Volume 99 Issue 12, December 2019

Obesity causes complications in the treatment of asthma. This manuscript explores the role of Notch pathway in animal models. The authors found that the inhibition of the Notch pathway by a γ-secretase inhibitor suppresses Th17-associated airway hyperresponsiveness in obese asthmatic mice. This finding may provide a novel insight into asthma treatment in the clinic.

The authors provide an in-depth explanation of how HO-1 activation, through PI3K/Akt pathway, protects the lung from oxidative injury in the setting of sepsis by regulating mitochondrial quality control. This study presents a rationale for developing HO-1 therapy to prevent sepsis-related lung injury.

This study investigates lipid droplet (LD) trafficking and LD velocity (LDV) in cancer. LD density correlated with prostate tumor grade and high grade tumors had significantly higher LDV when compared to low grade tumors. Acidifying conditions drove up velocities and LDV was normalized with blockade of H⁺ proton pump, V-ATPase.

This study was performed to evaluate role of RORα in mouse testicular structure. Lack of RORα expression induces apoptosis, reduces germ cells differentiation, and may cause infertility. RORα is one of the essential proteins regulating testicular structure. RORα-deficient mice may be a suitable model for studying mutation-induced of human infertility.

This study shows that scavenger receptor type I knockout mice (Scarb1-/-) have high adrenocorticotropic hormone (ACTH) levels but are osteopenic. Bone differentiation of Scarb1-/- mesenchymal stem cells at normal ACTH concentrations is reduced. However, 0–10 nM ACTH increases, but 100–1000 nM ACTH reduces wild-type osteoblast differentiation. Therefore, ACTH and the high-density lipoprotein receptor Scarb1 play independent roles in osteoblast differentiation.

CRISPR/dCas9 blocks TGF-β2-induced mouse double minute 2 (MDM2) expression by targeting its second promoter, without affecting the basal expression. Epithelial to mesenchymal transition is blocked by MDM2 suppression in retinal pigment epithelial cells. In this way, CRIPSR/dCas9 is a promising novel therapy for proliferative vitreoretinopathy without interfering basal gene function.

The authors show that Muc5ac^−/− mice develop spontaneous gastric antro-pyloric hyperplasia and adenomas. Interestingly, Muc5ac^−/− mice have suppression of gastric corpus mucous metaplasia and key proinflammatory cytokines (Tnfα and Il-17a) in a setting of enhanced Helicobacter pylori colonization, thus implying a complex role for Muc5ac in gastric homeostasis.

Vitamin D and its analogues demonstrated in this study antifibrotic effects in a murine fibrosis model compared to calcitriol. In this study, the hypocalcemic vitamin D analog paricalcitol was superior in respect to side effects and efficacy, indication that such analogs could be considered for the treatment of liver fibrosis.