A Novel Chinese Medicine Formula Inhibits Non-small Cell Lung Cancer by Triggering Oxidative Stress Dependent on Pentose Phosphate Pathway / 中国肺癌杂志

BACKGROUND@#Non-small cell lung cancer (NSCLC) is one of the most lethal malignancies worldwide. A novel Chinese medicine formula-01 (NCHF-01) has shown significant clinical efficacy in the treatment of NSCLC, but the mechanism of this formula in the treatment of NSCLC is not fully understood. The aim of this study is to investigate the molecular mechanism of NCHF-01 in inhibiting NSCLC.@*METHODS@#Lewis lung cells (LLC) tumor bearing mice were established to detect the tumor inhibitory effect of NCHF-01. The morphological changes of tissues and organs in LLC tumor-bearing mice were detected by hematoxylin-eosin (HE) staining. NSCLC cells were treated by NCHF-01. The effects of cell viability and proliferation were detected by MTT and crystal violet staining experiment. Flow cytometry was used to detect cell cycle, apoptosis and reactive oxygen species (ROS). Network pharmacology was used to predict the mechanism of its inhibitory effect of NSCLC. Western blot and immunohistochemistry (IHC) were used to detect the expression of related proteins.@*RESULTS@#NCHF-01 can inhibit tumor growth in LLC tumor-bearing mice, and has no obvious side effects on other tissues and organs. NCHF-01 could inhibit cell viability and proliferation, induce G2/M phase arrest and apoptosis, and promote the increase of ROS level. Network pharmacological analysis showed that NCHF-01 exerts anti-NSCLC effects through various biological processes such as oxidative stress and central carbon metabolism. NCHF-01 can reduce the protein expression and enzyme activity of the key enzymes 6-phosphate glucose dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) in the pentose phosphate pathway (PPP).@*CONCLUSIONS@#NCHF-01 can inhibit NSCLC through oxidative stress dependent on the PPP.

Estimation model for the exposure of mycophenolic acid in early renal transplant recipients / 中国药房

OBJECTIVE To establish the estimation model for the exposure of mycophenolic acid （MPA） in early renal transplant recipients [calculated by the area under the plasma concentration-time curve with 12 h （AUC0－12 h）]. METHODS Twenty kidney transplant recipients， who received triple immunosuppressive therapy of mycophenolate mofetil （MMF）+tacrolimus+ methylprednisolone， were selected and given MMF dispersible tablets （750 mg， q12 h） on the 15th day after the operation； the blood samples were collected from the patients before and 0.5， 1.0， 1.5， 2.0， 3.0， 4.0， 6.0， 8.0， 12.0 hours after the administration， respectively. The blood concentration of MPA was determined， and the pharmacokinetic parameters of MPA were calculated. The multivariate linear stepwise regression analysis method was used to fit an estimation formula for the finite sampling method suitable for MPA-AUC0－12 h of the recipients. Bland-Altman analysis was used to evaluate the agreement between the estimation formula and the classical pharmacokinetic method. RESULTS The main pharmacokinetic parameters of MPA in 20 renal transplant recipients： c0 was （1.53±0.84） μg/mL， cmax was （12.07±5.97） μg/mL， t1/2 was （5.41±3.67） h， tmax was （1.58±0.75） h， and the average AUC0－12 h calculated by the classical pharmacokinetic method was （33.95±13.40） μg·h/mL. MPA-AUC0－12 h was estimated with sampling points of “4.0， 8.0， 12.0 h”； the simplified calculation formula was AUC0－12 h＝12.058+2.819c4.0+7.045c8.0+ 3.879c12.0 （R 2＝0.934）. The predicted value had a good correlation and consistency with the measured value， and 95.0% of predicted values did not exceed the x±1.96SD （standard deviation） range. CONCLUSIONS The estimation model is established successfully for the exposure of MPA in early renal transplant recipients； the model has better prediction accuracy and fewer sampling points.

Effects of hypoxia/reoxygenation on apoptosis and gap junction in isolated renal tubular epithelial cells of rats / 中华麻醉学杂志

Objective To evaluate the effects of hypoxia/reoxygenation (H/R) on apoptosis and gap junction in isolated renal tubular epithelial cells of rats.Methods The renal tubular epithelial cells were seeded in 6-well plates at a density of 1 × 105 cells/ml and randomly divided into 2 groups (n =18 wells each) using a random number table:control group (group C) and H/R group.In group C,the cells were cultured in a regular incubator with 21％ oxygen at 37 ℃.In group H/R,the cells were incubated in an anaerobic chamber for 24 h and then returned to a regular incubator and incubated for 4 h.Hoechst33258 staining method and flow cytometry were used to detect the cell apoptosis.Gap junction function was determined by specific parachute assay.Gap function protein connexin 43(Cx43) expression was measured by Western blot.Results Compared with group C,the apoptosis rate was significantly increased and gap junction function and Cx43 expression were decreased in group H/R (P ＜ 0.05).Conclusion H/R promotes apoptosis in isolated renal tubular epithelial cells through destroying intercellular gap junction in rats.

Effects of propofol, etomidate and midazolam on gap junction function in rats / 中华麻醉学杂志

Objective To evaluate the effects of propofol,etomidate and midazolam on gap junction function in rats in vitro and in vivo.Methods Experiment Ⅰ NRK52E cells were seeded in 6-well plates with the density of 1.0 × 105/ml and randomly divided into 4 groups (n =6 wells each):control group (group C),propofol group (group P),etomidate group (group E) and midazolam group (group M).In group C,NRK52E cells were cultured in DMEM-F12 culture medium containing 10％ fetal bovine serum.In P,E and M groups,propofol,etomidate and midazolam (with the final concentrations of 15,8 and 4μmol/L,respectively) were added to the culture medium,respectively,and the cells were then incubated for 1 h.Parachute dye-coupling assay was used to measure the gap junction function in NRK52E cells.Experiment Ⅱ Twenty-four male Sprague-Dawley rats,aged 2 months,weighing 220-280 g,were randomly divided into 4 groups (n =6 each):propofol group (group P),etomidate group (group E),midazolam group (group M),and control group (group C).In P,E and M groups,propofol 100 mg/kg,etomidate 6 mg/kg and midazolam 5 mg/kg were injected intraperitoneally once a day for 3 consecutive days,respectively.The equal volume of normal saline was given instead in group C.The animals were sacrificed at 30 min after the last administration and the renal cortex was harvested to measure the gap junction function using tissue scrape and load assay.Results Compared with group C,the gap junction function was significantly decreased in P and E groups (P ＜ 0.05),and no significant change was found in the gap junction function in group M (P ＞ 0.05).Conclusion Propofol and etomidate significantly inhibit the gap junction function in NRK52E cells and renal tissues in rats,but midazolam produces no effect.