RESUMO

This study presents the cytotoxic activity evaluation of the natural diterpenes ent-kaurenoic acid (1) and its 15ß-hydroxy (2), 15ß-senecioyloxy (3), and 15ß-tiglinoyloxy (4) derivatives, isolated from Brazilian native plants, Baccharis retusa and B. lateralis (Asteraceae). Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay, it was observed that compound 1 displayed in vitro activity towards the aggressive MDA-MB-231 adenocarcinoma cell line and reduced toxicity against MCF-10A nontumorigenic epithelial cells, indicating expressive selectivity. On the contrary, compounds 2-4 exhibited reduced toxicity and selectivity in both tested cell lines. Based on the chemical structures of compounds 1-4, it is suggested that the presence of additional functional groups at the C-15 position-a hydroxyl group in compound 2 and isomeric isoprene units in compounds 3 and 4-might be responsible for the reduction in the potential/selectivity. In silico studies show, for compounds 1-4, good predictions regarding bioavailability and ADME (absorption, distribution, metabolism, and excretion) properties as well as no alerts for PAINS (pan-assay structures interference). In conclusion, ent-kaurenoic acid (1), a common diterpenoid isolated in high amounts from different plants belonging to the Baccharis genus, has been shown to be a promising cytotoxic agent against an aggressive adenocarcinoma cell line (MDA-MB-23) and, if well exploited, could be used as a scaffold in the development of molecular prototypes for the treatment of breast cancer.

Assuntos

Adenocarcinoma , Antineoplásicos , Baccharis , Diterpenos do Tipo Caurano , Diterpenos , Antineoplásicos/química , Baccharis/química , Diterpenos/farmacologia , Diterpenos do Tipo Caurano/química , Humanos , Relação Estrutura-Atividade

RESUMO

This work describes the effects of immunotherapy with Protein Aggregate Magnesium-Ammonium Phospholinoleate-Palmitoleate Anhydride in the treatment of non-muscle invasive bladder cancer in an animal model. NMIBC was induced by treating female Fischer 344 rats with N-methyl-N-nitrosourea. After treatment with MNU, the rats were distributed into four experimental groups: Control (without MNU) group, MNU (cancer) group, MNU-BCG (Bacillus Calmette-Guerin) group, and MNU-P-MAPA group. P-MAPA intravesical treatment was more effective in histopathological recovery from cancer state in relation to BCG treatment. Western blot assays showed an increase in the protein levels of c-Myc, COUP-TFII, and wild-type p53 in P-MAPA-treated rats in relation to BCG-treated rats. In addition, rats treated with P-MAPA intravesical immunotherapy showed the highest BAX protein levels and the lowest proliferation/apoptotic ratio in relation to BCG-treated rats, pointing out a preponderance of apoptosis. P-MAPA intravesical treatment increased the wild-type p53 levels and enhanced c-Myc/COUP-TFII-induced apoptosis mediated by p53. These alterations were fundamental for histopathological recovery from cancer and for suppress abnormal cell proliferation. This action of P-MAPA on apoptotic pathways may represent a new strategy for treating NMIBC.

Assuntos

Agentes de Imunomodulação/administração & dosagem , Ácidos Linoleicos/administração & dosagem , Ácidos Oleicos/administração & dosagem , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Imunoterapia/métodos , Invasividade Neoplásica , Proteínas Proto-Oncogênicas c-myc/metabolismo , Ratos Endogâmicos F344 , Proteínas Repressoras/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Proteína X Associada a bcl-2/metabolismo

RESUMO

The aim of the current review is to address updated research on a natural pigment called violacein, with emphasis on its production, biological activity and applications. New information about violacein's action mechanisms as antitumor agent and about its synergistic action in drug delivery systems has brought new alternatives for anticancer therapy. Thus, violacein is introduced as reliable drug capable of overcoming at least three cancer hallmarks, namely: proliferative signaling, cell death resistance and metastasis. In addition, antimicrobial effects on several microorganisms affecting humans and other animals turn violacein into an attractive drug to combat resistant pathogens. Emphasis is given to effects of violacein combined with different agents, such as antibiotics, anticancer agents and nanoparticles. Although violacein is well-known for many decades, it remains an attractive compound. Thus, research groups have been making continuous effort to help improving its production in recent years, which can surely enable its pharmaceutical and chemical application as multi-task compound, even in the cosmetics and food industries.

Assuntos

Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Indóis/farmacologia , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cosméticos , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Indústria Alimentícia , Humanos

RESUMO

Visceral Leishmaniasis and HIV-AIDS coinfection (VL/HIV) is considered a life-threatening pathology when undiagnosed and untreated, due to the immunosuppression caused by both diseases. Serological tests largely used for the VL diagnosis include the direct agglutination test (DAT), ELISA and immunochromatographic (ICT) assays. For VL diagnosis in HIV infections, different studies have shown that the use of the DAT assay facilitates the VL diagnosis in co-infected patients, since the performance of the most widely used ELISA and ICT tests, based on the recombinant protein rK39, are much less efficient in HIV co-infections. In this scenario, alternative recombinant antigens may help the development of new serological diagnostic methods which may improve the VL diagnosis for the co-infection cases. This work aimed to evaluate the use of the recombinant Lci2 antigen, related to, but antigenically more diverse than rK39, for VL diagnosis in co-infected sera through ELISA assays. A direct comparison between recombinant Lci2 and rK39 was thus carried out. The two proteins were first tested using indirect ELISA with sera from VL afflicted individuals and healthy controls, with similar performances. They were then tested with two different sets of VL/HIV co-infected cases and a significant drop in performance, for one of these groups, was observed for rK39 (32% sensitivity), but not for Lci2 (98% sensitivity). In fact, an almost perfect agreement (Kappa: 0.93) between the Lci2 ELISA and DAT was observed for the coinfected VL/HIV patients. Lci2 then has the potential to be used as a new tool for the VL diagnosis of VL/HIV co-infections.

Assuntos

Anticorpos Antiprotozoários/isolamento & purificação , Infecções por HIV/genética , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/diagnóstico , Proteínas Recombinantes/isolamento & purificação , Testes de Aglutinação , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Coinfecção/diagnóstico , Coinfecção/genética , Coinfecção/parasitologia , Ensaio de Imunoadsorção Enzimática , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/parasitologia , Infecções por HIV/virologia , Humanos , Leishmania infantum/genética , Leishmania infantum/patogenicidade , Leishmaniose Visceral/genética , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/virologia , Proteínas de Protozoários/imunologia , Proteínas Recombinantes/genética

RESUMO

BACKGROUND: This review outlines the current impact of violacein-derivative materials in several technological areas through patents. METHODS: A comprehensive examination of patent databases on violacein demonstrated the relevance of this pigment, as well as the pertinent topics related to its technological development in order to obtain adaptable new pharmaceuticals, cosmetics, and new quality fiber materials, together with other applications of violacein in different areas. RESULTS: At present, there is no efficient and economical technique for violacein preparation at the industrial scale. Many attempts have been made, but none have overcome the challenge of being an effective and inexpensive process. However, some potential applications of violacein in fields such as biomedicine make the pigment worthy of continuous investigation. In particular, violacein patents covering biosynthesis for different applications have been reported recently. CONCLUSION: Violacein has been used as a unique pigment in distinct specialty areas, such as in medical and industrial fields. This review of patents provides an update on violacein innovations that are useful for researchers working in the expanding and interesting field of biotechnology with natural pigments.

Assuntos

Indóis , Patentes como Assunto , Biotecnologia

RESUMO

Trypanosomatid-caused conditions (African trypanosomiasis, Chagas disease, and leishmaniasis) are neglected tropical infectious diseases that mainly affect socioeconomically vulnerable populations. The available therapeutics display substantial limitations, among them limited efficacy, safety issues, drug resistance, and, in some cases, inconvenient routes of administration, which made the scenarios with insufficient health infrastructure settings inconvenient. Pharmaceutical nanocarriers may provide solutions to some of these obstacles, improving the efficacy-safety balance and tolerability to therapeutic interventions. Here, we overview the state of the art of therapeutics for trypanosomatid-caused diseases (including approved drugs and drugs undergoing clinical trials) and the literature on nanolipid pharmaceutical carriers encapsulating approved and non-approved drugs for these diseases. Numerous studies have focused on the obtention and preclinical assessment of lipid nanocarriers, particularly those addressing the two currently most challenging trypanosomatid-caused diseases, Chagas disease, and leishmaniasis. In general, in vitro and in vivo studies suggest that delivering the drugs using such type of nanocarriers could improve the efficacy-safety balance, diminishing cytotoxicity and organ toxicity, especially in leishmaniasis. This constitutes a very relevant outcome, as it opens the possibility to extended treatment regimens and improved compliance. Despite these advances, last-generation nanosystems, such as targeted nanocarriers and hybrid systems, have still not been extensively explored in the field of trypanosomatid-caused conditions and represent promising opportunities for future developments. The potential use of nanotechnology in extended, well-tolerated drug regimens is particularly interesting in the light of recent descriptions of quiescent/dormant stages of Leishmania and Trypanosoma cruzi, which have been linked to therapeutic failure.

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) is a major neglected disease, potentially fatal, whose control is still impaired by inefficient and/or expensive treatment and diagnostic methods. The most promising approach for VL diagnosis uses serological assays with recombinant proteins, since they are more efficient and easier to perform. Tests developed for the human form of the disease, however, have not been shown to be efficient for its diagnosis in the canine host, the major reservoir for the American VL. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe a systematic approach aimed at the production of a new chimeric protein potentially able to be used for both human and canine VL diagnosis and based both on in silico gene design and experimental data. Starting from the previous identification of Leishmania infantum recombinant antigens efficient for the diagnosis of either human or canine VL, three of the best performing antigens were selected (Lci2, Lci3 and Lci12). After a preliminary evaluation validating the chimeric approach, DNA fragments encoding predicted antigenic regions from each protein, enriched with repeats, were joined in various combinations to generate a total of seventeen chimeric genes optimized for prokaryotic expression. These were assessed for optimal expression and purification yield, with four chimeric proteins being efficiently produced. Their diagnostic potential was then evaluated through ELISA assays with sera from VL afflicted humans and dogs. After two rounds of gene design, the results showed high levels of sensitivity for the best chimeric protein, named Q5, in humans (82%) and dogs (100%) with 100% specificity in comparison with healthy controls. A single non-specific reaction was seen with serum from individuals with tegumentary leishmaniasis. CONCLUSION: The newly described chimeric protein is potentially useful for the detection of both humans and dogs afflicted with VL, with its use in rapid tests necessary for validation as a new diagnostic tool.

Assuntos

Doenças do Cão/diagnóstico , Leishmaniose Visceral/veterinária , Testes Sorológicos/veterinária , Sequência de Aminoácidos , Animais , Antígenos de Protozoários/química , Doenças do Cão/sangue , Cães , Escherichia coli/metabolismo , Regulação da Expressão Gênica , Humanos , Leishmaniose Visceral/sangue , Leishmaniose Visceral/diagnóstico , Proteínas de Protozoários/química , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Sensibilidade e Especificidade , Testes Sorológicos/métodos , Transcriptoma

RESUMO

OBJECTIVE: To analyze sociodemographic and behavioral factors associated with vulnerability to HIV according to sexual orientation. METHOD: This is a cross-sectional study conducted using data on 3,818 people in the city of Imperatriz, Brazil, during 2015 and 2016. The survey's questionnaires addressed sociodemographic and behavioral variables. For the data analysis, association (chi-square test) and strength of association (odds ratio) were observed. A significance level of p < 0.05 and adjustment for age and gender were taken into consideration. RESULTS: A substantial portion of the sample stated they were heterosexual (88.8%). These individuals demonstrated a lower chance of HIV infection (p < 0.001), sexually transmitted infections (p < 0.001), alcohol use (p < 0.001) and condom use (p < 0.001), compared to men who have sex with men and/or bisexuals. In this group, after adjusting for confounding variables, the factors associated with HIV infection were being male (p < 0.001), unmarried (p < 0.001), having completed higher education (p < 0.001) and boasting multiple sexual partners (p < 0.001). CONCLUSION: Behavioral and sociodemographic factors of vulnerability to HIV are predominant among men who have sex with men and/or are bisexual.

RESUMO

Platelet-rich-plasma (PRP) is an autologous human platelet concentrate extracted from plasma. PRP has been investigated in order to be used in many fields, with emphasis on the musculoskeletal field applied to sports injuries, as well as on other medical fields such as cardiac surgery, gynecology, pediatric surgery, urology, ophthalmology and plastic surgery. Cancer treatment is another important field where PRP should be investigated; thus, it is important validating PRP preparation protocols to be used in clinical research. Many protocols should be revised since, overall, most studies do not provide necessary information to allow them to be multiplied or replicated. The current review focuses on several topics about cancer, mainly on innovative studies about PRP use as a feasible therapeutic alternative to treat bladder cancer - a field where it could play a key role. Relevant aspects such as platelets' contribution to immune regulation and the supportive role they play in innate and adaptive immune functions are also addressed. Another important topic reviewed in the current study refers to inflammatory process regulation associated with cancer and thrombosis sites, which indicated that tumor-induced platelet activation could be used as an important therapeutic target in the future. New aspects concerning nitric oxide's ability to restrain platelet adhesion and aggregation in order to slow metastasis progress in cancer patients provide an important advantage in cancer treatment. Finally, the current review has pointed out perspectives and the main concerns about, and possibilities of, PRP use in cancer treatment.

RESUMO

The purpose of this study was to investigate the effect of a single resistance training session on the glycemic and lipid response of women with Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) treated with Antiretroviral Therapy (ART). The sample consisted of 10 female subjects who underwent one resistance training session involving different muscle groups, that is, three sets of 8-12 repetitions with an interval of 90 seconds between the sets, and 120 seconds between exercises. The loads used in each exercise corresponded to an intensity equivalent to the interval of 5-7, which was in accordance with the OMNI-RES scale. The capillary glycemic levels were evaluated under the fed state before (Pre) and immediately after (Post) the exercise session. In order to evaluate the total cholesterol, HDL, and triglycerides (TG), blood samples were collected before (Pre) and one hour after the experimental protocol (Post). Non-HDL values were obtained using the Friedewald formula. The results showed that after a single resistance training session, alterations occurred in the glycemic response (p = 0.03), with a decrease of 11.4% in the values when comparing Pre and Post workout moments (99.8 ± 14.3 mg/dL vs. 87.3 ± 11.3 mg/dL, respectively). However, no significant result was observed regarding lipid response. In conclusion, a single resistance training session can reduce glycemic response in HIV positive people treated with ART without interfering with the lipid response.