33 research outputs found
Autophagy takes it all - autophagy inducers target immune aging
Autophagy, as the key nutrient recycling pathway, enables eukaryotic cells to adapt to surging cellular stress during aging and, thereby, delays age-associated deterioration. Autophagic flux declines with age and, in turn, decreases in autophagy contribute to the aging process itself and promote senescence. Here, we outline how autophagy regulates immune aging and discuss autophagy-inducing interventions that target senescent immune cells, which are major drivers of systemic aging. We examine how cutting-edge technologies, such as single-cell omics methods hold the promise to capture the complexity of molecular and cellular phenotypes associated with aging, driving the development of suitable putative biomarkers and clinical bioassays. Finally, we debate the urgency to initiate large-scale human clinical trials. We give special preference to small molecule probes and to dietary interventions that can extend healthy lifespan and are affordable for most of the world's population
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Proteostasis in T cell aging
Aging leads to a decline in immune cell function, which leaves the organism vulnerable to infections and age-related multimorbidities. One major player of the adaptive immune response are T cells, and recent studies argue for a major role of disturbed proteostasis contributing to reduced function of these cells upon aging. Proteostasis refers to the state of a healthy, balanced proteome in the cell and is influenced by synthesis (translation), maintenance and quality control of proteins, as well as degradation of damaged or unwanted proteins by the proteasome, autophagy, lysosome and cytoplasmic enzymes. This review focuses on molecular processes impacting on proteostasis in T cells, and specifically functional or quantitative changes of each of these upon aging. Importantly, we describe the biological consequences of compromised proteostasis in T cells, which range from impaired T cell activation and function to enhancement of inflamm-aging by aged T cells. Finally, approaches to improve proteostasis and thus rejuvenate aged T cells through pharmacological or physical interventions are discussed
Secondary metabolites from Calotropis procera (Aiton)
Three new metabolites, 5-hydroxy-3,7-dimethoxyflavone-4′-O-β-glucopyranoside (1), 2β,19-epoxy-3β,14β-dihydroxy-19-methoxy-5α-card-20(22)-enolide (4) and β-anhydroepidigitoxigenin-3β-O-glucopyranoside (5), along with two known compounds, uzarigenine (2) and β-anhydroepidigitoxigenin (3), were isolated from Calotropis procera (Asclepiadaceae). The structure elucidation was accomplished mainly by nuclear magnetic resonance (NMR) spectroscopic and mass spectrometric methods. To examine putative antimicrobial or cytotoxic activities, various bioassays were performed. Uzarigenine (2) demonstrated moderate cytotoxicity
Bioactive Metabolites from Propolis Inhibit Superoxide Anion Radical, Acetylcholinesterase and Phosphodiesterase (PDE4)
Cycloartane-triterpenes (cycloartenol, 3α-cycloartenol-26-oic acid and 3β-cycloartenol-26-oic acid) together with α-amyrin acetate
and flavonoids (pinostrobin, tectochrysin and chrysin) were isolated from Egyptian propolis for the first time. Their antioxidant
activity was evaluated with DPPH and superoxide anion radical (O2.-). All compounds possessed both (O2.-) scavenging as well as XOD
inhibitory activity in the range of 50 – 75 %. With DPPH, only the flavonoids showed scavenging activity (48 – 83 %).
Acetylcholinesterase (AChE) and phosphodiesterase type 4 (PDE4) inhibitors are currently considered as intracellular targets for treatment of Alzheimer’s disease and Chronic obstructive pulmonary disease (COPD). 3β-cycloartenol-26-oic acid moderately
inhibited AChE and PDE4 activities in vitro with IC50 values of 0.8±0.2 and 1.9±0.4 μM, respectively, while 3-cycloartenol-26-oic acid
inhibited AChE activity with an IC50 value of 2.1±0.1 μM. The flavonoids pinostrobin and chrysin reduced PDE4 activity by 43 and 40
%, respectively (10 μM) as well as moderately inhibited the growth of the HepG2 cell line, whereas chrysin reduced proliferation of
NIH-3T3 cells at 50 μM. Therefore, our results with 3β- and 3-cycloartenol-26-oic acids can contribute to further research on alternative drugs for the treatment of neurological and neurodegenerative diseases, as well as asthma and COPD
Autophagy takes it all – autophagy inducers target immune aging
Autophagy, as the key nutrient recycling pathway, enables eukaryotic cells to adapt to surging cellular stress during aging and, thereby, delays age-associated deterioration. Autophagic flux declines with age and, in turn, decreases in autophagy contribute to the aging process itself and promote senescence. Here, we outline how autophagy regulates immune aging and discuss autophagy-inducing interventions that target senescent immune cells, which are major drivers of systemic aging. We examine how cutting-edge technologies, such as single-cell omics methods hold the promise to capture the complexity of molecular and cellular phenotypes associated with aging, driving the development of suitable putative biomarkers and clinical bioassays. Finally, we debate the urgency to initiate large-scale human clinical trials. We give special preference to small molecule probes and to dietary interventions that can extend healthy lifespan and are affordable for most of the world's population
Grecocyclines: New angucyclines from streptomyces sp. Acta 1362
Two novel angucyclines were isolated from the streptomycete Acta 1362. The strain was of particular interest regarding the production of characteristic metabolites that were detected by HPLC-diode array profiling of the extracts. Grecocycline A and B were isolated and their structures were determined, Grecocycline A shows cytotoxic activity and grecocycline B inhibits protein tyrosine phosphatase IB. Moreover, shunt product grecocyline C was isolated and its structure was determined. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA
Micro machining of different steels with closed electrolytic free jet
Electrochemical Machining (ECM) with closed electrolytic free jet (Jet-ECM) is an innovative procedure in micro manufacturing technology which is based on anodic dissolution of metallic work pieces. Main advantage of Jet-ECM in comparison to other ECM processes is the restriction of the electric current to a limited area by the jet. Micro structured surfaces and complex three-dimensional micro geometries can be machined by help of different nozzle movements. In this study the Jet Electrochemical Machining is used to generate micro cavities in different steels to investigate the influence of the material properties on the removal process. Current efficiency, machined geometry and surface properties of the processed areas were analyzed and compared