Superoxide anion is a reactive oxygen species (ROS) of biological interest. More specifically, it plays a role in intra- and intercellular signaling, besides being associated with conditions such as inflammation and cancer. Given this, efforts have been made by the research community to devise new sensing strategies for this ROS species. Among them, the chemiluminescent reaction of marine Coelenterazine has been employed as a sensitive and dynamic probing approach. Nevertheless, chemiluminescent reactions are typically associated with lower emissions in aqueous solutions. Herein, here we report the synthesis of a new Coelenterazine derivative with the potential for superoxide anion sensing. Namely, this novel compound is capable of chemiluminescence in a dose-dependent manner when triggered by this ROS species. More importantly, the light-emission intensities provided by this derivative were relevantly enhanced (intensities 2.13 × 101 to 1.11 × 104 times higher) in aqueous solutions at different pH conditions when compared to native Coelenterazine. The half-life of the chemiluminescent signal is also greatly increased for the derivative. Thus, a new chemiluminescence molecule with significant potential for superoxide anion sensing was discovered and reported for the first time.
In the economic and social aftermath of the 2008 crisis there has been an important and growing new wave of highly qualified Portuguese emigration comprising scientists. No or very few public policies have been designed to reverse this phenomenon, risking the consequences of brain drain. International literature argues that professional reasons are central to scientists’ decision to migrate, even after the 2008 crisis. Spending some time in a foreign country to study, research, or teach, is perceived as a common step in an individual academic trajectory and an advantage for a successful professional career in academia. It is also encouraged by European Union policies. Twelve individual portraits of Portuguese scientists living in central Europe reveal how important other factors are to the migration decision‐making process. These factors include the economic crisis, student mobility programmes, and the current Portuguese scientific system revision.
Primary angle closure occurs as a result of crowded anterior segment anatomy, causing appositional contact between the peripheral iris and trabecular meshwork, thereby obstructing aqueous outflow. Several studies highlight the role of the crystalline lens in its pathogenesis. The objective of this work is to compare the long-term efficacy of phacoemulsification versus laser peripheral iridotomy (LPI) in the management of chronic primary angle closure (CPAC). Prospective case-control study with 30 eyes of 30 patients randomly divided in two groups: 15 eyes in the LPI group and 15 eyes in the IOL group. Patients in the LPI group underwent LPI using argon and Nd:YAG laser. Patients in the IOL group underwent phacoemulsification with posterior chamber intraocular lens (IOL) implantation. Examinations before and after the procedure included gonioscopy, Goldmann applanation tonometry, and anterior chamber evaluation using the Pentacam rotating Scheimpflug camera. The mean follow-up time was 31.13 ± 4.97 months. There was a statistically significant reduction in the intraocular pressure (IOP) and number of anti-glaucoma medications (p \ 0.01) only in the IOL group. Anterior chamber depth, angle, and volume were all higher in the IOL group (p \ 0.01) at the end of the follow-up period. Phacoemulsification with posterior chamber IOL implantation results in a higher anterior chamber depth, angle, and volume, when compared to LPI. Consequently, phacoemulsification has greater efficacy in lowering IOP and preventing its long-term increase in patients with CPAC and cataract.
Objective: To characterize in vivo dose distributions during pelvic intraoperative electron radiation therapy (IOERT) for rectal cancer and to assess the alterations introduced by irregular irradiation surfaces in the presence of bevelled applicators. Methods: In vivo measurements were performed with Gafchromic films during 32 IOERT procedures. 1 film per procedure was used for the first 20 procedures. The methodology was then optimized for the remaining 12 procedures by using a set of 3 films. Both the average dose and two-dimensional dose distributions for each film were determined. Phantom measurements were performed for comparison. Results: For flat and concave surfaces, the doses measured in vivo agree with expected values. For concave surfaces with step-like irregularities, measured doses tend to be higher than expected doses. Results obtained with three films per procedure show a large variability along the irradiated surface, with important differences from expected profiles. These results are consistent with the presence of surface hotspots, such as those observed in phantoms in the presence of step-like irregularities, as well as fluid build-up. Conclusion: Clinical dose distributions in the IOERT of rectal cancer are often different from the references used for prescription. Further studies are necessary to assess the impact of these differences on treatment outcomes. In vivo measurements are important, but need to be accompanied by accurate imaging of positioning and irradiated surfaces. Advances in knowledge: These results confirm that surface irregularities occur frequently in rectal cancer IOERT and have a measurable effect on the dose distribution.
Cancer is still a challenging disease to treat, both in terms of harmful side effects and therapeutic efficiency of the available treatments. Herein, to develop new therapeutic molecules, we have investigated the anticancer activity of halogenated derivatives of different components of the bioluminescent system of marine Coelenterazine: Coelenterazine (Clz) itself, Coelenteramide (Clmd), and Coelenteramine (Clm). We have found that Clz derivatives possess variable anticancer activity toward gastric and lung cancer. Interestingly, we also found that both brominated Clmd (Br-Clmd) and Clm (Br-Clm) were the most potent anticancer compounds toward these cell lines, with this being the first report of the anticancer potential of these types of molecules. Interestingly, Br-Clm possessed some safety profile towards noncancer cells. Further evaluation revealed that the latter compound induced cell death via apoptosis, with evidence for crosstalk between intrinsic and extrinsic pathways. Finally, a thorough exploration of the chemical space of the studied Br-Clm helped identify the structural features responsible for its observed anticancer activity. In conclusion, a new type of compounds with anticancer activity toward gastric and lung cancer was reported and characterized, which showed interesting properties to be considered as a starting point for future optimizations towards obtaining suitable chemotherapeutic agents.
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