Lung microbiota dysbiosis and the implications of SARS-CoV-2 infection in pregnancy.

There are a great number of beneficial commensal microorganisms constitutively colonizing the mucosal lining of the lungs. Alterations in the microbiota profile have been associated with several respiratory diseases such as pneumonia and allergies. Lung microbiota dysbiosis might play an important role in the pathogenic mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as elicit other opportunistic infections associated with coronavirus disease 2019 (COVID-19).

Epidemiological trends of Lassa fever in Nigeria from 2015-2021: A review.

Introduction: Lassa fever is a viral haemorrhagic fever with non-specific symptoms that has shown an upward trend in Nigeria and other West African countries, which is depicted by high incidence and case fatality in recent years. There are different reports on the yearly case burden of Lassa fever from the Federal Ministry of Health in Nigeria, through the regulatory body - Nigeria Centre for Disease Control (NCDC). Being the epicentre of the disease, Lassa fever has been exported from Nigeria to both neighbouring and distant countries.

Discovery of a highly potent, orally active mitosis/angiogenesis inhibitor r1530 for the treatment of solid tumors.

A new series of 7,8-disubstituted pyrazolobenzodiazepines based on the lead compound 1 have been synthesized and evaluated for their effects on mitosis and angiogenesis. Described herein is the design, synthesis, SAR, and antitumor activity of these compounds leading to the identification of R1530, which was selected for clinical evaluation.

Preclinical evaluation of the novel multi-targeted agent R1530.

Purpose: This study describes the antiproliferative activity of the multikinase inhibitor R1530 in vitro and its antitumor and anti-angiogenic activity, pharmacokinetics, and tolerability in vivo.

Methods: The antiproliferative activity of R1530 was investigated in a range of human tumor, endothelial and fibroblast cell lines. Tolerability and antitumor activity were assessed in mice bearing a range of human tumor xenografts, and anti-angiogenic properties were established in the murine corneal pocket assay.

Pyrazolobenzodiazepines: part I. Synthesis and SAR of a potent class of kinase inhibitors.

A novel series of pyrazolobenzodiazepines 3 has been identified as potent inhibitors of cyclin-dependent kinase 2 (CDK2). Their synthesis and structure-activity relationships (SAR) are described. Representative compounds from this class reversibly inhibit CDK2 activity in vitro, and block cell cycle progression in human tumor cell lines.

KU812 cells provide a novel in vitro model of the human IL-33/ST2L axis: functional responses and identification of signaling pathways.

Activation of interleukin-1 family receptor ST2L by its ligand interleukin-33 (IL-33) is an important component in inflammatory responses. Peripheral blood basophils, recognized as major effector cells in allergic inflammation that play a role in both innate and adaptive immunity, are activated by IL-33 through ST2L. However, studies are challenging due to the paucity of this cell population, representing less than 1% of peripheral blood leukocytes.

NMR characterization of interleukin-2 in complexes with the IL-2Ralpha receptor component, and with low molecular weight compounds that inhibit the IL-2/IL-Ralpha interaction.

Nuclear magnetic resonance (NMR) methods were employed to study the interaction of the cytokine Interleukin-2 (IL-2) with the alpha-subunit of its receptor (IL-2Ralpha), and to help understand the behavior of small molecule inhibitors of this interaction. Heteronuclear (1)H-(15)N HSQC experiments were used to identify the interaction surface of (15)N-enriched Interleukin-2 ((15)N-IL-2) in complex with human IL-2Ralpha. In these experiments, chemical shift and line width changes in the heteronuclear single-quantum coherence (HSQC) spectra upon binding of (15)N-IL-2 enabled classification of NH atoms as either near to, or far from, the IL-2Ralpha interaction surface.