The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.
Animals ; Apoptosis ; Aurora Kinase A ; antagonists & inhibitors ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Colonic Neoplasms ; pathology ; Humans ; Protein Kinase Inhibitors ; pharmacology ; Receptors, Vascular Endothelial Growth Factor ; metabolism ; Xenograft Model Antitumor Assays

OBJECTIVETo observe the anti-inflammatory effect of total saponins of Panax japonicus on LPS-induced RAW264. 7 macrophages.

METHODThe effect of total saponins of P. japonicus of different concentrations on RAW264. 7 cell viability was determined with the MTT method. The NO kit assay was adopted to detect the NO release of total saponins of P. japonicus to LPS-induced RAW264. 7 cells. The enzyme linked immunosorbent assay (ELISA) was used to detect the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (IL-1beta). The reverse transeriptase-polymerase chain reaction (RT-PCR) was used to determine the expression of inducible nitric oxide synthase (iNOS) ,TNF-alpha,IL-1beta. The protein expression of nuclear transcription factor-kappaB p65 (NF-kappaB p65) was tested by Western blot.

RESULTThe safe medication range of total saponins of P. japonicus was less than 80 mg x L(-1). Compared with the LPS model group, total saponins of P. japonicus high, middle and low dose groups (0.1, 1, 10, 40 mg x L(-1)) could significantly reduce the secretion of NO, TNF-alpha, IL-1beta of LPS-induced RAW264. 7 cells, and inhibit the expressions of iNOS, TNF-alpha and IL-1beta mRNA and the protein expression of NF-kappaB p65.

CONCLUSIONThis study preliminarily proves the protective effect of total saponins of P. japonicus on LPS-induced RAW264.7 macrophages. Its action mechanism may be related to NF-kappaB signal pathway.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Inflammation ; drug therapy ; genetics ; immunology ; Interleukin-1beta ; genetics ; immunology ; Lipopolysaccharides ; adverse effects ; Macrophages ; drug effects ; immunology ; Mice ; NF-kappa B ; genetics ; immunology ; Nitric Oxide ; immunology ; Nitric Oxide Synthase Type II ; genetics ; immunology ; Panax ; chemistry ; Protective Agents ; pharmacology ; Saponins ; pharmacology

Objective To investigate the impact of prior cerebral infarction (PCI) on in-hospital mortality in patients with Acute Myocardial Infarction (AMI).MethodsA retrospective analysis of documents of a total of 3572 consecutive patients with AMI admitted to Xuanwu Hospital of Capital Medical University from 2002 Jan.1 to 2009 Dec.31 were performed.Results There were 564 patients ( 15.8% )with PCI.Compared with the group of without PC1,the group with PCI were substantially older[(69.4 ±9.9) vs (64.2 ± 12.9)years,P =0.000],and had a higher prevalence of hypertensive disease,diabetes mellitus,prior myocardial infarction (MI) and non-ST-segment elevation myocardial infarction(NSTEMI)( respectively,71.0% vs 57.3%; 41.0% vs 25.7%,12.9% vs 9.5%; 14.9% vs 10.7%,P ＜ 0.01 ),and a higher in-hospital mortality ( 16.5% vs 10.0%,P= 0.000).Univariate analysis demonstrated that in-hospital mortality associated with age,gender,extensive anterior MI,anterior MI,diabetes mellitus,prior cerebral infarction,prior myocardial infarction,coronary angiography and percutaneous coronary intervention.Logistic regression analysis found that risk factors were age,extensive anterior MI,anterior MI,diabetes mellitus and prior cerebral infarction,and protective factors were coronary angiography and percutanous coronary intervention.PCI was independently associated with in-hospital mortality,OR 1.368,95% CI 1.047-1.787,P = 0.022.Conclusion In patients with acute myocardial infarction,the presence of PCI increases the risk of worse in-hospital outcome.

OBJECTIVE: To explore the application value of postmortem multi-slice spiral computed tomography (MSCT) by observing and analyzing the injury features in the traffic accident victims. METHODS: Ten traffic accident victims were scanned with whole body MSCT. The systemic autopsy was subsequently performed to compare with the results of MSCT. The advantages and disadvantages of autopsy and MSCT for obtaining the information of traffic accident injuries were then analyzed. RESULTS: MSCT could reveal 3D shape of fractures clearly and detect air accumulation in different positions of the body, which showed the obvious advantages compared with autopsy. However, the resolution of MSCT was limited compared to the detection of organ and soft tissue injuries. CONCLUSION A combination of MSCT and autopsy is the best way for determining the manner and the cause of death in traffic fatality victims.
Accidents, Traffic ; Autopsy ; Fractures, Bone ; Humans ; Soft Tissue Injuries ; Tomography, Spiral Computed

OBJECTIVETo explore the features of proton magnetic resonance spectroscopy (1H-MRS) of the hippocampus in schizophrenia patients before and after stereotactic neurosurgery.

METHODS1H-MRS was performed to determine NAA/Cr and CHO/Cr ratios on the bilateral hippocampal regions before and after stereotactic neurosurgery in 20 schizophrenia patients, with 20 healthy individuals as the controls.

RESULTSThe NAA/Cr ratio in the hippocampal regions was significantly lower and the CHO/Cr ratio significantly higher in schizophrenia patients before the surgery than in the healthy controls (P<0.01). The NAA/Cr and CHO/Cr ratios in the hippocampal regions underwent no significant changes in the patients after the surgeries (P>0.05).

CONCLUSIONNeuronal and cell membrane metabolism impairment is present in the hippocampus of schizophrenia patients, and stereotactic neurosurgery does not produce obvious adverse effects on the cell membrane metabolism in the hippocampus of the patients.

Adolescent ; Adult ; Aspartic Acid ; analogs & derivatives ; metabolism ; Case-Control Studies ; Choline ; metabolism ; Creatine ; metabolism ; Female ; Hippocampus ; metabolism ; pathology ; Humans ; Magnetic Resonance Spectroscopy ; methods ; Male ; Protons ; Schizophrenia ; metabolism ; pathology ; surgery ; Stereotaxic Techniques ; Young Adult

OBJECTIVETo evaluate the sperm quality of college students in Chengdu area.

METHODSA computer assisted sperm analysis (CASA) was made of the sperm concentration, grade A sperm, grade B sperm, sperm viability rate and movement parameters (VCL, VAP, VSL, LIN, STR) of 549 volunteers from 14 colleges in Chengdu area. The volunteers were divided into normal and abnormal groups according to the criteria (sperm concentration > or = 20 x 10(6)/ml, grade A and B sperm > or = 50% or grade A sperm > or = 25%). The results were compared with the data reported in China.

RESULTSAmong the 549 volunteers, the sperm concentration was (50.90 +/- 27.31) x 10(6)/ml, grade A and B sperm was (42.21 +/- 15.38)%, grade A sperm was (29.48 +/- 13.71)%, and the sperm viability rate was (56.40 +/- 14.77)%. The volunteers with normal sperm accounted for 62.84% (345/549) in contrast with abnormal (37.16%, 204/549). Among the 204 volunteers with abnormal sperms, there were 187 (90.67%) with abnormal motility, 39 (19.21%) with abnormal concentration, 22 (10.78%) with both abnormal concentration and abnormal motility. There were no volunteers without sperm. Among the 345 volunteers with normal sperm, the VCL, VAP and VSL were above 25 microns/s, and the VCL, VAP, VSL, LIN and STR were significantly higher than those of the abnormal group (P < 0.01). Moreover, the sperm concentration and the sperm viability rate in 549 volunteers, including 345 volunteers with normal sperm, were lower than the data reported in China.

CONCLUSIONSDue attention should be paid to the sperm quality of the college students in Chengdu area, whose sperm concentration and sperm viability rate have a tendency to decrease.

Adult ; Humans ; Male ; Sperm Count ; Sperm Motility

Objective:To study the optimal nutritional support strategy in critical patients with acute ischemic stroke.Methods:50 critical patients with acute ischemic stroke were divided into two groups.One group were started with enteral nutrition alone within 24h after admission,while the other group received sequential parenteral and enteral nutrition.The incidence of pulmonary infection,gastric retention,upper gastrointestinal bleeding,hypoglycemia and hyperglycemia were compared between the two groups.Another endpoint was discharge from ICU at day 20,and it was compared between the two groups using Kaplan-Meier methods.Results:There was no difference between the two groups in the rate of hypoglycemia or hyperglycemia (P ＞ 0.05).The incidences of pulmonary infection,gastric retention,upper gastrointestinal bleeding and diarrhea were lower in the PN+EN group than EN group (P ＜ 0.01).The length of ICU stay was also shorter in the PN+EN group.Conclusion:The strategy of sequential parenteral and enteral nutrition decreased the complication rate related to nutrition support,such as pulmonary infection,gastric retention,upper gastrointestinal bleeding.Also,it shortened the ICU stay in critical patients with acute ischemic stroke.

The phytase gene phyA(m) from Aspergillus niger N25 was recombined into E. coli expression vector pET-30b(+). Recombined at expression vectors pET30b-FphyA(m) was served as a template to amplify phytase gene, and the PCR product named elongation mutation gene phyA(e) was expanded with a 13 amino acid sequence from pET-30b-FphyA(m) vector at C-terminal of phytase gene phyA(m). Furthermore, phyA(e) gene was recombined into expression vector pPIC9k and expressed in Pichia pastoris. The comparison experiment of mutant phytase PP-NP0 with wild-type phytase PP-NP(m)-8 showed that: the optimum temperature of PP-NPe was increased by 3 degrees C, and its thermostability was increased by 21% when it was exposed to 10 min at 75 degrees C. Its effective reaction pH range with catalysis efficiency above 70% was pH 4.6 - pH 6.6, and wider 0.4 pH value than that of wild-type phytase.
6-Phytase ; biosynthesis ; genetics ; Amino Acid Sequence ; Aspergillus niger ; enzymology ; genetics ; Enzyme Stability ; genetics ; Escherichia coli ; enzymology ; genetics ; Fungal Proteins ; biosynthesis ; genetics ; Hot Temperature ; Molecular Sequence Data ; Mutation

The purpose of this study is to investigate the activity and mechanism of a new anti-tumor agent T03. MTT and colony formation assay were performed to determine anti-proliferation activity of T03 in vitro. Antitumor activity was observed by Renca xenograft model in vivo. The effect of T03 on cell cycle and apoptosis were measured by FCM analysis. Western blotting was performed to investigate the expression level of proteins in HepG2 cell lines treated with T03. T03 had anti-tumor activity by inhibiting tumor cell growth and colony formation in vitro, especially on hepatocellular carcinoma cells (HCC). At the concentration of 10 micromol x L(-1), T03 induced cell apoptosis and cell cycle arrest in HCC. Moreover, it proved that T03 reduced the tumor weight with the rate of 42.30% without any obviously side effect in Renca xenograft model. At the concentration of 2.0 micromol x L(-1), T03 was able to reduce the level of p-c-Raf (Ser259), and thus blocked Raf/MEK/ERK and AKT signaling in HepG2 cell lines. The result suggested that T03 has the potential to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo, particularly active against HCC, indicating T03 and its analogues may serve as a new anti-cancer drug against hepatocellular carcinoma.
Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; pathology ; Cell Cycle Checkpoints ; drug effects ; Cell Proliferation ; drug effects ; Hep G2 Cells ; drug effects ; Humans ; Liver Neoplasms ; pathology ; Signal Transduction ; drug effects ; Xenograft Model Antitumor Assays