Growth retardation and skin abnormalities of the Recql4-deficient mouse

Mutations in the Recql4 gene are very likely responsible for a subset of Rothmund-Thomson syndrome (RTS) cases, but until now there has been no animal model to confirm this. Knockout mice in which the Recql4 gene is disrupted at exons 5-8 exhibit embryonic lethality at embryonic day 3.5-6.5. We generated a helicase activity-inhibited mouse by deleting exon 13 of Recql4, which is one of the coding exons of the consensus RecQ-helicase domain. This domain is the primary site of mutations that have been identified in RTS patients. The exon 13-deleted Recql4-deficient mice are viable, but exhibit severe growth retardation and abnormalities in several tissues, and embryonic fibroblasts show a defect in cell proliferation. Abnormalities in the Recql4-deficient mice are similar to those in RTS patients, suggesting that defects in the Recql4 gene may indeed be responsible for RTS. We speculate that the loss of Recql4 helicase activity results in the prematurely aged appearance observed in some RecQ helicase diseases

Association between Pet Ownership and Obesity: A Systematic Review and Meta-Analysis

Obesity is a major risk factor for lifestyle-related diseases, including cardiovascular disease, type 2 diabetes, and hypertension. Several studies have investigated the association between pet ownership and obesity, but the findings have been inconsistent. This systematic literature review and meta-analysis assessed the association between pet ownership and obesity. Using PubMed and Scopus, we overviewed the literature published until December 2019 and selected pertinent data for meta-analysis. Two independent reviewers extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CIs) for obesity were calculated using the random-effects model with inverse-variance weighting. The 21 included articles were cross-sectional studies. Five publications (nine analyses) that reported adjusted RRs for BMI ≥ 25 were included in the meta-analysis. No significant association existed between pet ownership and obesity (pooled RR = 1.038; 95% CI, 0.922–1.167; I2 = 51.8%). After stratification by age group (children vs. adults), no significant association was detected (pooled RR = 0.844; 95% CI, 0.604–1.179; I2 = 64.1% vs. pooled RR = 1.099; 95% CI, 0.997–1.212; I2 = 25.2%). Similarly, no significant association was observed between dog ownership and obesity, indicating no association between pet ownership and obesity. However, no infer causation can be reported because all studies included in this meta-analysis were cross-sectional. Therefore, further prospective studies are needed

Synergistic effect of collagen and CXCL12 in the low doses on human platelet activation.

CXCL12, also known as stromal cell-derived factor-1, is a chemokine classified into CXC families, which exerts its function by binding to specific receptors called CXCR4 and CXCR7. Human platelets express CXCR4 and CXCR7 on the plasma membrane. It has been reported that CXCL12 potentiates to induce platelet aggregation in cooperation with agonists including collagen. However, the precise roles and mechanisms of CXCL12 in human platelet activation are not fully elucidated. In the present study, we investigated the effect of simultaneous stimulation with low doses of collagen and CXCL12 on the activation of human platelets. The simultaneous stimulation with collagen and CXCL12 induced the secretion of platelet-derived growth factor (PDGF)-AB and the release of soluble CD40 ligand (sCD40L) from human platelets in addition to their aggregation, despite the fact that the simultaneous stimulation with thrombin receptor-activating peptide (TRAP) or adenosine diphosphate (ADP), and CXCL12 had little effects on the platelet aggregation. The agonist of Glycoprotein (GP) Ⅵ convulxin and CXCL12 also induced platelet aggregation synergistically. The monoclonal antibody against CXCR4 but not CXCR7 suppressed the platelet aggregation induced by simultaneous stimulation with collagen and CXCL12. The phosphorylation of p38 mitogen-activated protein kinase (MAPK), but not p44/p42 MAPK, was induced by the simultaneous stimulation. In addition, the simultaneous stimulation with collagen and CXCL12 induced the phosphorylation of HSP27 and the subsequent release of phosphorylated-HSP27 from human platelets. SB203580, a specific inhibitor of p38 MAPK, attenuated the platelet aggregation, the phosphorylation of p38 MAPK and HSP27, the PDGF-AB secretion, the sCD40L release and the phosphorylated-HSP27 release induced by the simultaneous stimulation with collagen and CXCL12. These results strongly suggest that collagen and CXCL12 in low doses synergistically act to induce PDGF-AB secretion, sCD40L release and phosphorylated-HSP27 release from activated human platelets via p38 MAPK activation