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Retinal pigment epithelial (RPE) cells occupy the outer layer of the retina and perform various biological functions. Oxidative damage to RPE cells is a major risk factor for retinal degeneration that ultimately leads to vision loss. In this study, we investigated the role of spermidine in a hydrogen peroxide (H2O2)-induced oxidative stress model using human RPE cells. Our findings showed that 300 μM H2O2 increased cytotoxicity, apoptosis, and cell cycle arrest in the G2/M phase, whereas these effects were markedly suppressed by 10 μM spermidine. Furthermore, spermidine significantly reduced H2O2-induced mitochondrial dysfunction including mitochondrial membrane potential and mitochondrial activity. Although spermidine displays antioxidant properties, the generation of intracellular reactive oxygen species (ROS) upon H2O2 insult was not regulated by spermidine. Spermidine did suppress the increase in cytosolic Ca2+ levels resulting from endoplasmic reticulum stress in H2O2-stimulated human RPE cells. Treatment with a cytosolic Ca2+ chelator markedly reversed H2O2-induced cellular dysfunction. Overall, spermidine protected against H2O2-induced cellular damage by blocking the increase of intracellular Ca2+ independently of ROS. These results suggest that spermidine protects RPE cells from oxidative stress, which could be a useful treatment for retinal diseases.In the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), the Urban Green Infrastructure (UGI) has been traditionally targeted at reducing flood risk. However, other Ecosystem Services (ES) became increasingly relevant in response to the challenges of urbanization and climate change. In total, 90 scientific articles addressing ES considered crucial contributions to the quality of life in cities are reviewed. These are classified as (1) regulating ES that minimize hazards such as heat, floods, air pollution and noise, and (2) cultural ES that promote well-being and health. We conclude that the planning and design of UGI should balance both the provision of ES and their side effects and disservices, aspects that seem to have been only marginally investigated. Climate-sensitive planning practices are critical to guarantee that seasonal climate variability is accounted for at high-latitude regions. Nevertheless, diverging and seemingly inconsistent findings, together with gaps in the understanding of long-term effects, create obstacles for practitioners. Additionally, the limited involvement of end users points to a need of better engagement and communication, which in overall call for more collaborative research. Close relationships and interactions among different ES provided by urban greenery were found, yet few studies attempted an integrated evaluation. We argue that promoting interdisciplinary studies is fundamental to attain a holistic understanding of how plant traits affect the resulting ES; of the synergies between biophysical, physiological and psychological processes; and of the potential disservices of UGI, specifically in Nordic cities.
To evaluate prognostic factors for a favorable outcome (improvement of the visual acuity or visual fields) after fractionated stereotactic radiotherapy (fSRT) of optic nerve sheath meningioma (ONSM).
We performed a database search for ONSM treatments during the period from April 2008 to September 2019 in the prospective database for stereotactic radiosurgery/radiotherapy (SRS/SRT) of the Robert Janker Clinic Bonn (Department of Radiotherapy) and performed a literature review and meta-analysis of published data on ONSM between 2010 and 2019. Ophthalmic status before and after treatment was evaluated and the collective was dichotomized into two groups functional improvement (FI; improvement of either visual acuity or visual fields) and non functional improvement (NFI; with stable or deteriorating visual acuity or visual fields). The two groups were compared regarding different variables pretreatment visual acuity, age, gender, gross tumor volume (GTV), follow up (FU) time, tumor localization, and maximal re cases an improvement of the ophthalmic status with low morbidity and excellent tumor control in our series and the meta analysis. Patients with a favorable outcome had in all analysis a significantly higher visual acuity before treatment start. Therefore, we advocate using fSRT as early as possible before vision deterioration occurs.
FSRT for ONSM achieves in over 50% of cases an improvement of the ophthalmic status with low morbidity and excellent tumor control in our series and the meta analysis. Patients with a favorable outcome had in all analysis a significantly higher visual acuity before treatment start. Therefore, we advocate using fSRT as early as possible before vision deterioration occurs.Human obesity is associated with decreased circulating adiponectin and elevated leptin levels. Tofacitinib concentration In vitro experiments and studies in high fat diet (HFD)-fed mice suggest that interleukin-6 (IL-6) may regulate adiponectin and leptin release from white adipose tissue (WAT). Herein, we aimed to investigate whether IL-6 receptor blockade affects the levels of circulating adiponectin and leptin in obese human individuals. To this end, serum samples collected during a multicenter, double-blind clinical trial were analyzed. In the latter study, obese human subjects with or without type 2 diabetes were randomly assigned to recurrent placebo or intravenous tocilizumab (an IL-6 receptor antibody) administration during a 12-week exercise training intervention. Twelve weeks of tocilizumab administration (in combination with exercise training) trend wise enhanced the decrease in circulating leptin levels (-2.7 ± 8.2% in the placebo vs. -20.6 ± 5.6% in tocilizumab, p = 0.08) and significantly enhanced the increase in circulating adiponectin (3.4 ± 3.7% in the placebo vs. 27.0 ± 6.6% in tocilizumab, p = 0.01). In addition, circulating adiponectin levels were negatively correlated with the homeostatic model assessment of insulin resistance (HOMA-IR), indicating that increased adiponectin levels positively affect insulin sensitivity in people with obesity. In conclusion, IL-6 receptor blockade increases circulating adiponectin levels in people with obesity.