Accidents, Occupational ; mortality ; Humans ; Hydrogen Sulfide ; poisoning

The nuclear transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) plays a crucial role in maintaining cellular redox homeostasis. The aberrant NRF2 signaling confers enhanced antioxidant capacity, which is linked to tumor progression and therapeutic resistance. The current study investigates the biological effects and molecular mechanism of tribbles homolog 3 (TRIB3), a stress-induced protein, in regulating cell survival and apoptosis in lung cancer. This study first performed the RNA sequencing data analysis with 576 lung adenocarcinoma patients from the cancer genome atlas (TCGA) database. The NRF2- antioxidant response element (ARE) signature was enriched in patients with high TRIB3 expression. Dual-luciferase reporter assay and real-time quantitative polymerase chain reaction (PCR) were used to confirm the effect of TRIB3 on the kelch-like ECH-associated protein-1 (KEAP1)-NRF2 pathway. Abrogation of TRIB3 impaired NRF2 transcriptional activity and reduced the expression of its target genes. Moreover, TRIB3 enhanced NRF2 stability via blocking KEAP1-NRF2 interaction. TRIB3-depletion promoted reactive oxygen species (ROS) production, restrained cell proliferation, and enhanced carboplatin-induced apoptosis. In addition, NRF2 overexpression recovered the tumor inhibition effect of TRIB3-depletion. Consistently, TRIB3 failed to modulate apoptosis in NRF2 depletion cells. In summary, this study shows that TRIB3 inhibits the KEAP1-NRF2 interaction and upregulates the transcriptional activity of NRF2, thereby promoting lung cancer cell proliferation and reducing the sensitivity to chemotherapy. Targeting the TRIB3-NRF2 signal axis may become a new strategy for ROS homeostasis and lung cancer treatment.

ObjectiveTo investigate the effect of hyperbaric oxygen (HBO) on proliferation and differentiation of endogenous neural stem cells after acute spinal cord half cut-off in rats. MethodsThe differences of proliferation and differentiation of endogenous neural stem cells between injured group and intervention group were compared. ResultsThere were remarkable differences between injured group and intervention group. ConclusionHBO can promote the proliferation and differentiation of the neural stem cells in rats after spine cord injury.

OBJECTIVETo analyze irrational clinical application of Houttuynia Injection (HI) and the risk of adverse event (AE) occurrence, thus providing references for after-sales reevaluation and rational clinical application of HI.

METHODSLiteratures concerning unreasonable application of HI were searched (terminated by June 2010) from PubMed, EMBASE, Chinese Biomedical Disc (CBMdisc), Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Full-text Database (VIP), and etc. for case report, cross-sectional study, and clinical control study.

RESULTSA total of 342 papers with a total of 416 AE cases were retrieved. Of them, AE happened to 294 cases (including 290 children) of the 132 papers concerning contraindications, and 48 with allergic shock; AE happened to 57 cases in 9 papers reporting over-dose, and 6 with high risk combined medication. Sixteen irrational administration ways were reported in 195 papers. Of them, AE happened to 59 cases of seven administration ways (twenty cases by intracavitary injection, thirteen by aerosol inhalation, ten by rinse, eight by oral administration, one by enema, one by acupoint injection, and one by rectal administering). AE was not reported in the rest ten reports.

CONCLUSIONThe risk of AE occurrence was increased by changing clinical administration ways of HI without authorization, over-dose medication, high risk combined medication, and application in people with contraindications.

Databases, Factual ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; therapeutic use ; Houttuynia ; adverse effects ; Humans ; Injections

OBJECTIVETo investigate the effects of inward rectifier potassium channel blockers (BaCl2, CsCl) on the functions of endothelial progenitor cells (EPCs).

METHODSDensity gradient centrifugation-isolated rat hone marrow mononuclear cells were cultured in vitro. EPCs were harvested and seeded on six culture dish when cells grew to 3-5 passages. Before testing the EPCs were synchronized with M199, which contain 2% fetal calf serum. In the end, EPCs were treated with different intervention. The experiment mainly included two parts: (1) BaCl2 (100 micromol/L) and free BaC2 of Tyrodes solution; (2) CsCl (1 mmol/L) and control. Cell pretreated with blockers above mentioned for 12 h, then the gene expression of stromal cell-derived factor-1 (SDF-1), epoprotenol (PGI2) were assessed, beyond that the ability of adhesion, migration were assayed with different tests. In addition, the medium was collected when EPCs were treated for 3 days. The levels of SDF-1 were measured by sandwich enzyme-linked immunosorbent assay (ELISA). Going even further, EPCs were treated with the signal pathway blockers in advance, after repeat the above steps, in order to analyze the change of SDF-1 and then discuss its mechanism.

RESULTSCompared with control group, BaCl2, CsCl could increase EPC adhesion and migration to same extent. Moreover, the gene expression of SDF-1, PGI2 was significantly up-regulated and the production of SDF-1 increased evidently. Furthermore, the mechanism of SDF-1 secretion increasing mainly was associated with eNOS signaling pathways.

CONCLUSIONBa2+ and Cs+ play important roles in increasing EPCs functions, such as adhesion, migration and secretion.

Animals ; Barium Compounds ; pharmacology ; Cells, Cultured ; Cesium ; pharmacology ; Chemokine CXCL12 ; metabolism ; Chlorides ; pharmacology ; Endothelial Cells ; cytology ; Enzyme-Linked Immunosorbent Assay ; Potassium Channels, Inwardly Rectifying ; antagonists & inhibitors ; physiology ; Rats ; Stem Cells ; cytology

Background and Objective:Adenovirus vector has been widely used in tumor gene therapy.ING4 is a member of growth inhibiting factors and a potent anti-tumor gene which could induce apoptosis of many tumor cells.This study was to investigate the inhibitory effects of adenovirusmediated ING4(Ad-ING4)gene on the proliferation of human prostate cancer PC-3 cells in vitro and in vivo,and to explore its mechanisms.Methods:Ad-ING4 was obtained by virus-amplification technique.After transfection of purified Ad-ING4 into PC-3 cells,the expression of ING4 was detected by reverse transcription-polymerase chain reaction(RT-PCR);the influence of Ad-ING4 transfection on cell proliferation was evaluated using MTT assay.Cell apoptosis was assessed using Hoechst33258 staining and flow cytometry. RT-PCR was performed to detect the mRNA levels of the transcription of apoptosis-related genes such as bcl-2,bax,p53,and caspase-3.Athymic nude mice bearing PC-3 tumors were intratumorally injected with Ad-ING4 (100 μL,1×10~9 pfu/mL). Tumor growth was recorded.All nude mice were killed at the end of the experiment to observe the growth of xenografts. The expressions of Bcl-2, Bax, Caspase-3, and CD34 proteins in tumor tissues were detected by immunohistochemistry. Results: Human ING4 gene was successfully transcribed in PC-3 cells and induced apoptosis by up-regulating p53,bax,caspase-3 expression and down-regulating bcl-2 expression. Inhibition of cell proliferation was significant in PC-3 cells. Tumor growth was significantly inhibited in the Ad-ING4 group as compared with that in the Ad-GFP group and the PBS group (P＜0.05). The weight inhibitory rate was 37.0% in the Ad-ING4 group. The expressions of Bax and Caspase-3 were up-regulated,and the expressions of Bcl-2 and CD34 were downregulated in the Ad-GFP group. Conclusions: Adenovirus-mediated ING4 gene exhibits anti-tumor ability in human prostate cancer PC-3 cells in vitro and in vivo,and induces apoptosis. This may be related to the upregulations of p53, bax, Caspase-3 and down-regulation of bcl-2.

2,4-Dichlorophenoxyacetic Acid ; analogs & derivatives ; toxicity ; Animals ; Epididymis ; growth & development ; metabolism ; Female ; HSP70 Heat-Shock Proteins ; biosynthesis ; genetics ; Herbicides ; toxicity ; Male ; Rats ; Rats, Wistar ; Spermatozoa ; drug effects ; growth & development ; metabolism

OBJECTIVETo investigate the inhibitory effect of sorafenib in combination with arsenic trioxide (As2O3) on hepatocellular carcinoma cells and explore the mechanisms of the synergetic antitumor effects of the two agents.

METHODSHepG2 cells were treated with sorafenibor, As2O3 alone or their combination, with the untreated cells used as the control. The inhibitory effect of the treatment was analyzed by MTT assay, and the cell apoptosis and mitochondrial transmembrane potential (delta phi m) were detected by flow cytometry. Western blotting was performed to examine the expressions of ERK and pERK in the cells.

RESULTSSorafenib and As2O3 used alone or in combination both inhibited the proliferation of HepG2 cells, and a synergistic effect of the two agents was noted in their combined action (P<0.05). Combined treatment of the cells resulted in significantly higher apoptsis rate than that in the other groups (P<0.05), and was associated with a more obvious decrease in delta phi m. The expression of ERK was not affected by the two agents used either alone or in combination, but pERK expression was significantly lowered in the cells after combined treatment for 24 h.

CONCLUSIONA synergistic effect is observed between the sorafenib and As2O3 in their inhibition of HepG2 cell proliferation, the mechanisms of which may involve reduction of mitochondrial transmembrane potential and Raf/MEK/ERK pathway inhibition.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Benzenesulfonates ; pharmacology ; Blotting, Western ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Drug Synergism ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Flow Cytometry ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Membrane Potential, Mitochondrial ; drug effects ; Niacinamide ; analogs & derivatives ; Oxides ; pharmacology ; Phenylurea Compounds ; Pyridines ; pharmacology

BACKGROUNDEndothelial progenitor cells (EPCs) transplantation is a promising therapeutic strategy for ischemic retinopathy. The current study aimed to establish a simple, reliable and fluorescent labeling method for tracking EPCs with 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE) in laser-injured mouse retina.

METHODSEPCs were isolated from human umbilical cord blood mononuclear cells, cultivated, and labeled with various concentrations of CFSE. Based on fluorescence intensity and cell morphology, a 15 minutes incubation with 5 µmol/L CFSE at 37°C was selected as the optimal labeling condition. The survival capability and the apoptosis rate of CFSE-labeled EPCs were measured by Trypan blue staining and Annexin V/PI staining assay respectively. Fluorescence microscopy was used to observe the label stability during the extended culture period. Labeled EPCs were transplanted into the vitreous cavity of pigmented mice injured by retinal laser photocoagulation. Evans Blue angiography and flat mounted retinas were examined to track the labeled cells.

RESULTSEPCs labeled with 5 µmol/L CFSE presented an intense green fluorescence and maintained normal morphology, with no significant changes in the survival capability or apoptosis rate after being labeled for 2 days, 1 and 4 weeks. The fluorescence intensity gradually decreased in the cells at the end of 4 weeks. Evans Blue angiography of the retina displayed the retinal capillarity network clearly and fluorescence leakage was observed around photocoagulated spots in the laser-injured mouse model. One week after transplantation of labeled EPCs, the fluorescent cells were identified around the photocoagulated lesions. Four weeks after transplantation, fluorescent tube-like structures were observed in the retinal vascular networks.

CONCLUSIONEPCs could be labeled by CFSE in vitro and monitored in vivo for at least 4 weeks, and participate in the repair of injured retinal vessels.

Animals ; Cells, Cultured ; Endothelial Cells ; chemistry ; cytology ; Fluoresceins ; chemistry ; Fluorescent Dyes ; chemistry ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Microscopy, Fluorescence ; Retina ; cytology ; Stem Cells ; chemistry ; cytology ; Succinimides ; chemistry

BACKGROUNDSuccessful lung transplantation has been limited by the scarcity of donors. Brain death (BD) donors are major source of lung transplantation. Whereas BD process induces acute lung injury and aggravates lung ischemia reperfusion injury. Carbon monoxide (CO) inhalation at 50-500 parts per million (ppm) can ameliorate lung injury in several models. We examined in rats whether CO inhalation in BD donor would show favorable effects on lung grafts.

METHODSRats were randomly divided into 4 groups. In sham group, donor rats received insertion of a balloon catheter into the cranial cavity, but the balloon was not inflated. In BD-only group, donor rats were ventilated with 40% oxygen after BD confirmation. In BD+CO250 and BD+CO500 groups, donor rats inhaled, after BD confirmation, 250 ppm or 500 ppm CO for 120 minutes prior to lung procurement, and orthotopic lung transplantation was performed. The rats were sacrificed 120 minutes after the lung transplantation by exsanguination, and their blood and lung graft samples were obtained. A total of 8 rats fulfilling the criteria were included in each group.

RESULTSThe inhalation decreased the severity of lung injury in grafts from BD donors checked by histological examination. CO pretreatment reversed the aggravation of PaO2/FiO2 in recipients from BD donors. The CO inhalation down-regulated pro-inflammatory cytokines (TNF-alpha, IL-6) along with the increase of anti-inflammatory cytokine (IL-10) in recipient serum, and inhibited the activity of myeloperoxidase in grafts tissue. The inhalation significantly decreased cell apoptosis in lung grafts, inhibiting mRNA and protein expression of intercellular adhesion molecule-1 (ICAM-1) and caspase-3 in lung grafts. Further, the inhalation activated phosphorylation of p38 expression and inhibited phosphorylation of anti-extracellular signal-regulated kinase (ERK) expression in lung grafts. The effects of CO at 500 ppm were greater than those at 250 ppm.

CONCLUSIONSCO exerts potent protective effects on lung grafts from BD donor, exhibiting anti-inflammatory and anti-apoptosis functions by modulating the mitogen-activated protein kinase (MAPK) signal transduction.

Administration, Inhalation ; Animals ; Apoptosis ; Brain Death ; Carbon Monoxide ; administration & dosage ; Extracellular Signal-Regulated MAP Kinases ; antagonists & inhibitors ; Inflammation ; prevention & control ; Intercellular Adhesion Molecule-1 ; analysis ; genetics ; Lung Transplantation ; methods ; Male ; Phosphorylation ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Tissue Donors ; p38 Mitogen-Activated Protein Kinases ; metabolism