Activation of HIFa Pathway in Mature Osteoblasts Disrupts the Integrity of the Osteocyte/Canalicular Network

The hypoxia-inducible factors (HIFs), HIF-1α and HIF-2α, are the central mediators of the homeostatic response that enables cells to survive and differentiate in low-oxygen conditions. Previous studies indicated that disruption of the von Hippel-Lindau gene (Vhl) coincides with the activation of HIFα signaling. Here we show that inactivation of Vhl in mature osteoblasts/osteocytes induces their apoptosis and disrupts the cell/canalicular network. VHL-deficient (ΔVHL) mice exhibited a significantly increased cortical bone area resulting from enhanced proliferation and osteogenic differentiation of the bone marrow stromal cells (BMSCs) by inducing the expression of β-catenin in the BMSC. Our data suggest that the VHL/HIFα pathway in mature osteoblasts/osteocytes plays a critical role in the bone cell/canalicular network and that the changes of osteocyte morphology/function and cell/canalicular network may unleash the bone formation, The underlying mechanism of which was the accumulation of β-catenin in the osteoblasts/osteoprogenitors of the bone marrow.     

Using Contaminated Plants Involved in Phytoremediation for Anaerobic Digestion

This study investigated the anaerobic digestion capability of five plants and the effects of copper (Cu) and S,S’-ethylenediaminedisuccinic acid (EDDS, a chelator widely used in chelant-assisted phytoremediation) on biogas production to determine a feasible disposal method for plants used in remediation. The results showed that in addition to Phytolacca americana L., plants such as Zea mays L., Brassica napus L., Elsholtzia splendens Nakai ex F. Maekawa, and Oenothera biennis L. performed well in biogas production. Among these, O. biennis required the shortest period to finish anaerobic digestion. Compared to normal plants with low Cu content, the plants used in remediation with increased Cu levels (100 mg kg^?1) not only promoted anaerobic digestion and required a shorter anaerobic digestion time, but also increased the methane content in biogas. When the Cu content in plants increased to 500, 1000, and 5000 mg kg^?1, the cumulative biogas production decreased by 12.3%, 14.6%, and 41.2%, respectively. Studies also found that EDDS conspicuously restrained biogas production from anaerobic digestion. The results suggest that anaerobic digestion has great potential for the disposal of contaminated plants and may provide a solution for the resource utilization of plants used in remediation.     

Permeability of Plant Young Root Endodermis to Cu Ions and Cu-Citrate Complexes in Corn and Soybean

The non-selective apoplastic passage of Cu and Cu-citrate complexes into the root stele of monocotyledonous corn and dicotyledonous soybean was investigated using an inorganic-salt-precipitation technique. Either Cu ions or Cu-citrate complexes were drawn into root through the apoplast from the root growth medium, and K₄[Fe(CN)₆] was subsequently perfused through xylem vessels or the entire root cross section. Based on microscopic identification of the reddish-brown precipitates of copper ferrocyanide in the cell walls of the xylem of corn and soybean roots, Cu²⁺ passed through the endodermal barrier into the xylem of both species. When the solution containing 200 μM CuSO₄ and 400 μM sodium citrate (containing 199.98 μM Cu-citrate, 0.02 μM Cu²⁺) was drawn via differential pressure gradients into the root xylem while being perfused with K₄[Fe(CN)₆] through the entire root cross-section, reddish-brown precipitates were observed in the walls of the stele of soybean, but not corn root. However, when a CuSO₄ solution containing 0.02 or 0.2 μM free Cu²⁺ was used, no reddish-brown precipitates were detected in the stele of either of the two plants. Results indicated that endodermis was permeable to Cu-citrate complexes in primary roots of soybean, but not corn. The permeability of the endodermal barrier to the Cu-citrate complex may vary between dicotyledonous and monocotyledonous plants, which has considerable implications for chelant-enhanced phytoextraction.     

Luminescent properties of Ca3SiO4Cl2 co‐doped with Ce3+ and Eu2+ for near‐ultraviolet light‐emitting diodes

Ca₃SiO₄Cl₂ co‐doped with Ce³⁺,Eu²⁺ was prepared by high temperature reaction. The structure, luminescent properties and the energy transfer process of Ca₃SiO₄Cl₂: Ce³⁺,Eu²⁺ were investigated. Eu²⁺ ions can give enhanced green emission through Ce³⁺ → Eu²⁺ energy transfer in these phosphors. The green phosphor Ca_2.9775SiO₄Cl₂:0.0045Ce³⁺,0.018Eu²⁺ showed intense green emission with broader excitation in the near‐ultraviolet light range. A green light‐emitting diode (LED) based on this phosphor was made, and bright green light from this green LED could be observed by the naked eye under 20 mA current excitation. Hence it is considered to be a good candidate for the green component of a three‐band white LED. Copyright © 2015 John Wiley & Sons, Ltd.     

Hemostasis During Urologic Surgery: Fibrin Sealant Compared With Absorbable Hemostat

In the United States, fibrin sealants have been used to achieve hemostasis for nearly two decades. Although their clinical utility was first demonstrated in cardiac surgery, their effectiveness and safety have since been demonstrated to extend to a wide array of procedures. Fibrin sealants typically contain two components—fibrinogen and thrombin—that are combined and delivered simultaneously to a target bleeding site in order to achieve hemostasis. However, many commercial formulations contain other additional components, such as antifibrinolytic agents, that have been associated with adverse outcomes. This subanalysis compares the safety and effectiveness of a fibrin sealant versus an absorbable hemostat for achieving hemostasis during urologic procedures with mild to moderate bleeding.Key words: Hemostasis, Hemostatics, Fibrin tissue adhesive, Urologic surgical procedures, Surgical techniqueIn the United States, fibrin sealants have been used to achieve hemostasis for nearly two decades. Although their clinical utility was first demonstrated in cardiac surgery,¹ their effectiveness and safety have since been demonstrated to extend to a wide array of procedures, including cardiovascular, gastrointestinal, pneumothoracic, neurologic, urologic, otolaryngologic, dental, and reconstructive surgeries.^2,3 Within the field of urology, fibrin sealants have been used to manage bleeding from renal trauma,⁴ as well as to facilitate hemostasis during renal surgeries, including partial nephrectomies.^5–7Fibrin sealants typically contain two components—fibrinogen and thrombin—that are combined and delivered simultaneously to a target bleeding site (TBS) in order to achieve hemostasis.³ Many commercial formulations contain other additional components, such as antifibrinolytic agents, that have been associated with adverse outcomes. For example, in an observational study (N = 4374), the antifibrinolytic aprotinin was associated with an increased risk of long-term mortality within 5 years following coronary artery bypass graft surgery.⁸ Furthermore, repeated exposure to aprotinin may lead to allergic or potentially fatal anaphylactic reactions.^9–11 For this reason, the US Food and Drug Administration (FDA) issued an alert in 2006 indicating that caution should be used when using aprotinin in patients with a history of previous exposure to the product.¹² Tranexamic acid, another antifibrinolytic present in some commercial fibrin sealants, has been associated with alterations in neural tissue growth and adherence.¹³ Because of the risk of cerebral neurologic toxicity, fibrin sealants containing tranexamic acid are contraindicated for use in neurosurgery or in surgical procedures during which contact with cerebrospinal fluid or dura mater may occur.¹⁴In a phase III, randomized, single-blind, parallel-group, multicenter study,¹⁵ the fibrin sealant CROSSEAL™ (Ethicon, Inc., Somerville, NJ) significantly reduced the time to hemostasis during liver resection surgery compared with conventional hemostatic techniques. EVICEL® Fibrin Sealant (Human) (Ethicon, Inc.), the successor of CROSSEAL, requires no antifibrinolytic additive and is therefore both aprotinin and tranexamic acid free, and achieves hemostasis using exclusively human components.¹⁶ The effectiveness and safety of this fibrin sealant for hemostasis in soft tissue during elective retroperitoneal or intra-abdominal surgery were compared with an absorbable hemostat (SURGICEL® Absorbable Hemostat; Ethicon, Inc.) in a randomized, active-controlled, multicenter study.¹⁷ This article describes a subanalysis of data from the largest patient subgroup from that study, and evaluates the effectiveness and safety of a fibrin sealant versus an absorbable hemostat for patients who underwent urologic surgical procedures.     

Metabolic reprogramming orchestrates cancer stem cell properties in nasopharyngeal carcinoma

Cancer stem cells (CSCs) represent a subpopulation of tumor cells endowed with self-renewal capacity and are considered as an underlying cause of tumor recurrence and metastasis. The metabolic signatures of CSCs and the mechanisms involved in the regulation of their stem cell-like properties still remain elusive. We utilized nasopharyngeal carcinoma (NPC) CSCs as a model to dissect their metabolic signatures and found that CSCs underwent metabolic shift and mitochondrial resetting distinguished from their differentiated counterparts. In metabolic shift, CSCs showed a greater reliance on glycolysis for energy supply compared with the parental cells. In mitochondrial resetting, the quantity and function of mitochondria of CSCs were modulated by the biogenesis of the organelles, and the round-shaped mitochondria were distributed in a peri-nuclear manner similar to those seen in the stem cells. In addition, we blocked the glycolytic pathway, increased the ROS levels, and depolarized mitochondrial membranes of CSCs, respectively, and examined the effects of these metabolic factors on CSC properties. Intriguingly, the properties of CSCs were curbed when we redirected the quintessential metabolic reprogramming, which indicates that the plasticity of energy metabolism regulated the balance between acquisition and loss of the stemness status. Taken together, we suggest that metabolic reprogramming is critical for CSCs to sustain self-renewal, deter from differentiation and enhance the antioxidant defense mechanism. Characterization of metabolic reprogramming governing CSC properties is paramount to the design of novel therapeutic strategies through metabolic intervention of CSCs.     

Epigenetic regulation of autophagy by the methyltransferase EZH2 through an MTOR-dependent pathway

Macroautophagy is an evolutionarily conserved cellular process involved in the clearance of proteins and organelles. Although the autophagy regulation machinery has been widely studied, the key epigenetic control of autophagy process still remains unknown. Here we report that the methyltransferase EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) epigenetically represses several negative regulators of the MTOR (mechanistic target of rapamycin [serine/threonine kinase]) pathway, such as TSC2, RHOA, DEPTOR, FKBP11, RGS16 and GPI. EZH2 was recruited to these genes promoters via MTA2 (metastasis associated 1 family, member 2), a component of the nucleosome remodeling and histone deacetylase (NuRD) complex. MTA2 was identified as a new chromatin binding protein whose association with chromatin facilitated the subsequent recruitment of EZH2 to silenced targeted genes, especially TSC2. Downregulation of TSC2 (tuberous sclerosis 2) by EZH2 elicited MTOR activation, which in turn modulated subsequent MTOR pathway-related events, including inhibition of autophagy. In human colorectal carcinoma (CRC) tissues, the expression of MTA2 and EZH2 correlated negatively with expression of TSC2, which reveals a novel link among epigenetic regulation, the MTOR pathway, autophagy induction, and tumorigenesis.