Targeting RNS/caveolin-1/MMP signaling cascades to protect against cerebral ischemia-reperfusion injuries: potential application for drug discovery

Reactive nitrogen species (RNS) play important roles in mediating cerebral ischemia-reperfusion injury. RNS activate multiple signaling pathways and participate in different cellular events in cerebral ischemia-reperfusion injury. Recent studies have indicated that caveolin-1 and matrix metalloproteinase (MMP) are important signaling molecules in the pathological process of ischemic brain injury. During cerebral ischemia-reperfusion, the production of nitric oxide (NO) and peroxynitrite (ONOO-), two representative RNS, down-regulates the expression of caveolin-1 (Cav-1) and, in turn, further activates nitric oxide synthase (NOS) to promote RNS generation. The increased RNS further induce MMP activation and mediate disruption of the blood-brain barrier (BBB), aggravating the brain damage in cerebral ischemia-reperfusion injury. Therefore, the feedback interaction among RNS/Cav-1/MMPs provides an amplified mechanism for aggravating ischemic brain damage during cerebral ischemia-reperfusion injury. Targeting the RNS/Cav-1/MMP pathway could be a promising therapeutic strategy for protecting against cerebral ischemia-reperfusion injury. In this mini-review article, we highlight the important role of the RNS/Cav-1/MMP signaling cascades in ischemic stroke injury and review the current progress of studies seeking therapeutic compounds targeting the RNS/Cav-1/MMP signaling cascades to attenuate cerebral ischemia-reperfusion injury. Several representative natural compounds, including calycosin-7-O-β-D-glucoside, baicalin, Momordica charantia polysaccharide (MCP), chlorogenic acid, lutein and lycopene, have shown potential for targeting the RNS/Cav-1/MMP signaling pathway to protect the brain in ischemic stroke. Therefore, the RNS/Cav-1/MMP pathway is an important therapeutic target in ischemic stroke treatment.published_or_final_versio

Exposure to Antineoplastic Drugs in Occupational Settings: A Systematic Review of Biological Monitoring Data

The high toxicity of antineoplastic drugs (ADs) makes them dangerous not only for patients, but also for exposed workers. Therefore, the aim of this review was to provide an updated overview of the biological monitoring of occupational AD exposure in order to extrapolate information useful to improve risk assessment and management strategies in workplaces. Several studies demonstrated that remarkable portions of healthcare workers may have traces of these substances or their metabolites in biological fluids, although with some conflicting results. Nurses, directly engaged in AD handling, were the occupational category at higher risk of contamination, although, in some cases, personnel not involved in AD-related tasks also showed quantifiable internal doses. Overall, further research carried out on greater sample sizes appears necessary to gain deeper insight into the variability retrieved in the reported results. This may be important to understand the impact of the extent of ADs use, different handling, procedures, and cleaning practices, spill occurrence, training of the workforce, as well as the adoption of adequate collective and personal protective equipment in affecting the occupational exposure levels. This may support the achievement of the greatest clinical efficiency of such therapies while assuring the health and safety of involved workers

The impact of cystic fibrosis on the working life of patients: A systematic review

Advances in the treatment and management of cystic fibrosis (CF) have led to a substantial increase in patient life expectancy, thus facilitating healthier lives and labour force participation. This review aimed to address the impact of CF on the occupational functioning of patients. A significant proportion of patients were reported to retain a job on a full- or part-time schedule. Less physically demanding occupations were most frequently performed, perhaps due to CF-related inability to sustain a heavy workload. Disease severity parameters (e.g., lung function measurements, or personal, psycho-social, or economic conditions) have been reported as determinant or co-determinant factors for the development of work-related disability. Although further research is necessary, our results may be useful to inform interdisciplinary CF healthcare management, including the assessment of work function, and to define career counselling plans and workplace risk assessment and management strategies to support the personal, social and professional lives of patients

Hormetic dose responses induced by antibiotics in bacteria: A phantom menace to be thoroughly evaluated to address the environmental risk and tackle the antibiotic resistance phenomenon

The environmental contamination of antibiotics caused by their over or inappropriate use is a major issue for environmental and human health since it can adversely impact the ecosystems and promote the antimicrobial resistance. Indeed, considering that in the environmental matrices these drugs are present at low levels, the possibility that bacteria exhibit a hormetic response to increase their resilience when exposed to antibiotic subinhibitory concentrations might represent a serious threat. Information reported in this review showed that exposure to different types of antibiotics, either administered individually or in mixtures, is capable of exerting hormetic effects on bacteria at environmentally relevant concentrations. These responses have been reported regardless of the type of bacterium or antibiotic, thus suggesting that hormesis would be a generalized adaptive mechanism implemented by bacteria to strengthen their resistance to antibiotics. Hormetic effects included growth, bioluminescence and motility of bacteria, their ability to produce biofilm, but also the frequency of mutation and plasmid conjugative transfer. The evaluation of quantitative features of antibiotic-induced hormesis showed that these responses have both maximum stimulation and dose width characteristics similar to those already reported in the literature for other stressors. Notably, mixtures comprising individual antibiotic inducing stimulatory responses might have distinct combined effects based on antagonistic, synergistic or additive interactions between components. Regarding the molecular mechanisms of action underlying the aforementioned effects, we put forward the hypothesis that the adoption of adaptive/defensive responses would be driven by the ability of antibiotic low doses to modulate the transcriptional activity of bacteria. Overall, our findings suggest that hormesis plays a pivotal role in affecting the bacterial behavior in order to acquire a survival advantage. Therefore, a proactive and effective risk assessment should necessarily take due account of the hormesis concept to adequately evaluate the risks to ecosystems and human health posed by antibiotic environmental contamination

Aprendizaje en las escuelas del siglo XXI: Hacia la construcción de escuelas que promueven el aprendizaje, ofrecen seguridad y protegen el medio ambiente

En 2010, la Red de Educación organizó un seminario que examinó el estado de la infraestructura escolar en América Latina y el Caribe y el papel financiero del sector privado. El seminario de Infraestructura y Aprendizaje en el Siglo XXI se realizó en Santiago, Chile entre el 26 y 27 de octubre de 2010. Este libro recopila las presentaciones realizadas durante la conferencia, editados y, en algunos casos, revisados parea su publicación. Los capítulos de este libro siguen el orden de la agenda de la conferencia, enfocándose en el diseño, financiamiento, construcción y mantenimiento de edificios escolares.