Complex Positive Effects of SGLT-2 Inhibitor Empagliflozin in the Liver,Kidney and Adipose Tissue of Hereditary Hypertriglyceridemic Rats: Possible Contribution of Attenuation of Cell Senescence and Oxidative Stress

(1) Background: empagliflozin, sodium-glucose co-transporter 2 (SGLT-2) inhibitor, is an effective antidiabetic agent with strong cardio- and nephroprotective properties. The mechanisms behind its cardio- and nephroprotection are still not fully clarified. (2) Methods: we used male hereditary hypertriglyceridemic (hHTG) rats, a non-obese model of dyslipidaemia, insulin resistance, and endothelial dysfunction fed standard diet with or without empagliflozin for six weeks to explore the molecular mechanisms of empagliflozin effects. Nuclear magnetic resonance (NMR)-based metabolomics; quantitative PCR of relevant genes involved in lipid and glucose metabolism, or senescence; glucose and palmitic acid oxidation in isolated tissues and cell lines of adipocytes and hepatocytes were used. (3) Results: empagliflozin inhibited weight gain and decreased adipose tissue weight, fasting blood glucose, and triglycerides and increased HDL-cholesterol. It also improved insulin sensitivity in white fat. NMR spectroscopy identified higher plasma concentrations of ketone bodies, ketogenic amino acid leucine and decreased levels of pyruvate and alanine. In the liver, adipose tissue and kidney, empagliflozin up-regulated expression of genes involved in gluconeogenesis and down-regulated expression of genes involved in lipogenesis along with reduction of markers of inflammation, oxidative stress and cell senescence. (4) Conclusion: multiple positive effects of empagliflozin, including reduced cell senescence and oxidative stress, could contribute to its long-term cardio- and nephroprotective actions.     

Surviving-Channel-Power Transients in Second-Order Pumped Lumped Raman Fiber Amplifier: Experimentation and Modeling

In this paper, the effect of addition and/or dropping of wavelength-division-multiplexed channels in an all- optical gain-clamped (AOGC) second-order (SO) pumped lumped Raman fiber amplifier (LRFA) has been investigated experimentally and analyzed by numerical simulation. Channel addition/ removal was simulated by transmitting ten signals through a counter-directionally pumped LRFA consisting of a 16-km-long dispersion-compensating fiber. The light from eight lasers was square-wave modulated at 500 Hz; power transients of the surviving channels caused by cross-gain modulation of the LRFA were monitored at the output of the amplifier. All-optical feedback loop was implemented in the form of a ring laser. Gain-clamping properties of the SO-pumped LRFA are compared with those of the first-order pumped LRFA having the same ON/OFF Raman gain. Theoretical analysis of the AOGC LRFA was based on numerical solution of coupled propagation equations for the backward propagating pump, signals, and both forward and backward propagating spectral components of amplified spontaneous emission powers.     

Autonomous landing on a moving vehicle with an unmanned aerial vehicle

This paper addresses the perception, control, and trajectory planning for an aerial platform to identify and land on a moving car at 15 km/hr. The hexacopter unmanned aerial vehicle (UAV), equipped with onboard sensors and a computer, detects the car using a monocular camera and predicts the car future movement using a nonlinear motion model. While following the car, the UAV lands on its roof, and it attaches itself using magnetic legs. The proposed system is fully autonomous from takeoff to landing. Numerous field tests were conducted throughout the year‐long development and preparations for the Mohamed Bin Zayed International Robotics Challenge (MBZIRC) 2017 competition, for which the system was designed. We propose a novel control system in which a model predictive controller is used in real time to generate a reference trajectory for the UAV, which are then tracked by the nonlinear feedback controller. This combination allows to track predictions of the car motion with minimal position error. The evaluation presents three successful autonomous landings during the MBZIRC 2017, where our system achieved the fastest landing among all competing teams.     

The hepatocellular transport of sulfobromophthalein-glutathione by clofibrate treated,perfused rat liver

The hypolipidemic drug clofibrate is known to affect the hepatic transport of various organic anions including bilirubin, fatty acids and sulfobromophthalein. Changes in the rate of metabolism and/or intracellular transport have been claimed responsible for the effect. To evaluate these possibilities, the transport of sulfobromophthalein-glutathione, a model compound that does not require metabolism for biliary excretion, was studied in perfused livers isolated from clofibrate-treated and control rats. Cytosolic fatty acid binding protein and glutathione S-transferase activity were also measured. Clofibrate treatment significantly increased liver weight; as a result glutathione S-transferase activity (toward 1-chloro-2,4-dinitrobenzene) fell if expressed per gram of liver (4560±420 (SE) vs 7010±260 nmoles/min for clofibrate treated and controls respectively, p<0.002), but was unchanged when expressed per total liver (60.8±6.5 vs 64.6±3.5 μmoles/min for clofibrate and controls p>0.5). Irrespective of how it was expressed fatty acid binding protein was significantly increased by the drug treatment. Steady state sulfobromophthalein-glutathione removal velocity was saturble with increasing concentrations of sulfobromophthalein-glutathione in both control and clofibrate-treated livers. Steady state extraction ratio, as well as Vmax and Km for removal, did not differ between the two groups. In keeping with other observations, these data collectively indicate that the hepatic steady state removal of nonmetabolized compounds is not affected by clofibrate. Because the concomitant decrease in glutathione S-transferase activity only reflects an opposite change in liver weight, it remains to be determined whether clofibrate alters the hepatic transport of sulfobromophthalein and other compounds that are conjugated with glutathione solely by changing their rate of metabolism.     

Cancer Microenvironment: What Can We Learn from the Stem Cell Niche

Epidermal stem cells (ESCs) are crucial for maintenance and self- renewal of skin epithelium and also for regular hair cycling. Their role in wound healing is also indispensable. ESCs reside in a defined outer root sheath portion of hair follicle—also known as the bulge region. ECS are also found between basal cells of the interfollicular epidermis or mucous membranes. The non-epithelial elements such as mesenchymal stem cell-like elements of dermis or surrounding adipose tissue can also contribute to this niche formation. Cancer stem cells (CSCs) participate in formation of common epithelial malignant diseases such as basal cell or squamous cell carcinoma. In this review article, we focus on the role of cancer microenvironment with emphasis on the effect of cancer-associated fibroblasts (CAFs). This model reflects various biological aspects of interaction between cancer cell and CAFs with multiple parallels to interaction of normal epidermal stem cells and their niche. The complexity of intercellular interactions within tumor stroma is depicted on example of malignant melanoma, where keratinocytes also contribute the microenvironmental landscape during early phase of tumor progression. Interactions seen in normal bulge region can therefore be an important source of information for proper understanding to melanoma. The therapeutic consequences of targeting of microenvironment in anticancer therapy and for improved wound healing are included to article.     

Activity, Selectivity, and Long-Term Stability of Different Metal Oxide Supported Gold Catalysts for the Preferential CO Oxidation in H2-Rich Gas

A comparative study of the catalytic performance and long-term stability of various metal oxide supported gold catalysts during preferential CO oxidation at 80°C in a H₂-containing atmosphere (PROX) reveals significant support effects. Compared to Au/-Al₂O₃, where the support is believed to behave neutrally in the reaction process, catalysts supported on reducible transition metal oxides, such as Fe₂O₃, CeO₂, or TiO₂, exhibit a CO oxidation activity of up to one magnitude higher at comparable gold particle sizes. The selectivity is also found to strongly depend on the employed metal oxide, amounting, e.g., up to 75% for Au/Co₃O₄ and down to 35% over Au/SnO₂. The deactivation, which is observed for all samples with increasing time on stream, except for Au/-Al₂O₃, is related to the build-up of surface carbonate species. The long-term stability of the investigated catalysts in simulated methanol reformate depends crucially on the ability to form such by-products, with magnesia and Co₃O₄ supported catalysts being most negatively affected. Overall, Au/CeO₂ and, in particular, Au/-Fe₂O₃ represent the best compromise under the applied reaction conditions, especially due to the superior activity and the easily reversible deactivation of the latter catalyst.