Non-Invasive Physical Plasma Enhances the Membrane Permeability to Low Molecular Weight Compounds and Subsequently Leads to the Loss of Cellular ATP and the Devitalization of Epithelial Cancer Cells

Non-invasive physical plasma (NIPP) achieves biomedical effects primarily through the formation of reactive oxygen and nitrogen species. In clinical use, these species interact with cells of the treated tissue, affecting the cytoplasmic membrane first. The present study investigated the permeability of the cytoplasmic membrane of breast cancer cells with different fluorescent dyes after NIPP treatment and determined the subsequent effects on cell viability. After NIPP treatment and the associated formation of reactive oxygen species, low molecular weight compounds were able to pass through the cytoplasmic membrane in both directions to a higher extent. Consequently, a loss of cellular ATP into the extracellular space was induced. Due to these limitations in cell physiology, apoptosis was induced in the cancer cells and the entire cell population exhibited decreased cell growth. It can be concluded that NIPP treatment disturbs the biochemical functionality of the cytoplasmic membrane of cancer cells, which massively impairs their viability. This observation opens a vast application horizon of NIPP therapy to treat precancerous and malignant diseases beyond breast cancer therapy.

Resveratrol Blocks Retrotransposition of LINE-1 Through PPAR α and Sirtuin-6

The retroelement long interspersed element-1 (LINE-1 or L1) comprises about 17% of the human genome. L1 retrotransposition is known to cause genomic instability and related disorders, and resveratrol suppresses this retrotransposition; however, the underlying mechanism is still not elucidated. Recent observations showed that low-molecular-weight compounds might induce L1 retrotransposition through unknown mechanisms. This study aimed to determine polyphenol resveratrol (RV)’s effect on L1-RTP (retrotransposition) in somatic cells. Surprisingly, RV completely blocked L1-RTP. Experiments using the PPARα inhibitor GW6471 or siRNA-mediated PPARα depletion showed that RV-mediated L1-RTP’s inhibition depended on peroxisome proliferator-activated receptor α (PPARα). We demonstrated that RV inhibits p38 and CREB phosphorylation, which are involved in MAPK signaling, and the L1-ORF1 protein’s chromatin recruitment. Furthermore, RV increased the expression of sirtuin-6 (SIRT6), which inhibited the activation of L1. The sirtuins family, SIRT1, SIRT6, and SIRT7, but not SIRT3, are involved in RV-mediated inhibition of L1-RTP. Overall, our findings suggest that RV directly modulates PPARα-mediated L1-RTP in somatic cells and that MAPK signaling interacts with SIRT1, SIRT6, and SIRT7 closely and may play a role in preventing human diseases such as cancer.

Mass spectrometry based high-throughput bioanalysis of low molecular weight compounds: are we ready to support personalized medicine?

Liquid chromatography coupled to mass spectrometry (LC-MS) is the gold standard in bioanalysis for the development of quantitative assays to support drug development or therapeutic drug monitoring. High-throughput and low-cost gene sequencing have enabled a paradigm shift from one treatment fits all to personalized medicine (PM). However, gene monitoring provides only partial information about the health state. The full picture requires the combination of gene monitoring with the screening of exogenous compounds, metabolites, lipids, and proteins. This critical review discusses how mass spectrometry–based technologies and approaches including separation sciences, ambient ionization, and ion mobility are/could be used to support high-throughput bioanalysis of endogenous end exogenous low molecular weight compounds. It includes also various biological sample types (from blood to expired air), and various sample preparation techniques. Graphical abstract

Special Issue “Recent Advances in the Synthesis, Functionalization and Applications of Pyrazole-Type Compounds”

Pyrazoles and their reduced form, pyrazolines, are considered privileged scaffolds in medicinal chemistry, owing to their remarkable biological activities, physicochemical properties and occurrence in many low-molecular-weight compounds present in several marketed drugs (e [...]

Metallophores Production by Bacteria Isolated From Heavy Metal Contaminated Soil and Sediment at Lerma-chapala Basin

Environmental pollution derived from heavy metals (HMs) is a worldwide problem and the implementation of eco-friendly technologies for remediation of the pollution are necessary. The metallophores are low-molecular weight compounds that have important biotechnological applications in agriculture, medicine and biorremediation. The aim of this work was to isolate the HM resistant bacteria from soils and sediments of Lerma-Chapala basin, and to evaluate their abilities to produce metallophores and to promote plant growth. A total of 320 bacteria were recovered, and the siderophores synthesis was detected in cultures of 170 of the total isolates. The Lerma-Chapala Basin bacteria also produced metallophores for all the tested metal ions and presented a greater production of As3+ metallophores. The members in genera Delftia and Pseudomonas showed siderophores production above 92 percent siderophore units (psu). In addition, the hydroxamate was the most common fuctional group among the analyzed siderophores. Also, the bacteria showed high HM resistance especially to Zn2+, As5+ and Ni2+. Our results evidenced that Lerma-Chapala basin bacteria or their metallophores could be employed in biorremediation process or may even have potential for applications in other biotechnological purposes.

Advances in understanding key contamination risks in animal feed: mycotoxins

Mycotoxins are toxic secondary metabolites produced by certain filamentous fungi, especially Aspergillus, Fusarium, and Penicillium. Over 400 mycotoxins have been identified, most notably aflatoxins, trichothecenes, zearalenone, fumonisins and ochratoxins. These low molecular weight compounds are naturally occurring and (seem to be) unavoidable. In fact, a high percentage of feed samples have been reported to be contaminated with more than one mycotoxin. Mycotoxins accumulate in corn, cereals, soybeans, sorghum, peanuts, and other food and feed crops, directly in the field or during the transportation, processing or storage stages. Consumption of mycotoxin-contaminated food or feed can lead acute or chronic toxicity in humans and animals, as well as crop losses. This chapter reviews the toxicity of the six mycotoxins, the foods they commonly contaminate, and the current methods used to detect and control of these mycotoxins.

Interaction of clinical-stage antibodies with heme predicts their physiochemical and binding qualities

Immunoglobulin repertoires contain a fraction of antibodies that recognize low molecular weight compounds, including some enzymes’ cofactors, such as heme. Here, by using a set of 113 samples with variable region sequences matching clinical-stage antibodies, we demonstrated that a considerable number of these antibodies interact with heme. Antibodies that interact with heme possess specific sequence traits of their antigen-binding regions. Moreover they manifest particular physicochemical and functional qualities i.e. increased hydrophobicity, higher propensity of self-binding, higher intrinsic polyreactivity and reduced expression yields. Thus, interaction with heme is a strong predictor of different molecular and functional qualities of antibodies. Notably, these qualities are of high importance for therapeutic antibodies, as their presence was associated with failure of drug candidates to reach clinic. Our study reveled an important facet of information about relationship sequence-function in antibodies. It also offers a convenient tool for detection of liabilities of therapeutic antibodies.