Advancing diabetes primary care education and knowledge in Nepal: A scoping review and case study discussion.

AIMS: Diabetes mellitus (DM) is a chronic disorder of insulin and glucose metabolism. It affects more than 463 million people worldwide and is expected to reach 700 million by 2045. In the Southeast Asian region, the prevalence of DM has tripled to 115 million due to rapid urbanization, unhealthy diet, sedentary lifestyles, and genetic factors. In Nepal, a developing country, DM affects 8.5% of adults, with an alarming increase in recent years. Lack of diabetes education and limited populational adoption of behavioural changes further hamper care. METHODS: In the present study, we performed a scoping review to determine the status of awareness, attitudes, and knowledge about diabetes in the Nepalese population with a focus on the educational initiatives that have been implemented. We also conducted a two-week international case study discussion among medical students to brainstorm viable intervention strategies. RESULTS: Our findings indicate that limited data is available on the level of education or initiatives to improve knowledge and practice among healthcare professionals and community members. Targeted studies of people with diabetes also present heterogeneous results due to differences in the sample population, geographic location, education, age, and gender. Accordingly, we propose five interrelated education-based strategies that leverage existing networks to expand community outreach and engagement, improve system resilience, and improve health outcomes. CONCLUSIONS: Effective education for healthcare professionals, community, and patients with diabetes is vital in improving diabetes outcomes in Nepal and South Asia. Collaboration, funding, and evaluation are key areas needing reform.

PD-L1 dimerisation induced by biphenyl derivatives mediates anti-breast cancer activity via the non-immune PD-L1-AKT-mTOR/Bcl2 pathway.

Recent studies on biphenyl-containing compounds, a type of PD-1/PD-L1 blocker which binds to PD-L1 and induces dimerisation, have focussed on its immune function. Herein, 10 novel biphenyl derivatives were designed and synthesised. The results of the CCK-8 showed that compounds have different anti-tumour activities for tumour cells in the absence of T cells. Particularly, 12j-4 can significantly induce the apoptosis of MDA-MB-231 cells (IC50 = 2.68 ± 0.27 µM). In further studies, 12j-4 has been shown to prevent the phosphorylation of AKT by binding to cytoplasmic PD-L1, which induces apoptosis in MDA-MB-231 cells through non-immune pathways. The inhibition of AKT phosphorylation restores the activity of GSK-3ß, ultimately resulting in the degradation of PD-L1. Besides, in vivo study indicated that 12j-4 repressed tumour growth in nude mice. As these biphenyls exert their anti-tumour effects mainly through non-immune pathways, they are worthy of further study as PD-L1 inhibitors.