Use of a Novel Artificial Intelligence System Leads to the Detection of Significantly Higher Number of Adenomas During Screening and Surveillance Colonoscopy: Results From a Large, Prospective, US Multicenter, Randomized Clinical Trial.

INTRODUCTION: Adenoma per colonoscopy (APC) has recently been proposed as a quality measure for colonoscopy. We evaluated the impact of a novel artificial intelligence (AI) system, compared with standard high-definition colonoscopy, for APC measurement. METHODS: This was a US-based, multicenter, prospective randomized trial examining a novel AI detection system (EW10-EC02) that enables a real-time colorectal polyp detection enabled with the colonoscope (CAD-EYE). Eligible average-risk subjects (45 years or older) undergoing screening or surveillance colonoscopy were randomized to undergo either CAD-EYE-assisted colonoscopy (CAC) or conventional colonoscopy (CC). Modified intention-to-treat analysis was performed for all patients who completed colonoscopy with the primary outcome of APC. Secondary outcomes included positive predictive value (total number of adenomas divided by total polyps removed) and adenoma detection rate. RESULTS: In modified intention-to-treat analysis, of 1,031 subjects (age: 59.1 ± 9.8 years; 49.9% male), 510 underwent CAC vs 523 underwent CC with no significant differences in age, gender, ethnicity, or colonoscopy indication between the 2 groups. CAC led to a significantly higher APC compared with CC: 0.99 ± 1.6 vs 0.85 ± 1.5, P = 0.02, incidence rate ratio 1.17 (1.03-1.33, P = 0.02) with no significant difference in the withdrawal time: 11.28 ± 4.59 minutes vs 10.8 ± 4.81 minutes; P = 0.11 between the 2 groups. Difference in positive predictive value of a polyp being an adenoma among CAC and CC was less than 10% threshold established: 48.6% vs 54%, 95% CI -9.56% to -1.48%. There were no significant differences in adenoma detection rate (46.9% vs 42.8%), advanced adenoma (6.5% vs 6.3%), sessile serrated lesion detection rate (12.9% vs 10.1%), and polyp detection rate (63.9% vs 59.3%) between the 2 groups. There was a higher polyp per colonoscopy with CAC compared with CC: 1.68 ± 2.1 vs 1.33 ± 1.8 (incidence rate ratio 1.27; 1.15-1.4; P < 0.01). DISCUSSION: Use of a novel AI detection system showed to a significantly higher number of adenomas per colonoscopy compared with conventional high-definition colonoscopy without any increase in colonoscopy withdrawal time, thus supporting the use of AI-assisted colonoscopy to improve colonoscopy quality ( ClinicalTrials.gov NCT04979962).

In vitro evaluation of 2-(1H-pyrazol-1-yl)-1,3,4-thiadiazole derivatives against replicative and infective stages of Trypanosoma cruzi.

Current treatment of Chagas disease (CD) is based on two substances, nifurtimox (NT) and benzonidazole (BZ), both considered unsatisfactory mainly due to their low activities and high toxicity profile. One of the main challenges faced in CD management concerns the identification of new drugs active in the acute and chronic phases and with good pharmacokinetic profiles. In this work, we studied the bioactivity of twenty 2-(1H-pyrazol-1-yl)-1,3,4-thiadiazole derivatives against Trypanosoma cruzi epimastigotes and trypomastigotes. We identified seven derivatives with promising activity against epimastigote forms with IC50 values ranging from 6 µM to 44 µM. Most of the compounds showed no significant toxicity against murine macrophages. Our initial investigation on the mechanism of action indicates that this series of compounds may exert their anti-parasitic effect, inducing cell membrane damage. The results in trypomastigotes showed that one derivative, PDAN 78, satisfactorily inhibited metabolic alteration at all concentrations. Moreover, we used molecular modeling to understand how tridimensional and structural aspects might influence the observed bioactivities. Finally, we also used in silico approaches to assess the potential pharmacokinetic and toxicological properties of the most active compounds. Our initial results indicate that this molecular scaffold might be a valuable prototype for novel and safe trypanocidal compounds.

Naphthoquinones as a Promising Class of Compounds for Facing the Challenge of Parkinson's Disease.

Parkinson's disease (PD) is a degenerative disease that affects approximately 6.1 million people and is primarily caused by the loss of dopaminergic neurons. Naphthoquinones have several biological activities explored in the literature, including neuroprotective effects. Therefore, this review shows an overview of naphthoquinones with neuroprotective effects, such as shikonin, plumbagin and vitamin K, that prevented oxidative stress, in addition to multiple mechanisms. Synthetic naphthoquinones with inhibitory activity on the P2X7 receptor were also found, leading to a neuroprotective effect on Neuro-2a cells. It was found that naphthazarin can act as inhibitors of the MAO-B enzyme. Vitamin K and synthetic naphthoquinones hybrids with tryptophan or dopamine showed inhibition of the aggregation of α-synuclein. Synthetic derivatives of juglone and naphthazarin were able to protect Neuro-2a cells against neurodegenerative effects of neurotoxins. In addition, routes for producing synthetic derivatives were also discussed. With the data presented, 1,4-naphthoquinones can be considered as a promising class in the treatment of PD and this review aims to assist the scientific community in the application of these compounds. The derivatives presented can also support further research that explores their structures as synthetic platforms, in addition to helping to understand the interaction of naphthoquinones with biological targets related to PD.

Effect of 4-Ethylbenzaldehyde from the Volatilome of Annona muricata on Meloidogyne incognita.

The demand for new soil fumigants has increased as a result of more restrictive legislation regarding the use of pesticides. In the present study, the potent nematicidal activity of volatile organic compounds released by the Annona muricata leaf macerate was demonstrated. In addition, we searched in the A. muricata volatilome for a molecule with potential to be developed as a new fumigant nematicide. In the greenhouse, even the lowest concentration of soursop leaf macerate tested (1.0%) as a biofumigant caused a significant (P < 0.05) reduction in Meloidogyne incognita infectivity and reproduction when compared with the nontreated control (0%). Forty-one compounds were identified through gas chromatography-mass spectrometry analysis, of which three (sabinene, caryophyllene oxide, and 4-ethylbenzaldehyde) were selected for studies against the nematode. Among these compounds, in in vitro trails, only 4-ethylbenzaldehyde showed nematicidal activity at 250 µg ml-1. The effective doses of 4-ethylbenzaldehyde predicted to kill 50 and 95% of the M. incognita second-stage juvenile population after 48 h of exposure were 35 and 88 µg ml-1, respectively. In in vitro tests, 4-ethylbenzaldehyde at 150 µg ml-1 reduced M. incognita egg hatching to values similar (P > 0.05) to those of the commercial nematicide fluensulfone at a concentration of 200 µg ml-1. In plant experiments, as a soil fumigant, 4-ethylbenzaldehyde at a dose of 1 ml/liter of substrate had an effect similar (P > 0.05) to that of the commercial fumigant Dazomet (250 µg ml-1). Therefore, 4-ethylbenzaldehyde shows potential for development as a new nematicide.

In silico and pharmacological study of N,S-acetal juglone derivatives as inhibitors of the P2X7 receptor-promoted in vitro and in vivo inflammatory response.

Purinergic receptors are transmembrane proteins responsive to extracellular nucleotides and are expressed by several cell types throughout the human body. Among all identified subtypes, the P2×7 receptor has emerged as a relevant target for the treatment of inflammatory disease. Several clinical trials have been conducted to evaluate the effectiveness of P2×7R antagonists. However, to date, no selective antagonist has reached clinical use. In this work, we report the pharmacological evaluation of eleven N, S-acetal juglone derivatives as P2×7R inhibitors. Using in vitro assays and in vivo experimental models, we identified one derivative with promising inhibitory activity and low toxicity. Our in silico studies indicate that the 1,4-naphthoquinone moiety might be a valuable molecular scaffold for the development of novel P2×7R antagonists, as suggested by our previous studies.

Synthesis, Biological Evaluation and Molecular Modeling Studies of Naphthoquinone Sulfonamides and Sulfonate Ester Derivatives as P2X7 Inhibitors.

ATP acts in the extracellular environment as an important signal, activating a family of receptors called purinergic receptors. In recent years, interest in the potential therapeutics of purinergic components, including agonists and antagonists of receptors, has increased. Currently, many observations have indicated that ATP acts as an important mediator of inflammatory responses and, when found in high concentrations in the extracellular space, is related to the activation of the P2X7 purinergic receptor. In this sense, the search for new inhibitors for this receptor has attracted a great deal of attention in recent years. Sulfonamide derivatives have been reported to be potent inhibitors of P2X receptors. In this study, ten naphthoquinone sulfonamide derivatives and five naphthoquinone sulfonate ester derivatives were tested for their inhibitory activity on the P2X7 receptor expressed in peritoneal macrophages. Some compounds showed promising results, displaying IC50 values lower than that of A740003. Molecular docking and dynamic studies also indicated that the active compounds bind to an allosteric site on P2X7R. The binding free energy indicates that sulfonamides have an affinity for the P2X7 receptor similar to A740003. Therefore, the compounds studied herein present potential P2X7R inhibition.

Triazoles with inhibitory action on P2X7R impaired the acute inflammatory response in vivo and modulated the hemostatic balance in vitro and ex vivo.

OBJECTIVE: The present study aimed to investigate five triazole compounds as P2X7R inhibitors and evaluate their ability to reduce acute inflammation in vivo. MATERIAL: The synthetic compounds were labeled 5e, 8h, 9i, 11, and 12. TREATMENT: We administered 500 ng/kg triazole analogs in vivo, (1-10 µM) in vitro, and 1000 mg/kg for toxicological assays. METHODS: For this, we used in vitro experiments, such as platelet aggregation, in vivo experiments of paw edema and peritonitis in mice, and in silico experiments. RESULTS: The tested substances 5e, 8h, 9i, 11, and 12 produced a significant reduction in paw edema. Molecules 5e, 8h, 9i, 11, and 12 inhibited carrageenan-induced peritonitis. Substances 5e, 8h, 9i, 11, and 12 showed an anticoagulant effect, and 5e at a concentration of 10 µM acted as a procoagulant. All derivatives, except for 11, had pharmacokinetic, physicochemical, and toxicological properties suitable for substances that are candidates for new drugs. In addition, the ADMET risk assessment shows that derivatives 8h, 11, 5e, and 9i have high pharmacological potential. Finally, docking tests indicated that the derivatives have binding energies comparable to the reference antagonist with a competitive inhibition profile. CONCLUSIONS: Together, the results indicate that the molecules tested as antagonist drugs of P2X7R had anti-inflammatory action against the acute inflammatory response.

Semisynthetic triterpenes led to the generation of selective antitrypanosomal lead compounds.

Triterpenes α,ß-amyrin are naturally occurring molecules that can serve as building blocks for synthesizing new chemical entities. This study synthesized acyl, carboxyesther, NSAID, and nitrogenous derivatives and evaluated their antimicrobial activity. A cyclodextrin complexation method was developed to improve the solubility of the derivatives. Of the 17 derivatives tested, five exhibited activity against Trypanosoma cruzi, T. brucei, Leishmania infantum, Candida albicans, Staphylococcus aureus, and Escherichia coli. The 9a/9b mixture showed weak activity against the parasites (IC50 24.45-40.32 µM). However, it showed no activity for the other microorganisms. Derivatives 14a/14b exhibited potent activity against T. cruzi (IC50 2.0 nM) in this tested concentration did not show activity to the other microorganisms and were not cytotoxic. Derivatives 15a/15b and 16a/16b demonstrated relevant activity against the parasites (IC50 2.24-5.44 µM), but were also cytotoxic. Derivatives 17a/17b showed low activity against the tested parasites (IC50 21.70-22.79 µM), but they were selective since they did not show activity against other microorganisms. In docking studies, in general, all derivatives showed complementarity with the CYP51 binding site of the trypanosomatid mainly by hydrophobic interactions; thus, it is not conclusive that the molecules act by inhibiting this enzyme. Our results showed that triterpenes derivatives with antitrypanosomal activity could be synthesized by an inexpensive and rapid method.

Recent Progress in the Development of Indole-Based Compounds Active against Malaria, Trypanosomiasis and Leishmaniasis.

Human protozoan diseases represent a serious health problem worldwide, affecting mainly people in social and economic vulnerability. These diseases have attracted little investment in drug discovery, which is reflected in the limited available therapeutic arsenal. Authorized drugs present problems such as low efficacy in some stages of the disease or toxicity, which result in undesirable side effects and treatment abandonment. Moreover, the emergence of drug-resistant parasite strains makes necessary an even greater effort to develop safe and effective antiparasitic agents. Among the chemotypes investigated for parasitic diseases, the indole nucleus has emerged as a privileged molecular scaffold for the generation of new drug candidates. In this review, the authors provide an overview of the indole-based compounds developed against important parasitic diseases, namely malaria, trypanosomiasis and leishmaniasis, by focusing on the design, optimization and synthesis of the most relevant synthetic indole scaffolds recently reported.

Attraction and toxicity: Ways volatile organic compounds released by Pochonia chlamydosporia affect Meloidogyne incognita.

The production of volatile organic compounds (VOCs) acting against plant-parasitic nematodes has been characterized in different fungi; however, the role of VOCs emitted by Pochonia chlamydosporia in its trophic interaction with Meloidogyne incognita is still unknown. The aim of this study was to determine the effects of VOCs emitted by P. chlamydosporia strain Pc-10 on different stages (eggs, juveniles and female) of the M. incognita life cycle. Exposure of M. incognita eggs to VOCs released by Pc-10 resulted in a reduction up to 88 % in the nematode egg hatching, when compared to the control treatments. The VOCs emitted by Pc-10 also attracted M. incognita second-stage juveniles (J2). Through gas chromatography-mass spectrometry (GC-MS), three molecules were identified from the volatiles of the strain Pc-10, with 1,4-dimethoxybenzene being the major compound. In tests performed in vitro, 1,4-dimethoxybenzene at a concentration of 1050 µg mL-1 inhibited M. incognita egg hatching by up to 78.7 % compared to the control (0 µg mL-1) and attracted M. incognita J2 in all concentrations evaluated (1, 10, 100, 1000, and 10000 µg mL-1). The 1,4-dimethoxybenzene also showed fumigant and non-fumigant nematicidal activity against M. incognita. This compound presented lethal concentration for 50 % (LC50) of M. incognita J2 ranged from 132 to 136 µg mL-1. Fumigation with 1,4-dimethoxybenzene (100 mg) reduced egg hatching by up to 89 % and killed up to 86 % of M. incognita J2 compared to the control (0 µg mL-1). In vivo, the VOCs produced by Pc-10, 1,4-dimethoxybenzene, and the combination of both (Pc-10 + 1,4-dimethoxybenzene) attracted the M. incognita J2, compared to the respective controls. To the best of our knowledge, this is the first report on the attraction of M. incognita J2 and the toxicity to eggs and J2 by VOCs from P. chlamydosporia in which 1,4-dimethoxybenzene is the main toxin and attractant.

Juglone: A Versatile Natural Platform for Obtaining New Bioactive Compounds.

Juglone is a metabolite produced by several species of plants, in particular Juglans nigra. Additionally, juglone is a 1,4-naphthoquinone that has several biological actions. Antimicrobial, antifungal, sedative, oxidizing, antihypertensive, and especially anti-proliferative actions have been described for juglone. This justifies that 1,4-naphthoquinone is a privileged structure for Medicinal Chemistry, and it is useful for the development of new prototypes with varied actions. In this work, we make a profound review of juglone synthesis methodology, the biological actions of juglone, and mainly the synthesis and pharmacological actions of juglone derivatives. We hope that the potent biological actions described for these derivatives in this review will stimulate the continuous design, synthesis, and pharmacological evaluation of new juglone derivatives.

Costs and Benefits of Wax Production in the Larvae of the Ladybeetle Scymnus nubilus.

BACKGROUND: Larvae of the minute aphidophagous Scymnus nubilus Mulsant (Coleoptera: Coccinellidae) are common predators in apple orchards, covered by a wax layer that might act as a defense mechanism against natural enemies. However, the costs and benefits of protection conferred by wax remain to be assessed. We tested the following hypothesis: there is a trade-off in wax producing ladybeetles between the protection conferred by wax cover and the physiological or behavioral costs associated with its production. We predict that: (1) wax production is an efficient defensive mechanism (against intraguild predation), (2) wax production is associated with detrimental physiological (growth, reproduction) or behavioral effects (behavioral compensation: increased biomass consumption). RESULTS: Tests were carried out in the laboratory with wax and waxless larvae of S. nubilus, with and without lacewing larvae of Chrysoperla agilis (Neuroptera: Chrysopidae) being used as a potential intraguild predator of the coccinellid. Waxless individuals were more susceptible to intraguild predation by lacewing larvae. Adults originating from waxless larvae were lighter than the ones originating from wax larvae, suggesting a metabolic cost resulting from a constant need of wax production. Body-weight gain and conversion efficiency were lower in waxless larvae. Biomass consumption was similar, showing that waxless larvae did not compensate for the physiological cost by eating more aphid biomass. CONCLUSION: The results indicate the potential existence of a trade-off between growth and protection associated with wax production.

The potential involvement of P2X7 receptor in COVID-19 pathogenesis: A new therapeutic target?

Coronavirus disease 2019 (COVID-19) pathogenesis remains under investigation. Growing evidence indicates the establishment of a hyperinflammatory response, characterized by sustained production of cytokines, such as IL-1ß. The release and maturation of this cytokine are dependent on the activation of a catalytic multiprotein complex, known as "inflammasome". The most investigated is the NLRP3 inflammasome, which can be activated by various stimuli, such as the recognition of extracellular ATP by the P2X7 receptor. Based on the recent literature, we present evidence that supports the idea that the P2X7R/NLRP3 axis may be involved in the immune dysregulation caused by the SARS-CoV-2 infection.

Efficiency of cooling systems in broiler houses during hot days / Eficiência dos sistemas de resfriamento em aviários durante dias quentes

ABSTRACT: This study evaluated: (1) the vulnerability of broiler houses with different cooling systems, and (2) the spatial distribution of environmental variables during hot days. Four potentially vulnerable commercial broiler houses in southern Brazil were selected according to the following parameters: absence or presence of different cooling systems, broilers older than 28 days, and outside air dry-bulb temperature over 30°C. Broiler house vulnerability was classified according to the cooling and mechanical ventilation system: cellulose pad cooling (CPC), sprinkling (SPK), fogging (FOG), and mechanical ventilation without evaporative cooling system (VTL). The air dry-bulb temperature (Tdb, °C) and relative humidity (RH, %) were recorded every 10 min. For each broiler house, we evaluated: (1) relative cooling efficiency (RCE) and (2) inside spatial distribution of microclimate variables using a geostatistical technique. The CPC and SPK did not differ (P<0.05) in RCE (81.6% and 80.7%, respectively), but both differed from FOG (23.8%) and VLT (1.87%) systems. The highest variations in indoor Tdb were recorded in the FOG (7 °C), followed by the SPK (4 °C) and CPC (3 °C). In the CPC, there was an increase in RH from the middle to the end of the broiler house near the exhaust fans. In conclusion, the relative cooling efficiency and the inside spatial distributions of environmental variables in the broiler houses were influenced by the existing cooling system.

RESUMO: Os objetivos deste estudo foram (1) comparar a vulnerabilidade de aviários com diferentes sistemas de resfriamento, e (2) avaliar a distribuição espacial interna das variáveis ambientais durante dias quentes. Quatro aviários comerciais potencialmente vulneráveis no sul do Brasil foram selecionados de acordo com os seguintes parâmetros de elegibilidade: ausência ou presença de diferentes sistemas de resfriamento; frangos de corte com mais de 28 dias de idade; e temperatura de bulbo seco do ar externa acima de 30 °C. A vulnerabilidade do aviário foi classificada de acordo com o sistema de resfriamento e ventilação mecânica, sendo: resfriamento por pad cooling (CPC), aspersão (SPK), nebulização (FOG) e ventilação mecânica sem sistema de resfriamento evaporativo (VTL). A temperatura de bulbo seco do ar (Tbs, °C) e a umidade relativa do ar (UR, %) foram coletadas por registradores de dados autônomos a cada 10 min. Para cada aviário foram avaliados: (1) eficiência relativa de resfriamento (RCE) e (2) distribuição espacial interna das variáveis ambientais por técnica de geoestatística. O CPC e SPK não diferiram (P>0,05) na RCE (81,6% e 80,7% respectivamente), mas ambos diferiram do FOG (23,8%) e VLT (1,87%). As maiores variações na Tbs do ar interno foram registradas no FOG (7 °C), seguido pelo SPK (4 °C) e CPC (3 °C). No CPC, houve um aumento da umidade relativa do meio para o final do aviário, próximo aos exaustores. Em conclusão, a eficiência relativa de resfriamento, assim como a distribuição espacial das variáveis ambientais internas foram influenciadas pelo sistema de resfriamento de cada aviário.

Plant natural products as source of new P2 receptors ligands.

In recent years, interest in the research of P2 receptor (P2R)-mediated responses has grown significantly due to the recognition of the involvement of these receptors in various physiological and pathological processes. Despite all the progress made in the functional characterization of P2Rs, purinergic signaling research is still limited by the lack of selective or efficient ligands for different receptor subtypes. In this sense, several molecules have been tested towards these receptors as agonists or antagonists. Historically, natural products have always been sources of new bioactive substances for diverse purposes. However, compared to synthetic molecules, the number of natural products assessed for P2R ligands is still low. In this review, we present examples of studies that demonstrated plant natural products acting directly on P2R and modulating their functionality. In some cases, we highlight that the pharmacological activity previously described for the original organism could be correlated to an agonist or antagonist activity of a specific natural product on these receptors. These examples reinforce the need for more studies to investigate the pharmacological potential of new or known natural compounds targeting P2 receptors.

Synthesis of new N,S-acetal analogs derived from juglone with cytotoxic activity against Trypanossoma cruzi.

A series of 11 new N,S-acetal juglone derivatives were synthesized and evaluated against T. cruzi epimastigote forms. These compounds were obtained in good to moderate yields using a microwave irradiation protocol. Among all compounds, two N,S-acetal analogs, showed significant trypanocidal activity. Notably, one compound 11g exhibited selectivity index 10-fold higher than the reference drug benznidazole for epimastigote. The compound 11h was more effective for amastigote forms. Both prototypes exhibited S.I. higher than the benznidazole description. Thus, both compounds proving to be useful candidate molecules to further studies in infected animals.

Economic analysis of the risk of replacing corn grains (Zea mays) with pearl millet grains (Pennisetum glaucum) in the diet of feedlot cattle / Análise econômica do risco da substituição de grãos de milho (Zea mays) por grãos de milheto (Pennisetum glaucum) na dieta de bovinos confinados

ABSTRACT: The goal of the present study was to assess the economic viability relating to the risk of replacing corn with pearl millet in diets with 80% concentration for feedlot cattle confined for 89 days. Replacement levels were: 0, 33, 66, and 100%. The risk was estimated using Monte Carlo simulation, Spearman's rank correlation test between input variables, stochastic dominance, and analysis of sensitivity. The expected average values ± standard deviation for net present value (R$/animal) were ± 71.74 ± 283.32, 91.23 ± 285.18, 196.05 ± 273.79, and 223.80 ± 267.96 for diets containing 0, 33, 66, and 100% of pearl millet, respectively. The probability of ≥0 net present value was 63.4, 66.1, 78.4, and 82.4%, respectively. The net present values were statistically different (P<0.05), and the higher levels dominated the lower values. The items that most influenced the net present values were, in descending order, prices of unfinished and finished cattle, initial and final weights, prices of concentrate and forage, concentrate and forage consumption. Based on the results of the simulation, diet of 100% pearl millet exhibited the best economic viability.

RESUMO: O objetivo do estudo foi avaliar a viabilidade econômica relacionada ao risco da substituição de milho por milheto em dietas com 80% de concentrado no confinamento de bovinos por 89 dias. Os níveis de substituição foram: 0, 33, 66 e 100%. O risco foi estimado usando simulação de Monte Carlo, correlação de Spearman entre as variáveis ​​de entrada, dominância estocástica e análise de sensibilidade. Os valores médios esperados ± desvio padrão para o valor presente líquido (R$/animal) foram de ± 71,74 ± 283,32, 91,23 ± 285,18, 196,05 ± 273,79 e 223,80 ± 267,96 para dietas contendo 0, 33, 66 e 100% de milheto, respectivamente. A probabilidade de valor presente líquido ≥0 foi de 63,4, 66,1, 78,4 e 82,4%, respectivamente. Os valores presentes líquidos foram estatisticamente diferentes (p<0,05), e os níveis mais elevados dominaram os valores mais baixos. Os itens que mais influenciaram os valores presentes líquidos foram, em ordem decrescente, os preços de bovinos não terminados e acabados, pesos inicial e final, preços de concentrado e forragem, consumo de concentrado e forragem. Com base nos resultados da simulação, a dieta de 100% de milheto mostrou a melhor viabilidade econômica.

Pore forming channels as a drug delivery system for photodynamic therapy in cancer associated with nanoscintillators.

According to the World Health Organization (WHO), cancer is one of main causes of death worldwide, with 8.2 million people dying from this disease in 2012. Because of this, new forms of treatments or improvement of current treatments are crucial. In this regard, Photodynamic therapy (PDT) has been used to successfully treat cancers that can be easily accessed externally or by fibre-optic endoscopes, such as skin, bladder and esophagus cancers. In addition, this therapy can used alongside radiotherapy and chemotherapy in order to kill cancer cells. The main problem in implementing PDT is penetration of visible light deeper than 10 mm in tissues, due to scattering and absorption by tissue chromophores. Unfortunately, this excludes several internal organs affected by cancer. Another issue in this regard is the use of a selective cancer cell-photosensitizing compound. Nevertheless, several groups have recently developed scintillation nanoparticles, which can be stimulated by X-rays, thereby making this a possible solution for light production in deeper tissues. Alternative approaches have also been developed, such as photosensitizer structure modifications and cell membrane permeabilizing agents. In this context, certain channels lead to transitory plasma membrane permeability changes, such as pannexin, connexin hemmichannels, TRPV1-4 and P2×7, which allow for the non-selective passage of molecules up to 1,000 Da. Herein, we discuss the particular case of the P2×7 receptor-associated pore as a drug delivery system for hydrophilic substances to be applied in PDT, which could also be carried out with other channels. Methylene blue (MB) is a low cost dye used as a prototype photosensitizer, approved for clinical use in several other clinical conditions, as well as photodynamic therapy for fungi infections.

Searching for new drugs for Chagas diseases: triazole analogs display high in vitro activity against Trypanosoma cruzi and low toxicity toward mammalian cells.

Chagas disease is one of the most relevant endemic diseases in Latin America caused by the flagellate protozoan Trypanosoma cruzi. Nifurtimox and benzonidazole are the drugs used in the treatment of this disease, but they commonly are toxic and present severe side effects. New effective molecules, without collateral effects, has promoted the investigation to develop new lead compounds with to advance for clinical trials. Previously, 3-nitro-1H-1,2,4-triazole-based amines and 1,2,3-triazoles demonstrated significant trypanocidal activity against T. cruzi. In this paper, we synthesized a new series of 92 examples of 1,2,3-triazoles. Six compounds exhibited antiparasitic activity, 14, 25, 27, 31 and 40, 43 and were effective against epimastigotes of two strains of T. cruzi (Y and Dm28-C) and 25, 27 and 31 exhibited trypanocidal activity similar to benzonidazole. Notably, the compound 25 compared to benzonidazole increase the toxicity against T. cruzi, with no apparent toxicity to the cell line of mice macrophages or primary mice peritoneal macrophages. As results, we calculated selectivity indexes up to 2000 to 25 and 31 in both T. cruzi strains. Derivative 14 caused a trypanostatic effect because it did not damage external epimastigote membrane. Triazoles 40 and 43 impaired parasites viability using a pathway not dependent on ROS production.