Methods for Promoting the Revascularization and Reenervation of CNS Lesions

The present invention provides methods of promoting the revascularization and/or reenervation of central nervous system lesions using an in-situ crosslinkable hydrogel. The present invention also provides methods of treating a spinal cord injury by topically delivering to the spinal cord injury site a vehicle comprising a neurotrophic factor and/or anti-inflammatory agent. Also provided are methods of treating a spinal cord injury by topically administering or delivering a hydrogel to the injury site

Aqua­(2,9-dimethyl-1,10-phenanthroline-κ2 N,N′)bis­(3-hydroxy­benzoato-κO)manganese(II)–2,9-dimethyl-1,10-phenanthroline–water (1/1/1)

In the title compound, [Mn(C7H5O3)2(C14H12N2)(H2O)]·C14H12N2·H2O, the MnII ion is coordinated by a bidentate 2,9-dimethyl-1,10-phenanthroline (dmphen) ligand, two monodentate 3-hydroxy­benzoate anions (3-HBA) and one water mol­ecule in a distorted trigonal-bipyramidal environment. An uncoordinated dmphen and an uncoordinated water mol­ecule cocrystallized with each complex mol­ecule. Intra- and inter­molecular O—H⋯N and O—H⋯O hydrogen bonds are also present between the coordinated 3-HBA and water mol­ecules and the uncoordinated dmphen and water mol­ecules in the crystal. The packing of the structure is further stabilized by π–π stacking inter­actions involving dmphen mol­ecules, with a centroid–centroid separation of 3.705 (3) Å

Elastocaloric effect with a broad temperature window and low energy loss in a nanograin Ti-44Ni-5Cu-1Al (at%) shape memory alloy

Superelastic Ti-Ni-based shape memory alloys are promising elastocaloric materials for solid-state refrigeration. In this paper, we studied the mechanical properties and elastocaloric effect of a severely cold rolled Ti-44Ni-5Cu-1Al (at.%) alloy composed of nanograins (∼5-16 nm). The alloy exhibits partial stress-induced martensitic transformation with a large quasilinear reversible strain of ∼3.4 % and a small energy dissipation of ∼1.6 MJ/m3 when a maximum stress of 1 GPa is applied. The temperature decrease induced by adiabatic removal of a stress of 1 GPa is of about −5 K, which is mainly due to the reverse transition occurring during unloading. The effective working temperature window of elastocaloric effect larger than 200 K. The coefficient of performance of this alloy reaches ∼13, which is higher than values reported so far for Ti-Ni alloys

Cryptopleurine Targets NF-κB Pathway, Leading to Inhibition of Gene Products Associated with Cell Survival, Proliferation, Invasion, and Angiogenesis

Cryptopleurine, a phenanthroquinolizidine alkaloid, was known to exhibit anticancer activity; however, the underlying mechanism is poorly understood. Because the nuclear factor-κB (NF-κB) transcription factors control many physiological processes including inflammation, immunity, and development and progression of cancer, we investigated the effects of cryptopleurine on tumor necrosis factor alpha (TNF-α)-induced NF-κB activation pathway and on the expression of NF-κB-regulated gene products associated with many pathophysiological processes.MDA-MB231, MDA-MB435, MCF-7, HEK293, RAW264.7 and Hep3B cells were used to examine cryptopleurine's effect on the NF-κB activation pathway. Major assays were promoter-reporter gene assay, electrophoretic mobility shift assay (EMSA), in vitro immune complex kinase assay, real-time PCR, Western blot analysis, and Matrigel invasion assay. Experiments documenting cell proliferation and apoptosis were analyzed by MTT method and flow cytometry, respectively. The results indicated that cryptopleurine suppressed the NF-κB activation through the inhibition of IκB kinase (IKK) activation, thereby blocking the phosphorylation and degradation of the inhibitor of NF-κB alpha (IκBα) and the nuclear translocation and DNA-binding activity of p65. The suppression of NF-κB by cryptopleurine led to the down-regulation of gene products involved in inflammation, cell survival, proliferation, invasion, and angiogenesis.Our results show that cryptopleurine inhibited NF-κB activation pathway, which leads to inhibition of inflammation, proliferation, and invasion, as well as potentiation of apoptosis. Our findings provide a new insight into the molecular mechanisms and a potential application of cryptopleurine for inflammatory diseases as well as certain cancers associated with abnormal NF-κB activation

High-mobility-group box protein 1 A box reduces development of sodium laurate-induced thromboangiitis obliterans in rats

ObjectiveHigh-mobility-group box protein 1 (HMGB1), as a late mediator of inflammation, plays a key role in inflammatory responses by inducing and extending the production of proinflammatory cytokines. The effect of HGMB1 in the inflammatory disease thromboangiitis obliterans (TAO) is unknown. We aimed to investigate the role of HMGB1 in sodium laurate-induced TAO in rats.MethodsMale Wistar rats were randomly divided into five groups (n = 8 each) for treatment: normal, sham-operated, TAO model, and low-dose (15 mg/kg) or high-dose (30 mg/kg) recombinant A box (rA box) infection (administered intraperitoneally once daily for 15 days). The TAO model was induced by sodium laurate and graded by gross appearance on day 15 after femoral artery injection. Histologic changes were measured by histopathology in rat femoral arteries. Plasma levels of HMGB1, thromboxane B2, 6-keto-prostaglandin F1-α, and blood cell counts and blood coagulation levels were measured. Expression of HMGB1, receptor for advanced glycation end-products (RAGE), interleukin-6, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 was assessed by immunohistochemistry and immunofluorescence, Western blot analysis, and quantitative reverse-transcription polymerase chain reaction.ResultsThe typical signs and symptoms of TAO were observed on day 15 after sodium laurate injection. The expression of HMGB1, RAGE, interleukin-6, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 was markedly increased in rat femoral arteries. Plasma levels of HMGB1 and thromboxane B2 were elevated, but the level of 6-keto-prostaglandin F1-α was decreased. Blood was in a hypercoagulable state, and prothrombin, thrombin, and activated partial thromboplastin times were all significantly shortened, whereas fibrinogen level was increased in TAO rats compared with sham-operated rats. These effects were terminated by the HMGB1 antagonist rA box.ConclusionsHMGB1 is involved in the inflammatory state in a model of TAO induced by sodium laurate in rats, probably via its receptor RAGE. As the antagonist of HMGB1, rA box can attenuate the development of TAO, which may be a potential therapeutic target for the treatment of TAO.Clinical RelevanceThromboangiitis obliterans (TAO), or Buerger disease, is a segmental nonatherosclerotic inflammatory disorder. Patients with Buerger disease have a lower quality of life because of intermittent claudication, rest pain, ulcers, and superficial thrombophlebitis. The specific etiology and pathologic mechanisms remain not elucidated. High-mobility-group box protein 1, as a late mediator of inflammation, plays a key role in inflammatory responses to tissue injury and infection by inducing and extending the production of proinflammatory cytokines. Here, we explored the role of high-mobility-group box protein 1 in rat model of TAO, discovering a new damage marker in TAO. We also investigated the unique role of recombinant A box in the prevention and treatment of TAO

Effect of Modulating Activity of DLPFC and Gender on Search Behavior: A tDCS Experiment

Studies of search behavior have shown that individuals stop searching earlier and accept a lower point than predicted by the optimal, risk-neutral stopping rule. This behavior may be related to individual risk preferences. Studies have also found correlativity between risk preferences and the dorsolateral prefrontal cortex (DLPFC). As risk attitude plays a crucial role in search behavior, we studied whether modulating the activity of DLPFC, by using a transcranial direct current stimulation (tDCS) device, can change individual search behavior. We performed a sequential search task in which subjects decided when to accept a point randomly drawn from a uniform distribution. A total of 49 subjects (23 females, mean age = 21.84 ± 2.09 years, all right-handed) were recruited at Zhejiang University from May 2017 to September 2017. They repeated the task in 80 trials and received the stimulation at the end of the 40th trial. The results showed that after receiving right anodal/left cathodal stimulation, subjects increased their searching duration, which led to an increase in their accepted point from 778.17 to 826.12. That is, the subjects may have changed their risk attitude to search for a higher acceptable point and received a higher benefit. In addition, the effect of stimulation on search behavior was mainly driven by the female subjects rather than by the male subjects: the female subjects significantly increased their accepted point from 764.15 to 809.17 after right anodal/left cathodal stimulation, while the male subjects increased their accepted point from 794.18 to 845.49, but the change was not significant