Discovery of neuroprotective agents that inhibit human prolyl hydroxylase PHD2.

Prolyl hydroxylase (PHD) enzymes play a critical role in the cellular responses to hypoxia through their regulation of the hypoxia inducible factor α (HIF-α) transcription factors. PHD inhibitors show promise for the treatment of diseases including anaemia, cardiovascular disease and stroke. In this work, a pharmacophore-based virtual high throughput screen was used to identify novel potential inhibitors of human PHD2. Two moderately potent new inhibitors were discovered, with IC50 values of 4 µM and 23 µM respectively. Cell-based studies demonstrate that these compounds exhibit protective activity in neuroblastoma cells, suggesting that they have the potential to be developed into clinically useful neuroprotective agents.

An infodemiology study on exploring the quality and reliability of colorectal cancer immunotherapy information.

Background: Immunotherapy is a new treatment modality which promises hope for advanced colorectal cancer patients. To our knowledge, no previous studies have evaluated the quality of patient information available on this topic online. Objective: This study will explore the quality and reliability of colorectal cancer immunotherapy information using the Journal of the American Medical Association (JAMA) and DISCERN tools. Methods: Design thinking methodology was integrated with systematic scoping reviews framework to inform our descriptive observational media analysis study. Google Chrome was used to run four searches using prespecified search terms selected according to the top patient concerns about immunotherapy. The first 20 relevant results were identified (n = 80) and then duplicates were removed. Descriptive narrative univariate and bivariate analysis was done for the relevant variables. Results: The total of included websites was 17. Most websites score <3 points on JAMA and fair/poor on DISCERN. Most of the websites that score ≥3 points on JAMA and excellent/good on DISCERN have a charity affiliation. A total of 58.8% of the websites present the date, 41.2% demonstrate authorship, and sources are mentioned in 29.4% of the websites. Lack of content was noticed in providing the prognosis of patients if no treatment is given, clear aim and the effect of treatments on patient's quality of life. Conclusion: Assessing the reliability of information about cancer treatments online remains a challenge. Further research is required to understand the patient perceptions and use of online information and whether it has an impact on their behavioural health outcomes.