Developing an Amide-Spacered Triterpenoid Rhodamine Hybrid of Nano-Molar Cytotoxicity Combined with Excellent Tumor Cell/Non-Tumor Cell Selectivity.

Asiatic acid, a pentacyclic triterpene, was converted into a series of piperazinyl, homopiperazinyl, and 1,5-diazocinyl spacered rhodamine conjugates, differing in the type of spacer and the substitution pattern on the rhodamine moiety of the hybrids. The compounds were tested for cytotoxic activity in SRB assays and compound 12, holding an EC50 of 0.8 nM, was the most cytotoxic compound of this series, but compound 18 (containing a ring expanded 1,5-diazocinyl moiety and n-propyl substituents on the rhodamine) was the most selective compound exhibiting a selectivity factor of almost 190 while retaining high cytotoxicity (EC50 = 1.9 nM, for A2780 ovarian carcinoma).

Mitochondria-Targeting 1,5-Diazacyclooctane-Spacered Triterpene Rhodamine Conjugates Exhibit Cytotoxicity at Sub-Nanomolar Concentration against Breast Cancer Cells.

1,5-Diazacyclooctane was prepared by a simple synthetic sequence and coupled to pentacyclic triterpenoic acids oleanolic acid, ursolic acid, betulinic acid, platanic acid, and asiatic acid; these amides were activated with oxalyl chloride and reacted with rhodamine B or rhodamine 101 to yield conjugates. The conjugates were screened in SRB assays with various human breast cancer cell lines (MDA-MB-231, HS578T, MCF-7, and T47D) and found to exert cytotoxic activity even at a low concentration. Therefore, for an asiatic acid rhodamine 101 conjugate (28), an IC50 = 0.60 nM was determined and found to induce apoptosis in MDA-MB-231 and HS578T cells. Extra experiments showed the compound to act as a mitocan and to induce inhibition of proliferation or growth arrest in MDA-MB-231 cells at lower doses followed by an induction of apoptosis at higher doses. Furthermore, differential responses to proliferation inhibition and apoptosis induction may explain differential sensitivity of mammary cell lines to compound 28.

Metabolic profiling of bacterial co-cultures reveals intermicrobiome interactions and dominant species.

In animal production, the use of probiotic microorganisms has increased since the ban on antibiotic growth promoters in 2006. The added microorganisms interact with the microbiome of the animals, whereby the probiotic activity is not fully understood. Several microorganisms of the genus Bacillus are already known for their probiotic activity and are applied as feed supplements to increase the health status of the animals. They are thought to interact with Escherichia coli, one of the most abundant bacteria in the animal gut. In biotechnological applications, co-culturing enables the regulation of bacterial interaction or the production of target metabolites. The basic principles of multi-imaging high-performance thin-layer chromatography (HPTLC) with upstream cultivation were further developed to analyze the metabolic profiles of three axenic bacilli cultures compared to their co-cultures with E. coli DSM 18039 (K12). The comparative profiling visualized bacteria's metabolic interactions and showed how the presence of E. coli affects the metabolite formation of bacilli. The characteristic metabolic profile images showed not only the influence of microbiomes but also of inoculation, cultivation and nutrients on the commercial probiotic. The formation of antimicrobially active metabolites, detected via three different planar bioassays, was influenced by the presence of other microorganisms, especially in the probiotic. This first application of multi-imaging HPTLC in the field of co-culturing enabled visualization of metabolic interactions of bacteria via their produced chemical as well as bioactive metabolite profiles. The metabolic profiling provided evidence of bacterial interactions, intermicrobiome influences and dominant species in the co-culture.

Strain-specific quantification of probiotic Bacillus subtilis in feed by imaging high-performance thin-layer chromatography.

The European Union has banned the use of antibiotic growth promoters in animal production, which has led to increased use of probiotic microorganisms. These feed additives result in higher costs for farmers, which is why the demand for a quality control system to quantify probiotics in feeds has increased in recent years. Imaging high-performance thin-layer chromatography (HPTLC) was proven to be a robust method for determining the probiotic Bacillus subtilis DSM 29784 strain based on the production of selective bacterial metabolites and thus characteristic metabolite pattern. However, to quantify the specific probiotic strain in the feed, identification of a strain-specific metabolite not produced by genetically very similar bacteria is necessary. Compared to five bacteria with high genetic similarity, a strain-specific metabolite was formed in the probiotic bacteria by a two-step cultivation procedure. Among others, antimicrobial properties were found for this metabolite, which indicated probiotic activity. The hyphenation of normal-phase HPTLC with reversed-phase high-performance liquid chromatography diode array detection and high-resolution mass spectrometry allowed the preliminary assignment of this strain-specific metabolite to the molecular formula C35H44N6O2 (580.3527 Da). This metabolite, produced each time via an upstream cultivation process to generate the standard levels, was used for the quantification of probiotic active cells in the feed. Data on selectivity, linearity, detection limit, recovery, and precision have shown the good performance of the method.

Nickel and cobalt release from beauty tools: A field study in the German cosmetics trade.

BACKGROUND: Relevant nickel and cobalt release from hairdressing tools has recently been evidenced. Comparable data are not available for tools used in beauty salons. OBJECTIVES: Screening of beauty tools for nickel and cobalt release. METHODS/MATERIALS: Three hundred eight beauty tools were tested in seven beauty salons located in two North-German states. A nickel spot test and a cobalt spot test were used to test the tools for nickel release and cobalt release, respectively. RESULTS: One hundred forty-three of 308 beauty tools overall (46.4%; 95% confidence interval [CI]: 40.8%-52.2%) released nickel and 18 of 308 beauty tools overall (5.8%; 95%CI: 3.5%-9.1%) released cobalt. Nickel release was found in 22 of 99 metal tools (22.2%; 95%CI: 14.5%-31.7%) and 121 of 209 tools with metallic parts (57.9%; 95%CI: 50.9%-64.7%); cobalt release was detected in 3 of 99 metal tools (3.0%; 95%CI: 0.63%-8.6%) and 15 of 209 tools with metallic parts (7.2%; 95%CI: 4.1%-11.6%). CONCLUSIONS: Nickel and cobalt are emitted at allergologically relevant levels by a wide range of beauty tools (i.e., metal tools and tools with metallic parts) utilized in the German cosmetics trade. Beauty tools should thus be considered occupational sources of nickel and cobalt exposure.