Prevalence, causes and contexts of childhood overweight and obesity in the Pacific region: a scoping review.

Background: Non-communicable diseases (NCDs) are a major threat to health and development and account for 75% of deaths in the Pacific Islands Countries and Territories (PICTs). Childhood obesity has been identified as a main risk factor for NCDs later in life. This review compiled overweight and obesity (OWOB) prevalence (anthropometric data) for children aged six to 12 years old living in the Pacific region and identified possible related causes.

A novel tyrosine kinase inhibitor restores chondrocyte differentiation and promotes bone growth in a gain-of-function Fgfr3 mouse model.

Activating germline fibroblast growth factor receptor 3 (FGFR3) mutations cause achondroplasia (ACH), the most common form of human dwarfism and a spectrum of skeletal dysplasias. FGFR3 is a tyrosine kinase receptor and constitutive FGFR3 activation impairs endochondral ossification and triggers severe disorganization of the cartilage with shortening of long bones. To decipher the role of FGFR3 in endochondral ossification, we analyzed the impact of a novel tyrosine kinase inhibitor (TKI), A31, on both human and mouse mutant FGFR3-expressing cells and on the skeleton of Fgfr3(Y367C/+) dwarf mice.

Delayed bone age due to a dual effect of FGFR3 mutation in Achondroplasia.

Achondroplasia (ACH), the most common form of human dwarfism is caused by a mutation in the Fibroblast Growth Factor Receptor 3 (FGFR3) gene, resulting in constitutive activation of the receptor. Typical radiological features include shortening of the tubular bones and macrocephaly, due to disruption of endochondral ossification. Consequently, FGFR3 has been described as a negative regulator of bone growth.

Synthesis and biological evaluation of a triazole-based library of pyrido[2,3-d]pyrimidines as FGFR3 tyrosine kinase inhibitors.

A library of pyrido[2,3-d]pyrimidines was designed as inhibitors of FGFR3 tyrosine kinase allowing possible interactions with an unexploited region of the ATP binding-site. This library was built-up with an efficient step of click-chemistry giving easy access to triazole-based compounds bearing a large panel of substituents. Among the 27 analogues synthesized, more than half exhibited 55-89% inhibition of in vitro FGFR3 kinase activity at 2 microM and one (19g) was able to inhibit auto-phosphorylation of mutant FGFR3-K650M in transfected HEK cells.