Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/REF-1) is a multifunctional protein acting on cellular signaling pathways, including DNA repair and redox activities. APE1/REF-1 has emerged ...as a target for cancer therapy, and its role in breast cancer models would reveal new strategies for cancer therapy. APX2009 is a specific APE1/REF-1 redox inhibitor whose anticancer properties have not been described in breast cancer cells. Here, we investigated the effect of the APX2009 treatment in the breast cancer cell lines MDA-MB-231 and MCF-7. Breast cancer cell lines were cultured, and WST1 and colony formation assays were performed to evaluate cell proliferation. Annexin V-FITC/7-AAD and LDH-Glo™ assays were performed to evaluate cell death. The wound healing assay and Matrigel transwell assay were performed after APX2009 treatment to evaluate the cellular migration and invasion processes, respectively. Our findings demonstrated that APX2009 treatment decreased breast cancer cell proliferative, migratory, and invasive properties. Furthermore, it induced apoptosis in both cell lines. Our study is the first to show the effects of APX2009 treatment on apoptosis in a breast cancer cell. Therefore, this study suggested that APX2009 treatment is a promising anticancer molecule for breast cancer.
Global Biodiversity Conservation Priorities Brooks, T.M; Mittermeier, R.A; Fonseca, G.A.B. da ...
Science (American Association for the Advancement of Science),
07/2006, Volume:
313, Issue:
5783
Journal Article
Peer reviewed
Open access
The location of and threats to biodiversity are distributed unevenly, so prioritization is essential to minimize biodiversity loss. To address this need, biodiversity conservation organizations have ...proposed nine templates of global priorities over the past decade. Here, we review the concepts, methods, results, impacts, and challenges of these prioritizations of conservation practice within the theoretical irreplaceability/vulnerability framework of systematic conservation planning. Most of the templates prioritize highly irreplaceable regions; some are reactive (prioritizing high vulnerability), and others are proactive (prioritizing low vulnerability). We hope this synthesis improves understanding of these prioritization approaches and that it results in more efficient allocation of geographically flexible conservation funding.
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The prediction of the quaternary structure of biomolecular macromolecules is of paramount importance for fundamental understanding of cellular processes and drug design. In the era of integrative ...structural biology, one way of increasing the accuracy of modeling methods used to predict the structure of biomolecular complexes is to include as much experimental or predictive information as possible in the process. This has been at the core of our information-driven docking approach HADDOCK. We present here the updated version 2.2 of the HADDOCK portal, which offers new features such as support for mixed molecule types, additional experimental restraints and improved protocols, all of this in a user-friendly interface. With well over 6000 registered users and 108,000 jobs served, an increasing fraction of which on grid resources, we hope that this timely upgrade will help the community to solve important biological questions and further advance the field. The HADDOCK2.2 Web server is freely accessible to non-profit users at http://haddock.science.uu.nl/services/HADDOCK2.2.
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•The HADDOCK Web server has been upgraded to use HADDOCK version 2.2.•It supports mixed-type molecules, for example, protein–nucleic acid, such as nucleosomes.•NMR-based pseudocontact shifts and radius of gyration restraints are included.•The multi-body and solvated docking protocol are extended.•The HADDOCK Web server counts over 6000 users and has served more than 100,000 jobs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The management of psychosis in Parkinson’s disease (PD) has been considered a great challenge for clinicians and there is a need for new pharmacological intervention. Previously an antipsychotic and ...neuroprotective effect of Cannabidiol (CBD) has been suggested. Therefore, the aim of the present study was to directly evaluate for the first time, the efficacy, tolerability and safety of CBD on PD patients with psychotic symptoms. This was an open-label pilot study. Six consecutive outpatients (four men and two women) with the diagnosis of PD and who had psychosis for at least 3 months were selected for the study. All patients received CBD in flexible dose (started with an oral dose of 150 mg/day) for 4 weeks, in addition to their usual therapy. The psychotic symptoms evaluated by the Brief Psychiatric Rating Scale and the Parkinson Psychosis Questionnaire showed a significant decrease under CBD treatment. CBD did not worsen the motor function and decreased the total scores of the Unified Parkinson’s Disease Rating Scale. No adverse effect was observed during the treatment. These preliminary data suggest that CBD may be effective, safe and well tolerated for the treatment of the psychosis in PD.
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Introduction: Gene therapy is a promising approach to be applied in cardiac regeneration after myocardial infarction and gene correction for inherited cardiomyopathies. However, cardiomyocytes are ...crucial cell types that are considered hard-to- transfect. The entrapment of nucleic acids in non-viral vectors, such as lipid nanoparticles (LNPs), is an attractive approach for safe and effective delivery. Methods: Here, a mini-library of engineered LNPs was developed for pDNA delivery in cardiomyocytes. LNPs were characterized and screened for pDNA delivery in cardiomyocytes and identified a lead LNP formulation with enhanced transfection efficiency. Results: By varying lipid molar ratios, the LNP formulation was optimized to deliver pDNA in cardiomyocytes with enhanced gene expression in vitro and in vivo, with negligible toxicity. In vitro, our lead LNP was able to reach a gene expression greater than 80%. The in vivo treatment with lead LNPs induced a twofold increase in GFP expression in heart tissue compared to control. In addition, levels of circulating myeloid cells and inflammatory cytokines remained without significant changes in the heart after LNP treatment. It was also demonstrated that cardiac cell function was not affected after LNP treatment. Conclusion: Collectively, our results highlight the potential of LNPs as an efficient delivery vector for pDNA to cardiomyocytes. This study suggests that LNPs hold promise to improve gene therapy for treatment of cardiovascular disease. Keywords: lipid nanoparticles, ionizable lipids, pDNA delivery, heart, cardiomyocytes
► Red and blue light sources activated sensitizers with corresponding wavelength. ► Photodynamic therapy with toluidine blue reduced
S. mutans with biological relevance. ► Methylene blue generated ...the greatest reduction in the concentration of tryptophan. ► Photosensitizers with distinct characteristics result in variable activity in cells.
Several photosensitizers have been used against oral bacteria without standardization. Singlet oxygen (
1O
2) is an aggressive chemical species that can kill cells through apoptosis or necrosis. Objective: to compare the antimicrobial activity of photodynamic therapy (PDT) with different photosensitizers at the same concentration against
Streptococcus mutans. In addition, the
1O
2 production of each photosensitizer was determined. The photosensitizers (163.5
μM) methylene blue (MB), toluidine blue ortho (TBO) and malachite green (MG) were activated with a light-emitting diode (LED;
λ
=
636
nm), while eosin (EOS), erythrosine (ERI) and rose bengal (RB) were irradiated with a curing light (
λ
=
570
nm). Light sources were operated at 24
J
cm
−2. For each photosensitizer, 40 randomized assays (
n
=
10 per condition) were performed under one of the following experimental conditions: no light irradiation or photosensitizer, irradiation only, photosensitizer only or irradiation in the presence of a photosensitizer. After treatment, serial dilutions of
S. mutans were seeded onto brain heart infusion agar to determine viability in colony-forming units per milliliter (CFU
mL
−1). Generation of
1O
2 was analyzed by tryptophan photooxidation, and the decay constant was estimated. Results were analyzed by one-way ANOVA and the Tukey–Kramer test (
p
<
0.05). PDT with irradiation in the presence of the photosensitizers TBO and MG was effective in reducing
S. mutans counts by 3 and 1.4 logs, respectively (
p
<
0.01), compared to their respective untreated controls. MB generated 1.3 times more
1O
2 than TBO, and both produced significantly higher concentrations of singlet oxygen than the other photosensitizers. Since
in vitro bulk
1O
2 production does not indicate that
1O
2 was generated in the bacterial activity site, the bactericidal action against
S. mutans cannot be related to
in vitro singlet O
2 generation rate.
In vitro
S. mutans-experiments demonstrated TBO as the only photosensitizer that effectively reduced 99.9% of these microorganisms.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The need for more sustainable adhesive formulations has led to the use of silane-based adhesives in different industrial sectors, such as the automotive industry. In this work, the mechanical ...properties of a dual cure two-component prototype adhesive which combined silylated polyurethane resin (SPUR) with standard epoxy resin was characterized under quasi-static conditions. The characterization process consisted of tensile bulk testing, to determine the Young's modulus, the tensile strength and the tensile strain to failure. The shear stiffness and shear strength were measured by performing a thick adherend shear test. The in-plane strain field was obtained using a digital image correlation method. Double-cantilever beam and mixed-mode tests were performed to assess the fracture toughness under pure modes. The prototype adhesive showed promising but lower properties compared to commercial solutions. Furthermore, the adhesive was modified via the addition of three different resin modifier additives and characterized via measuring the shear and tensile properties, but no enhancements were found. Finally, the adhesive was formulated with three different SPUR viscosities. The critical energy release rate analysis showed an optimum value for the medium viscosity SPUR adhesive.
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This work reports on the antimicrobial activity in fresh sausage of marjoram (
Origanum majorana L.) essential oil against several species of bacteria. The in vitro minimum inhibitory concentration ...(MIC) was determined for 10 selected aerobic heterotrophic bacterial species. The antimicrobial activity of distinct concentrations of the essential oil based on the highest MIC value was tested in a food system comprising fresh sausage. Batch food samples were also inoculated with a fixed concentration of
Escherichia coli and the time course of the product was evaluated with respect to the action of the different concentrations of essential oil. Results showed that addition of marjoram essential oil to fresh sausage exerted a bacteriostatic effect at oil concentrations lower than the MIC, while a bactericidal effect was observed at higher oil concentrations which also caused alterations in the taste of the product.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The need for more sustainable adhesive formulations has presented the possibility of using silane-based adhesives in the automotive industry. In this work, a dual-cure two-component silylated ...polyurethane resin (SPUR) adhesive was tested in single-lap joints, to assess in-joint behaviour at room temperature under quasi-static conditions for aluminium substrates. The effect of two different overlap lengths, 25 and 50 mm, was also considered. A numerical model was built using cohesive zone modelling in finite element software, to reproduce the mechanical behaviour of the joint. The model was fed with data experimentally withdrawn from the first part of this paper. A triangular-shaped cohesive zone model (CZM) law was chosen as the adhesive behaviour was highly elastic and lacked yielding phenomena. The experimental results served as the base for the numerical validation, allowing accurate CZM parameters to be successfully determined.
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