Leucine-Rich Repeat Kinase 2 Modulates Retinoic Acid-Induced Neuronal Differentiation of Murine Embryonic Stem Cells

Background: Dominant mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most prevalent cause of Parkinson’s disease, however, little is known about the biological function of LRRK2 protein. LRRK2 is expressed in neural precursor cells suggesting a role in neurodevelopment. Methodology/Principal Findings: In the present study, differential gene expression profiling revealed a faster silencing of pluripotency-associated genes, like Nanog, Oct4, and Lin28, during retinoic acid-induced neuronal differentiation of LRRK2deficient mouse embryonic stem cells compared to wildtype cultures. By contrast, expression of neurotransmitter receptors and neurotransmitter release was increased in LRRK2+/2 cultures indicating that LRRK2 promotes neuronal differentiation. Consistently, the number of neural progenitor cells was higher in the hippocampal dentate gyrus of adult LRRK2-deficient mice. Alterations in phosphorylation of the putative LRRK2 substrates, translation initiation factor 4E binding protein 1 and moesin, do not appear to be involved in altered differentiation, rather there is indirect evidence that a regulatory signaling network comprising retinoic acid receptors, let-7 miRNA and downstream target genes/mRNAs may be affected in LRRK2deficient stem cells in culture. Conclusion/Significance: Parkinson’s disease-linked LRRK2 mutations that associated with enhanced kinase activity may affect retinoic acid receptor signaling during neurodevelopment and/or neuronal maintenance as has been shown in othe

Feeding Blueberry Diets in Early Life Prevent Senescence of Osteoblasts and Bone Loss in Ovariectomized Adult Female Rats

Appropriate nutrition during early development is essential for maximal bone mass accretion; however, linkage between early nutrition, childhood bone mass, peak bone mass in adulthood, and prevention of bone loss later in life has not been studied.In this report, we show that feeding a high quality diet supplemented with blueberries (BB) to pre-pubertal rats throughout development or only between postnatal day 20 (PND20) and PND34 prevented ovariectomy (OVX)-induced bone loss in adult life. This protective effect of BB is due to suppression of osteoblastic cell senescence associated with acute loss of myosin expression after OVX. Early exposure of pre-osteoblasts to serum from BB-fed rats was found to consistently increase myosin expression. This led to maintenance osteoblastic cell development and differentiation and delay of cellular entrance into senescence through regulation of the Runx2 gene. High bone turnover after OVX results in insufficient collagenous matrix support for new osteoblasts and their precursors to express myosin and other cytoskeletal elements required for osteoblast activity and differentiation.These results indicate: 1) a significant prevention of OVX-induced bone loss from adult rats can occur with only 14 days consumption of a BB-containing diet immediately prior to puberty; and 2) the molecular mechanisms underlying these effects involves increased myosin production which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence

Closed Expander Salvage With Dual-port Tissue Expander in Implant-based Breast Reconstruction for High Body Mass Index and Ptotic Patients

Background:Implant-based (IB) breast reconstruction is efficient and predictable but poses infection risks, especially in patients with high body mass index and/or macromastia. Postoperative infection management lacks standardized protocols for device salvage.Methods:We conducted a 1-year retrospective study on 59 high-risk patients (91 breasts) using dual-port tissue expanders for breast reconstruction. A Wise-pattern skin envelope reduction closed over an inferiorly based adipodermal lining flap was used. Using the dual port, a closed washout protocol with a Betadine solution was initiated for suspected infections. Patient characteristics, infection profiles, and outcomes were recorded. A control cohort of 54 patients (98 breasts) without dual-port expanders was analyzed for infection rates and outcomes.Results:In the experimental cohort, 18% of breasts had postoperative infections, with 38% successfully salvaged using oral antibiotics and the closed washout alone. The overall salvage rate was 75%, and the infectious reconstructive failure rate was 3.3%. Gram-positive bacteria were predominant. The control cohort had a 23.5% infection rate, with only 5% successful salvage and 19 explantations. No statistically significant differences in demographics or infection rates were observed.Conclusions:The study demonstrated the efficacy of a closed wash protocol with dual-port tissue expanders in high-risk IB breast reconstruction. This approach reduces surgical washouts, improves salvage rates, and minimizes reconstruction losses. The dual-port expander shows promise in enhancing salvage outcomes and decreasing reoperations for postoperative infections, providing a valuable addition to IB breast reconstruction strategies. The results suggest potential benefits of the dual-port expander in infection treatment