Objective To investigate the protective effects ofAngiotensin-(1-7) [Ang-(1-7)] against the focal cerebral ischemic-reperfusion injury in rats. Methods Spragne-Dawley rats were randomly divided into sham operated group, Ang-(1-7) treated group and aCSF treated group. The latter 2 groups were subjected to middle cerebral artery occlusion (MCAO). The 3 groups were administrated artificial cerebrospinal fluid (aCSF, 0.5 μL/h), Ang-(1-7) (100 pmol, 0.5 μL/h) and aCSF 0.5 μL/h,respectively, by implanted Alzet osmotic minipumps into lateral cerebral ventricle at reperfusion 24 h and 48 h. In all experimental rats, their neurological function scores, the brain edema at reperfusion 48 h and the cerebral infarct size at reperfusion 24 h were evaluated. And the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the ischemic cerebral tissue at reperfusion 24 h and 48 h were also determined. The number of apoptotic neurons within the tissue around the infarct at reperfusion 48 h was detected by the way of staining with terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick-end labeling (TUNEL). Results In the treatment of MCAO rats, Ang-(1-7) significantly ameliorated their neurological function score (P＜0.05), reduced the infarct size (P＜0.05), decreased the tissue MDA content (P＜0.05), increased the tissue SOD activity (P＜0.05). It also reduced markedly the number of apoptotic neurons around the infarct (P＜0.01), but had no effect on the water content in the brain. Conclusions Ang- (1-7) has a neuroprotective effect against cerebral ischemic-reperfusion injury, perhaps by its anti-oxidation stress and inhibition of neuronal apoptosis.

Dexamethasone ; therapeutic use ; Humans ; Liver Diseases ; drug therapy ; Reperfusion Injury ; drug therapy

Objective To investigate plasma levels of total carnitine (TC) and free camitine (FC) in patients undergoing hemodialysis and peritoneal dialysis.Methods 200 cases of normal group came from physical examination in this hospital,all testing cases were the in-hospital patients in the department of nephropathy.TC and FC were determined by use of an enzymatic cycle assay on Hitachi 7170 automatic biochemical analyzer.Results In 200 cases of normal group,TC level was (56.52?9.61) ?mol/L,and FC was (46.60?8.23) ?mol/L.In 37 hemodialysis patients,TC and FC levels were (41.47?13.22) ?mol/L and (24.58?8.91)?mol/L before dialysis,a statistic difference was observed against the control group (P0.05).Conclusions Carnitine deficiency was seen in most patients undergoing hemodialysis and peritoneal dialysis.Furthermore,the deficiency status got worse along with the dialysis course in hemodialysis patients.Carnitine infusion can effectively improve the status of these patients.

Objective To analyze the situation of smoking control calls at 12345 citizens′ hotline in Shanghai and investigate the smoking control hotspots concerned by citizens, the handling efficiency and quality of the hotline management, especially after the tobacco control ordinance was amended. Methods Statistical analysis was made on 48 945 smoking control calls, and data model established by natural language processing. Results After amendment of the tobacco control ordinance, there was a great increase in the number of smoking control calls, which reached a peak in 2017, and became 6.7 times that of 2016.Complaint report was the most important part of tobacco control calls, accounting for 76.24% of the total.Work and dining places were the main venue for complaints, while restaurants and offices were with the largest number of calls.The proportion of health departments in all responsible departments was the largest, accounting for 29.71%.Criticism and education were still the main way to deal with the problem, which was far from meeting the demands of citizens in this regard. Conclusion Publicity can mobilize the enthusiasm of the citizens to participate in tobacco control.The working efficiency and quality of responsible departments still needs to be improved.Citizen′s appeal can serve as a reference for future amendments to the law.

Signal transducer and activator of transcription (STAT) 3 is a critical transcription factor for cell proliferation and survival. It is activated within cells by many cytokines to mediate immune and inflammatory responses to injury. Inflammatory bowel disease (IBD), represented by Crohn′s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the intestinal tract. STAT3 has been shown to be abnormally activated in IBD colon tissues by many pro-inflammatory cytokines, leading to disruption of the intestinal mucosal barrier and excessive innate immune and Th17 responses. The persistent chronic inflammation eventually leads to intestinal fibrosis and stenosis. In addition to immune responses, STAT3 is also involved in intestinal fibrosis in IBD by promoting the transcription of fibrosis-related genes. Colitis-associated cancer (CAC) is a particularly aggressive subtype of colorectal cancer and is associated with chronic inflammation-induced IBD. STAT3 has also been associated with CAC initiation and development. STAT3 is overactivated in tumors, which leads to suppression of the anti-tumor activity of immune cells and promotion of cancer cell proliferation, tumor angiogenesis, invasion, and migration. In the present article, we summarize the role of STAT3 in IBD and CAC and the research progress of the related drugs developed for UC and CAC treatment.

AIMTo investigate the effects of NPPB, a chloride channel blocker, on proliferation of mesangial cells.

METHODSCell proliferation was determined by measuring cell number and 3H-thymidine incorporation. The LDH activity released from these cells was measured as evaluation of cell viability. The phase of cell cycle was detected by flow cytometry.

RESULTSCell proliferation assays showed that treatment with both NPPB (50 and 25 micromol x L(-1)) and in hypertonic media (100% increased osmolarity with D-mannitol ) significantly reduced the number of human MC and 3H-thymidine incorporation in a dose-dependent manner. But the LDH activity was not significantly altered in the treatment with 50 micromol x L(-1) NPPB. Flow cytometry experiments showed that 50 and 25 micromol x L(-1) NPPB arrested (84.2 +/- 2.4) % and (80.8 +/- 2.9) % of cells at G0/G1 stage, versus (70.5 +/- 1.4) % of control cells. Conclusion NPPB suppresses cell proliferation and produces growth arrest at G0/G1 phase in human MC by a mechanism probably associated with changes in cell volume.

Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Chloride Channels ; antagonists & inhibitors ; Dose-Response Relationship, Drug ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Mesangial Cells ; cytology ; metabolism ; Nitrobenzoates ; administration & dosage ; pharmacology

OBJECTIVETo observe the effects of Qiangjing Tablets (QJT) on the semen quality and Fas/FasL signaling pathway in male SD rats with infertility.

METHODSModels of infertility were made in 50 male SD rats by intragastric administration of Tripterygium (GTW) for 3 weeks, and another 20 rats were taken as blank controls. Then 40 successfully established rat models were randomly divided into four groups, model control, low-dose QJT, medium-dose QJT, and high-dose QJT, the latter three groups treated intragastrically with QJT at 58 mg, 105 mg, and 233 mg per kg of the body weight per day, respectively. After 4 weeks of medication, the rats were killed for examination of semen quality and determination of the expression of the apoptosis factor FasL in the testis tissue.

RESULTSCompared with the blank controls, the model rats showed significant decreases in sperm concentration ([71.99 ± 9.72] vs [10.94 ± 3.58] x 10⁶/ml, P < 0.01), motility ([48.95 ± 4.10] vs [9.31 ± 5.79]%, P < 0.01), and viability ( [82.06 ± 6.16] vs [24.03 ± 6.93]%, P < 0.01). In comparison with the model controls, the rats in the QJT groups exhibited remarkably increased sperm concentration, motility, and viability, more significantly in the high-dose group ([59.66 ± 4.53] x 10⁶/ml, [35.45 ± 5.21] %, and [61.97 ± 9.75]%) and medium-dose group ([40.89 ± 4.90] x 10⁶/ml, [24.41 ± 4.79]%, and [60.06 ± 10.62]%) (P < 0.05 or P < 0.01). The expression of FasL was markedly reduced in the low-, medium-, and high-dose QJT groups (0.5215 ± 0.0189, 0.5371 ± 0.0364, and 0.4556 ± 0.0215) as compared with that of the model controls (0.5989 ± 0.0448 ) (P < 0.05 or P < 0.01).

CONCLUSIONBy upregulating the Fas/FasL signaling pathway, Tripterygium glycosides may induce the apoptosis of spermatogenic cells and reduce sperm concentration, motility and viability, resulting in infertility. The Chinese medicine Qiangjing Tablets can improve the reproductive function of male rats by decreasing the expression of the apoptosis factor FasL in the testis.

Animals ; Apoptosis ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Fas Ligand Protein ; drug effects ; metabolism ; Germ Cells ; Glycosides ; Infertility, Male ; chemically induced ; drug therapy ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Semen ; drug effects ; Semen Analysis ; Signal Transduction ; Sperm Count ; Sperm Motility ; drug effects ; Tablets ; Testis ; drug effects ; metabolism ; Tripterygium

OBJECTIVEObserving the time course and establishing the model of kappaB-decoy oligodeoxynucleotides (rcB-decoy) inhibiting the activity of NF-kappaB in the PC12 cells.

METHODSPC12 cells cultivating in the 6 wells plate were divided into 3 groups, experimental group: adding kappaB-decoy complex (6 microg DNA/well), the control group: adding scrambled-decoy complex, the normal group: adding lipid-Lipofectamine 2000, transfer and cultivate 48 h, then lipopolysaccharide (LPS, 200 ng/ml) was added in the cells for 0.5-4 h. The immunocytochemistry and Western blot were used to measure the expression or the activity of NF-kappaB in PC12 cells.

RESULTSIn PC12 cells, compared with normal group, the expression of NF-kappaB enhanced obviously with the time of the stimulation of LPS in scrambled-decoy treated control group (P < 0.01), in 2-4 h the level reached the peak; the expression of NF-kappaB showed the stable level with the time of the stimulation of LPS in kappaB-decoy treated experimental group, compared with the control group, the expression levels were obviously lower than the respective time point of control groups (P < 0.01).

CONCLUSIONkappaB-decoy could reduce the expression of NF-kappaB in the normal PC12 cells and inhibit the activity of NF-cB in the pathologic PC12 cells.

Animals ; Cells, Cultured ; Lipopolysaccharides ; pharmacology ; NF-kappa B ; antagonists & inhibitors ; metabolism ; Oligodeoxyribonucleotides ; pharmacology ; PC12 Cells ; Rats

The paper is aimed to investigate the effect of cyclosporine A (CyA) on the pharmacokinetics of ginkgolide B (GB) in rats, and to look for the mechanism of the changes in pharmacokinetic behaviors of GB. GB concentration in plasma, brain homogenate and urine samples of rats was determined by LC-MS. Effects of CyA on plasma levels, brain distributions as well as urinary excretions after intravenous administration of GB were evaluated. CyA co administrated intravenously at 10 mg kg(-1) or 20 mg kg(-1) significantly increased AUC(0-360 min) (P < 0.01) and decreased total CL of GB in rats. While co administrated CYP3A inhibitor itraconazole (ICZ) has no appreciable effect on the pharmacokinetic behavior of GB. CyA increased the brain uptake of GB in a dose-dependent manner. The brain distribution of GB was significantly increased at 5 min by different doses of CyA (P < 0.001), while at 20 and 60 min only high dose of CyA could significantly increase the levels of GB in the brain (P < 0.01 and P < 0.001). Different P-gp inhibitors CyA or verapamil (VER) or digoxin (DGX) decreased the urinary GB excretion, the urinary excretion of GB in 0-8 h were about 34.8% (P < 0.001), 59.4% (P < 0.001) and 79.7% (P < 0.05) of the control, separately. No appreciable effect of ICZ was observed on urinary excretion of GB. Coadministration of P-gp inhibitors CyA could significantly increase the plasma level, accelerate the brain distribution and decrease the urinary excretion of GB.
Animals ; Cyclosporine ; pharmacology ; Ginkgolides ; pharmacokinetics ; Herb-Drug Interactions ; Lactones ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution

OBJECTIVETo study the protective effect of volatile anesthetics, isoflurane and sevoflurane, on ischemic neurons after cerebral ischemia-reperfusion in rats and its possible molecular mechanism.

METHODSRat cerebral ischemia-reperfusion model was developed by occlusion of the middle cerebral artery (MCA) and bilateral common carotid arteries (CCAs) 1 h after reperfusion. Using flow cytometry (FCM) and Northern blot hybridization, we calculated the number of apoptotic bodies and detected the expression of bcl-2 mRNA and interleukin-1beta converting enzyme (ICE) mRNA.

RESULTSThe apoptotic bodies in hippocampus analyzed by FCM peaked at appeared 24 h after reperfusion, and decreased about 54% and 40%, respectively, after treatment with isoflurane and sevoflurane, as compared with ischemic group. There was no significant difference in the expression of bcl-2 mRNA and ICE mRNA between the inhaled anesthetic groups and ischemic group in hippocampus 24 h after MCA/CCAs occlusion.

CONCLUSIONIsoflurane and sevoflurane partially inhibit apoptosis but have no significant effect on the expression of bcl-2 and ICE genes.

Anesthetics, Inhalation ; administration & dosage ; pharmacology ; Animals ; Apoptosis ; drug effects ; Brain Ischemia ; drug therapy ; Caspase 1 ; genetics ; metabolism ; Flow Cytometry ; Hippocampus ; drug effects ; pathology ; Isoflurane ; administration & dosage ; pharmacology ; Male ; Methyl Ethers ; administration & dosage ; pharmacology ; Neurons ; drug effects ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Rats ; Rats, Wistar ; Reperfusion