Ryk receptors on unmyelinated nerve fibers mediate excitatory synaptic transmission and CCL2 release during neuropathic pain induced by peripheral nerve injury.

Background Neuropathic pain is a major pathology of the central nervous system associated with neuroinflammation. Ryk (receptor-like tyrosine kinase) receptors act as repulsive axon-guidance molecules during development of central nervous system and neural injury. Increasing evidence suggests the potential involvement of Wnt/Ryk (wingless and Int) signaling in the pathogenesis of neuropathic pain. However, its underlying mechanism remains unknown. Results The expression and location of Ryk receptor as well as its ligand Wnt1 were detected by qPCR, Western blot, and immunohistochemistry. We found that Ryk, a specific Wnt receptor, was expressed in IB4+ (Isolectin B4) and CGRP+ (calcitonin gene-related peptide) dorsal root ganglia neurons and their ascending unmyelinated fibers in the dorsal horn of the spinal cord. Ryk was upregulated after spinal nerve ligation surgery. Wnt1 was also increased in activated astrocytes in the dorsal horn after spinal nerve ligation. The presynaptic mechanism of Ryk in regulation of neuropathic pain was determined by electrophysiology in spinal slice. Spinal nerve ligation model was established, and the therapeutic potential of inhibiting Ryk receptor was determined. Spine-specific blocking of the Wnt/Ryk receptor signaling attenuated the spinal nerve ligation-induced mechanical allodynia but not thermal hyperalgesia. Further, it also blocked Ca2+-dependent signals including CaMKII and PKCγ, subsequent release of CCL2 (CCR-like protein) in the dorsal horn. An in vitro study showed that inactivating Ryk receptors with anti-Ryk antibodies or lentiviral Ryk shRNA led to the inactivation of Wnt1 for excitatory synaptic transmission in spinal slices and subsequent decrease in CCL2 expression in the dorsal root ganglia neurons. Conclusion These studies demonstrate the existence of critical crosstalk between astrocytes and unmyelinated fibers, which indicate the presynaptic mechanism of Ryk in cytokine transmission of neuropathic pain and the therapeutic potential for Wnt/Ryk signaling pathway in the treatment of neuropathic pain.

Parthenolide Induces Reactive Oxygen Species-Mediated Autophagic Cell Death in Human Osteosarcoma Cells.

BACKGROUND AND AIM: Osteosarcoma is a devastating tumor of bone, primarily affecting adolescents. Parthenolide, a naturally occurring small molecule that interferes with NF-κB signaling, has recently attracted considerable attention because of its pharmacological action involving anti-cancer effects. However, the mechanism of the cytotoxic effect exerted by parthenolide on tumor cells is not clearly defined today. METHODS: In this study, the effects of parthenolide were evaluated and characterized in human osteosarcoma cancer cell. Cell viability was assessed by CCK-8. Apoptosis was assessed by Annexin V-FITC/PI Flow cytometry assay. Relative quantitative real-time PCR and western blot were used to determine the expressions of genes and proteins. RESULTS: Our results suggest that parthenolide did not cause caspase-dependent cell death in osteosarcoma cancer cells, as indicated by the absence of significant early apoptosis as well as caspase-3 cleavage. Instead, parthenolide increased the autophagy and mitophagy, as characterized by increased PINK1 and Parkin translocation to mitochondria and enhanced autophagy proteins. The induction of autophagy by parthenolide was associated with the increase of reactive oxygen species (ROS). ROS antioxidants N-acetylcysteine (NAC) attenuated parthenolide-induced autophagy activity. CONCLUSIONS: Our findings unveil a novel mechanism of drug action by parthenolide in osteosarcoma cancer cells and suggest a potential value of treating osteosarcoma cancer through a caspase-independent autophagic cell death by ROS activation.

Minimally invasive treatment for Neer IIb distal clavicle fractures with titanium cable.

BACKGROUND: Neer IIB distal clavicle fracture is associated with disruption of the coracoclavicular ligament and a variable degree of displacement. Surgical treatment using various implants such as intramedullary wires, screws, and plates has been described in the literature with satisfactory results. METHODS: We report our experience of minimally invasive treatment using titanium cable for type IIB clavicular fractures. A retrospective analysis was performed to evaluate the outcomes of patients with Neer IIB distal clavicle fractures that were treated with titanium cable between 2003 and 2008. Functional outcome was evaluated using the Karlsson's criteria. The mean follow-up was 32 months (range, 12-48 months). Twenty-nine patients met the inclusion criteria. RESULTS: All patients progressed to osseous union at a mean time of 12 weeks (range, 10-15 weeks). There was one metal work failure that did not affect functional recovery. According to Karlsson's criteria, radiographic representations (3 months after surgery) and postoperative shoulder functional recovery revealed an excellent and good rate in all cases. CONCLUSION: Minimally invasive surgery using titanium cable seems to be a good option for the treatment of Neer IIB distal clavicle fractures, with early functional recovery and no requirement for revision surgery.

Effects of He-Ne laser irradiation on chronic atrophic gastritis in rats.

AIM: To study the effects of He-Ne laser irradiation on experimental chronic atrophic gastritis (CAG) in rats. METHODS: Sixty-three male adult Wistar rats were randomly divided into five groups including normal control group, model control group and three different dosages He-Ne laser groups. The chronic atrophic gastritis (CAG) model in rats was made by pouring medicine which was a kind of mixed liquor including 2% sodium salicylate and 30% alcohol down the throat for 8 wk to stimulate rat gastric mucosa, combining with irregular fasting and compulsive sporting as pathogenic factors; 3.36, 4.80, and 6.24 J/cm(2) doses of He-Ne laser were used, respectively for three different treatment groups, once a day for 20 d. The pH value of diluted gastric acid was determined by acidimeter, the histopathological changes such as the inflammatory degrees in gastric mucosa, the morphology and structure of parietal cells were observed, and the thickness of mucosa was measured by micrometer under optical microscope. RESULTS: In model control group, the secretion of gastric acid was little, pathologic morphological changes in gastric mucosa such as thinner mucous, atrophic glands, notable inflammatory infiltration were found. After 3.36 J/cm(2) dose of He-Ne laser treatment for 20 d, the secretion of gastric acid was increased (P<0.05), the thickness of gastric mucosa was significantly thicker than that in model control group (P<0.01), the gastric mucosal inflammation cells were decreased (P<0.05). Morphology, structure and volume of the parietal cells all recuperated or were closed to normal. CONCLUSION: 3.36 J/cm(2) dose of He-Ne laser has a significant effect on CAG in rats.

Treatment of chitin-producing wastewater by micro-electrolysis-contact oxidization.

The technique of micro-electrolysis-contact oxidization was exploited to treat chitin-producing wastewater. Results showed that Fe-C micro-electrolysis can remove about 30% COD(cr), raise pH from 0.7 to 5.5. The COD(cr) removal efficiency by biochemical process can be more than 80%. During a half year's operation, the whole system worked very stably and had good results, as proved by the fact that every quality indicator of effluent met the expected discharge standards; which means that chitin wastewater can be treated by the technique of micro-electrolysis, contact oxidization.

CH4 emission and recovery from municipal solid waste in China.

Methane ( CH4) is an important greenhouse gas and a major environmental pollutant, second only to carbon dioxide (CO2) in its contribution to potential global warming. In many cases, methane emission from landfills otherwise emitted to the atmosphere can be removed and utilized, or significantly reduced in quantity by using coat-effective management methods. The gas can also be used as a residential, commercial, or industrial fuel. Therefore, emission reduction strategies have the potential to become low cost, or even profitable. The annual growth rate of Municipal Solid Waste (MSW) output in China is 6.24%, with the highest levels found in South China, Southwest China and East China. Cities and towns are developing quickly in these regions. MSW output was only 76.36 Mt in 1991 and increased to 109.82 Mt in 1997, registering an average increase of 43.8% . In China, methane emission from landfills also increased from 5.88 Mt in 1991 to 8.46 Mt in 1997; so the recovery of methane from landfills is a profitable project.