MicroRNA-23a promotes myelination in the central nervous system.

Demyelinating disorders including leukodystrophies are devastating conditions that are still in need of better understanding, and both oligodendrocyte differentiation and myelin synthesis pathways are potential avenues for developing treatment. Overexpression of lamin B1 leads to leukodystrophy characterized by demyelination of the central nervous system, and microRNA-23 (miR-23) was found to suppress lamin B1 and enhance oligodendrocyte differentiation in vitro. Here, we demonstrated that miR-23a-overexpressing mice have increased myelin thickness, providing in vivo evidence that miR-23a enhances both oligodendrocyte differentiation and myelin synthesis. Using this mouse model, we explored possible miR-23a targets and revealed that the phosphatase and tensin homologue/phosphatidylinositol trisphosphate kinase/Akt/mammalian target of rapamycin pathway is modulated by miR-23a. Additionally, a long noncoding RNA, 2700046G09Rik, was identified as a miR-23a target and modulates phosphatase and tensin homologue itself in a miR-23a-dependent manner. The data presented here imply a unique role for miR-23a in the coordination of proteins and noncoding RNAs in generating and maintaining healthy myelin

Revisiting the Pion Leading-Twist Distribution Amplitude within the QCD Background Field Theory

We study the pion leading-twist distribution amplitude (DA) within the framework of SVZ sum rules under the background field theory. To improve the accuracy of the sum rules, we expand both the quark propagator and the vertex (z\cdot \tensor{D})^n of the correlator up to dimension-six operators in the background field theory. The sum rules for the pion DA moments are obtained, in which all condensates up to dimension-six have been taken into consideration. Using the sum rules, we obtain \left|_{\rm 1\;GeV} = 0.338 \pm 0.032, \left|_{\rm 1\;GeV} = 0.211 \pm 0.030 and \left|_{\rm 1\;GeV} = 0.163 \pm 0.030. It is shown that the dimension-six condensates shall provide sizable contributions to the pion DA moments. We show that the first Gegenbauer moment of the pion leading-twist DA is $a^\pi_2|_{\rm 1\;GeV} = 0.403 \pm 0.093$, which is consistent with those obtained in the literature within errors but prefers a larger central value as indicated by lattice QCD predictions.Comment: 13 pages, 7 figure

Inhibition of Autophagy Signaling via 3-methyladenine Rescued Nicotine-Mediated Cardiac Pathological Effects and Heart Dysfunctions.

Rationale: Cigarette smoking is a well-established risk factor for myocardial infarction and sudden cardiac death. The deleterious effects are mainly due to nicotine, but the mechanisms involved and theranostics remain unclear. Thus, we tested the hypothesis that nicotine exposure increases the heart sensitivity to ischemia/reperfusion injury and dysfunction, which can be rescued by autophagy inhibitor. Methods: Nicotine or saline was administered to adult rats via subcutaneous osmotic minipumps in the absence or presence of an autophagy inhibitor, 3-methyladenine (3-MA). After 30 days of nicotine treatment, the rats underwent the cardiac ischemia/reperfusion (I/R) procedure and echocardiography analysis, and the heart tissues were isolated for molecular biological studies. Results: Nicotine exposure increased I/R-induced cardiac injury and cardiac dysfunction as compared to the control. The levels of autophagy-related proteins including LC3 II, P62, Beclin1, and Atg5 were upregulated in the reperfused hearts isolated from nicotine-treated group. In addition, nicotine enhanced cardiac and plasma ROS production, and increased the phosphorylation of GSK3β (ser9) in the left ventricle tissues. Treatment with 3-MA abolished nicotine-mediated increase in the levels of autophagy-related proteins and phosphorylation of GSK3β, but had no effect on ROS production. Of importance, 3-MA ameliorated the augmented I/R-induced cardiac injury and dysfunction in the nicotine-treated group as compared to the control. Conclusion: Our results demonstrate that nicotine exposure enhances autophagy signaling pathway, resulting in development of ischemic-sensitive phenotype of heart. It suggests a potentially novel therapeutic strategy of autophagy inhibition for the treatment of ischemic heart disease

Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice.

Strokes are one of the leading causes of mortality and chronic morbidity in the world, yet with only limited successful interventions available at present. Our previous studies revealed the potential role of the glucocorticoid receptor (GR) in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). In the present study, we investigate the effect of GR knockdown on acute ischemic brain injuries in a model of focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) in adult male CD1 mice. GR siRNAs and the negative control were administered via intracerebroventricular (i.c.v.) injection 48 h prior to MCAO. The cerebral infarction volume and neurobehavioral deficits were determined 48 h after MCAO. RT-qPCR was employed to assess the inflammation-related gene expression profiles in the brain before and after MCAO. Western Blotting was used to evaluate the expression levels of GR, the mineralocorticoid receptor (MR) and the brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling. The siRNAs treatment decreased GR, but not MR, protein expression, and significantly enhanced expression levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in the brain. Of interest, GR knockdown suppressed BDNF/TrkB signaling in adult mice brains. Importantly, GR siRNA pretreatment significantly increased the infarction size and exacerbated the neurobehavioral deficits induced by MCAO in comparison to the control group. Thus, the present study demonstrates the important role of GR in the regulation of the inflammatory responses and neurotrophic BDNF/TrkB signaling pathway in acute ischemic brain injuries in adult mice, revealing a new insight into the pathogenesis and therapeutic potential in acute ischemic strokes

Criticality of the O(N)O(N) universality via global solutions to nonperturbative fixed-point equations

Fixed-point equations in the functional renormalization group approach are integrated from large to vanishing field, where an asymptotic potential in the limit of large field is implemented as initial conditions. This approach allows us to obtain a global fixed-point potential with high numerical accuracy, that incorporates the correct asymptotic behavior in the limit of large field. Our calculated global potential is in good agreement with the Taylor expansion in the region of small field, and it also coincides with the Laurent expansion in the regime of large field. Laurent expansion of the potential in the limit of large field for general case, that the spatial dimension $d$ is a continuous variable in the range $2\leq d \leq 4$, is obtained. Eigenfunctions and eigenvalues of perturbations near the Wilson-Fisher fixed point are computed with the method of eigenperturbations. Critical exponents for different values of $d$ and $N$ of the $O(N)$ universality class are calculated.Comment: 10 pages, 4 figures, 1 table; v2: minor changes, discussions and references adde