Spring water quality monitoring using multiple bioindicators from multiple collection sites.

The aim of this study was to examine the water quality of the Extrema River spring in a Brazilian Cerrado area. Three collection sites (P1 - P3) were sampled in the dry and rainy seasons, which are close to industries from different sectors. In the physicochemical analysis, a decrease in dissolved oxygen levels (<5 mg/L) and pH (< 6) at P3 was detected. An increase in heterotrophic bacteria count was recorded at all sites (> 500 colonies/ml). In ecotoxicological analyses, P2 and P3 exhibited toxicity using Vibrio fischeri (> 20%). In evaluating toxicity, the reduction in seed germination was significant utilizing Lactuca sativa at all locations and with Allium cepa only at P2; rootlet length was decreased at P3 on L. sativa and at all sites with A. cepa. In contrast, loss of membrane integrity and mitochondrial function of meristems was adversely affected at all locations using both L. sativa and A. cepa assays. Principal components analysis (PCA) approach indicated that seasonality apparently did not markedly interfere with the obtained data, but it is important to include more collection locations to be evaluated with multiple bioindicators in the spring region. Our data indicate the urgent need for more rigorous programs to monitor the discharge of effluents into water springs.

In vitro hematotoxicity of Vernonanthura polyanthes leaf aqueous extract and its fractions.

Vernonanthura polyanthes, popularly known as 'assa-peixe', is widely used in Brazil for therapeutic purpose mainly to treat respiratory tract problems. However, few studies investigated its chemical safety. In this way, we first obtained the V. polyanthes leaf aqueous extract (VpLAE) and three fractions (aqueous; n-butanol, n-BF; and ethyl acetate), and we chemically characterized this material. Then, the cytogenotoxic potential of the VpLAE and its fractions was investigated against human erythrocytes and lymphocytes using Trypan blue exclusion test of cell viability and CometChip. The phytochemical screening of V. polyanthes leaf revealed the presence of total phenolic compounds, flavonoids, tannins, coumarins, terpenic compounds, and cardioactive heterosides. n-BF presented the highest total phenolic, flavonoids, and tannins contents and, consequently, the highest antioxidant activity, according to the DPPH free radical scavenging method. Although the VpLAE and its fractions did not cause death of erythrocytes, the cells acquired an echinocytic form. Regarding lymphocytes, VpLAE and its fractions presented cytotoxicity and genotoxicity. When VpLAE or its fractions were co-treated with doxorubicin (DXR), a recognized cytotoxic drug, we observed an enhancement of DXR cytotoxicity against lymphocytes, but the DXR genotoxicity decreased around 15%. Since the VpLAE and its fractions increased the DXR cytotoxicity and decreased its genotoxicity, further studies should be conducted for the development of an adjuvant drug from this extract to reduce the side effects of chemotherapy. Moreover, the indiscriminate use of 'assa-peixe' by local people should be discouraged.

Toxic Potential of Cerrado Plants on Different Organisms.

Cerrado has many compounds that have been used as biopesticides, herbicides, medicines, and others due to their highly toxic potential. Thus, this review aims to present information about the toxicity of Cerrado plants. For this purpose, a review was performed using PubMed, Science Direct, and Web Of Science databases. After applying exclusion criteria, 187 articles published in the last 20 years were selected and analyzed. Detailed information about the extract preparation, part of the plant used, dose/concentration tested, model system, and employed assay was provided for different toxic activities described in the literature, namely cytotoxic, genotoxic, mutagenic, antibacterial, antifungal, antiviral, insecticidal, antiparasitic, and molluscicidal activities. In addition, the steps to execute research on plant toxicity and the more common methods employed were discussed. This review synthesized and organized the available research on the toxic effects of Cerrado plants, which could contribute to the future design of new environmentally safe products.

New Insights on Glutathione's Supramolecular Arrangement and Its In Silico Analysis as an Angiotensin-Converting Enzyme Inhibitor.

Angiotensin-converting enzyme (ACE) inhibitors are one of the most active classes for cardiovascular diseases and hypertension treatment. In this regard, developing active and non-toxic ACE inhibitors is still a continuous challenge. Furthermore, the literature survey shows that oxidative stress plays a significant role in the development of hypertension. Herein, glutathione's molecular structure and supramolecular arrangements are evaluated as a potential ACE inhibitor. The tripeptide molecular modeling by density functional theory, the electronic structure by the frontier molecular orbitals, and the molecular electrostatic potential map to understand the biochemical processes inside the cell were analyzed. The supramolecular arrangements were studied by Hirshfeld surfaces, quantum theory of atoms in molecules, and natural bond orbital analyses. They showed distinct patterns of intermolecular interactions in each polymorph, as well as distinct stabilizations of these. Additionally, the molecular docking study presented the interactions between the active site residues of the ACE and glutathione via seven hydrogen bonds. The pharmacophore design indicated that the hydrogen bond acceptors are necessary for the interaction of this ligand with the binding site. The results provide useful information for the development of GSH analogs with higher ACE inhibitor activity.

Phytochemical Composition and Protective Effect of Vernonanthura polyanthes Leaf against In Vivo Doxorubicin-Mediated Toxicity.

Vernonanthura polyanthes (Spreng.) A.J. Vega & Dematt. (syn.: Vernonia polyanthes Less) is popularly known as "assa-peixe" and its leaves are used in folk medicine mainly to treat respiratory diseases. In this study, we evaluated the cytogenotoxic and anticytogenotoxic potential of the V. polyanthes leaf aqueous extract (VpLAE) and its n-butanol fraction (n-BF) in the presence or absence of doxorubicin (DXR) (pre-, co-, and post-treatments) on a murine model for 24 h or 120 h. The micronucleus test (MN) and the comet assay were used to assess the cytogenotoxic and anticytogenotoxic potential of VpLAE and n-BF (250, 500, and 1000 mg/kg) administered via gavage to Swiss Webster mice. The chemical profiles of VpLAE and n-BF were assessed by liquid chromatography coupled to mass spectrometry, and their metabolites were putatively identified. Lastly, the possible biological activities related to the (anti) cytogenotoxicity of the compounds were predicted using the PASS online webserver. The in vivo results showed that different doses of VpLAE and n-BF did not present cytotoxic activity; however, the MN test revealed a slight mutagenic activity for the 24 h treatments. Moderate genotoxic effects were demonstrated for all treatments in the comet assay. Regarding anticytotoxicity and antimutagenicity, VpLAE and n-BF presented a high cytoprotective potential against DXR toxic effects. In the co-treatment, VpLAE reduced the DXR genotoxicity by ~27%, and n-BF did not demonstrate antigenotoxic potential. In contrast, an antigenotoxic effect was observed for both VpLAE and n-BF in the pre- and post-treatments, reducing DXR genotoxicity by ~41% and ~47%, respectively. Chemical analysis of VpLAE and n-BF showed the presence of eight phenolic compounds, including seven chlorogenic acids and a flavonoid. The PASS online tool predicted antimutagenic, anticancer, antineoplastic, chemoprotective, antioxidant, and radical scavenging activities for all constituents identified in VpLAE and n-BF. V. polyanthes leaves presented a protective effect against DXR cytogenotoxicity. In general, VpLAE and n-BF showed a greater antigenotoxic potential in the pre- and post-treatments. The metabolites putatively identified in VpLAE and n-BF exhibited antioxidant and chemoprotective potential according to computational prediction analysis. Altogether, our results highlight the potential application of V. polyanthes to protect against toxic manifestations induced by DXR.

Hancornia speciosa serum fraction latex stimulates the angiogenesis and extracellular matrix remodeling processes.

The Hancornia speciosa latex reveals angiogenic, osteogenic, and anti-inflammatory properties, which present its potential for developing of wound healing drugs; however, the latex compounds responsible for angiogenesis remain unknown. One strategy to screen these active compounds is evaluation of latex fractions. This study aimed to obtain different fractions of latex and evaluate its angiogenic activity separately using the chick chorioallantoic membrane (CAM) assay. The serum (SE) fraction was responsible for angiogenesis, which was subject to biochemical characterization and computational simulations in order to understand the contribution of H. speciosa latex in wound healing process. Our results revealed weak antioxidant potential and absence of antimicrobial activity in the SE fraction. Phytochemical analysis identified chlorogenic acids (CGA) as the main compound of SE fraction. CGA bioactivity predictions identify different molecules associated with extracellular matrix (ECM) remodeling, such as metalloproteinases, which also are overexpressed in our CAM assay experiment. Docking simulations revealed the interactions between CGA and matrix metalloproteinase 2. In conclusion, SE latex fraction stimulates angiogenesis and may influence ECM remodeling. These properties may contribute to the wound healing process, and also confirm the widespread use of this plant.

In vivo assessment of cyto/genotoxic, antigenotoxic and antifungal potential of Costus spiralis (Jacq.) Roscoe leaves and stems.

Costus spiralis is a Brazilian native plant used in popular medicine, but the safety of this therapeutic use needs investigation. So, the aim of this study was to evaluate the cytogenotoxic and antigenotoxic effects of C. spiralis leaves or stems aqueous extracts on Allium cepa root cells. Moreover, a phytochemical screening and an antioxidant and antifungal activities evaluation were performed. C. spiralis aqueous extracts presented cytotoxicity, but no mutagenicity was observed. When the antigenotoxicity was evaluated, C. spiralis leaves aqueous extract presented preventive and modulatory effects on A. cepa root cells, reducing the sodium azide cytogenotoxic effects. In contrast, C. spiralis stems aqueous extract enhanced the sodium azide cytogenotoxicity in some conditions. The phytochemical screening revealed the presence of phenolic compounds in C. spiralis. When total phenolic content was determined, the leaves presented 73% more phenolic content than stems. Corroborating this data, C. spiralis leaves antioxidant potential was 30% higher than C. spiralis stems. However, these extracts did not present antifungal activity against Candida spp. In conclusion, empirical utilization of C. spiralis aqueous extracts should be avoided. Moreover, the cytotoxic effect of C. spiralis leaves and stems can play an important role in anticancer therapy and must be deeply studied.

Ureteroileal bypass: a new technic to treat ureteroenteric strictures in urinary diversion.

OBJECTIVE: To present our technique of ureteroileal bypass to treat uretero-enteric strictures in urinary diversion. MATERIALS AND METHODS: One hundred and forty-one medical records were reviewed from patients submitted to radical cystectomy to treat muscle-invasive bladder cancer between 2013 and 2015. Twelve (8.5%) patients developed uretero-enteric anastomotic stricture during follow-up. Five patients were treated with endoscopic dilatation and double J placement. Four were treated surgically with standard terminal-lateral implantation. Three patients with uretero-enteric anastomotic stricture were treated at our institution by "ureteroileal bypass", one of them was treated with robotic surgery. RESULTS: All patients had the diagnosis of uretero-enteric anastomotic stricture via computerized tomography and DTPA renal scan. Time between cystectomy and diagnosis of uretero-enteric anastomotic stricture varied from five months to three years. Mean operative time was 120±17.9 minutes (98 to 142 min) and hospital stay was 3.3±0.62 days (3 to 4 days). Mean follow-up was 24±39.5 months (6 to 72 months). During follow-up, all patients were asymptomatic and presented improvement in ureterohydronephrosis. Serum creatinine of all patients had been stable. CONCLUSIONS: Latero-lateral ureter re-implantation is feasible by open or even robotic surgery with positive results, reasonable operation time, and without complications.

Extraction protease expressed by Penicillium fellutanum from the Brazilian savanna using poly(ethylene glycol)/sodium polyacrylate/NaCl aqueous two-phase system.

The partitioning of protease expressed by Penicillium fellutanum from the Brazilian savanna in a novel inexpensive and stable aqueous two-phase system (ATPS) composed of poly(ethylene glycol) (PEG) and sodium polyacrylate (NaPA) was studied in this work using factorial design. The ATPS is formed by mixing both polymers with a salt (NaCl) and fermented broth of P. fellutanum. The effects of molar mass (2,000, 4,000, and 6,000 g ⋅ mol(-1)) and concentration (6, 8, and 10 wt%) of PEG and that of NaPA concentration (6, 8, and 10 wt%) on protease partitioning (K) at 25 °C were studied. A two-level factorial design (2(3)) was implemented. The effect of Na2 SO4 concentration (5, 10, and 15 wt%) on the reextraction of the enzyme was also analyzed. The partition coefficient K ranged from 77.51 to 1.21, indicating the versatility of the method. The reextraction was achieved with the addition of 5% Na2 SO4 , allowing the partitioning of the protease to the upper phase, whereas total proteins were directed to the bottom phase. The results of partitioning using the PEG/NaPA/NaCl system and that of the subsequent reextraction with Na2 SO4 suggest that this method can be used to purify proteases from fermented broth of P. fellutanum.

Bioactive Compounds Found in Brazilian Cerrado Fruits.

Functional foods include any natural product that presents health-promoting effects, thereby reducing the risk of chronic diseases. Cerrado fruits are considered a source of bioactive substances, mainly phenolic compounds, making them important functional foods. Despite this, the losses of natural vegetation in the Cerrado are progressive. Hence, the knowledge propagation about the importance of the species found in Cerrado could contribute to the preservation of this biome. This review provides information about Cerrado fruits and highlights the structures and pharmacologic potential of functional compounds found in these fruits. Compounds detected in Caryocar brasiliense Camb. (pequi), Dipteryx alata Vog. (baru), Eugenia dysenterica DC. (cagaita), Eugenia uniflora L. (pitanga), Genipa americana L. (jenipapo), Hancornia speciosa Gomes (mangaba), Mauritia flexuosa L.f. (buriti), Myrciaria cauliflora (DC) Berg (jabuticaba), Psidium guajava L. (goiaba), Psidium spp. (araçá), Solanum lycocarpum St. Hill (lobeira), Spondias mombin L. (cajá), Annona crassiflora Mart. (araticum), among others are reported here.

Advances in Legume Systematics 14. Classification of Caesalpinioideae. Part 2: Higher-level classification.

Caesalpinioideae is the second largest subfamily of legumes (Leguminosae) with ca. 4680 species and 163 genera. It is an ecologically and economically important group formed of mostly woody perennials that range from large canopy emergent trees to functionally herbaceous geoxyles, lianas and shrubs, and which has a global distribution, occurring on every continent except Antarctica. Following the recent re-circumscription of 15 Caesalpinioideae genera as presented in Advances in Legume Systematics 14, Part 1, and using as a basis a phylogenomic analysis of 997 nuclear gene sequences for 420 species and all but five of the genera currently recognised in the subfamily, we present a new higher-level classification for the subfamily. The new classification of Caesalpinioideae comprises eleven tribes, all of which are either new, reinstated or re-circumscribed at this rank: Caesalpinieae Rchb. (27 genera / ca. 223 species), Campsiandreae LPWG (2 / 5-22), Cassieae Bronn (7 / 695), Ceratonieae Rchb. (4 / 6), Dimorphandreae Benth. (4 / 35), Erythrophleeae LPWG (2 /13), Gleditsieae Nakai (3 / 20), Mimoseae Bronn (100 / ca. 3510), Pterogyneae LPWG (1 / 1), Schizolobieae Nakai (8 / 42-43), Sclerolobieae Benth. & Hook. f. (5 / ca. 113). Although many of these lineages have been recognised and named in the past, either as tribes or informal generic groups, their circumscriptions have varied widely and changed over the past decades, such that all the tribes described here differ in generic membership from those previously recognised. Importantly, the approximately 3500 species and 100 genera of the former subfamily Mimosoideae are now placed in the reinstated, but newly circumscribed, tribe Mimoseae. Because of the large size and ecological importance of the tribe, we also provide a clade-based classification system for Mimoseae that includes 17 named lower-level clades. Fourteen of the 100 Mimoseae genera remain unplaced in these lower-level clades: eight are resolved in two grades and six are phylogenetically isolated monogeneric lineages. In addition to the new classification, we provide a key to genera, morphological descriptions and notes for all 163 genera, all tribes, and all named clades. The diversity of growth forms, foliage, flowers and fruits are illustrated for all genera, and for each genus we also provide a distribution map, based on quality-controlled herbarium specimen localities. A glossary for specialised terms used in legume morphology is provided. This new phylogenetically based classification of Caesalpinioideae provides a solid system for communication and a framework for downstream analyses of biogeography, trait evolution and diversification, as well as for taxonomic revision of still understudied genera.

Molecular basis of two pyrimidine-sulfonylurea herbicides: from supramolecular arrangement to acetolactate synthase inhibition.

CONTEXT: The design and synthesis of safe and highly active sulfonylurea herbicides is still a challenge. Therefore, following some principles of structure-activity relationship (SAR) of sulfonylurea herbicides, this work focuses on evaluating two sulfonylurea derivatives bearing electron-withdrawing substituents, namely, -(CO)OCH3 and -NO2 on the aryl group, on herbicidal activity. To understand the effects caused by the substituent groups, the molecular and electronic structures of the sulfonylureas were evaluated by density functional theory. Likewise, the crystalline supramolecular arrangements of both compounds were analyzed by Hirshfeld surface, QTAIM, and NBO, with the aim of verifying changes in intermolecular interactions caused by substituent groups. Finally, through a toxicophoric analysis, we were able to predict the interacting groups in their biological target, acetolactate synthase, and verify the interactions with the binding site. METHODS: All theoretical calculations were conducted using the highly parameterized empirical exchange-correlation functional M06-2X accompanied by the diffuse and polarized basis set 6-311++G(d,p). The atomic coordinates were obtained directly from the crystalline structures, and from the energies of the frontier molecular orbitals (HOMO and LUMO), chemical descriptors were obtained that indicated the influence of the functional groups in the sulfonylureas on the reactivity of the molecules. The intermolecular interactions in the crystals were analyzed using the Hirshfeld, QTAIM, and NBO surfaces. Toxicophoric modeling was performed by the PharmaGist webserver and molecular docking calculations were performed by the GOLD 2022.1.0 software package so that the ligand was fitted to the binding site in a 10 Å sphere. For this, genetic algorithm parameters were used using the ChemPLP scoring function for docking and ASP for redocking.

Structural basis of antibacterial photodynamic action of curcumin against S. aureus.

Antimicrobial photodynamic therapy (aPDT) is an alternative tool to commercial antibiotics for the inactivation of pathogenic bacteria (e.g., S. aureus). However, there is still a lack of understanding of the molecular modeling of the photosensitizers and their mechanism of action through oxidative pathways. Herein, a combined experimental and computational evaluation of curcumin as a photosensitizer against S. aureus was performed. The radical forms of keto-enol tautomers and the energies of curcumin's frontier molecular orbitals were evaluated by density functional theory (DFT) to point out the photodynamic action as well as the photobleaching process. Furthermore, the electronic transitions of curcumin keto-enol tautomers were undertaken to predict the transitions as a photosensitizer during the antibacterial photodynamic process. Moreover, molecular docking was used to evaluate the binding affinity with the S. aureus tyrosyl-tRNA synthetase as the proposed a target for curcumin. In this regard, the molecular orbital energies show that the curcumin enol form has a character of 4.5% more basic than the keto form - the enol form is a more promising electron donor than its tautomer. Curcumin is a strong electrophile, with the enol form being 4.6% more electrophilic than its keto form. In addition, the regions susceptible to nucleophilic attack and photobleaching were evaluated by the Fukui function. Regarding the docking analysis, the model suggested that four hydrogen bonds contribute to the binding energy of curcumin's interaction with the ligand binding site of S. aureus tyrosyl-tRNA synthetase. Finally, residues Tyr36, Asp40, and Asp177 contact curcumin and may contribute to orienting the curcumin in the active area. Moreover, curcumin presented a photoinactivation of 4.5 log unit corroborating the necessity of the combined action of curcumin, light, and O2 to promote the photooxidation damage of S. aureus. These computational and experimental data suggest insights regarding the mechanism of action of curcumin as a photosensitizer to inactivate S. aureus bacteria.

"Non-metastatic, Castration-resistant Prostate Cancer: Diagnostic and Treatment Recommendations by an Expert Panel from Brazil".

INTRODUCTION: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC. METHODS: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented. RESULTS: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer. DISCUSSION: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings.

Misleading fruits: The non-monophyly of Pseudopiptadenia and Pityrocarpa supports generic re-circumscriptions and a new genus within mimosoid legumes.

Generic delimitation in Piptadenia and allies (mimosoid legumes) has been in a state of flux, particularly caused by over-reliance on fruit and seed morphology to segregate species out of Piptadenia into the genera Parapiptadenia, Pityrocarpa and Pseudopiptadenia. Although supporting their segregation from Piptadenia, previous phylogenetic analyses suggested that some of these segregated genera are not monophyletic. Here, we test the monophyly of Parapiptadenia, Pityrocarpa and Pseudopiptadenia with dense taxon sampling across these genera, including the type species of each genus. Our analysis recovers Parapitadenia as monophyletic, but places Pseudopiptadenia species in two distinct lineages, one of which includes all three species of Pityrocarpa. Given that the type species of both Pseudopiptadenia and Pityrocarpa are nested in the same clade, we subsume Pseudopiptadenia under the older name Pityrocarpa. The remaining Pseudopiptadenia species are assigned to the new genus Marlimorimia. Alongside high molecular phylogenetic support, recognition of Parapiptadenia, Pityrocarpa and Marlimorimia as distinct genera is also supported by combinations of morphological traits, several of which were previously overlooked.

Histological Variants of Urothelial Carcinoma Predict No Response to Neoadjuvant Chemotherapy.

BACKGROUND: Platinum-based neoadjuvant chemotherapy (NAC) in muscle-invasive urothelial bladder cancer (MIBC) has been adopted as a standard of care related to better survival outcomes. However, there is a considerable number of patients who do not respond, experiencing toxicity and delay in the surgical treatment. Our aim is to find biomarkers of response that could be easily adopted in the clinical practice. METHODS: Between January 2009 and July 2016, 52 patients with MIBC were submitted to radical cystectomy after NAC. A tissue microarray containing 25 cases, who met the inclusion criteria was built for immunohistochemical analysis of Cytokeratins 5/6, 7, and 20, GATA3, Her2, EGFR, p63, p53, Carbonic-anhydrase IX (CAIX), MLH1, MSH2, MSH6, and PMS2. The surgery was performed in a mean time of 58.7 (± 21) days after the end of the NAC. Fisher's exact test was used to analyze the relationship between response (≤pT1) and histopathological and immunohistochemical results and Kaplan-Meier curves were designed for survival analysis. RESULTS: Ten (40.0%) patients presented response to NAC. Histological variants of the urothelial carcinoma characterized by squamous, sarcomatous/rhabdoid, plasmacytoid, and micropapillary was present in 36.0% and none responded to NAC (P = .002). CAIX was expressed by 53.3% and none responded to NAC (P= .005). Lymph-node metastasis, divergent differentiation, and expression of cytokeratin 5/6 were related to short cancer specific survival. CONCLUSION: Histological variants and CAIX immune-expression are biomarkers of nonresponse to NAC of MIBC, and might be easily used in the clinical practice to select patients to be submitted to surgery upfront.

A new quinolinone-chalcone hybrid with potential antibacterial and herbicidal properties using in silico approaches.

Quinolinone-chalcones are hybrid compounds consisting of chalcone and quinolone moieties with biological activity related to their hybrid structure. This work seeks to describe the structural and theoretical parameters related to the physicochemical properties and biological activity of a new quinolinone-chalcone. The synthesis, structural characterization by X-ray diffraction, molecular topology by Hirshfeld surfaces and QTAIM, molecular electronic calculations, and pharmacophore analysis were described. The weak interactions C-H…O, C-H…π, and C-H…Br were responsible for crystal growth and stabilized the crystalline state. The DFT analysis shows that the sulfonamide group region is susceptible to observed interactions, and the frontier molecular orbitals indicate high kinetic stability. Also, pharmacophore analysis revealed potential antibacterial and herbicidal activity; by docking within the active site of TtgR, a transcription regulator for the efflux pump TtgABC from the highly resistant Pseudomonas putida (P. putida) strain DOT-TIE, we showed that the activation of TtgR relies upon the binding of aromatic-harboring compounds, which plays a crucial role in bacterial evasion. In this context, a new quinolinone-chalcone has a higher binding affinity than tetracycline, which suggests it might be a better effector for TtgR.

Can the sustainable development goals for cancer be met in Brazil? A population-based study.

Background: A one-third reduction in premature mortality (30-69 years) from chronic noncommunicable diseases is goal 3.4 of the United Nations Sustainable Development Goals (UN SDG). The burden of NCDs is expected to continue to increase in low- and middle-income countries, including Brazil. Objectives: The aim of this study was to assess geographical and temporal patterns in premature cancer mortality in Brazil between 2001 and 2015 and to predict this to 2030 in order to benchmark against the 3.4 SDG target. Methods: We used data on deaths from cancer in those aged 30-69, by age group, sex and cancer site, between 2001 and 2015 from the National Mortality Information System of Brazil (SIM). After correcting for ill-defined causes, crude and world age-standardised mortality rates per 100,000 inhabitants were calculated nationally and for the 5 regions. Predictions were calculated using NordPred, up to 2030. Results: The difference in observed (2011-2015) and predicted (2026-2030) mortality was compared against the SDG 3.4 target. Between 2011-2015 and 2026-2030 a 12.0% reduction in premature cancer age-standardised mortality rate among males and 4.6% reduction among females is predicted nationally. Across regions this varied from 2.8% among females in North region to 14.7% among males in South region. Lung cancer mortality rates are predicted to decrease among males but not among females nationally (men 28%, females 1.1% increase) and in all regions. Cervical cancer mortality rates are projected to remain very high in the North. Colorectal cancer mortality rates will increase for both sexes in all regions except the Southeast. Conclusions and recommendation: Cancer premature mortality is expected to decrease in Brazil, but the extent of the decrease will be far from the SDG 3.4 target. Nationally, only male lung cancer will be close to reaching the SDG 3.4 target, reflecting the government's long-term efforts to reduce tobacco consumption. Projected colorectal cancer mortality increases likely reflect the epidemiological transition. This and, cervical cancer control will continue to be major challenges. These results will help inform strategic planning for cancer primary prevention, early detection and treatment programs; such initiatives should take cognizance of the regional differences highlighted here.

Mechanism of action involved in the anxiolytic-like effects of Hibalactone isolated from Hydrocotyle umbellata L.

Background and aim: Hibalactone (HB) is a lignan related to the anxiolytic-like effects of Hydrocotyle umbellata L. However, there is a need to understand better the mechanism of action of this lignan to support the ethnopharmacological uses of the species. This work aimed to evaluate by in vivo and in silico analysis the mechanism of action of HB involved in its anxiolytic-like effects. Experimental procedure: The effects of HB in mice were evaluated on light-dark box (LDB) and elevated plus maze (EPM) tests. The participation of 5-HT1A receptor and the benzodiazepine site of GABAA receptor was evaluated to investigate the possible mechanism of action. In silico tools were used to better elucidate the anxiolytic-like effects of HB. Results: Oral treatment with HB at a dose of 33 mg/kg showed an anxiolytic-like effect in the LDB and EPM tests. Besides that, the treatment altered the ethological parameters, frequency of head dips, and stretched-attend postures (SAP), important to better describe the anxiolytic profile of HB. Pretreatment with flumazenil (2 mg/kg) reverted the anxiolytic-like effect of HB on LDB and EPM tests. On the other hand, pretreatment with NAN-190 (0.5 mg/kg) not reverted the activity observed. In silico predictions revealed the potential of HB to increase GABAergic neurotransmission. Pharmacophore modelling and docking simulations showed that HB might interact with the α1ß2γ2 GABAA receptor. Conclusion: Together, the results presented herein suggest that activation of the benzodiazepine site of the GABAA receptor contributes to the anxiolytic-like effect of HB.