Broad-Spectrum Solvent-free Layered Black Phosphorus as a Rapid Action Antimicrobial.

Antimicrobial resistance has rendered many conventional therapeutic measures, such as antibiotics, ineffective. This makes the treatment of infections from pathogenic micro-organisms a major growing health, social, and economic challenge. Recently, nanomaterials, including two-dimensional (2D) materials, have attracted scientific interest as potential antimicrobial agents.

Extending In-Plane Impedance Measurements from 2D to 3D Cultures: Design Considerations.

Three-dimensional (3D) cell cultures have recently emerged as tools for biologically modelling the human body. As 3D models make their way into laboratories there is a need to develop characterisation techniques that are sensitive enough to monitor the cells in real time and without the need for chemical labels. Impedance spectroscopy has been shown to address both of these challenges, but there has been little research into the full impedance spectrum and how the different components of the system affect the impedance signal.

Combined use of subclinical hydroxyurea and CHK1 inhibitor effectively controls melanoma and lung cancer progression, with reduced normal tissue toxicity compared to gemcitabine.

Drugs such as gemcitabine that increase replication stress are effective chemotherapeutics in a range of cancer settings. These drugs effectively block replication and promote DNA damage, triggering a cell cycle checkpoint response through the ATR-CHK1 pathway. Inhibiting this signalling pathway sensitises cells to killing by replication stress-inducing drugs.

Endogenous Replication Stress Marks Melanomas Sensitive to CHEK1 Inhibitors .

Checkpoint kinase 1 inhibitors (CHEK1i) have single-agent activity and Here, we have investigated the molecular basis of this activity. We have assessed a panel of melanoma cell lines for their sensitivity to the CHEK1i GNE-323 and GDC-0575 and The effects of these compounds on responses to DNA replication stress were analyzed in the hypersensitive cell lines. A subset of melanoma cell lines is hypersensitive to CHEK1i-induced cell death , and the drug effectively inhibits tumor growth In the hypersensitive cell lines, GNE-323 triggers cell death without cells entering mitosis.

Aurora A Is Critical for Survival in HPV-Transformed Cervical Cancer.

Human papillomavirus (HPV) is the causative agent in cervical cancer. HPV oncogenes are major drivers of the transformed phenotype, and the cancers remain addicted to these oncogenes. A screen of the human kinome has identified inhibition of Aurora kinase A (AURKA) as being synthetically lethal on the background of HPV E7 expression.

Identification of nephrotoxic compounds with embryonic stem-cell-derived human renal proximal tubular-like cells.

The kidney is a major target for drug-induced toxicity, and the renal proximal tubule is frequently affected. Nephrotoxicity is typically detected only late during drug development, and the nephrotoxic potential of newly approved drugs is often underestimated. A central problem is the lack of preclinical models with high predictivity.

A novel design of bioartificial kidneys with improved cell performance and haemocompatibility.

Treatment with bioartificial kidneys had beneficial effects in animal experiments and improved survival of critically ill patients with acute kidney injury in a Phase II clinical trial. However, a Phase II b clinical trial failed. This and other results suggested various problems with the current design of bioartificial kidneys.

The performance of primary human renal cells in hollow fiber bioreactors for bioartificial kidneys.

Bioartificial kidneys (BAKs) containing human primary renal proximal tubule cells (HPTCs) have been applied in clinical trials. The results were encouraging, but also showed that more research is required. Animal cells or cell lines are not suitable for clinical applications, but have been mainly used in studies on BAK development as large numbers of such cells could be easily obtained.