Selective upregulation of TNFα expression in classically-activated human monocyte-derived macrophages (M1) through pharmacological interference with V-ATPase.

Pharmacological interference with vacuolar-type H(+)-ATPase (V-ATPase), a proton-translocating enzyme involved in protein transport and pH regulation of cell organelles, is considered a potential strategy for cancer therapy. Macrophages are critically involved in tumor progression and may occur as pro-tumoral M2 phenotype, whereas classically-activated M1 can inhibit tumor development for example by releasing tumor-suppressing molecules, including tumor necrosis factor (TNF)α. Here, we show that targeting V-ATPase by selective inhibitors such as archazolid upregulates the expression and secretion of TNFα in lipopolysaccharide (LPS)- or LPS/interferon (INF)γ-activated M1-like macrophages derived from human blood monocytes.

Modulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy.

Tumour-associated macrophages mainly comprise immunosuppressive M2 phenotypes that promote tumour progression besides anti-tumoural M1 subsets. Selective depletion or reprogramming of M2 may represent an innovative anti-cancer strategy. The actin cytoskeleton is central for cellular homeostasis and is targeted for anti-cancer chemotherapy.

Genomics-Guided Exploitation of Lipopeptide Diversity in Myxobacteria.

Analysis of 122 myxobacterial genome sequences suggested 16 strains as producers of the myxochromide lipopeptide family. Detailed sequence comparison of the respective mch biosynthetic gene clusters informed a genome-mining approach, ultimately leading to the discovery and chemical characterization of four novel myxochromide core types. The myxochromide megasynthetase is subject to evolutionary diversification, resulting in considerable structural diversity of biosynthesis products.

Heterologous expression of the plant cysteine protease bromelain and its inhibitor in Pichia pastoris.

Expression of proteases in heterologous hosts remains an ambitious challenge due to severe problems associated with digestion of host proteins. On the other hand, proteases are broadly used in industrial applications and resemble promising drug candidates. Bromelain is an herbal drug that is medicinally used for treatment of oedematous swellings and inflammatory conditions and consists in large part of proteolytic enzymes.

Secondary metabolomics: the impact of mass spectrometry-based approaches on the discovery and characterization of microbial natural products.

Covering: up to the end of 2013 The in-depth analysis of secondary metabolomes of many microbes offers tremendous opportunities for the discovery of novel natural products which often exhibit promising biological activities. However, over the last years the increasing availability of whole-genome information has led to raised expectations, as bioinformatic analysis revealed that traditional strategies to discover novel secondary metabolites apparently have so far only scratched the surface of the real microbial "secondary metabolome landscape". Metabolomics-based approaches using modern mass spectrometry techniques can help to bridge the gap between genome-encoded potential for the production of secondary metabolites and the usually contradictory low numbers of compounds known from a specific producer.