Triterpene Acids from Frankincense and Semi-Synthetic Derivatives That Inhibit 5-Lipoxygenase and Cathepsin G

Age-related diseases, such as osteoarthritis, Alzheimer’s disease, diabetes, and cardiovascular disease, are often associated with chronic unresolved inflammation. Neutrophils play central roles in this process by releasing tissue-degenerative proteases, such as cathepsin G, as well as pro-inflammatory leukotrienes produced by the 5-lipoxygenase (5-LO) pathway. Boswellic acids (BAs) are pentacyclic triterpene acids contained in the gum resin of the anti-inflammatory remedy frankincense that target cathepsin G and 5-LO in neutrophils, and might thus represent suitable leads for intervention with age-associated diseases that have a chronic inflammatory component. Here, we investigated whether, in addition to BAs, other triterpene acids from frankincense interfere with 5-LO and cathepsin G. We provide a comprehensive analysis of 17 natural tetra- or pentacyclic triterpene acids for suppression of 5-LO product synthesis in human neutrophils. These triterpene acids were also investigated for their direct interference with 5-LO and cathepsin G in cell-free assays. Furthermore, our studies were expanded to 10 semi-synthetic BA derivatives. Our data reveal that besides BAs, several tetra- and pentacyclic triterpene acids are effective or even superior inhibitors of 5-LO product formation in human neutrophils, and in parallel, inhibit cathepsin G. Their beneficial target profile may qualify triterpene acids as anti-inflammatory natural products and pharmacological leads for intervention with diseases related to aging

Nachhaltigkeit im industriellen Umfeld

Im Rahmen der Lehrveranstaltung "Nachhaltigkeit im industriellen Umfeld" im Masterstudiengang Umwelt- und Verfahrenstechnik der Hochschulen Konstanz und Ravensburg-Weingarten wurde 2015 eine studentische Fachkonferenz durchgeführt. Die Studierenden entwickelten in Einzelarbeit oder als Zweierteam Konferenzbeiträge zu folgenden Themen: - Innovationen und Spannendes aus dem Bereich der Energieerzeugung und -wandlung - Aspekte der Schließung von Stoffkreisläufen und Vermeidung von Schadstoffeinträgen in die Umwelt - Chancen und Herausforderungen Nachwachsender Rohstoffe bei verschiedenen Einsatzmöglichkeiten sowie Themen der Nachhaltigkeit in der Landwirtschaft - verschiedene Blickwinkel auf das Thema Wasser (von der Abwasserreinigung bis zum Wasserkonsum der Konsumenten) - die Betrachtung spezifischer Industrien und Unternehmen sowie deren Werkzeuge zur Umsetzung von Nachhaltigkeit Die Ergebnisse der studentischen Fachkonferenz zur „Nachhaltigkeit im industriellen Umfeld“ werden in der vorliegenden Publikation präsentiert

A formin-nucleated actin aster concentrates cell wall hydrolases for cell fusion in fission yeast.

Cell-cell fusion is essential for fertilization. For fusion of walled cells, the cell wall must be degraded at a precise location but maintained in surrounding regions to protect against lysis. In fission yeast cells, the formin Fus1, which nucleates linear actin filaments, is essential for this process. In this paper, we show that this formin organizes a specific actin structure-the actin fusion focus. Structured illumination microscopy and live-cell imaging of Fus1, actin, and type V myosins revealed an aster of actin filaments whose barbed ends are focalized near the plasma membrane. Focalization requires Fus1 and type V myosins and happens asynchronously always in the M cell first. Type V myosins are essential for fusion and concentrate cell wall hydrolases, but not cell wall synthases, at the fusion focus. Thus, the fusion focus focalizes cell wall dissolution within a broader cell wall synthesis zone to shift from cell growth to cell fusion

Common characteristics of open source software development and applicability for drug discovery: a systematic review

<p>Abstract</p> <p>Background</p> <p>Innovation through an open source model has proven to be successful for software development. This success has led many to speculate if open source can be applied to other industries with similar success. We attempt to provide an understanding of open source software development characteristics for researchers, business leaders and government officials who may be interested in utilizing open source innovation in other contexts and with an emphasis on drug discovery.</p> <p>Methods</p> <p>A systematic review was performed by searching relevant, multidisciplinary databases to extract empirical research regarding the common characteristics and barriers of initiating and maintaining an open source software development project.</p> <p>Results</p> <p>Common characteristics to open source software development pertinent to open source drug discovery were extracted. The characteristics were then grouped into the areas of participant attraction, management of volunteers, control mechanisms, legal framework and physical constraints. Lastly, their applicability to drug discovery was examined.</p> <p>Conclusions</p> <p>We believe that the open source model is viable for drug discovery, although it is unlikely that it will exactly follow the form used in software development. Hybrids will likely develop that suit the unique characteristics of drug discovery. We suggest potential motivations for organizations to join an open source drug discovery project. We also examine specific differences between software and medicines, specifically how the need for laboratories and physical goods will impact the model as well as the effect of patents.</p

Critical evaluation of molecular tumour board outcomes following 2 years of clinical practice in a Comprehensive Cancer Centre

Recently, molecular tumour boards (MTBs) have been integrated into the clinical routine. Since their benefit remains debated, we assessed MTB outcomes in the Comprehensive Cancer Center Ostbayern (CCCO) from 2019 to 2021. Methods and results In total, 251 patients were included. Targeted sequencing was performed with PCR MSI-evaluation and immunohistochemistry for PD-L1, Her2, and mismatch repair enzymes. 125 treatment recommendations were given (49.8%). High-recommendation rates were achieved for intrahepatic cholangiocarcinoma (20/30, 66.7%) and gastric adenocarcinoma (10/16, 62.5%) as opposed to colorectal cancer (9/36, 25.0%) and pancreatic cancer (3/18, 16.7%). MTB therapies were administered in 47 (18.7%) patients, while 53 (21.1%) received alternative treatment regimens. Thus 37.6% of recommended MTB therapies were implemented (47/125 recommendations). The clinical benefit rate (complete + partial + mixed response + stable disease) was 50.0% for MTB and 63.8% for alternative treatments. PFS2/1 ratios were 34.6% and 16.1%, respectively. Significantly improved PFS could be achieved for m1A-tier-evidence-based MTB therapies (median 6.30 months) compared to alternative treatments (median 2.83 months; P = 0.0278). Conclusion The CCCO MTB yielded a considerable recommendation rate, particularly in cholangiocarcinoma patients. The discrepancy between the low-recommendation rates in colorectal and pancreatic cancer suggests the necessity of a weighted prioritisation of entities. High-tier recommendations should be implemented predominantly