In the present study, we examined the mechanisms of hydrogen-rich saline, a reported therapeutic antioxidant, in the treatment of acute spinal cord contusion injury. Male Sprague-Dawley rats were used to produce a standardized model of contuses spinal cord injury (125 kdyn force). Hydrogen-rich saline was injected intraperitoneally (5 ml/kg) immediately, and at 24 and 48 h after injury. All rats were sacrificed at 72 h after spinal cord injury (SCI). Apoptotic cell death, oxidative stress, inflammation, level of Brain derived neurotrophic factor (BDNF) were evaluated. In addition, locomotor behavior was assessed using the Basso, Beattice and Bresnahan (BBB) scale. We observed that administration of hydrogen-rich saline decreased the number of apoptotic cells, suppressed oxidative stress, and improved locomotor functions. Hydrogen-rich saline increased the release of BDNF. In conclusion, hydrogen-rich saline reduced acute spinal cord contusion injury, possibly by reduction of oxidative stress and elevation of BDNF.

The brain-derived neurotrophic factor (BDNF) plays a critical role in pain hypersensitivity. BDNF is the ligand of P2X4 receptors (P2X4R) in the microglia. The causative factors involving the P2X4R over expression in the microglia remains unclear. Mast cell activation has a close relation with pain hypersensitivity. However, the underlying mechanism between mast cell activation and pain hypersensitivity is unknown. The present study aimed to elucidate the mechanism by which mast cell activation promoted the expression of P2X4R in the microglia. The results of present study showed that mast cell activation markedly promoted the expression of P2X4R and BDNF in microglial cells, which significantly enhanced the release of BDNF from microglial cells upon exposure to adenosine triphosphate. Mast cell-derived tryptase activated PAR2 that resulted in promoting the expression of P2X4R in microglial cells. Pretreatment with antibodies against tryptase or PAR2, or using tryptase-deficient HMC-1 cells or PAR2-deficient microglial cells abolished the increase in P2X4R expression and BDNF release. Increase in mitogen activated protein kinase phosphorylation was observed in the processes of mast cell-induced BDNF release and P2X4R expression. We conclude that mast cell activation has the capacity to promote the expression of P2X4R and BDNF in microglial cells.

Ischemic stroke is a major cause of death and disability worldwide.At present, the strategy for the treatment of acute ischemic stroke is to perform revascularization within a strict time window, leading to ischemic/reperfusion injury, which comes with a series of biochemical cascades. 1 A previous study using an experimental ischemia model found that serine protein inhibitor A3N (serpinA3N) expression dramatically increases following stroke 1 , suggesting that it may play a role in stroke.

Background and Aims:Osteomyelitis is a common manifestation of invasive Staphylococcus aureus infection characterized by bone loss and destruction. We investigated the role of toll-like receptor 2 (TLR2) in bacterial recognition and clearance in response to infection with an osteomyelitis isolate of S. aureus. Methods:Apoptosis was assessed in the osteoblastic cell line MC3T3-E1 by Annexin V-FITC/PI staining and flow cytometry. The expression of TLR2 and apoptosis-related and mitogen-activated protein kinase pathway proteins was assessed by qRT-PCR and western blotting. Alkaline phosphatase (ALP) activity and calcium deposition were assessed by ALP activity assay and Alizarin red staining. Results:S. aureus induced apoptosis, upregulated TLR2 expression, and activated mitogen-activated protein kinase pathways in a time dependent manner. Inhibition of the c-Jun N-terminal kinase (JNK) pathway downregulated TLR2 and suppressed the S. aureus induced activation of pro-apoptotic pathways. Short-hairpin RNA mediated silencing of TLR2 reversed S. aureus induced apoptosis and decrease in ALP activity and calcium deposition, and inhibition of JNK had a similar effect. Conclusion:We showed that osteoblast apoptosis and osteogenic differentiation in response to bacterial invasion are dependent on TLR2 expression and JNK activation, suggesting novel potential therapeutic targets for the treatment of osteomyelitis.

Background Glaucoma is the world's second biggest cause of blindness, and patients progressively lose their eyesight. The current clinical treatment for glaucoma involves controlling intraocular pressure with drugs or surgery; however, some patients still progressively lose their eyesight. This treatment is also similar to the treatment of traumatic optic neuropathy. Thus, saving retinal ganglion cells (RGCs) from apoptosis is essential. Methods The role of Acteoside on autophagy modulation in the 661 W cell line. Results In this study, we first find that Acteoside inhibits autophagy, Rapamycin alleviates this inhibition and the PI3K inhibitor, 3‐MA or LY294002, synergistically promotes it. In a mechanistic study, we find that Optineurin (OPTN) mediates Acteoside regulation of autophagy. OPTN overexpression or knockdown activates or inhibits autophagy, respectively. OPTN is inhibited by autophagy inhibitors, such as Acteoside and 3‐MA and is promoted by the autophagy activator, Rapamycin. Meanwhile, PI3K and AKT are elevated by Acteoside and 3‐MA and inhibited by Rapamycin. Finally, we find that Acteoside inhibits apoptosis in parallel to autophagy and that this inhibition is also mediated by OPTN. Conclusion In summary, we conclude that Acteoside inhibits autophagy‐induced apoptosis in RGCs through the OPTN and PI3K/AKT/mTOR pathway, and glaucoma patients may benefit from Acteoside treatment alone or in combination with other autophagy inhibitors.

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Bone defect complicated by infection remains a major challenge in orthopedic surguries, and bone grafting for primary repair often associates with high failure rate. The rapid progress in the research spectrums of tissue-engineered bone and antibiotic delivery systems bring hope to solve this issue. Herein, we evaluated the local anti-infective and osteogenic potential of an injectable anti-infection tissue-engineered construct, which includes a fibrin gel scaffold and vancomycin alginate beads (Vanco-AB) to form composites, in the treatment of chronic osteomyelitis with bone defect in rabbit tibia. The infected bone defect model of rabbit tibia was established. Then, the bone defects in the proximal tibial metaphysis were implanted with the constructed composites, containing different combinations of mesenchymal stem cells and Vanco-AB. The in vivo capacities of anti-infection and local osteogenesis of the grafts were determined using radiographic assessment, histopathological observation, and microorganism cultures. Results showed that the injectable anti-infection tissue-engineered construct, comprising a fibrin gel scaffold and Vanco-AB led to efficient eradication of bacteria. At 1 and 3 months after transplantation, the radiographic assessment and microbiological examination demonstrated that the sustained antibiotic release by Vanco-AB significantly decreased the Norden scores of osteomyelitis, generated negative results for the presence of bacteria, and reduced the relapse of osteomyelitis. Meanwhile, tissue-engineered construct implanted in one-stage promoted local bone repair and reconstruction, and it exhibited more apparent osteogenic potential, compared to the control group (without Vanco-AB). In conclusion, the current study achieved the primary repair of bone defect with infection, thus providing an alternative treatment strategy for infected bone defect, which occurs commonly in chronic osteomyelitis.

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