Human tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL) might be developed as a novel anti-tumor drug due to its selective cytotoxicity in tumor cells. The predicted Macaca mulatta TRAIL (mmTRAIL) is highly homologous to hTRAIL in nucleotide acid as well as amino acid sequence, suggesting that mmTRAIL might induce apoptosis of human cancer cells. However, the cytotoxicity of mmTRAIL in human cancer cells has not been investigated. In this paper, it is reported that the gene encoding mmTRAIL has been cloned by using reverse-transcriptase polymerase chain reaction (RT-PCR) from monkey peripheral blood mononuclear cells (PBMCs) in our laboratory. Subsequently, an expression plasmid was constructed by inserting mmTRAIL gene into pQE30 plasmid. After induction by addition of Isopropyl β-D-1-Thiogalactopyranoside (IPTG), mmTRAIL was expressed. MmTRAIL was recovered from supernatant of sonicated bacteria by Ni-NTA agarose affinity chromatography. SDS-PAGE and gel filtration chromatography demonstrated that mmTRAIL forms trimer in solution. In vitro assays indicated that mmTRAIL was cytotoxic to human COLO205 tumor cells but not to normal cells at low concentration of nanomole. In addition, antitumor effect of mmTRAIL was evaluated in mice bearing human COLO205 tumor xenografts. Intratumorally injected mmTRAIL significantly inhibited growth of tumor grafts. These results suggested that mmTRAIL was valuable as candidate drug for cancer-targeted therapy.
Animals ; Antineoplastic Agents ; Apoptosis ; Cell Line, Tumor ; Cloning, Molecular ; Humans ; Leukocytes, Mononuclear ; Macaca mulatta ; Mice ; Plasmids ; TNF-Related Apoptosis-Inducing Ligand ; genetics ; metabolism ; Xenograft Model Antitumor Assays

Objective To investigate the value of dual-source CT perfusion imaging in evaluation of liver fibrosis stage.Methods Liver fibrosis models were established with 35 rabbits (experimental group)which were intraperitoneally injected with carbon tetra-chloride.Meanwhile,other 5 rabbits were regarded as control group which were intraperitoneally inj eced with physiological saline.7 rabbits of experimental group and 1 of control group were undergone dual-source CT perfusion scan at 4,6,8,10,12 weeks respec-tively.Arterial liver perfusion (ALP),portal venous perfusion (PVP),total hepatic perfusion (THP),hepatic perfusion index (HPI)were recorded,and staging of liver fibrosis were assessed by pathological method.Results With the increase of liver fibrosis degree,HPI showed an upward trend,whereas PVP was opposite.HPIs of S2,S3 and S4 stage were significantly different com-pared to that of control group respectively.The differences of HPI between S3,S4 stage to S0 and S1 stage were significant.PVP between S2,S3,S4 stage to S0 stage and S1 stage were also significant different.Conclusion HPI and PVP can reflect the perfu-sion changes of liver fibrosis stages.Combination of HPI and PVP may help the diagnosis of S2,S3 or S4 stage of liver fibrosis.

Objective To evaluate the influence of age on the surgical risk and prognosis for elderly patients who suffered from lumbar spinal stenosis.Methods A total of 129 patients above 70 years old with lumbar stenosis from January 2015 to August 2018 were divided into 4 groups by age:younger than 69 years,70-74 years,75-79 years and 80 years and above.50 patients below 69 years old were chosen at random as control group.Different parameters such as operation methods,predicted complication rate (POSSUM score),actual complication rate,number of operation levels,operation time,surgical blood loss,occult blood loss,total hospital stay,postoperative hospital stay,hospital cost and the ODI score in 3 months followup were recorded.The surgical risk and prognosis of elderly patients were analyzed by comparing the differences of above parameters between different age groups.Results There was no significant correlation between different age groups and surgical methods (F=15.637,P=0.208).The operation time and surgical blood loss both showed no significant difference between 4 groups.The predicted incidence of complications (POSSUM score) in group older than 80 years old (38.5％+12.34％) and 75-79 years old (41.1％+ 11.82％) were higher than the group younger than 69 years old (28.4％+ 15.44％).There was no significant difference between the two groups over 75 years old,and there was no significant difference between the 70-74 years old group and the other three groups.The actual incidence of complications was 43.75％ in group over 80 years old,42.86％ in group 75-79 years old and 42.03％ in group 70-74 years old.The actual complication rate of the group younger than 69 years was lower than other three groups,and the three other groups showed no significant difference between each other.The totally hospital stay and numbers of operation levels in groups 75-79 and 80 years and above were higher than groups 70-74 and 69 years and below.There was no significant difference in those parameters between groups 75-79 and 80 years and above,and between groups 70-74 years and 69 years and below.The ODI scores between 4 groups also showed no significant difference.Conclusion The risk of surgery for lumbar disc stenosis patients older than 75 years has increased,but the patient's surgical outcome has not decreased.Old age should not be a key factor in determining whether a patient is suitable for surgery.

Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Death, Sudden/etiology*

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups: biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer's disease, Parkinsons disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.
Alzheimer Disease ; chemically induced ; metabolism ; pathology ; physiopathology ; psychology ; Animals ; Behavior ; drug effects ; Biomarkers ; metabolism ; Brain ; metabolism ; pathology ; physiopathology ; Brain Diseases ; chemically induced ; pathology ; physiopathology ; Environmental Exposure ; adverse effects ; Humans ; Lead ; pharmacokinetics ; toxicity ; Lead Poisoning ; etiology ; metabolism ; pathology ; physiopathology ; psychology ; Neurotoxicity Syndromes ; etiology ; metabolism ; pathology ; physiopathology ; psychology ; Parkinson Disease, Secondary ; chemically induced ; metabolism ; pathology ; physiopathology ; psychology ; Schizophrenia ; chemically induced ; metabolism ; pathology ; physiopathology

Objective: To observe the clinical efficacy of long-time needle retaining at Baihui (GV 20) in treating post-stroke cognitive impairment. Methods: A total of 60 eligible patients with post-stroke cognitive impairment were randomized into a treatment group and a control group by random digital table, 30 cases in each group. The control group was intervened by basic treatment including routine therapy in Neurology department and Western medicine rehabilitation therapy, while the treatment group was intervened by same treatment in the control group combined with long-time needle retaining at Baihui (GV 20). Mental state of patients was evaluated by National Institute of Health stroke scale (NIHSS) and mini-mental state examination (MMSE) after 4 weeks of treatment. Results: After 4-week treatment, the NIHSS score dropped in both groups, and intra-group comparisons showed statistical significances (both P<0.05), and the score in the treatment group was statistically lower than that in the control group (P<0.01); the MMSE score in the treatment group was significantly higher than that in the control group, there was a statistical inter-group difference (P<0.01); the total effective rate was 93.3%, and the marked effective rate was 50.0% in the treatment group, versus 76.7% and 20.0% in the control group, there were significant differences in the total effective rate and the marked effective rate between the two groups (all P<0.05). Conclusion: Long-time needle retaining at Baihui (GV 20) can produce a safe valid therapeutic efficacy in treating post-stroke cognitive impairment.

BACKGROUND: Adipose-derived stem cells (ADSCs) represent one of the promising cell sources for myocardial regeneration due to their easy accessibility and efficacy in the improvement of cardiac function following myocardial infarction. However, previously reported studies on the underlying mechanism of ADSCs-mediated cardioprotective effect mainly focused on the ADSCs cultured at room air. OBJECTIVE: To test the paracrine actions and anti-apoptotic effect of ADSCs under hypoxic conditions. METHODS: After isolation and culture, neonatal rat myocardial cells were injured by hydrogen peroxide and co-cultured with rat ADSCs under normoxia and hypoxia (10% O2) conditions. Ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) in the cell pellet and levels of vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), and basic fibroblast growth factor (bFGF) were tested by ELISA. Expression of apoptotic proteins Bax and Bcl-2 were determined by western blot. RESULTS AND CONCLUSION: GSH/GSSG, VEGF, IGF-1, and bFGF were decreased in neonatal rat myocardial cells injured by hydrogen peroxide. ADSCs significantly attenuated hydrogen peroxide-induced myocardial apoptosis by increasing the ratio of GSH/GSSG and the secretion of VEGF, IGF-1 and bFGF. ADSCs also down-regulated Bax expression and up-regulated Bcl-2 expression. To conclude, hypoxic conditions can enhance the anti-apoptosis and cardioprotective effects of ADSCs through the paracrine mechanism.

objective To investigate the effects of knocking down of miR-19a and miR-19b on the biological characteristics of SNB19 glioblastoma cells. Methods Oligonucleotides inhibitor of miR-19a and miR-19b (miR-19a inhibitor or miR-19b inhibitor) mediated by lipofectamine2000 were transfected to SNB19 cells to knock down miR-19a and miR-19b; control group (without transfection),group D (performing transfection with nonsense sequence) and group E (performing transfection with both miR-19a inhibitor and miR-19b inhibitor) were established. Real time PCR was conducted to detect the expressions ofmiR-19a and miR-19b in these groups after the transfection. The cell proliferation rate and cell cycle kinetics were detected by 3-(4, 5-Dime- -thylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively; the cell invasive ability was evaluated by Transwell assay.Results As compared with those in control group and group D, the expressions of miR-19a and miR-19b, proliferation activity and invasive ability of cells in the miR-19a/19b inhibitor transfected cells (group A/B) were significantly reduced (P＜0.05). The expressions of miR-19a and miR-19b and the proliferation activity and invasive ability of cells 2, 3, 4 and 5 d after the transfection in group E were significantly reduced as compared with those in group A/B (P＜0.05). Delayed cell cycle in group A/B and group E was noted as compared with that in control group and group D; and group E enjoyed more obviously delayed eell cycle than group A/B (P＜0.05). Conclusion MiR-19a and miR-19b might be oncomiRs, and may be candidate target miRNAs for gene therapy of glioma.

OBJECTIVETo compare the expression differences of breast cancer resistance protein(BCRP/ABCG2) and P-glycoprotein(P-gp) in breast cancer tissue before chemotherapy and in residual breast cancer tissue, and to explore its correlation with breast cancer stem cells.

METHODSImmunohistochemistry was used to detect the expression of ABCG2, P-gp, and breast cancer stem cells(BCSCs) markers(CD44 and CD24) in breast cancer tissue before chemotherapy and residual breast cancer tissue after chemotherapy. Immunofluorescence was applied for determination of the CD44 and CD24 protein expressions of BCSCs microspheres cells. The monoclone-forming ability of BCSCs microspheres cells was detected by limited dilution assay. The expressions of ABCG2, P-gp, CD44, and CD24 proteins were detected by Western blot.

RESULTSCompared with those in breast cancer tissue before chemotherapy, the expression levels of ABCG2 and P-gp were positively correlated with the expression level of CD44 protein(Χ(2)=41.34, r=0.83;Χ(2)=22.81, r=0.61) in residual breast cancer tissue after chemotherapy;meanwhile, they were negatively correlated with the expression of CD24 protein(Χ(2)=-21.25, r=0.72;Χ(2)=-17.26, r=0.65) (all P<0.05) .The diameter of BCSCs microspheres were increased significantly after chemotherapy.The content of BCSCs increased by about 2.5 times after chemotherapy.The expressions of ABCG2, P-gp and CD44 proteins significantly increased and that of CD24 protein significantly declined(P<0.05) .

CONCLUSIONChemotherapy endows residual breast cancer tissue with cancer stem cells-like features, leading to multidrug resistance of breast cancer.

ATP Binding Cassette Transporter, Sub-Family B ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; metabolism ; ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Adult ; Aged ; Breast Neoplasms ; drug therapy ; metabolism ; CD24 Antigen ; metabolism ; Cell Culture Techniques ; Drug Resistance, Neoplasm ; Female ; Humans ; Hyaluronan Receptors ; metabolism ; Middle Aged ; Neoplasm Proteins ; metabolism ; Neoplasm, Residual ; Neoplastic Stem Cells ; cytology ; metabolism

BACKGROUND/AIMS: The recognition of a correlation between patatin-like phospholipase domain containing-protein 3 (PNPLA3) rs738409 (C>G) and the severity of liver steatosis or fibrosis in chronic hepatitis C (CHC) has not reached a consensus. This meta-analysis sought to investigate with accuracy the association between the PNPLA3 rs738409 (C>G) polymorphism and liver steatosis and advanced fibrosis in CHC patients. METHODS: We performed a comprehensive literature search from the PubMed, Embase, Web of Science, and Google Scholar databases up to December 31, 2014. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistical analyses were performed using Stata 12.0 software. RESULTS: The meta-analysis revealed the severity of liver fibrosis was significantly higher in CHC patients with PNPLA3 rs738409 GG in Caucasians (versus CC+CG: OR, 2.29; 95% CI, 1.57 to 3.35; p<0.05) but not Asian populations. In Caucasians, liver steatosis was also more severe in CHC patients with rs738409 GG (versus CC+CG; OR, 4.33; 95% CI, 2.59 to 7.22; p<0.05). The sensitivity analysis indicated the results of this meta-analysis were stable and no publication bias was detected. CONCLUSIONS: PNPLA3 rs738409 (C>G) was associated with the risk of both advanced liver fibrosis and steatosis in patients with CHC, especially among Caucasian populations.
Asian Continental Ancestry Group ; Consensus ; Fatty Liver ; Fibrosis* ; Hepatitis C, Chronic* ; Hepatitis, Chronic* ; Humans ; Liver Cirrhosis ; Odds Ratio ; Phospholipases ; Publication Bias