Genetically modified mice as a tool for the study of human diseases.

Modeling a human disease is an essential part of biomedical research. The recent advances in the field of molecular genetics made it possible to obtain genetically modified animals for the study of various diseases. Not only monogenic disorders but also chromosomal and multifactorial disorders can be mimicked in lab animals due to genetic modification.

Noncovalent Self-Assembly of Single-Layer MoS Nanosheets and Zinc Porphyrin into Stable SURMOF Nanohybrids with Multimodal Photocatalytic Properties.

A noncovalent integration of nanosheets of molybdenum disulfide (MoS) and the zinc porphyrin complex Zn(II) 5,10,15,20-tetrakis(4-carboxyphenyl)porphine (ZnTCPP) through coordination bonding with metal clusters of zinc acetate (Zn[OAc]) was applied for synthesis of stable hybrid nanomaterial avoiding surface prefunctionalization. The X-ray powder diffraction in combination with the BET nitrogen adsorption method confirms formation of a ZnTCPP-based surface-attached metal-organic framework (SURMOF) with micropores of 1.63 nm on the MoS nanosheets.

Cyclophilin A as a Pro-Inflammatory Factor Exhibits Embryotoxic and Teratogenic Effects during Fetal Organogenesis.

The precise balance of Th1, Th2, and Th17 cytokines is a key factor in successful pregnancy and normal embryonic development. However, to date, not all humoral factors that regulate and influence physiological pregnancy have been completely studied. Our data here pointed out cyclophilin A (CypA) as the adverse pro-inflammatory factor negatively affecting fetal development and associated with pregnancy complications.

Antimicrobial activity of photosensitizers: arrangement in bacterial membrane matters.

Porphyrins are well-known photosensitizers (PSs) for antibacterial photodynamic therapy (aPDT), which is still an underestimated antibiotic-free method to kill bacteria, viruses, and fungi. In the present work, we developed a comprehensive tool for predicting the structure and assessment of the photodynamic efficacy of PS molecules for their application in aPDT. We checked it on a series of water-soluble phosphorus(V) porphyrin molecules with OH or ethoxy axial ligands and phenyl/pyridyl peripheral substituents.

Limitations of Tamoxifen Application for In Vivo Genome Editing Using Cre/ER System.

Inducible Cre-dependent systems are frequently used to produce both conditional knockouts and transgenic mice with regulated expression of the gene of interest. Induction can be achieved by doxycycline-dependent transcription of the wild type gene or OH-tamoxifen-dependent nuclear translocation of the chimeric Cre/ER protein. However, both of these activation strategies have some limitations.

Gene Transcription as a Therapeutic Target in Leukemia.

Blood malignancies often arise from undifferentiated hematopoietic stem cells or partially differentiated stem-like cells. A tight balance of multipotency and differentiation, cell division, and quiescence underlying normal hematopoiesis requires a special program governed by the transcriptional machinery. Acquisition of drug resistance by tumor cells also involves reprogramming of their transcriptional landscape.

Cheminformatics-driven discovery of polymeric micelle formulations for poorly soluble drugs.

Many drug candidates fail therapeutic development because of poor aqueous solubility. We have conceived a computer-aided strategy to enable polymeric micelle-based delivery of poorly soluble drugs. We built models predicting both drug loading efficiency (LE) and loading capacity (LC) using novel descriptors of drug-polymer complexes.

QSAR Modeling and Prediction of Drug-Drug Interactions.

Severe adverse drug reactions (ADRs) are the fourth leading cause of fatality in the U.S. with more than 100,000 deaths per year.

Existing and Developing Approaches for QSAR Analysis of Mixtures.

This review is devoted to the critical analysis of advantages and disadvantages of existing mixture descriptors and their usage in various QSAR/QSPR tasks. We describe good practices for the QSAR modeling of mixtures, data sources for mixtures, a discussion of various mixture descriptors and their application, recommendations about proper external validation specific for mixture QSAR modeling, and future perspectives of this field. The biggest problem in QSAR of mixtures is the lack of reliable data about the mixtures' properties.

QSAR analysis of [(biphenyloxy)propyl]isoxazoles: agents against coxsackievirus B3.

Background: Antiviral drugs are urgently needed for the treatment of acute and chronic diseases caused by enteroviruses such as coxsackievirus B3 (CVB3). The main goal of this study is quantitative structure-activity relationship (QSAR) analysis of anti-CVB3 activity (clinical CVB3 isolate 97927 [log IC50, µM]) and investigation of the selectivity of 25 ([biphenyloxy]propyl)isoxazoles, followed by computer-aided design and virtual screening of novel active compounds.

Discussion: The 2D QSAR obtained models are quite satisfactory (R(2) = 0.

Per aspera ad astra: application of Simplex QSAR approach in antiviral research.

This review explores the application of the Simplex representation of molecular structure (SiRMS) QSAR approach in antiviral research. We provide an introduction to and description of SiRMS, its application in antiviral research and future directions of development of the Simplex approach and the whole QSAR field. In the Simplex approach every molecule is represented as a system of different simplexes (tetratomic fragments with fixed composition, structure, chirality and symmetry).