Celso Vataru Nakamura - Academia.edu (original) (raw)

Papers by Celso Vataru Nakamura

Antibiotics

Candida auris has been found to be a persistent colonizer of human skin and a successful pathogen... more Candida auris has been found to be a persistent colonizer of human skin and a successful pathogen capable of causing potentially fatal infection, especially in immunocompromised individuals. This fungal species is usually resistant to most antifungal agents and has the ability to form biofilms on different surfaces, representing a significant therapeutic challenge. Herein, the effect of metabolites of Pseudomonas aeruginosa LV strain, alone and combined with biologically synthesized silver nanoparticles (bioAgNP), was evaluated in planktonic and sessile (biofilm) cells of C. auris. First, the minimal inhibitory and fungicidal concentration values of 3.12 and 6.25 μg/mL, respectively, were determined for F4a, a semi-purified bacterial fraction. Fluopsin C and indolin-3-one seem to be the active components of F4a. Like the semi-purified fraction, they showed a time- and dose-dependent fungicidal activity. F4a and bioAgNP caused severe changes in the morphology and ultrastructure of fu...

Antioxidants

Cervical cancer is a health problem among women worldwide. Considering the limitations of prevent... more Cervical cancer is a health problem among women worldwide. Considering the limitations of prevention and antineoplastic chemotherapy against cervical cancer, research is needed to discover new, more effective, and safe antitumor agents. In the present study, we investigated the in vitro cytotoxicity of a new synthetic dibenzylideneacetone derived from 1,5-diaryl-3-oxo-1,4-pentadienyl (A3K2A3) against cervical cancer cells immortalized by HPV 16 (SiHa), and 18 (HeLa) by MTT assay. Furthermore, we performed spectrofluorimetry, flow cytometry, and Western blot analyzes to explore the inhibitory mechanism of A3K2A3 in cervical cancer cells. A3K2A3 showed cytotoxic activity against both cell lines. Mitochondrial depolarization and reduction in intracellular ATP levels were observed, which may be dependent on the redox imbalance between increased ROS and reduced levels of the antioxidant defense. In addition, damage to the cell membrane and DNA, and effective blocking of cell division in ...

LUMINÁRIA

As doenças tropicais se constituem em um grave problema de saúde pública, por serem negligenciada... more As doenças tropicais se constituem em um grave problema de saúde pública, por serem negligenciadas e atingirem especialmente as populações mais pobres. Entre os principais problemas mundiais de saúde, a leishmaniose se destaca por apresentar altas taxas de mortalidade. Grandes esforços tem sido empregados na busca por novos medicamentos nas ultimas décadas, sendo o uso da fitoterapia investigado com grande interesse, devido às plantas serem consideradas uma ampla fonte de compostos com potencial biomedicinal. A atividade anti-protozoário da substância p-Cimeno sobre formas promastigotas e amastigotas axênicas de Leishmania amazonensis, foi avaliado. Após 72 horas de cultivo, o p-Cimeno apresentou concentração inibitória de 50% (CI50) igual à 65,0 µg/mL e 55,0 µg/mL sobre as formas promastigotas e amastigotas axênicas, respectivamente. Análises de citotoxicidade do p-Cimeno, foram realizadas por meio do método colorimétrico da sulforodamina-B sobre macrófagos J774G8 e a concentração ...

International Journal of Biological Macromolecules, 2018

Biomimetic nanocomposite based on hydroxyapatite mineralization over chemically modified cellulos... more Biomimetic nanocomposite based on hydroxyapatite mineralization over chemically modified cellulose nanowhiskers: An active platform for osteoblast proliferation. Biomac (2018),

Fitoterapia, 2017

Porphyromonas gingivalis is a pathogen strongly involved in chronic and aggressive forms of perio... more Porphyromonas gingivalis is a pathogen strongly involved in chronic and aggressive forms of periodontitis. Natural products, mainly polyphenols, have been described for advanced treatment of periodontitis by inhibition of the bacterial adhesion of P. gingivalis to the epithelial host cells. An acetone:water extract (LBE) from the rhizomes of Limonium brasiliense (Boiss.) Kuntze was tested under in vitro conditions for potential antiadhesive effects against P. gingivalis to human KB cells and for inhibition of the proteolytic activity of gingipains, the main virulence factor of P. gingivalis. LBE  100 µg/mL had no cytotoxicity against the bacteria and did not influence the cell physiology of human epithelial KB cells. At 100 µg/mL LBE reduced the adhesion of P. gingivalis to KB cells significantly by about 80%. LBE at 20 µg/mL reduced the proteolytic activity of the arginin-specific Rgp gingipain by about 75%. Chemical profiling of LBE indicated the presence of gallic acid, epigallocatechin-3-O-gallate and samarangenins A and B as lead compounds. UHPLC by using MS and UV detection displays a suitable method for quality control of the extract for identification and quantification of the lead compounds.

Journal of colloid and interface science, Jan 9, 2015

A facile and reproducible route that can lead to two-dimensional arrays of nanopores in thin poly... more A facile and reproducible route that can lead to two-dimensional arrays of nanopores in thin polymer films is demonstrated. The formation of the pores in the polymer films involves breath figure phenomenon and occurs during the film deposition by spin coating. The formation of nanoporous thin films takes only few seconds, and the method does not require complex equipment or expensive chemicals. This method also constitutes a straightforward approach to control the size of the pores formed in thin films. Besides allowing control over the average pore size of the porous films, the use of dynamic deposition with the breath figure phenomenon causes the reduction in the pore size to nanometer scale. The nanoporous arrays obtained by the breath figure are applied as substrates for cell growth, and the effect of their nanopore size on cell growth was evaluated. Notably, it is found that cell viability is related to pore size, where 2D nanoporous structure is more beneficial for cell cultur...

Revista da Sociedade Brasileira de Medicina Tropical, 2009

A etiologia do processo diarréico na AIDS pode ser causada por vírus, bactérias, fungos, protozoá... more A etiologia do processo diarréico na AIDS pode ser causada por vírus, bactérias, fungos, protozoários e helmintos, assim como pelo próprio HIV. Este trabalho avaliou enteropatogenos relacionados à diarréia em pacientes HIV que fazem uso de terapia anti-retroviral. Os métodos parasitológicos utilizados foram Faust, Hoffmann e Kinyoun. O isolamento e cultura dos fungos foram realizados conforme metodologia recomendada por NCCLS M27-A standard. A identificação das espécies de leveduras foi realizada através da reação em cadeia da polimerase. O isolamento de bactérias, foi feito em agar Mac Conkey e agar SS, a identificação das espécies através do Enterokit B (Probac do Brasil) e métodos bioquímicos. Foram avaliados 49 pacientes, 44,9% apresentaram enteroparasitas, 48,1% Candida sp com 61,5% Candida albicans, 7,6% Candida sp e 30,7% Candida não- albicans. Foram isoladas bactérias de 72% dos pacientes, 49% Escherichia coli, 13% Salmonella parathyphi, Klebsiella sp ou Proteus e 6% Citroba...

Molecules

Breast cancer is the most common type of cancer and the leading cause of cancer mortality among w... more Breast cancer is the most common type of cancer and the leading cause of cancer mortality among women worldwide. Considering the limitations of the current treatments available, we analyzed the in vitro cytotoxic potential of ((4-Fluoro-phenyl)-{2-[(1-phenyl-9H-β-carboline-3-carbonyl)-amino]-ethylamino}-methyl)-phosphonic acid dibutyl ester (BCP-1) in breast cancer cells (MCF-7 and MDA-MB-231) and in a non-tumor breast cell line (MCF-10A). BCP-1 has an α-aminophosphonate unit linked to the β-carboline nucleus, and the literature indicates that compounds of these classes have high biological potential. In the present study, the mechanism of action of BCP-1 was investigated through methods of spectrofluorimetry, flow cytometry, and protein expression analysis. It was found that BCP-1 inhibited the proliferation of both cancer cell lines. Furthermore, it induced oxidative stress and cell cycle arrest in G2/M. Upregulation of apoptosis-related proteins such as Bax, cytochrome C, and cas...

Research, Society and Development

The aim of this study was to compare the antimicrobial activity of the essential oil (EO) of cinn... more The aim of this study was to compare the antimicrobial activity of the essential oil (EO) of cinnamon (Cinnamomum verum) and its major compound cinnamaldehyde against Staphylococcus aureus (ATCC 14458) and bacteria isolated from mastitic milk. Cinnamon EO was chemically characterized by gas chromatography/mass spectrometry (GC-MS). The Minimum Inhibitory Concentration (MIC) and the Minimum Bactericidal Concentration (MBC) of cinnamon EO and cinnamaldehyde were determined, as well as the effects of MIC and CBM on S. aureus cells, visualized by Scanning Electron Microscopy (SEM) and Microscopy Transmission Electronics (TEM). A synergistic evaluation of the EO of cinnamon and cinnamaldehyde with conventional antimicrobials was also performed. Results: The substance cis-cinnamaldehyde (58.7%) was identified as the major component of cinnamon EO. The MIC values determined against all tested strains ranged between 0.8 and 1.6 mg.mL-1. SEM and TEM images (post-treatment with cinnamon EO an...

Research, Society and Development

In the present study, we provided the synthesis of a series of R-(+)- and S-(-)-limonene-based th... more In the present study, we provided the synthesis of a series of R-(+)- and S-(-)-limonene-based thiosemicarbazones containing different pentacyclic heterocyclic nucleus moiety focused in the search of novel antitumor and antileishmanial agents. In the antitumor assay, the derivative imidazole of S-(-)-limonene 8 was the most active compound, especially for U-251, UACC-62 and K562 human tumor cell lines with GI50 ranging from 1.0 to <0.25 µg.mL-1. On the other hand, the imidazole-thiosemicarbazone of R-(+)-limonene 4 was the most promising derivative against the promastigote form of L. amazonensis (IC50=5.9µM). Meanwhile, thiosemicarbazones without limonene moiety (9-12) showed the lowest activities in the biological assays performed. The results demonstrated the influence of the lipophilic molecular character and stereochemistry of chiral monoterpene on the evaluated activities.

Research, Society and Development

Copaiba oil (CO) is an oleoresin containing resinous acids, comprising mainly of diterpenes, and ... more Copaiba oil (CO) is an oleoresin containing resinous acids, comprising mainly of diterpenes, and volatile compounds, comprising of sesquiterpenes. CO has been used for many years as a therapeutic agent and cosmetic, being the β-caryophyllene (CAR) one of the main sesquiterpene markers found in CO samples. During the last years, some analytical methods have been developed for analysis of sesquiterpenes like CAR from CO. However, these methods are based on gas chromatography, and requiring additional steps, such as derivatization or extraction of the essential fraction of the CO for sesquiterpenes analysis. Liquid chromatography methodologies have been proposed only for analysis of diterpenes. Therefore, the aim of this study was to develop a high-performance liquid chromatography (HPLC) assay for CAR analysis in CO samples (Copaifera reticulata Ducke) and in emulsion systems containing CO. The HPLC system suitability was determined through the capacity factor, repeatability, relative...

Memórias do Instituto Oswaldo Cruz, 2022

Over the past years, natural products have been explored in order to find biological active subst... more Over the past years, natural products have been explored in order to find biological active substances to treat various diseases. Regarding their potential action against parasites such as trypanosomatids, specially Trypanosoma cruzi and Leishmania spp., much advance has been achieved. Extracts and purified molecules of several species from genera Piper, Tanacetum, Porophyllum, and Copaifera have been widely investigated by our research group and exhibited interesting antitrypanosomal and antileishmanial activities. These natural compounds affected different structures in parasites, and we believe that the mitochondrion is a strategic target to induce parasite death. Considering that these trypanosomatids have a unique mitochondrion, this cellular target has been extensively studied aiming to find more selective drugs, since the current treatment of these neglected tropical diseases has some challenges such as high toxicity and prolonged treatment time. Here, we summarise some results obtained with natural products from our research group and we further highlighted some strategies that must be considered to finally develop an effective chemotherapeutic agent against these parasites.

March 2021, 2021

Herpes simplex virus (HSV) type 1 and type 2 are responsible for causing infections whose symptom... more Herpes simplex virus (HSV) type 1 and type 2 are responsible for causing infections whose symptoms can vary from subclinical to severe manifestations. Cordia americana is a plant used by traditional communities for the treatment of wounds and diarrhoea, as well as infections like flu and syphilis. Scientific evidence has shown that, among other biological activities, the plant possesses antiviral properties; however, the evaluation of the in vivo toxicity of preparations of this plant is still lacking. This study assessed the in vitro anti-HSV-1 and anti-HSV-2 activity of a crude extract (CE) obtained from the leaves of C. americana, as well as its aqueous (FAq) and ethyl-acetate fractions (FAc). In addition, the in vivo toxicity of the FAq was assessed. The sulforhodamine B method was performed to determine the antiviral activity and the in vivo toxicity was evaluated according to Brazilian federal regulations. The CE, FAq, and FAc demonstrated antiviral activity against HSV-1 in v...

Characterization of Candida spp. isolated from vaginal fluid: identification, antifungal suscepti... more Characterization of Candida spp. isolated from vaginal fluid: identification, antifungal susceptibility, and virulence profile Acta Scientiarum. Health Sciences, vol. 35, núm. 1, enero-junio, 2013, pp. 1-8 Universidade Estadual de Maringá

Research, Society and Development, 2021

Alicyclobacillus spp. is composed of Gram-positive, aerobic, thermoacidophilic, endospore-forming... more Alicyclobacillus spp. is composed of Gram-positive, aerobic, thermoacidophilic, endospore-forming bacteria that cause food and beverage spoilage. The presence of Alicyclobacillus spp. may result in the production of guaiacol, which leads to sensory changes in the odour and taste of citrus juices and acidic foods. Tabernaemontana catharinensis (A. DC) is a plant belonging to the family Apocynaceae that produces milky latex with several biological activities described as antioxidant, antiviral, antimicrobial, trypanocidal and anti-leishmanicidal. Therefore, this study aims to evaluate the antimicrobial activity of the crude latex of T. catharinensis (A. DC) against microorganisms of the genus Alicyclobacillus spp. The minimum inhibitory concentration of latex was 7.81 μg/ml for the five Alicyclobacillus species analysed. The minimum bactericidal concentration for the species Alicyclobacillus acidoterrestris 0244T, A. hesperidum 0298T, A. acidiphilus 0247T and A. cycloheptanicus 0297T ...

This work reports the effect of 15 medicinal plants on cell growth and differentiation of Herpeto... more This work reports the effect of 15 medicinal plants on cell growth and differentiation of Herpetomonas samuelpessoai, a non-pathogenic trypanosomatid, used as biological model for its similar antigens to Trypanosoma cruzi. Crude extracts (1,000 µg/ml) or essential oil (250 µg/ml) were added in a defined medium. Cell growth was estimated by counting in Neubauer's chamber and cell differentiation was examined by light microscope. Ocimum gratissimum, Lippia alba, Piper regnellii, Stryphnodendron adstringens, and Tanacetum vulgare showed antiprotozoan activity, Psidium guajava and Punica granatum a lower activity and Achillea millefolium, Eugenia uniflora, Mikania glomerata, Plantago major, and Spilanthes acmella had no activity. In contrast, Arctium lappa, Erythrina speciosa, and Sambucus canadensis stimulated H. samuelpessoai growth. Only L. alba and S. acmella stimulated cell differentiation in this flagellate. These results indicate that medicinal plants possess active compounds...

O Cissus sicyoides L. (Vitaceae) e um vegetal conhecido como insulina, e uma planta nativa do est... more O Cissus sicyoides L. (Vitaceae) e um vegetal conhecido como insulina, e uma planta nativa do estado do Parana(Brasil), as partes aereas do Cissus sicyoides L. tem sido usado na medicina popular como hipoglicemiante. O extrato etanolico apresentou atividades antimicrobianas sobre o Bacillus subtilis. Do fruto foram isolados um alcaloide e um triterpenoide, por metodos de cromatografia de exclusao e identificados por cromatografia de camada delgada.

Frontiers in Bioengineering and Biotechnology, 2020

Exposure to ultraviolet radiation is a major contributor to premature skin aging and carcinogenes... more Exposure to ultraviolet radiation is a major contributor to premature skin aging and carcinogenesis, which is mainly driven by overproduction of reactive oxygen species (ROS). There is growing interest for research on new strategies that address photoaging prevention, such as the use of nanomaterials. Cerium oxide nanoparticles (nanoceria) show enzyme-like activity in scavenging ROS. Herein, our goal was to study whether under ultraviolet A rays (UVA)-induced oxidative redox imbalance, a low dose of nanoceria induces protective effects on cell survival, migration, and proliferation. Fibroblasts cells (L929) were pretreated with nanoceria (100 nM) and exposed to UVA radiation. Pretreatment of cells with nanoceria showed negligible cytotoxicity and protected cells from UVA-induced death. Nanoceria also inhibited ROS production immediately after irradiation and for up to 48 h and restored the superoxide dismutase (SOD) activity and GSH level. Additionally, the nanoceria pretreatment prevented apoptosis by decreasing Caspase 3/7 levels and the loss of mitochondrial membrane potential. Nanoceria significantly improved the cell survival migration and increased proliferation, over a 5 days period, as compared with UVA-irradiated cells, in wound healing assay. Furthermore, it was observed that nanoceria decreased cellular aging and ERK 1/2 phosphorylation. Our study suggests that nanoceria might be a potential ally to endogenous, antioxidant enzymes, and enhancing the redox potentials to fight against UVA-induced photodamage and consequently modulating the cells survival, migration, and proliferation.

Cells, 2019

Hemozoin is an insoluble crystalline pigment produced by the malaria parasite Plasmodia upon dige... more Hemozoin is an insoluble crystalline pigment produced by the malaria parasite Plasmodia upon digesting host hemoglobin inside red blood cells. Red blood cell rupture releases hemozoin crystals into the circulation from where they are cleared by phagocytes such as neutrophils. We speculated that plasma proteins would affect the ability of neutrophils to clear hemozoin crystals. To test this, we cultured human blood neutrophils with hemozoin ex vivo and found that neutrophils ingested hemozoin (0.1–1 µm crystal size) in a dose-dependent manner into phagosomes and vesicles/vacuoles, resulting in morphological changes including nuclear enlargement, and vesicle formation, but not cell membrane rupture or release of neutrophil extracellular traps. The presence of human plasma significantly inhibited the ability of neutrophils to ingest hemozoin crystals. Platelet-poor plasma further inhibited the uptake of hemozoin by neutrophils. Selective exposure to fibrinogen completely replicated the...

Cells, 2020

Ion-exchange resins are commonly used to manage complications of chronic kidney disease, such as ... more Ion-exchange resins are commonly used to manage complications of chronic kidney disease, such as hyperphosphatemia, hyperkalemia, and hypercholesterolemia. Occasionally, these drugs can irritate the gastrointestinal lining and cause life-threatening intestinal necrosis. Currently, the pathophysiology of drug crystal-induced intestinal necrosis is not well understood. We hypothesized that crystals of ion-exchange resins like sevelamer, polystyrene sulfonate, and cholestyramine can trigger the formation of neutrophil and monocyte extracellular traps by contributing to intestinal barrier dysfunction. Light and fluorescence microscopy of the colonic resection specimen from a patient with chronic kidney disease revealed severe intestinal necrosis, ulceration, sevelamer crystals, and inflammation upon oral intake of sevelamer, as well as the formation of neutrophil extracellular traps in proximity to small sevelamer crystals. Indeed, drug crystals reduced metabolic activity and induced ba...

Antibiotics

Candida auris has been found to be a persistent colonizer of human skin and a successful pathogen... more Candida auris has been found to be a persistent colonizer of human skin and a successful pathogen capable of causing potentially fatal infection, especially in immunocompromised individuals. This fungal species is usually resistant to most antifungal agents and has the ability to form biofilms on different surfaces, representing a significant therapeutic challenge. Herein, the effect of metabolites of Pseudomonas aeruginosa LV strain, alone and combined with biologically synthesized silver nanoparticles (bioAgNP), was evaluated in planktonic and sessile (biofilm) cells of C. auris. First, the minimal inhibitory and fungicidal concentration values of 3.12 and 6.25 μg/mL, respectively, were determined for F4a, a semi-purified bacterial fraction. Fluopsin C and indolin-3-one seem to be the active components of F4a. Like the semi-purified fraction, they showed a time- and dose-dependent fungicidal activity. F4a and bioAgNP caused severe changes in the morphology and ultrastructure of fu...

Antioxidants

Cervical cancer is a health problem among women worldwide. Considering the limitations of prevent... more Cervical cancer is a health problem among women worldwide. Considering the limitations of prevention and antineoplastic chemotherapy against cervical cancer, research is needed to discover new, more effective, and safe antitumor agents. In the present study, we investigated the in vitro cytotoxicity of a new synthetic dibenzylideneacetone derived from 1,5-diaryl-3-oxo-1,4-pentadienyl (A3K2A3) against cervical cancer cells immortalized by HPV 16 (SiHa), and 18 (HeLa) by MTT assay. Furthermore, we performed spectrofluorimetry, flow cytometry, and Western blot analyzes to explore the inhibitory mechanism of A3K2A3 in cervical cancer cells. A3K2A3 showed cytotoxic activity against both cell lines. Mitochondrial depolarization and reduction in intracellular ATP levels were observed, which may be dependent on the redox imbalance between increased ROS and reduced levels of the antioxidant defense. In addition, damage to the cell membrane and DNA, and effective blocking of cell division in ...

LUMINÁRIA

As doenças tropicais se constituem em um grave problema de saúde pública, por serem negligenciada... more As doenças tropicais se constituem em um grave problema de saúde pública, por serem negligenciadas e atingirem especialmente as populações mais pobres. Entre os principais problemas mundiais de saúde, a leishmaniose se destaca por apresentar altas taxas de mortalidade. Grandes esforços tem sido empregados na busca por novos medicamentos nas ultimas décadas, sendo o uso da fitoterapia investigado com grande interesse, devido às plantas serem consideradas uma ampla fonte de compostos com potencial biomedicinal. A atividade anti-protozoário da substância p-Cimeno sobre formas promastigotas e amastigotas axênicas de Leishmania amazonensis, foi avaliado. Após 72 horas de cultivo, o p-Cimeno apresentou concentração inibitória de 50% (CI50) igual à 65,0 µg/mL e 55,0 µg/mL sobre as formas promastigotas e amastigotas axênicas, respectivamente. Análises de citotoxicidade do p-Cimeno, foram realizadas por meio do método colorimétrico da sulforodamina-B sobre macrófagos J774G8 e a concentração ...

International Journal of Biological Macromolecules, 2018

Biomimetic nanocomposite based on hydroxyapatite mineralization over chemically modified cellulos... more Biomimetic nanocomposite based on hydroxyapatite mineralization over chemically modified cellulose nanowhiskers: An active platform for osteoblast proliferation. Biomac (2018),

Fitoterapia, 2017

Porphyromonas gingivalis is a pathogen strongly involved in chronic and aggressive forms of perio... more Porphyromonas gingivalis is a pathogen strongly involved in chronic and aggressive forms of periodontitis. Natural products, mainly polyphenols, have been described for advanced treatment of periodontitis by inhibition of the bacterial adhesion of P. gingivalis to the epithelial host cells. An acetone:water extract (LBE) from the rhizomes of Limonium brasiliense (Boiss.) Kuntze was tested under in vitro conditions for potential antiadhesive effects against P. gingivalis to human KB cells and for inhibition of the proteolytic activity of gingipains, the main virulence factor of P. gingivalis. LBE  100 µg/mL had no cytotoxicity against the bacteria and did not influence the cell physiology of human epithelial KB cells. At 100 µg/mL LBE reduced the adhesion of P. gingivalis to KB cells significantly by about 80%. LBE at 20 µg/mL reduced the proteolytic activity of the arginin-specific Rgp gingipain by about 75%. Chemical profiling of LBE indicated the presence of gallic acid, epigallocatechin-3-O-gallate and samarangenins A and B as lead compounds. UHPLC by using MS and UV detection displays a suitable method for quality control of the extract for identification and quantification of the lead compounds.

Journal of colloid and interface science, Jan 9, 2015

A facile and reproducible route that can lead to two-dimensional arrays of nanopores in thin poly... more A facile and reproducible route that can lead to two-dimensional arrays of nanopores in thin polymer films is demonstrated. The formation of the pores in the polymer films involves breath figure phenomenon and occurs during the film deposition by spin coating. The formation of nanoporous thin films takes only few seconds, and the method does not require complex equipment or expensive chemicals. This method also constitutes a straightforward approach to control the size of the pores formed in thin films. Besides allowing control over the average pore size of the porous films, the use of dynamic deposition with the breath figure phenomenon causes the reduction in the pore size to nanometer scale. The nanoporous arrays obtained by the breath figure are applied as substrates for cell growth, and the effect of their nanopore size on cell growth was evaluated. Notably, it is found that cell viability is related to pore size, where 2D nanoporous structure is more beneficial for cell cultur...

Revista da Sociedade Brasileira de Medicina Tropical, 2009

A etiologia do processo diarréico na AIDS pode ser causada por vírus, bactérias, fungos, protozoá... more A etiologia do processo diarréico na AIDS pode ser causada por vírus, bactérias, fungos, protozoários e helmintos, assim como pelo próprio HIV. Este trabalho avaliou enteropatogenos relacionados à diarréia em pacientes HIV que fazem uso de terapia anti-retroviral. Os métodos parasitológicos utilizados foram Faust, Hoffmann e Kinyoun. O isolamento e cultura dos fungos foram realizados conforme metodologia recomendada por NCCLS M27-A standard. A identificação das espécies de leveduras foi realizada através da reação em cadeia da polimerase. O isolamento de bactérias, foi feito em agar Mac Conkey e agar SS, a identificação das espécies através do Enterokit B (Probac do Brasil) e métodos bioquímicos. Foram avaliados 49 pacientes, 44,9% apresentaram enteroparasitas, 48,1% Candida sp com 61,5% Candida albicans, 7,6% Candida sp e 30,7% Candida não- albicans. Foram isoladas bactérias de 72% dos pacientes, 49% Escherichia coli, 13% Salmonella parathyphi, Klebsiella sp ou Proteus e 6% Citroba...

Molecules

Breast cancer is the most common type of cancer and the leading cause of cancer mortality among w... more Breast cancer is the most common type of cancer and the leading cause of cancer mortality among women worldwide. Considering the limitations of the current treatments available, we analyzed the in vitro cytotoxic potential of ((4-Fluoro-phenyl)-{2-[(1-phenyl-9H-β-carboline-3-carbonyl)-amino]-ethylamino}-methyl)-phosphonic acid dibutyl ester (BCP-1) in breast cancer cells (MCF-7 and MDA-MB-231) and in a non-tumor breast cell line (MCF-10A). BCP-1 has an α-aminophosphonate unit linked to the β-carboline nucleus, and the literature indicates that compounds of these classes have high biological potential. In the present study, the mechanism of action of BCP-1 was investigated through methods of spectrofluorimetry, flow cytometry, and protein expression analysis. It was found that BCP-1 inhibited the proliferation of both cancer cell lines. Furthermore, it induced oxidative stress and cell cycle arrest in G2/M. Upregulation of apoptosis-related proteins such as Bax, cytochrome C, and cas...

Research, Society and Development

The aim of this study was to compare the antimicrobial activity of the essential oil (EO) of cinn... more The aim of this study was to compare the antimicrobial activity of the essential oil (EO) of cinnamon (Cinnamomum verum) and its major compound cinnamaldehyde against Staphylococcus aureus (ATCC 14458) and bacteria isolated from mastitic milk. Cinnamon EO was chemically characterized by gas chromatography/mass spectrometry (GC-MS). The Minimum Inhibitory Concentration (MIC) and the Minimum Bactericidal Concentration (MBC) of cinnamon EO and cinnamaldehyde were determined, as well as the effects of MIC and CBM on S. aureus cells, visualized by Scanning Electron Microscopy (SEM) and Microscopy Transmission Electronics (TEM). A synergistic evaluation of the EO of cinnamon and cinnamaldehyde with conventional antimicrobials was also performed. Results: The substance cis-cinnamaldehyde (58.7%) was identified as the major component of cinnamon EO. The MIC values determined against all tested strains ranged between 0.8 and 1.6 mg.mL-1. SEM and TEM images (post-treatment with cinnamon EO an...

Research, Society and Development

In the present study, we provided the synthesis of a series of R-(+)- and S-(-)-limonene-based th... more In the present study, we provided the synthesis of a series of R-(+)- and S-(-)-limonene-based thiosemicarbazones containing different pentacyclic heterocyclic nucleus moiety focused in the search of novel antitumor and antileishmanial agents. In the antitumor assay, the derivative imidazole of S-(-)-limonene 8 was the most active compound, especially for U-251, UACC-62 and K562 human tumor cell lines with GI50 ranging from 1.0 to <0.25 µg.mL-1. On the other hand, the imidazole-thiosemicarbazone of R-(+)-limonene 4 was the most promising derivative against the promastigote form of L. amazonensis (IC50=5.9µM). Meanwhile, thiosemicarbazones without limonene moiety (9-12) showed the lowest activities in the biological assays performed. The results demonstrated the influence of the lipophilic molecular character and stereochemistry of chiral monoterpene on the evaluated activities.

Research, Society and Development

Copaiba oil (CO) is an oleoresin containing resinous acids, comprising mainly of diterpenes, and ... more Copaiba oil (CO) is an oleoresin containing resinous acids, comprising mainly of diterpenes, and volatile compounds, comprising of sesquiterpenes. CO has been used for many years as a therapeutic agent and cosmetic, being the β-caryophyllene (CAR) one of the main sesquiterpene markers found in CO samples. During the last years, some analytical methods have been developed for analysis of sesquiterpenes like CAR from CO. However, these methods are based on gas chromatography, and requiring additional steps, such as derivatization or extraction of the essential fraction of the CO for sesquiterpenes analysis. Liquid chromatography methodologies have been proposed only for analysis of diterpenes. Therefore, the aim of this study was to develop a high-performance liquid chromatography (HPLC) assay for CAR analysis in CO samples (Copaifera reticulata Ducke) and in emulsion systems containing CO. The HPLC system suitability was determined through the capacity factor, repeatability, relative...

Memórias do Instituto Oswaldo Cruz, 2022

Over the past years, natural products have been explored in order to find biological active subst... more Over the past years, natural products have been explored in order to find biological active substances to treat various diseases. Regarding their potential action against parasites such as trypanosomatids, specially Trypanosoma cruzi and Leishmania spp., much advance has been achieved. Extracts and purified molecules of several species from genera Piper, Tanacetum, Porophyllum, and Copaifera have been widely investigated by our research group and exhibited interesting antitrypanosomal and antileishmanial activities. These natural compounds affected different structures in parasites, and we believe that the mitochondrion is a strategic target to induce parasite death. Considering that these trypanosomatids have a unique mitochondrion, this cellular target has been extensively studied aiming to find more selective drugs, since the current treatment of these neglected tropical diseases has some challenges such as high toxicity and prolonged treatment time. Here, we summarise some results obtained with natural products from our research group and we further highlighted some strategies that must be considered to finally develop an effective chemotherapeutic agent against these parasites.

March 2021, 2021

Herpes simplex virus (HSV) type 1 and type 2 are responsible for causing infections whose symptom... more Herpes simplex virus (HSV) type 1 and type 2 are responsible for causing infections whose symptoms can vary from subclinical to severe manifestations. Cordia americana is a plant used by traditional communities for the treatment of wounds and diarrhoea, as well as infections like flu and syphilis. Scientific evidence has shown that, among other biological activities, the plant possesses antiviral properties; however, the evaluation of the in vivo toxicity of preparations of this plant is still lacking. This study assessed the in vitro anti-HSV-1 and anti-HSV-2 activity of a crude extract (CE) obtained from the leaves of C. americana, as well as its aqueous (FAq) and ethyl-acetate fractions (FAc). In addition, the in vivo toxicity of the FAq was assessed. The sulforhodamine B method was performed to determine the antiviral activity and the in vivo toxicity was evaluated according to Brazilian federal regulations. The CE, FAq, and FAc demonstrated antiviral activity against HSV-1 in v...

Characterization of Candida spp. isolated from vaginal fluid: identification, antifungal suscepti... more Characterization of Candida spp. isolated from vaginal fluid: identification, antifungal susceptibility, and virulence profile Acta Scientiarum. Health Sciences, vol. 35, núm. 1, enero-junio, 2013, pp. 1-8 Universidade Estadual de Maringá

Research, Society and Development, 2021

Alicyclobacillus spp. is composed of Gram-positive, aerobic, thermoacidophilic, endospore-forming... more Alicyclobacillus spp. is composed of Gram-positive, aerobic, thermoacidophilic, endospore-forming bacteria that cause food and beverage spoilage. The presence of Alicyclobacillus spp. may result in the production of guaiacol, which leads to sensory changes in the odour and taste of citrus juices and acidic foods. Tabernaemontana catharinensis (A. DC) is a plant belonging to the family Apocynaceae that produces milky latex with several biological activities described as antioxidant, antiviral, antimicrobial, trypanocidal and anti-leishmanicidal. Therefore, this study aims to evaluate the antimicrobial activity of the crude latex of T. catharinensis (A. DC) against microorganisms of the genus Alicyclobacillus spp. The minimum inhibitory concentration of latex was 7.81 μg/ml for the five Alicyclobacillus species analysed. The minimum bactericidal concentration for the species Alicyclobacillus acidoterrestris 0244T, A. hesperidum 0298T, A. acidiphilus 0247T and A. cycloheptanicus 0297T ...

This work reports the effect of 15 medicinal plants on cell growth and differentiation of Herpeto... more This work reports the effect of 15 medicinal plants on cell growth and differentiation of Herpetomonas samuelpessoai, a non-pathogenic trypanosomatid, used as biological model for its similar antigens to Trypanosoma cruzi. Crude extracts (1,000 µg/ml) or essential oil (250 µg/ml) were added in a defined medium. Cell growth was estimated by counting in Neubauer's chamber and cell differentiation was examined by light microscope. Ocimum gratissimum, Lippia alba, Piper regnellii, Stryphnodendron adstringens, and Tanacetum vulgare showed antiprotozoan activity, Psidium guajava and Punica granatum a lower activity and Achillea millefolium, Eugenia uniflora, Mikania glomerata, Plantago major, and Spilanthes acmella had no activity. In contrast, Arctium lappa, Erythrina speciosa, and Sambucus canadensis stimulated H. samuelpessoai growth. Only L. alba and S. acmella stimulated cell differentiation in this flagellate. These results indicate that medicinal plants possess active compounds...

O Cissus sicyoides L. (Vitaceae) e um vegetal conhecido como insulina, e uma planta nativa do est... more O Cissus sicyoides L. (Vitaceae) e um vegetal conhecido como insulina, e uma planta nativa do estado do Parana(Brasil), as partes aereas do Cissus sicyoides L. tem sido usado na medicina popular como hipoglicemiante. O extrato etanolico apresentou atividades antimicrobianas sobre o Bacillus subtilis. Do fruto foram isolados um alcaloide e um triterpenoide, por metodos de cromatografia de exclusao e identificados por cromatografia de camada delgada.

Frontiers in Bioengineering and Biotechnology, 2020

Exposure to ultraviolet radiation is a major contributor to premature skin aging and carcinogenes... more Exposure to ultraviolet radiation is a major contributor to premature skin aging and carcinogenesis, which is mainly driven by overproduction of reactive oxygen species (ROS). There is growing interest for research on new strategies that address photoaging prevention, such as the use of nanomaterials. Cerium oxide nanoparticles (nanoceria) show enzyme-like activity in scavenging ROS. Herein, our goal was to study whether under ultraviolet A rays (UVA)-induced oxidative redox imbalance, a low dose of nanoceria induces protective effects on cell survival, migration, and proliferation. Fibroblasts cells (L929) were pretreated with nanoceria (100 nM) and exposed to UVA radiation. Pretreatment of cells with nanoceria showed negligible cytotoxicity and protected cells from UVA-induced death. Nanoceria also inhibited ROS production immediately after irradiation and for up to 48 h and restored the superoxide dismutase (SOD) activity and GSH level. Additionally, the nanoceria pretreatment prevented apoptosis by decreasing Caspase 3/7 levels and the loss of mitochondrial membrane potential. Nanoceria significantly improved the cell survival migration and increased proliferation, over a 5 days period, as compared with UVA-irradiated cells, in wound healing assay. Furthermore, it was observed that nanoceria decreased cellular aging and ERK 1/2 phosphorylation. Our study suggests that nanoceria might be a potential ally to endogenous, antioxidant enzymes, and enhancing the redox potentials to fight against UVA-induced photodamage and consequently modulating the cells survival, migration, and proliferation.

Cells, 2019

Hemozoin is an insoluble crystalline pigment produced by the malaria parasite Plasmodia upon dige... more Hemozoin is an insoluble crystalline pigment produced by the malaria parasite Plasmodia upon digesting host hemoglobin inside red blood cells. Red blood cell rupture releases hemozoin crystals into the circulation from where they are cleared by phagocytes such as neutrophils. We speculated that plasma proteins would affect the ability of neutrophils to clear hemozoin crystals. To test this, we cultured human blood neutrophils with hemozoin ex vivo and found that neutrophils ingested hemozoin (0.1–1 µm crystal size) in a dose-dependent manner into phagosomes and vesicles/vacuoles, resulting in morphological changes including nuclear enlargement, and vesicle formation, but not cell membrane rupture or release of neutrophil extracellular traps. The presence of human plasma significantly inhibited the ability of neutrophils to ingest hemozoin crystals. Platelet-poor plasma further inhibited the uptake of hemozoin by neutrophils. Selective exposure to fibrinogen completely replicated the...

Cells, 2020

Ion-exchange resins are commonly used to manage complications of chronic kidney disease, such as ... more Ion-exchange resins are commonly used to manage complications of chronic kidney disease, such as hyperphosphatemia, hyperkalemia, and hypercholesterolemia. Occasionally, these drugs can irritate the gastrointestinal lining and cause life-threatening intestinal necrosis. Currently, the pathophysiology of drug crystal-induced intestinal necrosis is not well understood. We hypothesized that crystals of ion-exchange resins like sevelamer, polystyrene sulfonate, and cholestyramine can trigger the formation of neutrophil and monocyte extracellular traps by contributing to intestinal barrier dysfunction. Light and fluorescence microscopy of the colonic resection specimen from a patient with chronic kidney disease revealed severe intestinal necrosis, ulceration, sevelamer crystals, and inflammation upon oral intake of sevelamer, as well as the formation of neutrophil extracellular traps in proximity to small sevelamer crystals. Indeed, drug crystals reduced metabolic activity and induced ba...