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A formação em nível superior de docentes indígenas vem se constituindo como uma necessidade das escolas indígenas brasileiras a partir das mudanças ocorridas na política educacional, nos anos de 1990, com o estabelecimento da interculturalidade, do bilinguismo e as especificidades na/da educação escolar indígena. Com isso, verificam-se ações governamentais a partir da institucionalização de documentos orientadores, o que não tem sido suficiente para formar um número suficiente de docentes indígenas. Neste trabalho, objetivou-se discutir a legislação brasileira para a formação de professores indígenas, mais especificamente em Matemática, bem como a ação pedagógica com esta disciplina em escolas indígenas interculturais. A pesquisa se caracteriza como um ensaio teórico do tipo análise documental, acompanhada de relatos de estudantes indígenas como ilustração às discussões. Como resultados, é destacada a relevância da formação acadêmica visando à articulação de saberes indígenas aos conteúdos escolares para o fortalecimento de uma Matemática Intercultural nas escolas indígenas.

Evidencia os interesses dos organismos multilaterais na interface trabalho e educação por trás da retórica de combate e eliminação da pobreza. A metodologia utilizada foi um levantamento documental das produções e relatórios dos organismos multilaterais compreendidos enquanto desdobramento da Conferência Mundial sobre Educação Para Todos (1990), assim como, a revisão bibliográfica de autores que debatem a temática. Verifica-se nos documentos a análise da relação entre trabalho e educação sob a égide do combate e eliminação da pobreza e, a educação assume, assim, um caráter salvacionista. A orientação das reformas educacionais se dá em face da dinâmica do capital prover as necessidades básicas de aprendizagem, competências, habilidades e qualificações necessárias para o desenvolvimento econômico e social, na busca de uma suposta equidade social. Ancorada no binômio pobreza-segurança, a veemência da política-ideológica e de seu direcionamento de reformas estruturais nas políticas educacionais está na pretensão de combater a pobreza por propiciar clima desfavorável aos negócios. Nessa perspectiva, a educação colabora na sustentação do controle político da burguesia mundial sobre os processos educativos direcionados para reestruturação produtiva na divisão internacional do trabalho. O trabalho permite concluir que a interface “educação e trabalho” nesta perspectiva, assume um caráter pragmático e unidimensional para formação de recursos humanos – o chamado Capital Humano.

A series of Plectranthus spp. plant extracts (aqueous, acetonic, methanolic and ethyl acetic) obtained from eight different species, and previously isolated compounds (ranging from polyphenols, diterpenes and triterpenes), were assayed for in vitro inhibition of the skin-related enzymes tyrosinase, collagenase and elastase, and for studying their antioxidant properties. The ethyl acetic extracts of P. grandidentatus and P. ecklonii registered the highest antioxidant activity, whereas acetonic, methanolic and ethyl acetic extracts of P. ecklonii, P. grandidentatus, P. madagascariensis and P. saccatus concerning the enzymatic inhibition assays revealed high anti-tyrosinase and anti-collagenase activities. From the isolated compounds tested, abietane diterpenes and triterpenes were highly active against tyrosinase and elastase activity. Overall, the experimental results showed the powerful antioxidant and inhibitory action on skin-related enzymes tyrosinase, collagenase and elastase of Plectranthus spp. extracts and/or isolated compounds, supporting their further research as bioactive metabolites against skin sagging and hyperpigmentation in cosmetic and pharmaceutical formulations., Graphical Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder linked to protein misfolding and aggregation. AD is pathologically characterized by senile plaques formed by extracellular Amyloid-β (Aβ) peptide and Intracellular Neurofibrillary Tangles (NFT) formed by hyperphosphorylated tau protein. Extensive synaptic loss and neuronal degeneration are responsible for memory impairment, cognitive decline and behavioral dysfunctions typical of AD. Amyloidosis has been implicated in the depression of acetylcholine synthesis and release, overactivation of N-methyl-D-aspartate (NMDA) receptors and increased intracellular calcium levels that result in excitotoxic neuronal degeneration. Current drugs used in AD treatment are either cholinesterase inhibitors or NMDA receptor antagonists; however, they provide only symptomatic relief and do not alter the progression of the disease. Aβ is the product of Amyloid Precursor Protein (APP) processing after successive cleavage by β- and γ-secretases while APP proteolysis by α-secretase results in non-amyloidogenic products. According to the amyloid cascade hypothesis, Aβ dyshomeostasis results in the accumulation and aggregation of Aβ into soluble oligomers and insoluble fibrils. The former are synaptotoxic and can induce tau hyperphosphorylation while the latter deposit in senile plaques and elicit proinflammatory responses, contributing to oxidative stress, neuronal degeneration and neuroinflammation. Aβ-protein-targeted therapeutic strategies are thus a promising disease-modifying approach for the treatment and prevention of AD. This review summarizes recent findings on Aβ-protein targeted AD drugs, including β-secretase inhibitors, γ-secretase inhibitors and modulators, α-secretase activators, direct inhibitors of Aβ aggregation and immunotherapy targeting Aβ, focusing mainly on those currently under clinical trials.

Cytotoxicity screenings have identified Plectranthus plants as potential sources of antitumor lead compounds. In this work, several extracts from Plectranthus madagascariensis were prepared using different solvents (acetone, methanol, and supercritical CO2) and extraction techniques (maceration, ultrasound-assisted, and supercritical fluid extraction), and their chemical composition was detailed using high-performance liquid chromatography with a diode array detector. The cytotoxic activity of the major compounds identified, namely, rosmarinic acid (1) and abietane diterpenes 7α,6β-dihydroxyroyleanone (2), 7α-formyloxy-6β-hydroxyroyleanone (3), 7α-acetoxy-6β-hydroxyroyleanone (4), and coleon U (5), was evaluated in a battery of human cancer cell lines, including breast (MDA-MB-231, MCF-7), colon (HCT116), and lung (NCI-H460, NCI-H460/R) cancer, and also in healthy lung (MCR-5) cells. Royleanone (3) was isolated for the first time from P. madagascariensis, and its full spectroscopic characterization (proton and carbon nuclear magnetic resonance) was accomplished. A high selectivity for lung cancer cells was observed for royleanones (2, 4) with selectivity indexes of 4.3 and 3.2, respectively. The observed results combined with literature data allowed the establishment of important structure–activity relationships for substituted royleanone abietanes, such as the requirement for an electron-donating group at positions 6 and/or 7 in the abietane skeleton, and an improved cytotoxic effect for substituents with log P values between 2 and 5.

The exponential growth of cancer cases worldwide together with recent advances concerning the pathophysiological mechanisms of the disease at the molecular level led to a paradigm shift in chemotherapy, from monotherapy to targeted drug combination regimens. However, adverse effects and the emergence of multidrug resistance (MDR) limit the effectiveness of these therapies. In this context, hybrid combinations mixing anticancer drugs and bioactive phytochemical components from medicinal plants, or even plant extracts, that can act synergistically on multiple targets and signaling pathways represent a promising approach with the potential to expand the current therapeutic arsenal. This review aims to provide a synopsis on anticancer hybrid combinations based on their multi-target mechanisms and synergistic effects from an extensive literature search focusing mainly on publications from the last ten years. In most of these combinations, the phytochemical component was shown to enhance the anticancer activity of the chemotherapeutic agent and to sensitize chemoresistant tumors in several types of cancer. Hybrid combinations, due to synergistic interactions, are also associated with less severe adverse events since lower doses can be used to achieve the same therapeutic effect. Further preclinical and clinical studies are needed, as well as the development of an adequate regulatory framework, before hybrid combination therapy can be translated into clinical practice.

Cancer is a major cause of morbidity and mortality worldwide. Chemotherapeutic agents currently used in cancer treatment are associated with severe side effects and development of resistance. Thus, there is a pressing need for novel and more potent anticancer drugs with high selectivity for tumor cells and reduced toxicity to normal tissue. Natural products remain an important source of bioactive compounds and drug prototypes that can lead to new and more effective antitumor agents. Coniferous plants are rich in abietane diterpenoids with a wide range of biological activities that provide useful templates for synthetic modification. Abietic acid and dehydroabietic acid (DHA), the major diterpenic resin acids from Pinus rosin, and dehydroabietylamine found in commercial disproportionated rosin amine, display antibacterial and antitumor properties. These compounds and their synthetic derivatives have been reported as promising anticancer agents with potent growth inhibitory activity against several types of human cancer cell lines, including breast, ovarian, prostate, colon, liver, lung and cervical carcinoma cells. Their mechanisms of action are diverse and include DNA binding, induction of apoptosis or oncosis, tubulin polymerization inhibition and disruption of intracellular cholesterol transport. This review covers the main aspects of natural rosin abietane diterpenoids (abietic acid, DHA and DHAA) and synthetic derivatives concerning their anti-proliferative, cytotoxic and antitumor activities, mechanisms of action and structure- activity relationships relevant for the development of novel anticancer agents for cancer chemotherapy.

The antimicrobial activity of dehydroabietic acid (DHA) for its use as an antibiofilm agent was tested in this work. DHA was assayed against a collection of Gram-positive, Gram-negative sensitive and resistant bacteria and yeasts through the minimum inhibitory concentration (MIC), MIC with Bioburden challenge, minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), MBIC with Bioburden challenge and growth curve studies. Toxicological studies (Artemia salina, sulforhodamine B (SRB) assay) were done to assess if the compound had antimicrobial and not cytotoxic properties. Furthermore, microencapsulation and stability studies were carried out to evaluate the chemical behavior and stability of DHA. On MIC results, Gram-positive bacteria Staphylococcus aureus ATCC 1228 and Mycobacterium smegmatis ATCC 607 presented a high efficiency (7.81 µg/mL), while on Gram-negative bacteria the highest MIC value of 125 µg/mL was obtained by all Klebsiella pneumoniae strains and Escherichia coli isolate strain HSM 303. Bioburden challenge showed that MIC, MBIC and percentage biofilm inhibition (BI) values suffered alterations, therefore, having higher concentrations. MBIC values demonstrated that DHA has a higher efficiency against S. aureus ATCC 43866 with a percentage of BI of 75.13 ± 0.82% at 0.49 µg/mL. Growth curve kinetic profiles of DHA against S. aureus ATCC 25923 were observed to be bacteriostatic. DHA-alginate beads had a average size of 2.37 ± 0.20 and 2.31 ± 0.17 × 103 µm2 with an encapsulation efficiency (EE%) around 99.49 ± 0.05%, a protection percentage (PP%) of 60.00 ± 0.05% in the gastric environment and a protection efficiency (PE%) around 88.12 ± 0.05% against UV light. In toxicological studies DHA has shown IC50 of 19.59 ± 7.40 µg/mL and a LC50 of 21.71 ± 2.18%. The obtained results indicate that DHA is a promising antimicrobial candidate against a wide range of bacteria and biofilm formation that must be further explored.

Dados Censitários (INEP, 2017), indicam um expressivo aumento no número de matrículas na educação básica nas escolas localizadas em Terras Indígenas. Discutimos neste artigo a Educação Infantil Indígena, tema pouco abordado, e um direito recente no Brasil. Problematizamos as políticas e orientações para essa etapa da educação básica, a participação indígena e o papel das famílias na educação infantil em uma comunidade Kaingang no Paraná, evidenciando aspectos da infância e da educação indígena, a formação e os dados sobre os professores da educação infantil, o espaço, as práticas e materiais didáticos, buscando explicitar a inserção da criança indígena na escola com a presença de mães indígenas que acompanham o processo. Essas discussões resultam de uma pesquisa documental e empírica com aporte da Teoria Histórico-Cultural. Os resultados evidenciam que os povos indígenas, em sua resistência organizada, atuam em espaços institucionais locais e governamentais, visando à inclusão no sistema de ensino, porém com ações para ressignificá-lo. Palavras-Chave: Crianças Kaingang. Educação Infantil Indígena Professores Indígenas.

Lipoaminoacids (LAA) are an important group of biosurfactants, formed by a polar hydrophilic part (amino acid) and a hydrophobic tail (lipid). The gemini LAA structures allow the formation of a supramolecular complex with bioactive molecules, like DNA, which provides them with good transfection efficiency. Since lipases are naturally involved in lipid and protein metabolism, they are an alternative to the chemical production of LAA, offering an eco-friendly biosynthetic process option. This work aimed to design the production of novel cystine derived gemini through a bioconversion system using immobilized lipases. Three lipases were used: porcine pancreatic lipase (PPL), lipase from Thermomyces lanuginosus (TLL), and lipase from Rizhomucor miehei (RML). PPL was immobilized in sol-gel lenses. L-cystine dihydrochloride and dodecylamine were used as substrates for the bioreaction. The production of LAA was evaluated by thin layer chromatography (TLC), and colorimetric reaction with eosin. The identification and quantification was carried out by High Performance Liquid Chromatographer-Mass Spectrometry (HPLC-MS/MS). The optimization of media design included co-solvent (methanol, dimethylsulfoxide), biphasic (n-hexane and 2-propanol) or solvent-free media, in order to improve the biocatalytic reaction rates and yields. Moreover, a new medium was tested where dodecylamine was melted and added to the cystine and to the biocatalyst, building a system of mainly undissolved substrates, leading to 5 mg/mL of LAA. Most of the volume turned into foam, which indicated the production of the biosurfactant. For the first time, the gemini derived cystine lipoaminoacid was produced, identified, and quantified in both co-solvent and solvent-free media, with the lipases PPL, RML, and TLL.

Urinary and intravascular catheters are two of the most used invasive medical devices; however, microbial colonization of catheter surfaces is responsible for most healthcare-associated infections (HAIs). Several antimicrobial-coated catheters are available, but recurrent antibiotic therapy can decrease their potential activity against resistant bacterial strains. The aim of this Review is to question the actual effectiveness of currently used (coated) catheters and describe the progress and promise of alternative antimicrobial coatings. Different strategies have been reviewed with the common goal of preventing biofilm formation on catheters, including release-based approaches using antibiotics, antiseptics, nitric oxide, 5-fluorouracil, and silver as well as contact-killing approaches employing quaternary ammonium compounds, chitosan, antimicrobial peptides, and enzymes. All of these strategies have given proof of antimicrobial efficacy by modifying the physiology of pathogens or disrupting their structural integrity. The aim for synergistic approaches using multitarget processes and the combination of both antifouling and bactericidal properties holds potential for the near future. Despite intensive research in biofilm preventive strategies, laboratorial studies still present some limitations since experimental conditions usually are not the same and also differ from biological conditions encountered when the catheter is inserted in the human body. Consequently, in most cases, the efficacy data obtained from in vitro studies is not properly reflected in the clinical setting. Thus, further well-designed clinical trials and additional cytotoxicity studies are needed to prove the efficacy and safety of the developed antimicrobial strategies in the prevention of biofilm formation at catheter surfaces.

The use of invasive medical devices is becoming more common nowadays, with catheters representing one of the most used medical devices. However, there is a risk of infection associated with the use of these devices, since they are made of materials that are prone to bacterial adhesion with biofilm formation, often requiring catheter removal as the only therapeutic option. Catheter-related urinary tract infections (CAUTIs) and central line-associated bloodstream infections (CLABSIs) are among the most common causes of healthcare-associated infections (HAIs) worldwide while endotracheal intubation is responsible for ventilator-associated pneumonia (VAP). Therefore, to avoid the use of biocides due to the potential risk of bacterial resistance development, antifouling strategies aiming at the prevention of bacterial adherence and colonization of catheter surfaces represent important alternative measures. This review is focused on the main strategies that are able to modify the physical or chemical properties of biomaterials, leading to the creation of antiadhesive surfaces. The most promising approaches include coating the surfaces with hydrophilic polymers, such as poly(ethylene glycol) (PEG), poly(acrylamide) and poly(acrylates), betaine-based zwitterionic polymers and amphiphilic polymers or the use of bulk-modified poly(urethanes). Natural polysaccharides and its modifications with heparin, have also been used to improve hemocompatibility. Recently developed bioinspired techniques yielding very promising results in the prevention of bacterial adhesion and colonization of surfaces include slippery liquid-infused porous surfaces (SLIPS) based on the superhydrophilic rim of the pitcher plant and the Sharklet topography inspired by the shark skin, which are potential candidates as surface-modifying approaches for biomedical devices. Concerning the potential application of most of these strategies in catheters, more in vivo studies and clinical trials are needed to assure their efficacy and safety for possible future use.

The physicochemical, antioxidant and antimicrobial properties of selected Portuguese commercial honeys have been characterized aiming at establishing correlations between honey bioactivity and the physicochemical descriptors. All honey samples met the European regulations on honey quality criteria, including moisture and sugar content, free acidity, diastase activity, electrical conductivity, ashes, hydroxymethylfurfural and proline content. Antioxidant activity was evaluated based on phenolic and flavonoid content, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing antioxidant power (FRAP) and oxygen radical antioxidant capacity (ORAC) assays. The honeys showed antibacterial and antifungal activity with minimum inhibitory concentrations (MIC) between 6.25–25% (w/v) and minimum fungicidal concentrations (MFC) in the range 12.5–50% (w/v), respectively. The bioactivity and physicochemical parameters of honey samples were correlated and depended on the honey floral source. The darkest honey, i.e. heather honey, showed the highest antioxidant and antimicrobial activities, which can be attributed to its higher phenolic, flavonoid and protein content.

Aim: Confirm the use of Plectanthus spp. plants in traditional medicine, particularly as anti-inflammatory and anti-infective agents. Materials & Methods: Compounds previously isolated from Plectranthus spp. were studied for their anti-inflammatory activity using the SNAP assay and RAW 264.7 cells, by the quantification of nitric oxide. An halimane diterpene and its derivatives were tested in infected macrophages with M. tuberculosis H37Rv, using CFU counts assay, at their minimum inhibitory concentration values. Results: The isolated compounds tested at noncytotoxic concentrations, did not reveal nitric oxide scavenging in the S-nitroso-N-acetylpenicillamine and the cellular assays. On the other hand, promising results were obtained regarding one semisynthetic halimane derivative (11R*,13E)-halima-5,13-diene-11,15-diol), previously prepared (2.1 × 105 CFU/mL), with an effect similar to the antitubercular drugs ethambutol (2.0 × 105 CFU/mL) and isoniazid (1.2 × 105 CFU/mL). Conclusion: The present report demonstrates the relevance of Plectranthus spp. in medicinal chemistry drug development for TB and other infective respiratory complaints. Also, this work suggests that further studies involving other inflammatory mediators are needed to validate the anti-inflammatory use of these medicinal plants.

Ranitidine is a histamine H2-receptor antagonist that inhibits gastric acid secretion, commonly used in the treatment and prophylaxis of peptic ulcer and gastroesophageal reflux disease. Over-the-counter ranitidine hydrochloride tablets are available in several European countries as well as the US for the relief of indigestion and heartburn. Commercial tablets containing the equivalent of 150 mg of ranitidine were analysed following extraction. Ranitidine is water-soluble, thus avoiding the use of organic solvents. Standard aqueous solutions of ranitidine hydrochloride were used to construct a calibration curve. This graduate laboratory experiment describes a simple, inexpensive, safe, and “green” procedure for the quantification of ranitidine tablets by UV spectrophotometry. The entire procedure provides an pedagogical opportunity to approach a realistic analytical scenario, typical of a quality control laboratory, by designing an attractive and engaging hands-on session. An average content of 148 ± 1 mg of ranitidine was determined using both standard addition and external calibration methods and results are in agreement with Pharmacopoeia. Keywords: Analytical chemistry, ranitidine, drugs/pharmaceuticals, quantitative analysis, UV-Vis spectroscopy

Amphotericin B (AmB), a broad-spectrum polyene antibiotic in the clinic for more than fifty years, remains the gold standard in the treatment of life-threatening invasive fungal infections and visceral leishmaniasis. Due to its poor water solubility and membrane permeability, AmB is conventionally formulated with deoxycholate as a micellar suspension for intravenous administration, but severe infusion-related side effects and nephrotoxicity hamper its therapeutic potential. Lipid-based formulations, such as liposomal AmB, have been developed which significantly reduce the toxic side effects of the drug. However, their high cost and the need for parenteral administration limit their widespread use. Therefore, delivery systems that can retain or even enhance antimicrobial efficacy while simultaneously reducing AmB adverse events are an active area of research. Among those, lipid systems have been extensively investigated due to the high affinity of AmB for binding lipids. The development of a safe and cost-effective oral formulation able to improve drug accessibility would be a major breakthrough, and several lipid systems for the oral delivery of AmB are currently under development. This review summarizes recent advances in lipid-based systems for targeted delivery of AmB focusing on non-parenteral nanoparticulate formulations mainly investigated over the last five years and highlighting those that are currently in clinical trials.

According to the World Health Organization, tuberculosis (TB) is one of the major causes of death worldwide from an infectious disease. The causative agent of TB, Mycobacterium tuberculosis (Mtb), has evolved elaborate survival mechanisms in the human host, allowing it to remain in a clinically latent infection state before eventually progressing to the active disease. The strain H37Rv of Mtb is a harmful pathogen and some studies revealed that to achieve successful infection, Mtb must rely on macrophages for its replication and, more importantly, the macrophage should remain viable. Researching for natural products active against Mtb has increased with the development of easier, faster, and safer screening techniques. Indeed, flavones, flavonoids, and related metabolites have been reported to exhibit mild activity. In 2010, Rijo and co-workers reported that royleanone abietanes found in several Plectranthus spp. were highly active against MDR-Mtb strains, regarding 6β,7α-dihydroxyroyleanone, horminone, 6,7-dehydroroyleanone (MIC 12.5 mg/mL), and 7α-acetoxy-6β-hydroxyroyleanone (MIC 3.12 mg/mL), when compared to first-line anti-TB drugs isoniazid (MIC 4 mg/mL) and rifampicin (MIC 16 mg/mL). On the other hand, new findings reported two genes found in a small operon, Rv3377c and Rv3378c that encode a diterpene synthase to produce tuberculosinol and isotuberculosinol, responsible for Mtb phagosomal arrest. Interestingly, these compounds were found to be very similar to the halimane diterpenes isolated from Plectranthus spp. This derivative could interact with the binding site, thus inhibiting the production of tuberculosinols, ultimately avoiding the phagocytosis suppression. The worldwide interest in the use of natural products has been growing, with its beneficial effects being rediscovered for the development of new drugs. Therefore, new therapeutic agents with specific targets and less adverse side effects support the need to extend the studies on natural products as lead compounds against tuberculosis.

Biosurfactant compounds have been studied in many applications, including biomedical, food, cosmetic, agriculture, and bioremediation areas, mainly due to their low toxicity, high biodegradability, and multifunctionality. Among biosurfactants, the lipoplexes of lipoaminoacids play a key role in medical and pharmaceutical fields. Lipoaminoacids (LAAs) are amino acid-based surfactants that are obtained from the condensation reaction of natural origin amino acids with fatty acids or fatty acid derivatives. LAA can be produced by biocatalysis as an alternative to chemical synthesis and thus become very attractive from both the biomedical and the environmental perspectives. Gemini LAAs, which are made of two hydrophobic chains and two amino acid head groups per molecule and linked by a spacer at the level of the amino acid residues, are promising candidates as both drug and gene delivery and protein disassembly agents. Gemini LAA usually show lower critical micelle concentration, interact more efficiently with proteins, and are better solubilising agents for hydrophobic drugs when compared to their monomeric counterparts due to their dimeric structure. A clinically relevant human gene therapy vector must overcome or avoid detect and silence foreign or misplaced DNA whilst delivering sustained levels of therapeutic gene product. Many non-viral DNA vectors trigger these defence mechanisms, being subsequently destroyed or rendered silent. The development of safe and persistently expressing DNA vectors is a crucial prerequisite for a successful clinical application, and it one of the main strategic tasks of non-viral gene therapy research.

Different types of treatments are being employed to overcome cancer, which is characterized by abnormal cell growth involving cell division without control. However, their usually lack of selectivity and the development of resistance result in limited efficacy or ineffectiveness of the therapies. For these reasons, seeking new treatment options for this disease is necessary. Nowadays, the acknowledge bioactive properties of some secondary metabolites such as polyphenols, have made antitumour hybrid combinations a promising therapeutic approach. This work aims to provide a synopsis into Anticancer Hybrid Combinations involving phenolic compounds, focusing on their multi-target mechanisms of action and synergistic effects. These combinations consist on the therapeutic mixture of synthetic drugs with chemically defined constituents from plants (secondary metabolites, in this case, phenolic compounds) aiming to increase the pharmacological activity of the formulation and simultaneously reduce the toxic side-effects of the drugs, interaction known as synergy. Antitumour hybrid combinations are a promising therapeutic strategy to minimize adverse effects and to reduce cancer resistance to different treatments. At the same time, it shows selectivity to tumour cells and potentiate the activity of the drug that make them an interesting option to cure cancer. References: [1] Dominguez-Martin EM, Diaz-Lanza AM, Faustino CMC (2018) Curr Pharm Des 24, 4312-4333.[2] Wagner H, Efferth T. (2017) Phytomedicine, 37, 1-3.[3] Mahbub AA, Le Maitre CL, Haywood-Small S, Cross NA, Nicola Jordan-Mahy N (2019) Oncotarget 10, 4570-86[4] Zhong C, Qiu S, Li J, Shen J, Zu Y, Shi J, Sui G (2019) Phytomedicine 59, 152921

A Educação Escolar Indígena se consolidou no âmbito das reformas do Estado, nos anos de 1990, sob as bases da diferença, do bilinguismo e da especificidade, no momento de reorganização do sistema orientado pelos organismos e agências internacionais. Pela diversidade cultural e linguística dos povos indígenas no Brasil, pelas condições de extrema pobreza em que vivem, o tema da avaliação da aprendizagem ou a avaliação institucional é extremamente complexo haja vista o histórico de exclusão e as políticas assimilacionistas. Este texto aborda a avaliação da educação básica indígena analisando os limites da avaliação padronizada para um contexto de especificidade cultura e de exclusão social destacando a necessidade de construção de novos parâmetros, desenhados e operados em conjunto com os povos indígenas.

Medicinal plants of the Plectranthus genus (Lamiaceae) are known for their ethnopharmacological relevance, mainly against infectious, dermatologic and gastrointestinal pathologies. Three Plectranthus species originated from South Africa, namely P. madagascariensis, P. neochilus and the rare P. porcatus were hereby screened for their antimicrobial and cytotoxic activities related with their known and/or potential ethnomedicinal uses. Twenty-six extracts were prepared by the combination of extraction methods (infusion, decoction, microwave-assisted, ultrasound-assisted, maceration and supercritical fluid extraction) with different polarity solvents (water, methanol, acetone and supercritical CO2). The comparison study of these extracts was elucidated through the corresponding chemical characterization and cytotoxic activity data. Therefore, the acetone extract from P. madagascariensis prepared by ultrasound extraction method revealed potent antibacterial activity against Gram-positive bacteria (1.95 < minimum inhibitory concentration (MIC) < 7.81 μg/mL), including a methicillin-resistant Staphylococcus aureus (MRSA) strain. Additionally, acetone extracts from both P. madagascariensis and P. neochilus exhibited relevant antibacterial activity against Gram-negative Klebsiella pneumonia (0.48 < MIC < 3.91 μg/mL), validating the traditional uses of such plants as anti-infectious agents. All methanolic extracts showed potent antioxidant effects at 100 μg/mL measured as their radical scavenging activity (60.8−89.0%) in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The P. madagascariensis extract obtained by maceration in acetone showed moderate cytotoxic effects in the MDA-MB-231 cell line (triple negative human breast carcinoma). The extract concentration that caused a 50% inhibition in cell viability (IC50) was 64.52 μg/mL. All extracts in this comparative study were profiled by high-performance liquid chromatography-HPLC with a diode-array detector-DAD (HPLC-DAD) and the main known bioactive components were identified in each extract, which included polyphenols (caffeic 1, chlorogenic 2 and rosmarinic 3 acids), abietane diterpenes (7α-acetoxy-6β-hydroxyroyleanone 4 and coleon U 5) and flavone glycosides (rutin 6 and naringin 7).

Entre os Kaingang no Paraná a escrita em língua portuguesa tem sido usada, reivindicada e aprendida desde o aldeamento, no início do século XX, quando estes povos foram retirados de seus territórios e passaram a viver sob a política de integração. Neste texto, por meio de pesquisa bibliográfica e empírica, abordamos o ensino da leitura e escrita em uma comunidade Kaingang no Vale do Ivaí, Paraná. Destacamos elementos da vivência das crianças e algumas formas próprias de aprender com autonomia nos grupos familiares. Analisamos como a escola organiza o ensino a partir da decisão da comunidade pela alfabetização em língua portuguesa. Os resultados evidenciam a necessidade de fortalecimento do bilinguismo e da escrita em língua kaingang por meio da formação de professores indígenas e da produção de materiais didático diversificados.

As relações de trabalho, construídas ao longo da história, influenciaram diretamente as transformações sociais, culturais, as práticas educacionais e a organização da escola pública. O presente artigo apresenta uma reflexão sobre o trabalho no sistema capitalista e suas implicações na construção do processo educacional. Objetiva analisar as relações entre as mudanças no processo de produção e as formas de trabalho empregadas com a educação, a institucionalização da escola pública e as práticas pedagógicas, para compreender a necessidade e o caminho para a conquista da emancipação humana, consequentemente, da consciência de classe. Discute a organização da produção, do trabalho e da sociedade, seguido por um debate sobre suas implicações na formação da prática educacional e o papel da educação no processo emancipador dos indivíduos. Destaca o importante papel do trabalho e da educação na construção do conhecimento, da consciência de classe e na emancipação humana. Elaborado a partir de análise bibliográfica.

Os estudos sobre a educação escolar indígena foram incrementados nos últimos anos a partir da expansão do Ensino Superior, com a criação das Licenciaturas Interculturais por meio do Programa de Apoio à Formação Superior e Licenciaturas Indígenas, e outras formas para o acesso de indígenas às universidades. Destacam-se também, as experiências de programas governamentais que ampliaram as políticas de diversidade, inclusão social e valorização da educação escolar indígena em todo o País. No estado do Paraná, um importante avanço foi a criação de uma política de vagas suplementares para ingresso de indígenas nas universidades públicas, e a estadualização das escolas indígenas em 2009, com a expansão da Educação Básica nas comunidades. Reconhecendo os avanços nas políticas de formação destinadas aos povos indígenas, por meio de estudo documental, neste texto são discutidas as perspectivas atuais para o Ensino Médio. Observam-se poucos progressos em relação a esta etapa, que requer ações específicas e diferenciadas, interculturais e bilíngues, visando à inovação e à melhoria, em atendimento aos anseios dos povos e jovens indígenas.

Ha estudos sobre os indios Kaingang no Parana que contribuem para o entendimento da sua historia, cultura, organizacao social e linguistica. Entretanto, sobre a escolarizacao e a apropriacao da linguagem escrita, tanto da lingua kaingang, como da lingua portuguesa, sao raras as publicacoes e pesquisas sobre um tema que e muito relevante, haja vista o ritmo acelerado da perda de linguas minoritarias no mundo e no Brasil, a partir de uma politica neoliberal de estado minimo e pouco investimento em formacao de professores para atuarem em areas socialmente relevantes como as linguas, dentre elas as linguas indigenas que requer investimento na formacao de professores e linguistas indigenas. Neste artigo apresentamos aspectos historicos sobre registros desta lingua indigena, o projeto de alfabetizacao bilingue implementado no Brasil e como esta vem ocorrendo com os povos Kaingang na regiao do Vale do Ivai, no Parana, com criancas do ensino fundamental. Por meio de pesquisa bibliografica e empirica foi possivel perceber que o ensino da lingua materna indigena, mesmo entre criancas monolingues em kaingang, entra no curriculo como ensino de lingua estrangeira, o que pode comprometer seriamente a aprendizagem, a alfabetizacao, tanto da lingua indigena como da lingua portuguesa. Evidencia-se que o investimento na formacao continuada de professores indigenas e uma das estrategias para a superacao de tal situacao.

The authors wish to make the following erratum to this paper [...]

The growing incidence of cancer, the toxic side-effects associated with conventional chemotherapeutic agents and the development of multidrug resistance (MDR) drive the search for novel and more effective drugs with multi-target activity and selectivity towards cancer cells. Stilbenes are a group of naturally occurring phenolic compounds of plant origin derived from the phenylpropanoid pathway that may exist as cis- or trans-isomers. Although the trans-isomer is the more common and stable configuration, resveratrol being a representative compound, cis-stilbenes are potent cytotoxic agents that bind to and inhibit tubulin polymerization, destabilizing microtubules. This review summarizes the chemistry and biological evaluation of cytotoxic stilbenes and their synthetic derivatives as promising antimitotic leads for cancer therapy, focusing on the most potent compounds, the combretastatins. Combretastatins isolated from the South African bushwillow Combretum caffrum are among the most potent antimitotic and vascular disrupting agents (VDAs) of natural origin. Preclinical studies have demonstrated their potent antitumor effects in a wide variety of tumors, both in vitro and in vivo, being currently under evaluation in phase 2 and phase 3 clinical trials for several types of solid tumors. Topics covered herein include synthetic medicinal chemistry, modes of action, structure-activity relationships (SAR), preclinical and clinical studies as VDAs in cancer therapy, either as single agents or in combination with cytotoxic anticancer drugs, antiangiogenic agents, or radiation therapy, and development of appropriate formulations based on nanocarriers (e.g., liposomes, nanoemulsions, polymeric, lipid and ceramic nanoparticles, carbon nanotubes) for improved bioavailability and targeted delivery of combretastatins to the tumor vasculature.

The worldwide interest in the use of medicinal plants has been growing, and its beneficial effects being rediscovered for the development of new drugs. Based on their vast ethnopharmacological applications, which inspired current research in drug discovery, natural products can provide new and important leads against various pharmacological targets. This work pioneers an extensive and an updated literature review on the current state of research on Rosmarinus officinalis L., elucidating which compounds and biological activities are the most relevant. Therefore, a search was made in the databases PubMed, ScienceDirect and Web of Science with the terms ‘rosemary’, ‘Rosmarinus officinalis’, ‘rosmarinic acid’ ‘carnosol’ and ‘carnosic acid’, which included 286 articles published since 1990 about rosemary's pharmacological activities and their isolated compounds. According to these references, there has been an increasing interest in the therapeutic properties of this plant, regarding carnosic acid, carnosol, rosmarinic acid and the essential oil. The present manuscript provides an updated review upon the most reported activities on R. officinalis and its active constituents., Lay abstract The worldwide interest in the use of medicinal plants has been growing, and their beneficial effects being rediscovered for the development of new drugs. Actually, current research in drug discovery has been inspired on the vast ethnopharmacological applications of natural products, providing new and important leads against various pharmacological targets. In this work, an updated literature review is presented to clarify the current state of research on Rosmarinus officinalis L., elucidating its constituents and their most relevant biological activities. Therefore, this work provides an updated review upon the most reported medicinal properties, namely, antitumoral, anti-inflammatory, analgesic, neurodegenerative, endocrinal, anti-infective and antioxidant.

Lipoamino acid-based micelles have been developed as delivery vehicles for the hydrophobic drug amphotericin B (AmB). The micellar solubilisation of AmB by a gemini lipoamino acid (LAA) derived from cysteine and its equimolar mixtures with the bile salts sodium cholate (NaC) and sodium deoxycholate (NaDC), as well as the aggregation sate of the drug in the micellar systems, was studied under biomimetic conditions (phosphate buffered-saline, pH 7.4) using UV-vis spectroscopy. Pure surfactant systems and equimolar mixtures were characterized by tensiometry and important parameters were determined, such as critical micelle concentration (CMC), surface tension at the CMC (γCMC), maximum surface excess concentration (Γmax), and minimum area occupied per molecule at the water/air interface (Amin). Rheological behaviour from viscosity measurements at different shear rates was also addressed. Solubilisation capacity was quantified in terms of molar solubilisation ratio (χ), micelle-water partition coefficient (KM) and Gibbs energy of solubilisation (ΔGs°). Formulations of AmB in micellar media were compared in terms of drug loading, encapsulation efficiency, aggregation state of AmB and in vitro antifungal activity against Candida albicans. The LAA-containing micellar systems solubilise AmB in its monomeric and less toxic form and exhibit in vitro antifungal activity comparable to that of the commercial formulation Fungizone.

Amphotericin B (AmB) is a hydrophobic polyene antibiotic used in the therapy of systemic fungal infections. Due to its poor water solubility, it is formulated as a colloidal suspension for intravenous administration using deoxycholate as the solubilizing agent (Fungizone). However, severe toxicity of the formulation has prompted the development of more efficient and safer delivery agents. Gemini amino acid-based surfactants constitute a promising alternative to the biological bile salt surfactant(s), as both biocompatible and biodegradable drug carriers. The supramolecular behaviour of an anionic gemini surfactant derived from cysteine, (C 8 Cys) 2 , was characterized by tensiometry and its solubilization capability towards the hydrophobic drug AmB was evaluated under biomimetic conditions (phosphate buffered-saline, pH 7.4). Important aggregation parameters, such as critical micelle concentration (CMC), surface tension at the CMC ( γ cmc ), maximum surface excess concentration ( Γ max ) and minimum area occupied per molecule at the water/air interface ( A min ) were determined. Solubilization power was quantified in terms of molar solubilization ratio ( χ ), micelle-water partition coefficient ( K p ) and Gibbs energy of solubilization ( Δ G s 0 ) . The aggregation state of AmB in the micellar media was assayed by UV–Vis spectroscopy and in vitro antifungal activity was evaluated. Results were compared with the ones obtained for sodium deoxycholate (NaDC) and discussed in terms of drug loading, efficacy and efficiency. Complementary rheological measurements were performed as NaDC solutions formed a shear-thinning gel at concentrations of 0.01 mol L −1 and higher, in the experimental conditions employed.

Sophorolipids (SLs) are glycolipid biosurfactants, produced as a mixture of several compounds by some nonpathogenic yeast. In the current study, separation of individual SLs from mixtures with further evaluation of their surface properties and biologic activity on MDA-MB-321 breast cancer cell line were investigated. SLs were biosynthesized by Starmerella bombicola in a culture media supplemented with borage oil. A reverse-phase flash chromatography method with an automated system coupled with a prepacked cartridge was used to separate and purify the main SLs. Compositional analysis of SLs was performed by high-performance liquid chromatography with electrospray ionization mass spectrometry and tandem mass spectrometry. The following diacetylated lactonic SLs were isolated and purified: C18:0, C18:1, C18:2, and C18:3. The critical micelle concentration (CMC) and surface tension at CMC (γCMC ) of the purified SLs showed an increase with the number of double bonds. High cytotoxic effect against MDA-MB-231 cells was observed with C18:0 and C18:1 lactonic SLs. The cytotoxic effects of C18:3 lactonic SL on cancerous cells were for the first time studied. This cytotoxic effect was considerably higher than the promoted by acidic SLs; however, it induced a lower effect than the previously mentioned SLs, C18:0 and C18:1. To our knowledge, for the first time, C18:1 lactonic SL, in selected concentrations, proved to be able to inhibit MDA-MB-231 cell migration without compromising cell viability and to increase intracellular reactive oxygen species.

The transport of molecules across biological membranes are critical for most cellular processes. Membrane permeability is also a key determinant for drug absorption, distribution, and elimination. Diffusion, that is, the migration of matter down a concentration gradient, is a simple mechanism by which both endogenous and drug molecules can enter (or exit) cells. This paper describes a simple and engaging physical chemistry undergraduate laboratory experiment for health and life sciences students studying diffusion of drug and dye molecules in solution. In this experiment, the diffusion of amitriptyline hydrochloride, ranitidine hydrochloride, and tartrazine across a cellulose dialysis membrane is evaluated using an innovative macro and microscale approach. Compound concentration in solution as a function of time is obtained both from conductivity measurements of 25 mL solutions and from absorbance measurements of 100 μL samples taken in a 96-well microplate. By using solutions of different concentrations,...

Este texto se propõe a analisar a produção científica na área da educação física e as concepções de educação física escolar indígena que apresentam. A pesquisa, de abordagem qualitativa, buscou articular esta produção e a contextualização de alguns aspectos do contato da sociedade capitalista em expansão e os povos indígenas no Brasil. As fontes envolvem seis edições do CONBRACE – Congresso Brasileiro de Ciências do Esporte, realizado bienalmente em diferentes cidades brasileiras no período de 2001 a 2011. Em conformidade com documentos internacionais da UNESCO e Banco Mundial, disseminados nos anos de 1990, as publicações destacam a importância de se promover na escola um conhecimento cotidiano, como pressuposto e possibilidade de participação na cidadania. Considerando os princípios dessa política, reafirmamos as origens do conceito de cidadania explicitando que, desde suas origens, se limita a direitos políticos permanecendo a desigualdade histórica, gerada pela sociedade capitalista que, apesar da veiculação de um amplo discurso sobre inclusão, continua permitindo aos “excluídos” apenas a venda de sua força de trabalho, único meio que lhes resta nesta sociedade para satisfazer suas necessidades.