptive activities of the hydrometanolic fraction (FHMeOH) of A. nutans leaves previously reported, the present study aimed to evaluate in vivo anti-inflammatory and antinociceptive activities of a subfraction obtained from FHMeOH, the butanolic fraction (FBuOHf). Intraperitoneal (i.p.) treatment with FBuOHf (50 and 100 mg · kg-1) inhibited paw edema induced by carrageenan. Moreover, FBuOHf (100 mg · kg-1, i.p.) also suppressed polymorphonuclear (PMN) leukocyte migration in the footpad. Regarding the antinociceptive activity, FBuOHf (50, 100, and 200 mg · kg-1, i.p.) inhibited acetic acid-induced abdominal writhing. In the formalin test, this fraction (200 mg · kg-1, i.p.) reduced licking time only in the inflammatory phase. The FBuOHf contents flavonoids and cinnamic acid derivatives, such as quercetin-3-O-galactoside, quercetin-3-O-glucoside, isorhamnetin-3-O-galactoside, quercetin-3-O-ß-D-apio-furanosyl-(1â2)-galactopyranoside and chlorogenic acid, identified and quantified by LC-MS. The FBuOHf possesses anti-inflammatory and peripheral antinociceptive activities.
Assuntos
Annona , Annonaceae , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Carragenina , Edema/induzido quimicamente , Edema/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de PlantaRESUMO
Gliomas account for nearly 70% of the central nervous system tumors and present a median survival of approximately 12-17 months. Studies have shown that administration of novel natural antineoplastic agents is been highly effective for treating gliomas. This study was conducted to investigate the antitumor potential (in vitro and in vivo) of Miconia chamissois Naudin for treating glioblastomas. We investigated the cytotoxicity of the chloroform partition and its sub-fraction in glioblastoma cell lines (GAMG and U251MG) and one normal cell line of astrocytes. The fraction showed cytotoxicity and was selective for tumor cells. Characterization of this fraction revealed a single compound, Matteucinol, which was first identified in the species M. chamissois. Matteucinol promoted cell death via intrinsic apoptosis in the adult glioblastoma lines. In addition, Matteucinol significantly reduced the migration, invasion, and clonogenicity of the tumor cells. Notably, it also reduced tumor growth and angiogenesis in vivo. Moreover, this agent showed synergistic effects with temozolomide, a chemotherapeutic agent commonly used in clinical practice. Our study demonstrates that Matteucinol from M chamissois is a promising compound for the treatment of glioblastomas and may be used along with the existing chemotherapeutic agents for more effective treatment.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Cromonas/uso terapêutico , Glioblastoma/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Embrião de Galinha , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/efeitos dos fármacos , Cromonas/isolamento & purificação , Cromonas/farmacologia , Glioblastoma/irrigação sanguínea , Humanos , Melastomataceae , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Extratos Vegetais , Folhas de PlantaRESUMO
Sm16 is an immunomodulatory protein that seems to play a key role in the suppression of the cutaneous inflammatory response during Schistosoma mansoni penetration of the skin of definitive hosts. Therefore, Sm16 represents a potential target for protective immune responses induced by vaccination. In this work, we generated the recombinant protein rSm16 and produced polyclonal antibodies against this protein to evaluate its expression during different parasite life-cycle stages and its location on the surface of the parasite. In addition, we analyzed the immune responses elicited by immunization with rSm16 using two different vaccine formulations, as well as its ability to induce protection in Balb/c mice. In order to explore the biological function of Sm16 during the course of experimental infection, RNA interference was also employed. Our results demonstrated that Sm16 is expressed in cercaria and schistosomula and is located in the schistosomula surface. Despite humoral and cellular immune responses triggered by vaccination using rSm16 associated with either Freund's or alum adjuvants, immunized mice presented no reduction in either parasite burden or parasite egg laying. Knockdown of Sm16 gene expression in schistosomula resulted in decreased parasite size in vitro but had no effect on parasite survival or egg production in vivo. Thus, our findings demonstrate that although the vaccine formulations used in this study succeeded in activating immune responses, these failed to promote parasite elimination. Finally, we have shown that Sm16 is not vital for parasite survival in the definitive host and hence may not represent a suitable target for vaccine development.
Assuntos
Proteínas de Helminto/imunologia , Interações Hospedeiro-Parasita/imunologia , Imunomodulação , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/parasitologia , Animais , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia , Sequência de Bases , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Técnicas de Silenciamento de Genes , Proteínas de Helminto/química , Proteínas de Helminto/genética , Imunização , Camundongos , Proteínas Recombinantes/imunologia , Schistosoma mansoni/crescimento & desenvolvimento , Esquistossomose mansoni/genética , Esquistossomose mansoni/prevenção & controle , Vacinas/imunologiaRESUMO
Great efforts have been made to identify promising antigens and vaccine formulations against schistosomiasis. Among the previously described Schistosoma vaccine candidates, cyclophilins comprise an interesting antigen that could be used for vaccine formulations. Cyclophilin A is the target for the cyclosporine A, a drug with schistosomicide activity, and its orthologue from Schistosoma japonicum induces a protective immune response in mice. Although Schistosoma mansoni cyclophilin A also represents a promising target for anti-schistosome vaccines, its potential to induce protection has not been evaluated. In this study, we characterized the cyclophilin A (SmCyp), initially described as Smp17.7, analyzed its allergenic potential using in vitro functional assays, and evaluated its ability to induce protection in mice when administered as an antigen using different vaccine formulations and strategies. Results indicated that SmCyp could be successfully expressed by mammalian cells and bacteria. The recombinant protein did not promote IgE-reporter system activation in vitro, demonstrating its probable safety for use in vaccine formulations. T and B-cell epitopes were predicted in the SmCyp sequence, with two of them located within the active isomerase site. The most immunogenic antigen, SmCyp (107-121), was then used for immunization protocols. Immunization with the SmCyp gene or protein failed to reduce parasite burden but induced an immune response that modulated the granuloma area. In contrast, immunization with the synthetic peptide SmCyp (107-121) significantly reduced worm burden (48-50%) in comparison to control group, but did not regulate liver pathology. Moreover, the protection observed in mice immunized with the synthetic peptide was associated with the significant production of antibodies against the SmCyp (107-121) epitope. Therefore, in this study, we identified an epitope within the SmCyp sequence that induces a protective immune response against the parasite, thus representing a promising antigen that could be used for vaccine formulation against schistosomiasis.
Assuntos
Ciclofilina A/imunologia , Epitopos/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia , Feminino , Proteínas de Helminto/imunologia , Imunização/métodos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/imunologia , Vacinação/métodos , Vacinas/imunologiaRESUMO
OBJECTIVE: The aim of this study was to evaluate the immunohistochemical expressions of PD1, CD4+, and CD8+ in premalignant lesions (OPML) that were transformed into oral squamous cell carcinoma OSCC (OPML-OSCC), in OSCC and also in premalignant lesions that were not transformed into OSCC (OPML-NOSSC). MATERIALS AND METHODS: Retrospective analyses were performed in order to verify the demographic characteristics of the patients. CD4, CD8, and PD1 IMH studies were carried out on OPML and OSCC samples from 11 patients with OPML-OSCC and OPML, together with samples from 14 patients with OPML-NOSCC. The differences between OPML-OSCC and OPML-NOSCC were analyzed. RESULTS: Non-homogenous leukoplakia, together with the related oral subsite, and the lack of an exposure to tobacco, were all associated with malignant transformations. There were no statistical differences in the PD1 expression and the CD4+ cells in OPML-OSCC and OPML-NOSCC. A significant increment in the CD8+ cells was noted in the OPML that evolved into carcinomas when compared with OPML-NOSCC (p = 0.05), whereas there were higher CD8+ cells levels in the carcinomas when compared with the OPML that evolved into carcinomas (p = 0.027). CONCLUSIONS: CD8+ cells infiltrate more in OPML-NOSCC than in OPML-OSCC. Carcinoma is more infiltrated by CD8+ cells than its associated OPML. CLINICAL RELEVANCE: Understanding immunological factors associated with malignant transformation of oral premalignant lesions can open a new way to treat this disease.
Assuntos
Linfócitos T CD8-Positivos/citologia , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas , Carcinoma de Células Escamosas/imunologia , Feminino , Humanos , Masculino , Neoplasias Bucais/imunologia , Estudos RetrospectivosRESUMO
The leaves of Byrsonima verbascifolia (Malpighiaceae) are traditionally used to treat various diseases including inflammatory conditions. The main goal of this study was to evaluate the in vivo anti-inflammatory activity of the polar constituents from the butanolic fraction of B. verbascifolia leaves (BvBF), as well as to investigate the mechanisms involved in the anti-inflammatory activity. The polar constituents were identified by liquid chromatography coupled to diode array detector and mass spectrometry (LC-DADMS) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to obtain a complete chemical profile of the fraction. Forty-five compounds were detected in the BvBF by LC-DADMS/MS, including condensed tannins, phenolic acids, flavonoids (flavones and flavonols) and other compounds. In addition, several condensed tannins were identified by MALDI-MS/MS, which are composed predominantly by procyanidin units (PCY) and up to six flavan-3-ol units. The BvBF exhibited significant antioxidant and anti-inflammatory activities. The BvBF inhibited paw edema and polymorphonuclear (PMN) leukocyte migration to the footpad and pleural cavity induced by carrageenan. Furthermore, a minor dose (12.50 mg/kg) of BvBF effectively decreased tumor necrosis factor alpha (TNF-α) and prostaglandin E2 (PGE2) levels in the footpad. These findings suggest that the mechanism of the anti-inflammatory action in the BvBF is linked to the inhibition of the production of inflammatory mediators such as TNF-α and PGE2 and the PMN cell migration.
Assuntos
Anti-Inflamatórios não Esteroides/imunologia , Edema/tratamento farmacológico , Malpighiaceae/imunologia , Neutrófilos/efeitos dos fármacos , Extratos Vegetais/imunologia , Animais , Anti-Inflamatórios não Esteroides/química , Butanóis/química , Carragenina , Movimento Celular/efeitos dos fármacos , Dinoprostona/metabolismo , Edema/induzido quimicamente , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/imunologia , Extratos Vegetais/química , Folhas de Planta , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIM: The present study evaluated the expression of α1 and ß1 Na,K-ATPase, as well as the effects of digoxin (DGX) on oral squamous cell carcinomas (OSCCs). PATIENTS AND METHODS: Immunohistochemical expression of α1 and ß1 Na,K-ATPase were evaluated in 60 patients who underwent treatment at the São João de Deus Hospital. SCC-25 viability was assessed by the colorimetric assay. Chi-square or Fisher's exact tests were used to analyze the association of α1 and ß1 Na,K-ATPase expression with the variables. RESULTS: Immunoexpression of α1 and ß1 Na,K-ATPase were observed in 28% and 55% of the tumors, however these proteins were not significant prognostic factors. Tobacco was significantly associated with α1 expression. SCC-25 viability decreased significantly after treatment with 1 µM DGX at 24 h. CONCLUSION: The smoking status of OSCC patients was significantly associated with α1 expression and DGX affected the SCC-25 viability in a dose- and duration-dependent manner.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Digoxina/farmacologia , Inibidores Enzimáticos/farmacologia , Neoplasias Bucais/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Gradação de Tumores , Estadiamento de Neoplasias , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Fatores de Risco , ATPase Trocadora de Sódio-Potássio/genéticaRESUMO
Oral squamous cell carcinoma (OSCC) corresponds to 95% of all malignant tumours of the mouth. The association between alcohol and tobacco is the major risk factor for this disease, increasing the chances for the development of OSCC by 35-fold. The plant, Cannabis sativa is smoked as cigarettes or blunts and is commonly used in association with tobacco and alcohol. Any type of smoking habit exposes individuals to a wide range of carcinogens or pro-carcinogens, such as polycyclic aromatic hydrocarbons, as well as some ethanol derived substances such as acetaldehyde (AA), and all are genotoxic in the same way. In addition, ethanol acts in the oral mucosa as a solvent and therefore increases the cellular membrane permeability to carcinogens. Carcinogens found in tobacco are also concentrated in marijuana, but the latter also contains high levels of cannabinoids, bioactive compounds responsible for several effects such as euphoria and analgesia. However, Δ(9)-tetrahydrocannabinol (Δ(9)-THC), the major psychotropic cannabinoid found in plants, causes a reduction of cellular metabolism and induction of apoptosis, both of which are anti-neoplastic properties. Apart from limited epidemiologic and experimental data, the effects of concomitant chronic exposure to marijuana (or Δ(9)-THC), tobacco and alcohol in OSCC development and progression is poorly known. This paper reviews the most recent findings on the effects of marijuana over cellular proliferation, as well as in the risk for OSCC, with emphasis on its interaction with tobacco and ethanol consumption.