Overexpression of CXCL14 Alleviates Ventilator-Induced Lung Injury through the Downregulation of PKM2-Mediated Cytokine Production.

Ventilator-induced lung injury (VILI) is one of the most common complications of mechanical ventilation (MV), which strongly impacts the outcome of ventilated patients. Current evidences indicated that inflammation is a major contributor to the pathogenesis of VILI. Our results showed that MV induced excessive proinflammatory cytokine productions together with decreased CXCL14 and increased PKM2 expressions in injured lungs. In addition, CXCL14 overexpression downregulated PKM2 expression and attenuated VILI with reduced inflammation. Moreover, the overexpression of PKM2 markedly diminished the protective effects of CXCL14 against VILI as reflected by worsened morphology and increased cytokine production, whereas PKM2 knockdown decreased cytokine production and attenuated VILI. Collectively, these results suggested that CXCL14 overexpression attenuates VILI through the downregulation of PKM2-mediated proinflammatory cytokine production.

Nitrosporeusine A attenuates sepsis-associated acute kidney injury through the downregulation of IL-6/sIL-6R axis activation-mediated PGC-1α suppression.

Nitrosporeusine A (NA) has been recently reported to exert anti-inflammatory and renal protective effects, but whether NA can attenuate sepsis-associated acute kidney injury (AKI) has not yet been reported. In this study, our results found that cecal ligation and puncture (CLP) reduced renal PGC-1α expression and induced oxidative stress in C57BL/6 mice. PGC-1α overexpression attenuated CLP-induced AKI with decreased oxidative stress, whereas worsened AKI with excessive reactive oxygen species (ROS) production was observed in renal specific PGC-1α knockout (NiPKO) mice. In addition, PGC-1α expression is retained in IL-6-/- mice and wild-type (WT) C57BL/6 mice received JAK2/STAT3 inhibition. Finally, administration of NA attenuated CLP-induced AKI with decreased IL-6/sIL-6R axis activation, increased PGC-1α expression, and diminished ROS production in injured kidneys. However, NA failed to attenuate CLP-induced AKI in NiPKO mice. Together, these results suggested that NA attenuates sepsis-associated AKI through the downregulation of IL-6/sIL-6R axis activation-mediated renal PGC-1α suppression.

Quantification of prochlorperazine maleate in human plasma by liquid chromatography-mass spectrometry: Application to a bioequivalence study.

A sensitive and specific method using a one-step liquid-liquid extraction with dichloromethane followed by liquid chromatographic-electrospray ionization-mass spectrometric was developed and validated to determine prochlorperazine maleate in human plasma using amitriptyline hydrochloride as an internal standard. The samples were separated using a Thermo Hypersil-Hypurity C18 reversed-phase column (150mmx2.1mm i.d., 5mum). A mobile phase containing 10mM ammonium acetate (pH 3.6)-methanol-acetonitrile (27:68:5, v/v/v) was used isocratically eluting at a flow rate of 0.22ml/min. The average extraction recovery of prochlorperazine and internal standard were 81.8+/-2.2% and 79.5+/-3.7%, respectively. Prochlorperazine maleate and internal standard were measured by electrospray ion source in positive selective ion monitoring mode. The method demonstrated that good linearity ranged from 0.20 to 6.40ng/ml with r(2)=0.9989. The limit of quantification for prochlorperazine maleate in the plasma was 0.20ng/ml. The established method has been successfully applied to a bioequivalence study of two prochlorperazine maleate formulations in 18 healthy male Chinese volunteers.

[Comparison of ferulic acid and paeoniflorin between traditional slice decoction and dispensing granule decoction of Siwu Tang].

OBJECTIVE: To compare the contents of ferulic acid and paeoniflorin between traditional slice decoction and dispensing granule decoction of Siwu Tang. METHODS: A HPLC method detected ferulic acid and paeoniflorin with Diamonsil C18 (4.6 mm x 250 mm, 5 microm) column. The column temperature was setup at 35 degrees C and the flow rate was 1 ml/min. The mobile phase for ferulic acid was a mixed solution of MeOH-H2O-0.05% H3PO4 (40:50:10) and the wavelength was 327 nm, while for paeoniflorin was a mixed solution of CH3CN-H2O-0.05% H3PO4 (16:74:10) and the wavelength was 230 nm. RESULTS: The contents of ferulic acid and paeoniflorin in the dispensing granule decoction were 8.91 mg/dose and 83.57 mg/dose, in the traditional slice decoction were 8. 90 mg/dose and 78. 51 mg/dose, and in the dispensing granule decoction from different factories were from 3.36 to 7.67 mg/dose and from 48.13 to 67.52 mg/dose. CONCLUSION: The HPLC chromatotograms are similar in the two forms of Siwu Tang and the contents of ferulic acid and paeoniflorin are equivalent, but discrepant in the dispensing granule decoction from different factories.