Structural effects of morpholine replacement in ZSTK474 on Class I PI3K isoform inhibition: Development of novel MEK/PI3K bifunctional inhibitors.

Established roles for PI3K and MAPK signaling pathways in tumorigenesis has prompted extensive research towards the discovery of small-molecule inhibitors as cancer therapeutics. However, significant compensatory regulation exists between these two signaling cascades, leading to redundancy among survival pathways. Consequently, initial clinical trials aimed at either PI3K or MEK inhibition alone have proven ineffective and highlight the need for development of targeted and innovative therapeutic combination strategies.

Enhanced mitochondrial fission suppresses signaling and metastasis in triple-negative breast cancer.

Background: Mitochondrial dynamics underlies malignant transformation, cancer progression, and response to treatment. Current research presents conflicting evidence for functions of mitochondrial fission and fusion in tumor progression. Here, we investigated how mitochondrial fission and fusion states regulate underlying processes of cancer progression and metastasis in triple-negative breast cancer (TNBC).

Development and Application of Extraction Methods for LC-MS Quantification of Microcystins in Liver Tissue.

A method was developed to extract and quantify microcystins (MCs) from mouse liver with limits of quantification (LOQs) lower than previously reported. MCs were extracted from 40-mg liver samples using 85:15 (v:v) CHCN:HO containing 200 mM ZnSO and 1% formic acid. Solid-phase extraction with a C18 cartridge was used for sample cleanup.

Treated rice husk as a recyclable sorbent for the removal of microcystins from water.

Microcystins (MCs) appear during harmful algal blooms (HABs) in water sources worldwide, and represent a threat for humans and animals ingesting or inhaling MCs from the environment. Herein, treated rice husk (RH) was tested as a recyclable sorbent for removal of six MCs (MC-RR, MC-LR, MC-YR, MC-LA, MC-LF, and MC-LW) from water. RH was refluxed with hydrochloric acid and heated to 250 °C to produce the sorbent material.

Development and applications of solid-phase extraction and liquid chromatography-mass spectrometry methods for quantification of microcystins in urine, plasma, and serum.

The protocols for solid-phase extraction (SPE) of six microcystins (MCs; MC-LR, MC-RR, MC-LA, MC-LF, MC-LW, and MC-YR) from mouse urine, mouse plasma, and human serum are reported. The quantification of those MCs in biofluids was achieved using HPLC-orbitrap-MS in selected-ion monitoring (SIM) mode, and MCs in urine samples were also quantified by ultra-HPLC-triple quadrupole-tandem mass spectrometry (UHPLC-QqQ-MS/MS) in multiple reaction monitoring (MRM) mode. Under optimal conditions, the extraction recoveries of MCs from samples spiked at two different concentrations (1 μg/L and 10 μg/L) ranged from 90.

Solid-phase extraction, quantification, and selective determination of microcystins in water with a gold-polypyrrole nanocomposite sorbent material.

A novel sorbent material, gold-polypyrrole (Au-PPy) nanocomposite-coated silica, is described for the efficient solid-phase extraction (SPE) of six common microcystins (MCs) well below the recommended United States EPA and World Health Organization (WHO) guidelines. With the optimized SPE protocol, samples spiked with MCs were determined at ng/L concentrations by liquid chromatography-mass spectrometry (LC-MS) in different aqueous sample matrices, including HPLC-grade, tap, and lake water. The average recoveries for all MCs tested in the three water matrices ranged from 94.