Apoptosis ; Down-Regulation ; Electron Transport Complex IV ; chemistry ; genetics ; metabolism ; Humans ; Mitochondria ; metabolism ; Mutation ; Neoplasms ; genetics ; metabolism ; pathology

OBJECTIVETo investigate the value of(99m)Tc-MIBI/(18)F-FDG-dual-isotope simultaneous acquisition (DISA) in diagnosis and treatment of patients with myocardial infarction.

METHODSSixty-three patients with myocardial infarction who underwent DISA before and after treatment were enrolled in the study. All cases were divided into subgroups based on different treatment and myocardial viability: Group A1 (n = 16) with coronary revascularization and viable myocardium, A2 (n = 9) same as A1 but no viable myocardium; B1 (n = 6) with coronary revascularization + stem cell transplantation and viable myocardium, B2 (n = 7) same as B1 but no vital myocardium; C1 (n = 8) with stem cell transplantation and viable myocardium, C2 (n = 17) same as C1 but on viable myocardium. The changes of uptake rate of (99m)Tc-MIBI/(18)F-FDG before and after treatment were analyzed with SPSS 13.0 software.

RESULTThere were statistical significances in DF value of (99m)Tc-MIBI or (18)F-FDG imaging before and after treatment in all groups (P <0.05), except Group A2 (P>0.05). The improvement of blood perfusion and metabolism in cardiac survival groups was more marked than that in non-cardiac survival groups after treatment (P<0.05). Furthermore, Group B1 was superior to Groups A1 and C1; Group B2 was superior to Group A2 and Group C2 (P<0.05 or<0.01).

CONCLUSION(99m)Tc-MIBI/(18)F-FDG DISA can detect myocardial viability and is of value for patients with myocardial infarction to choose appropriate therapeutic strategies. The degree of cardiac improvement after treatment can be evaluated by DISA.

Aged ; Female ; Fluorodeoxyglucose F18 ; Heart ; diagnostic imaging ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; diagnostic imaging ; therapy ; Radionuclide Imaging ; Retrospective Studies ; Technetium Tc 99m Sestamibi ; Treatment Outcome

OBJECTIVE5-Fluorouracil (5-FU)-based combination therapies are standard treatments for gastrointestinal cancer, where the modulation of autophagy is becoming increasingly important in offering effective treatment for patients in clinical practice. This review focuses on the role of autophagy in 5-FU-induced tumor suppression and cancer therapy in the digestive system.

DATA SOURCESAll articles published in English from 1996 to date those assess the synergistic effect of autophagy and 5-FU in gastrointestinal cancer therapy were identified through a systematic online search by use of PubMed. The search terms were "autophagy" and "5-FU" and ("colorectal cancer" or "hepatocellular carcinoma" or "pancreatic adenocarcinoma" or "esophageal cancer" or "gallbladder carcinoma" or "gastric cancer").

STUDY SELECTIONCritical reviews on relevant aspects and original articles reporting in vitro and/or in vivo results regarding the efficiency of autophagy and 5-FU in gastrointestinal cancer therapy were reviewed, analyzed, and summarized. The exclusion criteria for the articles were as follows: (1) new materials (e.g., nanomaterial)-induced autophagy; (2) clinical and experimental studies on diagnostic and/or prognostic biomarkers in digestive system cancers; and (3) immunogenic cell death for anticancer chemotherapy.

RESULTSMost cell and animal experiments showed inhibition of autophagy by either pharmacological approaches or via genetic silencing of autophagy regulatory gene, resulting in a promotion of 5-FU-induced cancer cells death. Meanwhile, autophagy also plays a pro-death role and may mediate cell death in certain cancer cells where apoptosis is defective or difficult to induce. The dual role of autophagy complicates the use of autophagy inhibitor or inducer in cancer chemotherapy and generates inconsistency to an extent in clinic trials.

CONCLUSIONAutophagy might be a therapeutic target that sensitizes the 5-FU treatment in gastrointestinal cancer.

Antimetabolites, Antineoplastic ; therapeutic use ; Autophagy ; physiology ; Drug Resistance, Neoplasm ; Fluorouracil ; therapeutic use ; Gastrointestinal Neoplasms ; drug therapy ; pathology ; Humans

OBJECTIVETo isolate and chondro-inductive culture of human adipose tissue-derived stromal cells and to study their heterotopic chondrogenesis by loading them on alginate gel.

METHODSLiposuction human adipose tissues were minced and digested with collagenase type I. The obtained stromal cells were primarily cultured in BGJb medium for ten days. Secondary harvested cells were cultured in DMEM-F12 medium supplemented with 10%FBS, 6.25 mg/L insulin, 10 mg/L TGF-beta1, 50 mg/L of freshly prepared L-ascorbate for 14 days. After in vitro assay of chondrogenic phenotypes, the cells at density of 10(10)/L were mixed with 1.2% alginate sodium and 102 mmol/L CaCl(2). The cross-linking cell-alginate gel were injected into four BALB/C athymic mice subcutaneously (1 ml for each mouse). Meanwhile, the auto-controls were set by injecting equal dose of simple alginate gel and pure cells in two opposite buttocks of the same mouse subcutaneously. Two mice were sacrificed at fourth and eighth week postoperatively and all samples were removed, fixed, embedded in paraffin and cut into sections of 5 micro m thick. HE staining, Alcian blue and modified Masson's trichrome staining were employed to observe chondrogenesis histologically.

RESULTSAlcian blue and immunocytochemical staining revealed chondroitin sulfate and collagen II in cell matrix after having been chondro-inductive cultured for 14 days. At intervals of fourth and eighth week, heterotopic chondrogenesis is (cartilage formed) within cell-alginate injected sites were found in all mice but negatively in auto-controls. Histologically the hypertrophic chondrocytes were among cartilage matrix in different staining. All alginate gel and solitory cells absorbed within two to three weeks postoperatively in auto-controls.

CONCLUSIONIt seems that stromal cells derived from human adipose tissue presents a potential for chondrogenic differentiation.

Adipose Tissue ; cytology ; Alginates ; pharmacology ; Animals ; Cell Differentiation ; Cells, Cultured ; Chondrocytes ; cytology ; metabolism ; Chondrogenesis ; Female ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Stem Cell Transplantation ; Stromal Cells ; cytology ; metabolism ; transplantation ; Tissue Engineering

BACKGROUNDThe results of clinical trials of rapamycin-eluting stents reduce restenosis have been quite promising. The main purpose of this study was to characterize the in vivo pharmacokinetics of high dose rapamycin (Rapa)-eluting stents in a miniswine coronary model.

METHODSTen miniswines underwent placement of 18 high dose Rapa-eluting stents in the left anterior descending and right coronary arteries. At the planned times of the 1.5th, 12th, 24th hour, 3th, 7th and 28th day, the animals (n = 1, 1, 2, 2, 2, and 2, respectively) were euthanized after completion of coronary angiography. Blood samples were obtained at 0, 10, 20, 30 minutes; 1, 2, 6, 24 hours; and 3, 7, 28 days to determine systemic Rapa levels. Rapa levels in whole blood, arterial wall, heart, renal and liver tissues were determined by high-performance liquid chromatography/mass spectroscopy.

RESULTSPeak whole blood concentration (Cmax), time to peak concentration (tmax), elimination half-life (t1/2beta), area under the curve (AUC), and apparent systemic clearance (Cl/F) were (10.91 +/- 1.28) ng/ml, (2.0 +/- 0.2) hours, (7.25 +/- 0.63) hours, (1.15 +/- 0.11) ng x h x ml(-1), and (180 +/- 12) ml x h(-1) x kg(-1), respectively. More than 95% Rapa detected is localized in the coronary artery surrounding the stent and heart.

CONCLUSIONStent-based delivery of Rapa via a copolymer stent is feasible and safe. This strategy holds promise for the prevention of stent restenosis.

Animals ; Chromatography, High Pressure Liquid ; Coronary Restenosis ; prevention & control ; Male ; Mass Spectrometry ; Sirolimus ; administration & dosage ; pharmacokinetics ; Stents ; Swine ; Swine, Miniature ; Tissue Distribution

BACKGROUNDRecently, 1,5-dicaffeoylquinic acid (1,5-DQA), a caffeoylquinic acid derivative isolated from Aster scaber, was found to have neuroprotective effects. However, the protective mechanisms of 1,5-DQA have not yet been clearly identified. The purpose of this study was to explore the protective mechanisms of 1,5-DQA on neuronal culture.

METHODSWe investigated the neuroprotective effects of 1,5-DQA against amyloid β(1-42) (Aβ(42))-induced neurotoxicity in primary neuronal culture. To evaluate the neuroprotective effects of 1,5-DQA, primary cultured cortical neurons from neonate rats were pretreated with 1,5-DQA for 2 hours and then treated with 40 µmol/L Aβ(42) for 6 hours. Cell counting kit-8, Hoechst staining and Western blotting were used for detecting the protective mechanism. Comparisons between two groups were evaluated by independent t test, and multiple comparisons were analyzed by one-way analysis of variance (ANOVA).

RESULTS1,5-DQA treated neurons showed increased neuronal cell viability against Aβ(42) toxicity in a concentration-dependent manner, both phosphoinositide 3-kinase (PI3K)/Akt and extracellular regulated protein kinase 1/2 (Erk1/2) were activated by 1,5-DQA with stimulating their upstream tyrosine kinase A (Trk A). However, the neuroprotective effects of 1,5-DQA were blocked by LY294002, a PI3K inhibitor, but not by PD98059, an inhibitor of mitogen-activated protein kinase kinase. Furthermore, 1,5-DQA's anti-apoptotic potential was related to the enhanced inactivating phosphorylation of glycogen synthase kinase 3β (GSK3β) and the modulation of expression of apoptosis-related protein Bcl-2/Bax.

CONCLUSIONThese results suggest that 1,5-DQA prevents Aβ(42)-induced neurotoxicity through the activation of PI3K/Akt followed by the stimulation of Trk A, then the inhibition of GSK3β as well as the modulation of Bcl-2/Bax.

Amyloid beta-Peptides ; pharmacology ; Animals ; Apoptosis ; drug effects ; Blotting, Western ; Cell Survival ; drug effects ; Cells, Cultured ; Cinnamates ; pharmacology ; Neurons ; cytology ; drug effects ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects

Objective To explore the surgical effect to traumatic tentorial herniation with bilater- al mydriasis.Methods The patients were divided into three groups,ie,epidural hematoma group,a- cute diffuse brain swelling group and cerebral contusion and/or subdural hematoma group,to perform clinical outcome analysis.Half year after operation,the neurological outcome was scored according to the Glasgow Outcome Scale.Results Of all,there were three cases with good recovery,10 with moderate disability,nine with severe disability and 10 with vegetative survival but 35 deaths.The outcome was the best in epidural hemotoma group but the poorest in acute diffuse brain swelling group.Conclusions The operative effect of traumatic cerebral herniation with bilateral mydriasis is related with the type of orig- inal injury that is important for selection of operation.Patients with cerebral herniation caused by epidural hematoma should receive immediate operation that will induce better outcome.The operation is not vital for those with cerebral herniation caused by acute diffuse brain swelling.Emergent surgery can save lives of some patients with cerebral contusion and/or subdural hematoma.Rapid diagnosis,correct operation and perioperative treatment may ensure the success of surgery.

Objective To better understand the characteristics of spatial distribution of malaria epidemics in Hainan province and to explore the relationship between malaria epidemics and environmental factors, as well to develop prediction model on malaria epidemics. Methods Data on Malaria and meteorological factors were collected in all 19 counties in Hainan province from May to Oct. , 2000, and the proportion of land use types of these counties in this period were extracted from digital map of land use in Hainan province. Land surface temperatures (LST)were extracted from MODIS images and elevations of these counties were extracted from DEM of Hainan province. The coefficients of correlation of malaria incidences and these environmental factors were then calculated with SPSS 13.0, and negative binomial regression analysis were done using SAS 9.0. Results The incidence of malaria showed (1) positive correlations to elevation, proportion of forest land area and grassland area; (2) negative correlations to the proportion of cultivated area, urban and rural residents and to industrial enterprise area, LST; (3) no correlations to meteorological factors, proportion of water area, and unemployed land area. The prediction model of malaria which came from negative binomial regression analysis was: Ⅰ(monthly, unit:1/1 000 000) = exp( - 1. 672 - 0. 399 × LST). Conclusion Spatial distribution of malaria epidemics was associated with some environmental factors, and prediction model of malaria epidemic could be developed with indexes which extracted from satellite remote sensing images.

Magnetic molecularly imprinted polymers(MMIPs) were prepared with ZL006 as template, acrylamide(AA) as the functional monomer, and acetonitrile as pore-forming agent; then Fourier transform infrared spectroscopy(FT-IR) and scanning electron microscopy(SEM) were used to characterize their forms and structures. Simultaneously, the MMIPs prepared previously were used as sorbents for dispersive magnetic solid phase extraction(DSPE) to capture and identify potential nNOS-PSD-95 uncouplers from extracts of Trifolium pratense and the the activities of the screened compounds were evaluated by the neuroprotective effect and co-immunoprecipitation test. The experiment revealed that the successfully synthesized MMIPs showed good dispersiveness, suitable particle size and good adsorption properties. Formononetin, prunetin and biochanin A were separated and enriched from Trifolium pratense by using the MMIPs as artificial antibodies and finally biochanin A was found to have higher cytoprotective action and uncoupling action according to the neuroprotective effect and co-immunoprecipitation test.
Adsorption ; Genistein ; chemistry ; Molecular Imprinting ; Phytochemicals ; chemistry ; Polymers ; chemistry ; Solid Phase Extraction ; Spectroscopy, Fourier Transform Infrared ; Trifolium ; chemistry

To study the effects of Smad4 on liver fibrosis and hepatocarcinogenesis in mice treated with CCl(4)/ethanol. The wild-type mice (Smad4 +/+) and the Smad4 knockout mice (Smad4 +/-) were injected subcutaneously with carbon tetrachloride(CCl(4))/ethanol twice a week for twenty weeks. The expression of Smad4, TGFbeta1, Smad2, Smad3, Smad6, TIMP1, MMP2 and MMP9 was detected by RT-PCR. In the cirrhotic liver, the expression of Smad4 mRNA was significantly higher than that in the normal liver. Comparing with wild-type mice (Smad4 +/+), the TGFbeta1-Smad4 signaling was markedly attenuated in the Smad4 knockout mice (Smad4 +/-). After induction by CCl(4)/ethanol, the hepatic fibrosis in the Smad4 knockout mice (Smad4 +/-) was obviously alleviated compared with the wild-type mice (Smad4 +/+), and the incidence rate of hepatocarcinogenesis of the former was also lower than that of the latter(32.0% vs 41.9%). These results indicate that knocking out Smad4 can delay the progression of liver fibrosis and liver cancer.
Animals ; Carbon Tetrachloride ; administration & dosage ; Disease Models, Animal ; Ethanol ; administration & dosage ; Female ; Liver Cirrhosis, Experimental ; chemically induced ; metabolism ; pathology ; Liver Neoplasms, Experimental ; chemically induced ; metabolism ; pathology ; Male ; Mice ; Mice, Knockout ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Smad Proteins ; genetics ; metabolism ; Smad4 Protein ; genetics ; metabolism ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism