Exosomal circ_0004136 enhances the progression of pediatric acute myeloid leukemia depending on the regulation of miR-570-3p/TSPAN3 axis.

Circular RNAs (circRNAs) have been implicated in the progression of pediatric acute myeloid leukemia (AML). Although circ_0004136 has been found to play a crucial role in AML, our understanding of its molecular mechanism remains very limited. The levels of circ_0004136, miR-570-3p and tetraspanin 3 (TSPAN3) were determined by quantitative real-time PCR or western blot. Cell viability, migration, invasion, cell cycle and apoptosis were detected using the Cell Counting Kit-8, transwell and flow cytometry assays. Targeted relationships among circ_0004136, miR-570-3p and TSPAN3 were validated by dual-luciferase reporter and RNA immunoprecipitation assays. Our data showed that circ_0004136 could be transmitted by exosomes, and exosomal circ_0004136 was highly expressed in AML serum and cells. Circ_0004136 was unusually stable and mainly localized in the cytoplasm. Circ_0004136 knockdown mediated by exosomes hampered AML cell viability, cell cycle progression, migration and invasion, and promoted cell apoptosis. Moreover, circ_0004136 worked as a sponge of miR-570-3p and TSPAN3 was a functional target of miR-370-3p in AML cells. The suppression of circ_0004136 knockdown mediated by exosomes on AML cell malignant progression was reversed by miR-570-3p downregulation, and the increased miR-570-3p expression hindered the progression of aggressive AML by downregulating TSPAN3. Furthermore, circ_0004136 worked as a miR-570-3p sponge to modulate TSPAN3 expression. Our findings identified a novel regulatory mechanism in which exosome-mediated circ_0004136 knockdown restrained AML cell malignant progression at least partly through targeting the miR-570-3p/TSPAN3 axis, highlighting a novel therapeutic strategy for AML management.

Protective effects of berberine on senile osteoporosis in mice.

INTRODUCTION: The incidence of osteoporosis is positively correlated with age. Berberine has been reported to treat osteoporosis due to its beneficial actions on bone formation. However, the direct effects of berberine on senile osteoporosis remain unclear. The present study investigated the protective effects of berberine on senile osteoporosis in mice and preliminarily evaluated its potential mechanism. MATERIALS AND METHODS: 20-month-old male C57BL/6 J mice were used as senile osteoporosis mouse model and treated with strontium ranelate (SR) or berberine or solvent control by daily gavage for 2 months. Thereafter, bone mass and microstructure parameters were assessed. Histological staining was performed to identify the osteogenic, adipogenic and osteoclastic activity of bone tissue. Moreover, role of cAMP/PKA/CREB signaling pathway in berberine affecting bone marrow mesenchymal stem cells (BMSCs) differentiation was clarified by enzyme-linked immunosorbent assay and western blot analysis. RESULTS: The results showed that the SR-treated group displayed a high trabecular bone mass phenotype. For mice administrated with berberine, cancellous bone mass was upregulated in a dose-dependent manner, as indicated by gradually increased bone mass, trabecular bone volume fraction and trabecular number. Furthermore, berberine promotes osteogenic and inhibits adipogenic differentiation of BMSCs via cAMP/PKA/CREB signaling. Also, bone resorption effect becomes more obvious with increasing dose of berberine in vitro. CONCLUSION: The present results suggest that berberine exerts potent bone protective effects by promoting bone formation, inhibiting marrow fat accumulation and bone resorption. This effect may be achieved through cAMP/PKA/CREB signaling pathway.

Quaternized chitin used as chiral stationary phase for HPLC and the high enantioseparation of 1,2,3,4-tetrahydro-1-naphthalenamine racemates.

Quaternized chitin (QC) with different degrees of substitution (DSs) and molecular weight (Mw) were homogeneously synthesized. Eight novel chiral stationary phases (CSPs) for HPLC were prepared by coating the QC on 3-aminopropyl silica gel, which were firstly used to separate 1,2,3,4-tetrahydro-1-naphthalenamine (THNA) racemates. Enantioseparation capability of the CSPs was evaluated and the influence factors including DS and Mw of QCs were explored respectively. The results demonstrated that the successful separation of THNA enantiomers was obtained by all the new CSPs of the chitin derivatives. Resolution (Rs) increased from 1.12 to 1.58 with the increase of DS of QC from 0.40 to 0.62, while the Rs decreased with the reduction of Mw of the products from 2.8 × 105 to 9.7 × 104. The maximum Rs is 2.29. A simple pathway for the fabrication of novel CSPs of cationic chitin derivatives is developed, which has potential application for the separation of THAN racemates.

Significance of amplitude integrated electroencephalography in early stage of neonatal hypoxic-ischemic encephalopathy and cerebral function monitoring in Neonatal Intensive Care Units.

OBJECTIVE: To investigate the role of amplitude integrated electroencephalography (aEEG) diagnosis in early stage of neonatal hypoxic-ischemic encephalopathy (HIE), and to evaluate the feasibility of aEEG in cerebral function monitoring in Neonatal Intensive Care Units (NICU). METHODS: 60 cases of term infants with neonatal HIE were included in the observation group, and 50 healthy term infants were enrolled as the control group. Both groups received aEEG monitoring within 6 hours after birth, and the results were analyzed. RESULTS: The correlation coefficient between the degree of asphyxia, SWC, SA and aEEG background activity was r = 0.571 (P<0.001); r = 0.512 (P<0.001) and r = 0.293 (P<0.001), respectively. The correlation coefficient between HIE degree and aEEG background activity, SWC was r = 0.742 (P<0.001) and r = 0.763 (P<0.001), respectively. The Gessell scores of the control group at 1, 3, 6, 9, and 12 months after birth were higher than those of the mild asphyxia group and the severe asphyxia group, and the mild asphyxia group showed higher Gessell scores than the severe asphyxia group (P<0.001). The predicted ROC curve of aEEG monitoring on the occurrence of neonatal HIE showed the area under the curve (AUC) = 0.6354, Std. Error = 0.05668 (95% CI: 0.5243-0.7465, P = 0.0209). CONCLUSION: aEEG had obvious diagnostic value in brain injury in the early stage of full-term neonates with asphyxia, and could be used to monitor the cerebral function of NICU, which is helpful for early clinical detection of brain injury of full-term neonates with asphyxia, so as to improve early diagnosis and treatment.