Bioassay protocol metadata annotation: Proposed standards adoption.

We present a standardized metadata template for assays used in pharmaceutical drug discovery research, according to the FAIR principles. We also describe the use of an automated tool for annotating assays from a variety of sources, including PubChem, commercial assay providers, and the peer-reviewed literature, to this metadata template. Adoption of a standardized metadata template will allow drug discovery scientists to better understand and compare the increasing amounts of assay data becoming available, and will facilitate the use of artificial intelligence tools and other computational methods for analysis and prediction.

A Comprehensive Review of Protein Biomarkers for Invasive Lung Cancer.

Invasion and metastasis are important hallmarks of lung cancer, and affect patients' survival. Early diagnostics of metastatic potential are important for treatment management. Recent findings suggest that the transition to an invasive phenotype causes changes in the expression of 700-800 genes.

Comparison of EMT-Related and Multi-Drug Resistant Gene Expression, Extracellular Matrix Production, and Drug Sensitivity in NSCLC Spheroids Generated by Scaffold-Free and Scaffold-Based Methods.

Multicellular 3D tumor models are becoming a powerful tool for testing of novel drug products and personalized anticancer therapy. Tumor spheroids, a commonly used 3D multicellular tumor model, more closely reproduce the tumor microenvironment than conventional 2D cell cultures. It should be noted that spheroids can be produced using different techniques, which can be subdivided into scaffold-free (SF) and scaffold-based (SB) methods.

Cathepsin S Cleaves BAX as a Novel and Therapeutically Important Regulatory Mechanism for Apoptosis.

Certain lysosomal cathepsin proteins have come into focus as being good candidates for therapeutic targeting, based on them being over-expressed in a variety of cancers and based on their regulation of the apoptotic pathway. Here, we report novel findings that highlight the ability of cathepsin S expression to be up-regulated under Paclitaxel-stimulatory conditions in kidney cell lines and it being able to cleave the apoptotic p21 BAX protein in intact cells and in vitro. Consistent with this, we demonstrate that this effect can be abrogated in vitro and in mammalian cells under conditions that utilize dominant-inhibitory cathepsin S expression, cathepsin S expression-knockdown and through the activity of a novel peptide inhibitor, CS-PEP1.

Best practices for artificial intelligence in life sciences research.

We describe 11 best practices for the successful use of artificial intelligence and machine learning in pharmaceutical and biotechnology research at the data, technology and organizational management levels.

Unravelling the Network of Nuclear Matrix Metalloproteinases for Targeted Drug Design.

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are responsible for the degradation of a wide range of extracellular matrix proteins, which are involved in many cellular processes to ensure the normal development of tissues and organs. Overexpression of MMPs has been observed to facilitate cellular growth, migration, and metastasis of tumor cells during cancer progression. A growing number of these proteins are being found to exist in the nuclei of both healthy and tumor cells, thus highlighting their localization as having a genuine purpose in cellular homeostasis.

Making Connections: p53 and the Cathepsin Proteases as Co-Regulators of Cancer and Apoptosis.

While viewed as the "guardian of the genome", the importance of the tumor suppressor p53 protein has increasingly gained ever more recognition in modulating additional modes of action related to cell death. Slowly but surely, its importance has evolved from a mutated genetic locus heavily implicated in a wide array of cancer types to modulating lysosomal-mediated cell death either directly or indirectly through the transcriptional regulation of the key signal transduction pathway intermediates involved in this. As an important step in determining the fate of cells in response to cytotoxicity or during stress response, lysosomal-mediated cell death has also become strongly interwoven with the key components that give the lysosome functionality in the form of the cathepsin proteases.

Cysteine Cathepsins Inhibition Affects Their Expression and Human Renal Cancer Cell Phenotype.

Renal cancer would greatly benefit from new therapeutic strategies since, in advanced stages, it is refractory to classical chemotherapeutic approaches. In this context, lysosomal protease cysteine cathepsins may represent new pharmacological targets. In renal cancer, they are characterized by a higher expression, and they were shown to play a role in its aggressiveness and spreading.

Novel applications of modification of thiol enzymes and redox-regulated proteins using S-methyl methanethiosulfonate (MMTS).

S-Methyl methanethiosulfonate (MMTS) is used in experimental biochemistry for alkylating thiol groups of protein cysteines. Its applications include mainly trapping of natural thiol-disulfide states of redox-sensitive proteins and proteins which have undergone S-nitrosylation. The reagent can also be employed as an inhibitor of enzymatic activity, since nucleophilic cysteine thiolates are commonly present at active sites of various enzymes.

"Terhune-like" transformation of the terahertz polarization ellipse "mutually induced" by three-wave joint propagation in liquid.

In this Letter, we show experimentally for the first time, to the best of our knowledge, the possibility to observe the effect of polarization mutual action of three elliptically polarized waves, with one of them at terahertz frequency, when they propagate in the isotropic nonlinear medium. When three light pulses are propagated at frequencies , 2, and through liquid nitrogen, we observed the rotation of the ellipse main axis and the ellipticity change. We have shown that this effect is very well described theoretically in the framework of a physical approach analogous to the self-rotation of the polarization ellipse first described in 1964 by Maker et al.

Toroidal sensor arrays for real-time photoacoustic imaging.

This article addresses theoretical and numerical investigation of image formation in photoacoustic (PA) imaging with complex-shaped concave sensor arrays. The spatial resolution and the size of sensitivity region of PA and laser ultrasonic (LU) imaging systems are assessed using sensitivity maps and spatial resolution maps in the image plane. This paper also discusses the relationship between the size of high-sensitivity regions and the spatial resolution of real-time imaging systems utilizing toroidal arrays.

Rational Design of Recombinant Papain-Like Cysteine Protease: Optimal Domain Structure and Expression Conditions for Wheat-Derived Enzyme Triticain-α.

Triticain-α is a papain-like cysteine protease from wheat ( L.) that possesses activity towards toxic gluten-derived peptides, and was thus proposed as a novel therapeutic tool for celiac disease. We report an original approach employing rational design of domain architecture of Triticain-α and selection of the appropriate expression system for development of cheap and efficient protocol yielding active recombinant enzyme.

Glutenase and collagenase activities of wheat cysteine protease Triticain-α: feasibility for enzymatic therapy assays.

Insufficient and/or improper protein degradation is associated with the development of various human pathologies. Enzymatic therapy with proteolytic enzymes aimed to improve insufficient proteolytic activity was suggested as a treatment of protease deficiency-induced disorders. Since in many cases human degradome is incapable of degrading the entire target protein(s), other organisms can be used as a source of proteases exhibiting activities distinct from human enzymes, and plants are perspective candidates for this source.

The receptor binding fragment of alpha-fetoprotein is a promising new vector for the selective delivery of antineoplastic agents.

The alpha-fetoprotein (AFP) binding protein, a putative AFP receptor, is a tumour marker that is present on the surfaces of malignant cells. AFP enters cells through receptor-mediated endocytosis. The recombinant C-terminal fragment of AFP (AFP-3BC, which consists of amino acid residues 473-596) was obtained by the expression in Escherichia coli.

Filamentation of arbitrary polarized femtosecond laser pulses in case of high-order Kerr effect.

We developed a model of femtosecond filamentation which includes high-order Kerr effect and an arbitrary polarization of a laser pulse. We show that a circularly polarized pulse has maximum filament intensity. Also, we show that, independently of the initial pulse polarization, the value of a maximum filament intensity tends to the maximum intensity of either linearly or circularly polarized pulse.

Recombinant alpha-fetoprotein C-terminal fragment: the new recombinant vector for targeted delivery.

The specific receptor of alpha-fetoprotein (AFP) is a universal tumor marker, being expressed on the surface of many tumor cells, but not in normal human tissues. AFP enters the cell by receptor-mediated endocytosis; its receptor-binding site is hypothetically localized in the third domain of AFP. A recombinant C-terminal AFP fragment, which contains all the third and a part of the second domains of hAFP, was produced.