Cardiac progenitor cells derived from adult heart have emerged as one of the most promising stem cell types for cardiac protection and repair. Exosomes are known to mediate cell-cell communication by ...transporting cell-derived proteins and nucleic acids, including various microRNAs (miRNAs). Here we investigated the cardiac progenitor cell (CPC)-derived exosomal miRNAs on protecting myocardium under oxidative stress. Sca1(+)CPCs-derived exosomes were purified from conditional medium, and identified by nanoparticle trafficking analysis (NTA), transmission electron microscopy and western blotting using CD63, CD9 and Alix as markers. Exosomes production was measured by NTA, the result showed that oxidative stress-induced CPCs secrete more exosomes compared with normal condition. Although six apoptosis-related miRNAs could be detected in two different treatment-derived exosomes, only miR-21 was significantly upregulated in oxidative stress-induced exosomes compared with normal exosomes. The same oxidative stress could cause low miR-21 and high cleaved caspase-3 expression in H9C2 cardiac cells. But the cleaved caspase-3 was significantly decreased when miR-21 was overexpressed by transfecting miR-21 mimic. Furthermore, miR-21 mimic or inhibitor transfection and luciferase activity assay confirmed that programmed cell death 4 (PDCD4) was a target gene of miR-21, and miR-21/PDCD4 axis has an important role in anti-apoptotic effect of H9C2 cell. Western blotting and Annexin V/PI results demonstrated that exosomes pre-treated H9C2 exhibited increased miR-21 whereas decreased PDCD4, and had more resistant potential to the apoptosis induced by the oxidative stress, compared with non-treated cells. These findings revealed that CPC-derived exosomal miR-21 had an inhibiting role in the apoptosis pathway through downregulating PDCD4. Restored miR-21/PDCD4 pathway using CPC-derived exosomes could protect myocardial cells against oxidative stress-related apoptosis. Therefore, exosomes could be used as a new therapeutic vehicle for ischemic cardiac disease.
Single-molecule magnets that contain one spin centre may represent the smallest possible unit for spin-based computational devices. Such applications, however, require the realization of molecules ...with a substantial energy barrier for spin inversion, achieved through a large axial magnetic anisotropy. Recently, significant progress has been made in this regard by using lanthanide centres such as terbium(III) and dysprosium(III), whose anisotropy can lead to extremely high relaxation barriers. We contend that similar effects should be achievable with transition metals by maintaining a low coordination number to restrict the magnitude of the d-orbital ligand-field splitting energy (which tends to hinder the development of large anisotropies). Herein we report the first two-coordinate complex of iron(I), Fe(C(SiMe3)3)2(-), for which alternating current magnetic susceptibility measurements reveal slow magnetic relaxation below 29 K in a zero applied direct-current field. This S = complex exhibits an effective spin-reversal barrier of Ueff = 226(4) cm(-1), the largest yet observed for a single-molecule magnet based on a transition metal, and displays magnetic blocking below 4.5 K.
holds for the entropy flux \mathsf {F}(K,\kappa ), the electrostatic capacity \mathsf {C}(K)=\mathsf {C}(\partial K) and the graphical mass \mathsf {M}(\mathbb{R}^n\setminus K^\circ ,\delta ...+df\otimes df) generated by a compact K\subset \mathbb{R}^{n\ge 3} with nonempty interior K^\circ and smooth boundary \partial K.>
Highlights • Extracellular factors and pathways in oligodendrocyte specification and development. • Key modulators of oligodendrocyte process extension and myelin thickness. • Recent ChIP-Seq ...findings for key oligodendrocyte transcription factors.
Summary
Background
Probiotic bacteria may be effective in the treatment of allergic inflammation and food allergy, but efficacy and underlying mechanisms remain unclear.
Objective
The present study ...investigated the effects of probiotic strain Bifidobacterium longum BB536 in the treatment of Japanese cedar pollinosis (JCPsis).
Methods
In a randomized, double‐blind, placebo‐controlled trial, 44 JCPsis subjects received BB536 or placebo for 13 weeks during the pollen season. Subjective symptoms and self‐care measures were recorded daily and blood samples were taken before and during intervention to measure blood levels of parameters related to JCPsis.
Results
BB536 intake was associated with a significant reduction in number of subjects prematurely terminated due to severe symptoms and pollinosis medication (P=0.0057 vs. placebo group). Comparison of subjective symptom scores indicated significant decreases in rhinorrhea, nasal blockage and composite scores in the BB536 group compared with the placebo group. Comparison of medical scores showed marked improvements in all symptoms on BB536 intake. A T‐helper type 2 (Th2)‐skewed immune response occurring along with pollen dispersion was observed. BB536 significantly suppressed increases in plasma thymus‐ and activation‐regulated chemokine and tended to suppress elevations of Japanese cedar pollen (JCP)‐specific IgE.
Conclusion
These results suggest the efficacy of BB536 in relieving JCPsis symptoms, probably through the modulation of Th2‐skewed immune response.
Congenital scoliosis is a common type of vertebral malformation. Genetic susceptibility has been implicated in congenital scoliosis.
We evaluated 161 Han Chinese persons with sporadic congenital ...scoliosis, 166 Han Chinese controls, and 2 pedigrees, family members of which had a 16p11.2 deletion, using comparative genomic hybridization, quantitative polymerase-chain-reaction analysis, and DNA sequencing. We carried out tests of replication using an additional series of 76 Han Chinese persons with congenital scoliosis and a multicenter series of 42 persons with 16p11.2 deletions.
We identified a total of 17 heterozygous TBX6 null mutations in the 161 persons with sporadic congenital scoliosis (11%); we did not observe any null mutations in TBX6 in 166 controls (P<3.8×10(-6)). These null alleles include copy-number variants (12 instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants (1 nonsense and 4 frame-shift mutations). However, the discordant intrafamilial phenotypes of 16p11.2 deletion carriers suggest that heterozygous TBX6 null mutation is insufficient to cause congenital scoliosis. We went on to identify a common TBX6 haplotype as the second risk allele in all 17 carriers of TBX6 null mutations (P<1.1×10(-6)). Replication studies involving additional persons with congenital scoliosis who carried a deletion affecting TBX6 confirmed this compound inheritance model. In vitro functional assays suggested that the risk haplotype is a hypomorphic allele. Hemivertebrae are characteristic of TBX6-associated congenital scoliosis.
Compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital scoliosis cases in the series that we analyzed. (Funded by the National Basic Research Program of China and others.).
Abstract Objectives Many studies have shown that insomnia is a common problem among university students, but there are wide variations in the prevalence of insomnia. In this systematic review, we ...aimed to explore the prevalence of insomnia among university students using scientific and conclusive methods. Study design A systematic review is designed to analyze the studies reporting on prevalence of insomnia among university students. Methods Systemic searches were conducted in PubMed, BioMed Central, EBSCO, ScienceDirect, Ovid LWW and Medline databases between January 2000 and July 2014, The Meta analyst software was used to calculate the prevalence rate of each study, the pooled means of prevalence rates and 95% CIs across studies were then calculated and presented. Results Seven articles that met the inclusion and exclusion criteria were selected. The overall sample size in the current review was 16,478, with a minimum of 219 and a maximum of 10,322. The prevalence rates of the seven studies ranged between 9.4% (95%CI 8.8–10.0%) and 38.2% (95% CI 35.4–41.1%). Overall, the total students studied with a weighted mean prevalence of 18.5% (95% CI 11.2–28.8%), considerably higher than rates of 7.4% (95% CI 5.8–9.0%) reported in general population. Conclusions This review emphasized that insomnia prevalence in university students is considerably higher than that in general population, suggested that more attention should be paid to insomnia in university students.
Chronic kidney disease (CKD) is a major public health problem. Identifying novel risk factors for CKD, including widely prevalent environmental exposures, is therefore important. Perfluoroalkyl ...chemicals (PFCs), including perfluorooctanoic acid and perfluorooctane sulfonate, are manmade chemicals that have been detected in the blood of more than 98% of the US population. Results from experimental animal studies have suggested that an association between PFCs and CKD is plausible. However, in humans, the relation between serum PFCs and CKD has not been examined. The authors examined the relation of serum PFCs and CKD in 4,587 adult participants (51.1% women) from the combined 1999-2000 and 2003-2008 cycles of the National Health and Nutritional Examination Survey for whom PFC measurements were available. The main outcome was CKD, defined as a glomerular filtration rate of less than 60 mL/minute/1.73 m2. The authors found that serum levels of PFCs, including perfluorooctanoic acid and perfluorooctane sulfonate, were positively associated with CKD. This association was independent of confounders such as age, sex, race/ethnicity, body mass index, diabetes, hypertension, and serum cholesterol level. Compared with subjects in quartile 1 (referent), the multivariable odds ratio for CKD among subjects in quartile 4 was 1.73 (95% confidence interval: 1.04, 2.88; P for trend = 0.015) for perfluorooctanoic acid and 1.82 (95% confidence interval: 1.01, 3.27; P for trend = 0.019) for perfluorooctane sulfonate. The present results suggest that elevated PFC levels are associated with CKD.