A selective competitive inhibitor of aldehyde dehydrogenase 1A3 hinders cancer cell growth, invasiveness and stemness in vitro

Aldehyde dehydrogenase 1A3 (ALDH1A3) belongs to an enzymatic superfamily composed by 19 different isoforms, with a scavenger role, involved in the oxidation of a plethora of aldehydes to the respective carboxylic acids, through a NAD+‐dependent reaction. Previous clinical studies highlighted the high expression of ALDH1A3 in cancer stem cells (CSCs) correlated to a higher risk of cancer relapses, chemoresistance and a poor clinical outcome. We report on the structural, biochemical, and cellular characterization of NR6, a new selective ALDH1A3 inhibitor derived from an already published ALDH non‐selective inhibitor with cytotoxic activity on glioblastoma and colorectal cancer cells. Crystal structure, through X‐Ray analysis, showed that NR6 binds a non‐conserved tyrosine residue of ALDH1A3 which drives the selectivity towards this isoform, as supported by computational binding simulations. Moreover, NR6 shows anti‐metastatic activity in wound healing and invasion assays and induces the downregulation of cancer stem cell markers. Overall, our work confirms the role of ALDH1A3 as an important target in glioblastoma and colorectal cells and propose NR6 as a promising molecule for future preclinical studies. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

50 JAHRE PRÜFSTANDSKOMPLEX M11 IN LAMPOLDSHAUSEN – FORSCHUNG FÜR RAUMFAHRTANTRIEBE VON MORGEN

Am Prüfstandskomplex M11 des Instituts für Raumfahrtantriebe am DLR-Standort Lampoldshausen, der 1966 errichtet wurde, werden grundlagenorientierte Forschungsaktivitäten und schubkammerrelevante Technologieentwicklungsarbeiten für Raketen- und Staustrahlantriebe durchgeführt. In diesen 50 Jahren wurden wesentliche Erkenntnisse in den vielfältigen Arbeitsbereichen erworben, was durch eine Vielzahl an Publikationen belegt ist. Heutzutage fokussieren sich die Arbeiten auf Brennkammerprozessentwicklungen für fortschrittliche grüne Treibstoffe. Diese Veröffentlichung gibt einen kurzen Überblick über die Geschichte des Prüfstandskomplexes und einen kurzen Einblick in aktuelle Aktivitäten

Sounding Rocket "HEROS" - A Low-Cost Hybrid Rocket Technology Demonstrator

The inherent safety of hybrid rocket propulsion offers some unique advantages com- pared to solid and liquid propellant rocket engines. This makes it especially attractive for space tourism, Micro-launcher and hands-on experiments in the education of students. On November 8th, 2016 at 10:30 a.m. the hybrid sounding rocket HEROS 3 was launched from the ESRANGE Space Center to an apogee altitude of 32,300m (106,000 ft). This set a new altitude record for European student and amateur rocketry and a world altitude record for hybrid rockets built by students. The 7.5m long rocket was using Nitrous Oxide (N2O) and a Paraffin-based fuel to produce 10,000N of thrust. The dry mass of the rocket was only 75 kg thanks to a carbon fibre structure for the most part. The rocket performed the record breaking flight at perfect weather and visibility conditions, reaching a maximum airspeed of 720 m/s and Mach 2.3. The rocket performed a soft landing with two parachutes and can be reused. Flight data and engine performance data are published and analyzed. The flight data shows excellent stability of the rocket. Engine performance data proves very high efficiency and stable combustion as in the ground tests. The subsystem design and verification before the launch is reported. Engine and flight trajectory simulations show very good agreements with the flight data. Furthermore, the overall project, the rocket design, the subsystems as well as the launch campaign are presented here in detail

Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes

AIMS: Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes. METHODS AND RESULTS: We examined two datasets: 24 012 patients with HF from four large randomized trials and an administrative database of 4 million individuals, 103 857 of whom with HF. In the former, survival was examined using Cox proportional hazards models adjusted for baseline variables and separately for propensity scores. Fine-Gray competing risk regression models were used to assess the risk of hospitalization for HF. For the latter, a case-control nested within a population-based cohort study was conducted with propensity score. Prevalence of diabetes mellitus at study entry ranged from 25.5% to 29.5% across trials. Insulin alone or in combination with oral hypoglycaemic drugs was prescribed at randomization to 24.4% to 34.5% of the patients with diabetes. The rates of death from any cause and hospitalization for HF were higher in patients with vs. without diabetes, and highest of all in patients prescribed insulin [propensity score pooled hazard ratio for all-cause mortality 1.27 (1.16-1.38), for HF hospitalization 1.23 (1.13-1.33)]. In the administrative registry, insulin prescription was associated with a higher risk of all-cause death [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.87-2.19] and rehospitalization for HF (OR 1.42, 95% CI 1.32-1.53). CONCLUSIONS: Whether insulin use is associated with poor outcomes in HF should be investigated further with controlled trials, as should the possibility that there may be safer alternative glucose-lowering treatments for patients with HF and type 2 diabetes mellitus

Cost-effectiveness of the adherence with recommendations for clinical monitoring of patients with diabetes

Background and aims: To validate a set of indicators for monitoring the quality of care of patients with diabetes in ‘real-life’ practice through its relationship with measurable clinical outcomes and healthcare costs. Methods and results: A population-based cohort study was carried out by including the 20,635 patients, residents in the Lombardy Region (Italy), who in the year 2012 were newly taken-in-care for diabetes. Adherence with clinical recommendations (i.e., controls for glycated haemoglobin, lipid profile, urine albumin excretion and serum creatinine) was recorded during the first year after the patient was taken-in-care, and categorized according whether he/she complied with none or almost none (0 or 1), just some (2) or all or almost all (3 or 4) the recommendations, respectively denoted as poor, intermediate and high adherence. Short- and long-term complications of diabetes, and healthcare cost incurred by the National Health Service, were assessed during follow-up. Compared with patients with poor adherence, those with intermediate and high adherence respectively showed (i) a delay in outcome occurrence of 13 days (95% CI, −2 to 27) and 23 days (9–38), and (ii) a lower healthcare cost of 54 € and 77 €. In average, a gain of 18 Euros and 15 Euros for each day free from diabetic complication by increasing adherence respectively from poor to intermediate and from poor to high were observed. Conclusion: Close control of patients with diabetes through regular clinical examinations must be considered the cornerstone of national guidance, national audits, and quality improvement incentive schemes