Blocking postsynaptic density-93 binding to C-X3-C motif chemokine ligand 1 promotes microglial phenotypic transformation during acute ischemic stroke.

We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357-395 of C X3 C motif chemokine ligand 1 (CX3CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3CL1 (comprising amino acids 357-395 of CX3CL1) disrupts the interaction between postsynaptic density-93 and CX3CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3CL1 (357-395aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3CL1. Furthermore, the a disintegrin and metalloprotease domain 17 (ADAM17) inhibitor GW280264x, which inhibits metalloprotease activity and prevents CX3CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3CL1 formation. Additionally, Tat-CX3CL1 (357-395aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31-34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3CL1 (357-395aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3CL1 (357-395aa) is a potential therapeutic agent for ischemic stroke.

Effects of inverse ratio ventilation combined with lung protective ventilation on pulmonary function in patients with severe burns for surgery.

OBJECTIVE: To investigate the effects of inverse ratio ventilation combined with lung-protective ventilation on pulmonary function and inflammatory factors in severe burn patients undergoing surgery. Populations and Methods: Eighty patients with severe burns undergoing elective surgery were divided randomly into two groups: control (CG, n = 40) and experiment (EG, n = 40). The CG had conventional ventilation, whereas the EG were ventilated with tidal volume (TV) of 6-8 ml/kg, I (inspiration): E (expiration) of 2:1, and positive end-expiratory pressure (PEEP) 5 cm H2O. The following variables were evaluated before (T0), 1 h after start of surgery (T1) and after surgery (T2): oxygenation index (OI), partial pressure of carbon dioxide (PaCO2), TV, peak airway pressure (Ppeak), mean airway pressure (Pmean), PEEP, pulmonary dynamic compliance (Cdyn), alveolar-arterial difference of oxygen partial pressure D(A-a)O2, lactic acid (Lac), interleukin (IL)-6 and IL-10, and lung complications. Results: At T1 and T2 time points, the OI, Pmean and Cdyn were significantly greater in the EG than in the CG while the TV, Ppeak, D(A-a)O2, IL-6 and IL-10 were significantly smaller in the EG than in the CG. At the end of the surgery, the Lac was significantly smaller in the EG than in the CG (1.28 ± 0.19 vs. 1.40 ± 0.23 mmol/L). Twenty-four hours after the surgery, significantly more patients had hypoxemia (27.5 vs. 10.0%), increased expectoration (45.0 vs. 22.5%), increased lung texture or exudation (37.5 vs. 17.5%) in the CG than in the EG. Conclusions: Inverse ratio ventilation combined with lung-protective ventilation can reduce Ppeak, increase Pmean and Cdyn, improve the pulmonary oxygenation function, and decrease ILs in severe burn surgery patients.

Effects of tacrolimus on proliferation, apoptosis, and fluorouracil sensitivity of liver cancer cell line of SMMC-7721.

BACKGROUND: The effect of tacrolimus (FK506) and 5-fluorouracil (5-FU) on hepatocellular carcinoma remains elusive. The aim of this study was to assess the effect of tacrolimus on the proliferation, and apoptosis in liver cancer cell line of SMMC-7721 and its sensitivity to fluorouracil (5-FU). METHODS: The liver cancer cell line of SMMC-7721 was cultured in vitro, and the MTT assay was used to examine the antiproliferative effect of FK506. Flow cytometry (FCM) was used to examine the effect of 5-FU alone or in combination with FK506 on the apoptosis and cell cycle of SMMC-7721 cells. RESULTS: FK506 produced concentration-dependent antiproliferative effect on SMMC-7721 cells at all experimental concentrations (P<0.05), but no effect on induction of apoptosis. 5-FU induced apoptosis in a concentration-dependent manner, whereas the percentage of G0/G1-phase cells and proliferation index (PI) were increased with the increased concentration of 5-FU. Pretreatment with FK506 for 2 hours enhanced the effect of 5-FU on the induction of apoptosis. CONCLUSIONS: FK506 inhibits the growth of SMMC-7721 cells and enhances their sensitivity to 5-FU. This may be associated with the synergic effect of FK506 and 5-FU in inducing apoptosis and G0/G1-phase stasis.

[Raman spectra of YBCO superconductor with hot ultrapressing treatment].

Laser Raman spectra of YBCO oxide superconductor with hot ultrapressing and annealing treatment are reported. In addition to improving physical properties, the spectra data show that the processing can also perfect orthorhombie phase and enhance lattice on orientation trend as well as is good for formation of two dimension CuO2 net. The relation between structure and the superconductivity has been discussed.