Bis(1,10-phenanthroline-κ2 N,N′)(sulfato-O)copper(II) ethane-1,2-diol monosolvate

In the title compound, [Cu(SO4)(C12H8N2)2]·C2H6O2, the CuII ion is five-coordinated in a distorted square-pyramidal manner by four N atoms from two chelating 1,10-phenanthroline (phen) ligands and one O atom from a monodentate sulfate anion. The four N atoms comprise a square and the one O atom the apex of a square pyramid. The two chelating N2C2 groups are oriented at 71.1 (2)°. In the crystal, the components are connected by inter­molecular O—H⋯O hydrogen bonding. The presence of pseudosymmetry in the structure suggests the higher symmetry space group C2/c, but attempts to refine the structure in this space group resulted in an unsatisfactory model

Bis(1,10-phenanthroline-κ2 N,N′)(sulfato-κ2 O,O′)cadmium(II) propane-1,3-diol solvate

In the title compound, [Cd(SO4)(C12H8N2)2]·C3H8O2, the CdII atom has a distorted octa­hedral coordination composed of four N atoms from two chelating 1,10-phenanthroline ligands and two O atoms from an O,O′-bidentate sulfate group. The two chelating NCCN groups subtend a dihedral angle of 82.21 (9)°. The CdII ion, the S atom and the middle C atom of the propane-1,3-diol solvent mol­ecule are located on special positions, site symmetry 2. The solvate features a pair of O—H⋯O hydrogen bonds with the uncoordinated O atoms of the sulfate ion. The OH group of the propane-1,3-diol solvent is disordered over two positions of equal occupancy

Bis(1,10-phenanthroline-κ2 N,N′)(sulfato-κ2 O,O′)zinc(II) propane-1,3-diol solvate

In the title compound, [Zn(SO4)(C12H8N2)2]·C3H8O2, the Zn2+ ion (site symmetry 2) is coordinated by two chelating 1,10-phenanthroline ligands and an O,O′-bidentate sulfate ion (S site symmetry 2), resulting in a distorted cis-ZnO2N4 octa­hedral geometry for the metal ion. The complete propane-1,3-diol mol­ecule is generated by crystallographic twofold symmetry and two O—H⋯O hydrogen bonds are formed with the uncoordinated O atoms of the sulfate group

Bis(1,10-phenanthroline-κ2 N,N′)(sulfato-κ2 O,O′)nickel(II) propane-1,3-diol solvate

In the structure of the title compound, [Ni(SO4)(C12H8N2)2]·C3H8O2, the NiII ion (site symmetry 2) is six-coordinated in a distorted octa­hedral manner by four N atoms from two chelating 1,10-phenanthroline (phen) ligands and two O atoms from a bidentate sulfate ligand (2 symmetry). The dihedral angle between the two chelating NCCN groups is 80.9 (1)°. The central C atom of the propane-1,3-diol solvent mol­ecule is likewise located on a twofold rotation axis. In the crystal structure, the [Ni(SO4)(C12H8N2)2] and C3H8O2 entities are connected through inter­molecular O—H⋯O hydrogen bonding

Tris(1,10-phenanthroline-κ2 N,N′)nickel(II) bis­(2,4,5-tricarb­oxy­benzo­ate) monohydrate

In the title compound, [Ni(C12H8N2)3](C10H5O8)2·H2O, the NiII cation is coordinated by six N atoms of the three bidentate chelating 1,10-phenanthroline ligands in a slightly distorted octa­hedral coordination geometry. The Ni—N bond lengths range from 2.074 (2) to 2.094 (2) Å. The dihedral angles between the three chelating NCCN groups to each other are 85.71 (3), 73.75 (2) and 85.71 (3)°, respectively. The Ni cation, the phenyl ring of the 1,10-phenanthroline ligand and the lattice water molecule are located on special positions (site symmetry 2). In the crystal, the uncoordinated 2,4,5-tricarb­oxy­benzeno­ate anions join with each other through O—H⋯O hydrogen bonds, forming a two-dimensional hydrogen-bonded layer structure along the bc plane. The layers are further linked via additional O—H⋯O inter­actions between water and carboxyl groups, resulting in a three-dimensional supra­molecular network

Small molecule-mediated tribbles homolog 3 promotes bone formation induced by bone morphogenetic protein-2.

Although bone morphogenetic protein-2 (BMP2) has demonstrated extraordinary potential in bone formation, its clinical applications require supraphysiological milligram-level doses that increase postoperative inflammation and inappropriate adipogenesis, resulting in well-documented life-threatening cervical swelling and cyst-like bone formation. Recent promising alternative biomolecular strategies are toward promoting pro-osteogenic activity of BMP2 while simultaneously suppressing its adverse effects. Here, we demonstrated that small molecular phenamil synergized osteogenesis and bone formation with BMP2 in a rat critical size mandibular defect model. Moreover, we successfully elicited the BMP2 adverse outcomes (i.e. adipogenesis and inflammation) in the mandibular defect by applying high dose BMP2. Phenamil treatment significantly improves the quality of newly formed bone by inhibiting BMP2 induced fatty cyst-like structure and inflammatory soft-tissue swelling. The observed positive phenamil effects were associated with upregulation of tribbles homolog 3 (Trib3) that suppressed adipogenic differentiation and inflammatory responses by negatively regulating PPARγ and NF-κB transcriptional activities. Thus, use of BMP2 along with phenamil stimulation or Trib3 augmentation may be a promising strategy to improve clinical efficacy and safety of current BMP therapeutics

PI3K/Akt/mTOR pathway participates in neuroprotection by dexmedetomidine inhibits neuronic autophagy following traumatic brain injury in rats

Dexmedetomidine (Dex) has been demonstrated to provide neuroprotective effect against brain injury in the central nervous system. However, the underlying mechanism of this neuroprotection remains unclear. In this study, we explored whether Dex has the protective potential in rat models of traumatic brain injury(TBI). More importantly, our study further investigated the role of neuronic autophagy induced by PI3K/Akt/mTOR pathway in this neuroprotective action. Adult male Sprague-Dawley rats were subjected to a diffuse cortical impact injury caused by a modified weight-drop device and Dex (15ug/kg, i.v.) was administered immediately after TBI. Wet-dry weight method was used to evaluate brain edema. Motor function outcome was assessed by Neurologic Severity Score and the spatial learning ability was evaluated in a Morris water maze. The co-localization of microtubule-associated protein 1 light chain 3(LC3) and neuronal nuclei (NeuN), or LC3 and mammalian target of rapamycin (mTOR) were analyzed by immunofluorescence respectively. The expression of LC3, Phosphorylated protein kinase B (p-Akt) and p-mTOR were quantified using Western blot analysis. Our results showed treatment of rats exposed to TBI with Dex caused not only marked reduction in cerebral edema, motor and cognitive functions deficits, but also a decrease in LC3 levels and a increase in p-Akt and p-mTOR levels. Taken together, these findings indicated that treatment with Dex after TBI could inhibited neuronic autophagy in the hippocampus mediated by the activation of the PI3K/Akt/mTOR pathway, finally promoting neurological recovery.Abbreviations: TBI, Traumatic brain injury; Dex, Dexmedetomidine; LC3, Light chain 3; NeuN, Neuronal nuclei; mTOR, Mammalian target of rapamycin; Akt, Protein kinase

Enhanced Osteogenesis of Adipose-Derived Stem Cells by Regulating Bone Morphogenetic Protein Signaling Antagonists and Agonists.

UnlabelledAlthough adipose-derived stem cells (ASCs) are an attractive cell source for bone tissue engineering, direct use of ASCs alone has had limited success in the treatment of large bone defects. Although bone morphogenetic proteins (BMPs) are believed to be the most potent osteoinductive factors to promote osteogenic differentiation of ASCs, their clinical applications require supraphysiological dosage, leading to high medical burden and adverse side effects. In the present study, we demonstrated an alternative approach that can effectively complement the BMP activity to maximize the osteogenesis of ASCs without exogenous application of BMPs by regulating levels of antagonists and agonists to BMP signaling. Treatment of ASCs with the amiloride derivative phenamil, a positive regulator of BMP signaling, combined with gene manipulation to suppress the BMP antagonist noggin, significantly enhanced osteogenic differentiation of ASCs through increased BMP-Smad signaling in vitro. Furthermore, the combination approach of noggin suppression and phenamil stimulation enhanced the BMP signaling and bone repair in a mouse calvarial defect model by adding noggin knockdown ASCs to apatite-coated poly(lactic-coglycolic acid) scaffolds loaded with phenamil. These results suggest novel complementary osteoinductive strategies that could maximize activity of the BMP pathway in ASC bone repair while reducing potential adverse effects of current BMP-based therapeutics.SignificanceAlthough stem cell-based tissue engineering strategy offers a promising alternative to repair damaged bone, direct use of stem cells alone is not adequate for challenging healing environments such as in large bone defects. This study demonstrates a novel strategy to maximize bone formation pathways in osteogenic differentiation of mesenchymal stem cells and functional bone formation by combining gene manipulation with a small molecule activator toward osteogenesis. The findings indicate promising stem cell-based therapy for treating bone defects that can effectively complement or replace current osteoinductive therapeutics

Label-free quantitative proteomic analysis of molting-related proteins of Trichinella spiralis intestinal infective larvae

International audienceAbstractMolting is a key step for body-size expansion and environmental adaptation of parasitic nematodes, and it is extremely important for Trichinella spiralis growth and development, but the molting mechanism is not fully understood. In this work, label-free LC–MS/MS was used to determine the proteome differences between T. spiralis muscle larvae (ML) at the encapsulated stage and intestinal infective larvae (IIL) at the molting stage. The results showed that a total of 2885 T. spiralis proteins were identified, 323 of which were differentially expressed. These proteins were involved in cuticle structural elements, regulation of cuticle synthesis, remodeling and degradation, and hormonal regulation of molting. These differential proteins were also involved in diverse intracellular pathways, such as fatty acid biosynthesis, arachidonic acid metabolism, and mucin type O-glycan biosynthesis. qPCR results showed that five T. spiralis genes (cuticle collagen 14, putative DOMON domain-containing protein, glutamine synthetase, cathepsin F and NADP-dependent isocitrate dehydrogenase) had significantly higher transcriptional levels in 10 h IIL than ML (P < 0.05), which were similar to their protein expression levels, suggesting that they might be T. spiralis molting-related genes. Identification and characterization of T. spiralis molting-related proteins will be helpful for developing vaccines and new drugs against the early enteral stage of T. spiralis

The effect of Er3+ concentration on the kinetics of multiband upconversion in NaYF4:Yb/Er microcrystals

In Yb-Er co-doped upconversion (UC) nanomaterials, upconversion luminescence (UCL) can be modulated to generate multiband UCL emissions by changing the concentration of activator Er3+. Nonetheless, the effect of the Er3+ concentrations on the kinetics of these emissions is still unknown. We here study the single β-NaYF4:Yb3+/Er3+ microcrystal (MC) doped with different Er3+ concentrations by nanosecond time-resolved spectroscopy. Interestingly, different Er3+ doping concentrations exhibit different UCL emission bands and UCL response rates. At low Er3+ doping concentrations (1 mol%), multiband emission in β-NaYF4:Yb3+/Er3+ (20/1 mol%) MCs could not be observed and the response rate of UCL was slow (5–10 μs) in β-NaYF4:Yb3+/Er3+. Increasing the Er3+ doping concentration to 10 mol% can shorten the distance between Yb3+ ions and Er3+ ions, which promotes the energy transfer between them. β-NaYF4:Yb3+/Er3+ (20/10 mol%) can achieve obvious multiband UCL and a quick response rate (0.3 µs). However, a further increase in the Er doping concentration (80 mol%) makes MCs limited by the CR process and cannot achieve the four-photon UC process (4F5/2 → 2K13/2 and 2H9/2 → 2D5/2). Therefore, the result shows that changing the Er3+ doping concentration could control the energy flow between the different energy levels in Er3+, which could affect the response time and UCL emission of the Yb/Er doped rare earth materials. Our work can facilitate the development of fast-response optoelectronics, optical-sensing, and display industries