Hydrogen Sulfide Maintains Mesenchymal Stem Cell Function and Bone Homeostasis via Regulation of Ca2+ Channel Sulfhydration

Gaseous signaling molecules such as hydrogen sulfide (H2S) are produced endogenously and mediate effects through diverse mechanisms. H2S is one such gasotrasmitter which regulates multiple signaling pathways in mammalian cells, and abnormal H2S metabolism has been linked to defects in bone homeostasis. Here, we demonstrate that bone marrow mesenchymal stem cells (BMMSCs) produce H2S to regulate their self-renewal and osteogenic differentiation, and H2S deficiency results in defects in BMMSC differentiation. H2S deficiency causes aberrant intracellular Ca2+ influx, due to reduced sulfhydration of cysteine residues on multiple Ca2+ TRP channels. This decreased Ca2+ flux downregulates PKC/Erk-mediated Wnt/β-catenin signaling which controls osteogenic differentiation of BMMSCs. Consistently, H2S-deficient mice display an osteoporotic phenotype, which can be rescued by small molecules which release H2S. These results demonstrate H2S regulates BMMSCs, and restoring H2S levels via non-toxic donors may provide treatments for diseases such as osteoporosis which can arise from H2S deficiencies

The c-Myc-regulated lncRNA NEAT1 and paraspeckles modulate imatinib-induced apoptosis in CML cells

Abstract Chronic myeloid leukemia (CML) is a clonal disease characterized by the presence of the constitutively active tyrosine kinase BCR-ABL oncoprotein. Although BCR-ABL is crucially important for pathogenesis and treatment response, it is thought that some additional factors might be involved in the regulation of these processes. Aberrant expression of long noncoding RNAs (lncRNAs) has recently been identified to be involved in various diseases including cancer, suggesting that lncRNAs may play a role in BCR-ABL-mediated CML. In this study, we found that nuclear-enriched abundant transcript 1 (NEAT1), a lncRNA essential for the formation of nuclear body paraspeckles, is significantly repressed in primary CML cells. NEAT1 expression could be restored by inhibiting BCR-ABL expression or its kinase activity in K562 cells. We also demonstrated that NEAT1 is regulated by c-Myc. Knockdown of NEAT1 could promote imatinib (IM)-induced apoptosis, and we demonstrated that the NEAT1-binding paraspeckle protein splicing factor proline/glutamine-rich (SFPQ) is required for NEAT1-mediated apoptosis in K562 cells. RNA-seq analysis revealed that SFPQ regulates cell growth and death pathway-related genes, confirming its function in IM-induced apoptosis. Collectively, these results assign a biological function to the NEAT1 lncRNA in CML apoptosis and may lead to fuller understanding of the molecular events leading to CML

Additional file 1: Figure S1. of Overexpression of the long non-coding RNA PVT1 is correlated with leukemic cell proliferation in acute promyelocytic leukemia

PVT1 expression in NB4-R2 cells treated with ATRA. NB4-R2 cells were cultured in RPMI 1640 supplemented with 10 % FBS in the presence and absence of 1 μM ATRA for the indicated time points. Total RNA was extracted, and PVT1 levels were determined by qPCR. (DOCX 51 kb

Effects of Water Masses and Circulation on the Surface Water Partial Pressure of Carbon Dioxide in Summer in Eastern Beibu Gulf, China

A gulf is a typical ecological zone where carbon cycle is jointly affected by complex environmental factors and strong human activities, and the Beibu Gulf has complex water masses and circulation structures. In this study, we used underway, continuous observational data of the surface water partial pressure of carbon dioxide (pCO2), temperature (SST), salinity (SSS), dissolved oxygen (DO), and chlorophyll α along with vertical profile observations of temperature, salinity, carbonate system parameters and nutrients to determine the spatiotemporal variations and research effects of water masses and circulation on summer pCO2 in the eastern part of Beibu Gulf. In the summers of 2011 and 2014, the mean pCO2 in the eastern part of Beibu Gulf was 417 μatm and 405 μatm, respectively, and the mean sea–air CO2 flux was 3.3 mmol m−2 d−1 and 1.6 mmol m−2 d−1, respectively. In the summer of 2011, the northern part of the Beibu Gulf was controlled by a cyclonic circulation, and pCO2 at the center of the cyclonic circulation increased by more than 15 μatm to a mean value of more than 10 μatm above that of the surrounding waters. The southern part of the Beibu Gulf was affected by an anticyclonic circulation and western coastal water masses, with a high temperature, low salinity, low pCO2, and downwelling surface waters. In the summer of 2011, the mean pCO2 was approximately 17 μatm lower than that in the surrounding waters, and no clear downwelling was observed in summer 2014. The eastern part of Beibu Gulf was a source of atmospheric CO2 in the summer, only the region affected by the northern coastal water in the eastern part of Beibu Gulf was a sink of atmospheric CO2, and pCO2 had distinctly different spatiotemporal distributions under the influence of complex water masses and circulation structures