Determination and comparison of the chemical composition of Calendula L. species growing in Continental Portugal

11th National Meeting of Organic Chemistry and 4th Meeting of Therapeutic Chemistry.The flora of Continental Portugal includes three species of Calendula L. (Calendula officinalis L., C. arvensis L., C. suffruticosa Vahl), one of which comprises three subspecies (C. suffruticosa subsp. algarbiensis (Boiss.) Nyman, C. suffruticosa subsp. lusitanica (Boiss.) Ohle and C. suffruticosa subsp. cinerea (Ohle) P.Silveira & A.C.Gonç.). C. officinalis is recognised for its medical properties and its chemical composition has been widely studied (Muley, B. P., et al. J. Pharm. Res. 2009, 8, 455; Safdar, W., et al. Int. J. Cell Mol. Biol. 2010, 1, 108). Nevertheless, little is known about the chemical composition of C. arvensis and even less regarding the different subspecies of C. suffruticosa. Therefore, the present study aims the elucidation of these plants’ chemical composition and to compare and identify differences and/or similarities among them. […].Instituto da Conservação da Natureza e das Florestas; Universidade de Aveiro; FCT / MEC (FCT UID / QUI / 00062/2013); UEM CESAM (UID / AMB / 50017); FEDER (Acordo de Parceria PT2020).info:eu-repo/semantics/publishedVersio

Ultrasonographic evaluation of the kidney in 5/6 nephrectomized rats: Correlation with biochemical and histopathological findings

To characterize the kidney alterations associated with renal mass reduction by two-dimensional ultrasound and assess the correlation of the ultrasonographic parameters with the histological and biochemical findings. Materials and Methods: Rats were divided into two groups: sham-operated animals (n=13), and animals which underwent renal mass reduction (RMR) through 5/6 nephrectomy (n=14). Renal length, renal thickness, cortical thickness, medullary length and echogenicity of the kidneys were evaluated by ultrasonography at 3 and 6 months after the RMR. Results: Except for the renal length, the renal dimensions at 3 and 6 months were significantly higher in the RMR group when compared to the sham-operated group (p < 0.05). Furthermore, the cortical and medullary echogenicity was significantly higher in the RMR group when compared to the sham-operated group (p < 0.05). A significant correlation was observed between the plasma creatinine level and the renal length 3 months after RMR (r=-0.612, p=0.045). Conclusion: These data support future application of ultrasonography for monitoring the progression of renal damage in chronic studies with the 5/6 nephrectomy model.This work was supported by : European Investment Funds by FEDER/COMPETE/POCI Operational Competitiveness and Internationalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT – the Portuguese Foundation for Science and Technology, under project UID/AGR/04033/2013; and by European Investment Funds by FEDER/COMPETE/POCI Operational Competitiveness and Internationalization Programme, under Project POCI-01-0145-FEDER-016728 and National Funds by FCT – the Portuguese Foundation for Science and Technology, under the project PTDC/DTP-DES/6077/2014.info:eu-repo/semantics/publishedVersio

Effect of chaetomellic acid on hematocrit, urine specific gravity and urinary volume values in a rat model of renal mass reduction

Chaetomellic acid (CA) is a potent and highly specific inhibitor of ras farnesyl-protein transferase that seems to reduce both functional and histological damage in uninephrectomized rats subjected to renal ischaemia-reperfusion injury. The aim of this work was to evaluate the effect of chronic treatment with CA on hematocrit, urine specific gravity and urinary volume in a model of renal mass reduction. Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been placed in four experimental groups: RMR rats without treatment (n=13); RMR rats treated with CA (n=13); SO rats without treatment (n=13); SO rats treated with CA (n=13). CA was intraperitoneally administered in a dose of 0.23 μg/kg three times a week for three months. We observed that animals from SO groups showed a higher hematocrit and urine specific gravity, and a lower urinary volume than animals from RMR groups (p<0.05). We did not observe differences between treated and no treated animals. These results suggest that three months of treatment with CA does not have a beneficial effect on hematocrit, urine specific gravity and urinary volume. However, these are preliminary data that warrant a larger scale study

Charge effect on the photoinactivation of Gram-negative and Gram-positive bacteria by cationic meso-substituted porphyrins

<p>Abstract</p> <p>Background</p> <p>In recent times photodynamic antimicrobial therapy has been used to efficiently destroy Gram (+) and Gram (-) bacteria using cationic porphyrins as photosensitizers. There is an increasing interest in this approach, namely in the search of photosensitizers with adequate structural features for an efficient photoinactivation process. In this study we propose to compare the efficiency of seven cationic porphyrins differing in <it>meso</it>-substituent groups, charge number and charge distribution, on the photodynamic inactivation of a Gram (+) bacterium (<it>Enterococcus faecalis</it>) and of a Gram (-) bacterium (<it>Escherichia coli</it>). The present study complements our previous work on the search for photosensitizers that might be considered good candidates for the photoinactivation of a large spectrum of environmental microorganisms.</p> <p>Results</p> <p>Bacterial suspension (10⁷CFU mL^-1) treated with different photosensitizers concentrations (0.5, 1.0 and 5.0 μM) were exposed to white light (40 W m^-2) for a total light dose of 64.8 J cm^-2. The most effective photosensitizers against both bacterial strains were the Tri-Py⁺-Me-PF and Tri-Py⁺-Me-CO₂Me at 5.0 μM with a light fluence of 64.8 J cm^-2, leading to > 7.0 log (> 99,999%) of photoinactivation. The tetracationic porphyrin also proved to be a good photosensitizer against both bacterial strains. Both di-cationic and the monocationic porphyrins were the least effective ones.</p> <p>Conclusion</p> <p>The number of positive charges, the charge distribution in the porphyrins' structure and the <it>meso</it>-substituent groups seem to have different effects on the photoinactivation of both bacteria. As the Tri-Py⁺-Me-PF porphyrin provides the highest log reduction using lower light doses, this photosensitizer can efficiently photoinactivate a large spectrum of environmental bacteria. The complete inactivation of both bacterial strains with low light fluence (40 W m^-2) means that the photodynamic approach can be applied to wastewater treatment under natural light conditions which makes this technology cheap and feasible in terms of the light source.</p

The usefulness of mesocosms for ecotoxicity testing with lacertid lizards

Mesocosms (i.e., outdoor, man-made representations of natural ecosystems) have seldom been used to study the impact of contaminants on terrestrial ecosystems. However, mesocosms can be a useful tool to provide a link between field and laboratory studies. We exposed juvenile lacertid lizards for a period of over one year to pesticides (herbicides and insecticides) in mesocosm enclosures with the intention of validating field observations obtained in a previous study that examined the effects of corn pesticides in Podarcis bocagei. Our treatments replicated field conditions and consisted of a control, an herbicides only treatment (alachlor, terbuthylazine, mesotrione and glyphosate) and an herbicides and insecticide treatment (including chlorpyrifos). We used a multi-biomarker approach that examined parameters at an individual and sub-individual level, including growth, locomotor performance, standard metabolic rate, biomarkers of oxidative stress, esterases and liver histopathologies. Although mortality over the course of the exposures was high (over 60%), surviving individuals prospered relatively well in the mesocosms and displayed a broad range of natural behaviours. The low numbers of replicate animals compromised many of the statistical comparisons, but in general, surviving lizards exposed to pesticides in mesocosm enclosures for over one year, thrived, and displayed few effects of pesticide exposure. Despite the difficulties, this work acts as an important stepping-stone for future ecotoxicology studies using lizards.publishe

Anatomy and imaging of rat prostate: practical monitoring in experimental cancer-induced protocols

The rat has been frequently used as a model to study several human diseases, including cancer. In many research protocols using cancer models, researchers find it difficult to perform several of the most commonly used techniques and to compare their results. Although the protocols for the study of carcinogenesis are based on the macroscopic and microscopic anatomy of organs, few studies focus on the use of imaging. The use of imaging modalities to monitor the development of cancer avoids the need for intermediate sacrifice to assess the status of induced lesions, thus reducing the number of animals used in experiments. Our work intends to provide a complete and systematic overview of rat prostate anatomy and imaging, facilitating the monitoring of prostate cancer development through different imaging modalities, such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI).publishe

Discovery of thiazolo [5,4-c] isoquinoline based compounds as acetylcholinesterase inhibitors through computational target prediction, molecular docking and bioassay

We thank Nathalie Reichmann and Leendert Hamoen (University of Amsterdam) for critical reading of the manuscript, Ana Velic (Proteome Center Tübingen) for help with proteome analysis and Mike VanNieuwenhze (Indiana University) for the generous gift of HADA. This study was funded by the European Research Council through grant ERC‐2017‐CoG‐771709 (to MGP), by national funds through FCT– Fundação para a Ciência e a Tecnologia, PTDC/BIA‐MIC/6982/2020 (to HV); PTDC/BIA‐PLA/3432/2012 (to SRF); FCT through MOSTMICRO‐ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020) and FCT fellowship SFRH/BD/147052/2019 (to BMS); by the Swiss National National Foundation through P300P3_155346 (to AJ); by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska‐Curie grant agreement No 839596 (to SS) and by the European Molecular Biology Organization through award ALTF 673‐2018 (to SS). Figure 6D and Appendix Fig S7 were created with Biorender.com .A computer-aided drug design (CADD) approach was developed for a focused chemical library comprising a series of sixteen thiazolo[5,4-c]isoquinoline derivatives. Little is known about this group of heteroaromatic compounds, both from the point of view of their synthesis and their biological properties. First, our CADD approach included target prediction by Mondrian conformal prediction with the ChEMBL database. The acetylcholinesterase (AChE) was identified as having a high probability of thiazolo[5,4-c]isoquinolines being active against it. Secondly, the molecular docking predictions revealed four promising thiazoloisoquinolines (2, 7, 13 and 14) according to their prominent ligand-protein energy scores and relevant binding affinities with the AChE pocket residues. The subsequent in vitro evaluation of promising hits and related ones revealed a set of novel AChE inhibitors. Therefore, the findings reported herein may provide a new strategy for discovering novel AChE inhibitors.publishersversionpublishe

Anatomy and Imaging of Rat Prostate: Practical Monitoring in Experimental Cancer-Induced Protocols

[EN] The rat has been frequently used as a model to study several human diseases, including cancer. In many research protocols using cancer models, researchers find it difficult to perform several of the most commonly used techniques and to compare their results. Although the protocols for the study of carcinogenesis are based on the macroscopic and microscopic anatomy of organs, few studies focus on the use of imaging. The use of imaging modalities to monitor the development of cancer avoids the need for intermediate sacrifice to assess the status of induced lesions, thus reducing the number of animals used in experiments. Our work intends to provide a complete and systematic overview of rat prostate anatomy and imaging, facilitating the monitoring of prostate cancer development through different imaging modalities, such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI)SIThis research was funded by National Funds by FCT—Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2019 and FEDER/COMPETE/POCI—Operational Competitiveness and Internationalization Program, under Project POCI-01-0145-FEDER-016728 and National Funds by FCT—Portuguese Foundation for Science and Technology, under the project PTDC/DTP-DES/6077/201

New nitroindazole-porphyrin conjugates: synthesis, characterization and antibacterial properties

The synthesis of new porphyrin-indazole hybrids by a Knoevenagel condensation of 2-formyl-5,10,15,20-tetraphenylporphyrin and N-methyl-nitroindazolylacetonitrile derivatives is reported. The target compounds were isolated in moderate to good yields (32-57%) and some of the isolated porphyrin-indazole conjugates showed good performance in the generation of singlet oxygen when irradiated with visible light. Their efficiency as photosensitizers in the photoinactivation of methicillin resistant Staphylococcus aureus-MRSA was evaluated. All derivatives showed to be able to photoinactivate the MRSA bacteria. Compound 3a appears to be the most promising photosensitiser (PS) in the photoinactivation of these bacteria, despite being the least efficient in singlet oxygen generation. The addition of potassium iodide (KI) significantly potentiated the antimicrobial Photodynamic Therapy (aPDT) process mediated by all the analysed porphyrin-indazole conjugates. The combined action of nitroindazole-porphyrins with potassium iodide (KI) action appears to be promising in the photoinactivation of MRSA.publishe

Customized tracheal design using 3D printing of a polymer hydrogel: influence of UV laser cross-linking on mechanical properties

H2020-ICT-2014-1,TransFlexTeg645241 ERC-CoG-2014, CapTherPV, 647596 Pest-UID/FIS/00068/2013The use of 3D printing of hydrogels as a cell support in bio-printing of cartilage, organs and tissue has attracted much research interest. For cartilage applications, hydrogels as soft materials must show some degree of rigidity, which can be achieved by photo- or chemical polymerization. In this work, we combined chemical and UV laser polymeric cross-linkage to control the mechanical properties of 3D printed hydrogel blends. Since there are few studies on UV laser cross-linking combined with 3D printing of hydrogels, the work here reported offered many challenges.publishe