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Biomedical subjects

J Ding

Publications and source records attributed to J Ding.

At least 73 records · Page 4Linked to original sources

Induction of apoptosis in human leukemia K-562 and gastric carcinoma SGC-7901 cells by salvicine, a novel anticancer compound.

Salvicine (a novel diterpenoid quinone compound) exhibited a marked antitumor activity on human solid tumor cell lines and BALB/c-nu human carcinoma xenografts in our earlier studies, and it has been chosen as a candidate anticarcinogenic compound in the preclinical research stage. The present study was undertaken in order to observe whether or not the antitumor effect of salvicine is associated with its ability to induce apoptosis. Our results show that salvicine is capable of inhibiting cell proliferation and inducing characteristic changes of apoptosis in both human leukemia K-562 and gastric carcinoma SGC-7901 cells. These effects are dose and time dependent. The results of this study strongly suggest that the antitumor effect of salvicine is associated with its ability to induce apoptosis. Meanwhile, this study also shows that the activity of salvicine against K-562 and SGC-7901 cells is similar with regards to both growth inhibition and apoptosis induction, further indicating that salvicine causes these particular effects on solid tumor cells.

Adenocarcinoma↗

Hypoxia combined with Escherichia coli produces irreversible gut mucosal injury characterized by increased intestinal cytokine production and DNA degradation.

The objective of the present study was to determine whether hypoxia/reoxygenation in the absence or presence of intestinal bacteria would affect the integrity of the gut mucosal epithelium (as evidenced by histologic changes) and increase the local production of cytokines (interleukin 6 [IL-6] and tumor necrosis factor [TNF]). Rat ileal mucosal membranes were harvested and their electrophysiologic properties and barrier function were measured ex vivo in the Ussing chamber system. Membranes were exposed to normoxia, normoxia + Escherichia coli, hypoxia for 40 min followed by normoxia, or hypoxia for 40 min + E. coli followed by normoxia for 3 h. IL-6 and TNF levels were measured using cytokine-dependent cellular assays. Morphological changes and the degree of DNA fragmentation were used as quantitative markers of gut mucosal injury. Mucosal integrity was maintained in the normoxia group. The addition of bacteria increased the IL-6 response and reduced mucosal integrity. During the hypoxic period, a transient decline in resistance (R) occurred and cytokine production was reduced. In the hypoxic ileal membranes not exposed to E coli, reoxygenation reversed the change in R and increased IL-6 production. The combination of hypoxia/reoxygenation plus E. coli bacterial challenge resulted in the greatest extent of gut mucosal injury and increase in TNF production. The results of this study support the hypothesis that the combination of increased intestinal bacterial levels superimposed on an ischemia/reperfusion injury increases the magnitude of gut mucosal injury and the production and subsequent release of proinflammatory cytokines.

Animals↗

IGFs stimulate zebrafish cell proliferation by activating MAP kinase and PI3-kinase-signaling pathways.

Insulin-like growth factor (IGF)-I and -II have been cloned from a number of teleost species, but their cellular actions in fish are poorly defined. In this study, we show that both IGF-I and -II stimulated zebrafish embryonic cell proliferation and DNA synthesis in a concentration-dependent manner, whereas insulin had little mitogenic activity. Affinity cross-linking and immunoblotting studies revealed the presence of IGF receptors with the characteristics of the mammalian type I IGF receptor. Competitive binding assay results indicated that the binding affinities of the zebrafish IGF-I receptors to IGF-I, IGF-II, and insulin are 1.9, 2.6, and >190 nM, indicating that IGF-I and -II bind to the IGF-I receptor(s) with approximately equal high affinity. To further investigate the cellular mechanism of IGF actions, we have studied the effects of IGFs on two major signal transduction pathways: mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3 kinase). IGFs activated MAPK in zebrafish embryonic cells in a dose-dependent manner. This activation occurred within 5 min of IGF-I stimulation and disappeared after 1 h. IGF-I also caused a concentration-dependent activation of protein kinase B, a downstream target of PI3 kinase, this activation being sustained for several hours. Inhibition of MAPK activation by the MAPK kinase inhibitor PD-98059 inhibited the IGF-I-stimulated DNA synthesis. Similarly, use of the PI3 kinase inhibitor LY-294002 also inhibited IGF-I-stimulated DNA synthesis. When both the MAPK and PI3 kinase pathways were inhibited using a combination of these compounds, the IGF-I-stimulated DNA synthesis was completely negated. These results indicate that both IGF-I and -II are potent mitogens for zebrafish embryonic cells and that activation of both the MAPK and PI3 kinase-signaling pathways is required for the mitogenic action of IGFs in zebrafish embryonic cells.

Animals↗

Study of the role of the low-affinity neurotrophin receptor p75 in naturally occurring cell death during development of the rat retina.

The aim of this study was to examine the tempo-spatial expression of low-affinity neurotrophin receptor p75, or p75(NTR), and its role in the induction of retinal ganglion cell (RGC) apoptosis in the rat retina during development. The cellular distribution of p75 in the retina was demonstrated with immunohistochemistry and double-immunofluorescent staining. Apoptosis in the developing rat retina was detected by DNA gel electrophoresis, and the number of RGCs undergoing apoptosis was estimated by terminal deoxyribonucleotidyl-mediated dUTP-digoxigenin nick end labeling (TUNEL). To localize p75 on apoptotic RGCs, p75 immunofluorescence and TUNEL fluorescent staining was performed on sections with Fluoro-Gold-prelabeled RGCs. p75 immunoreactivities were not detected either on the RGCs or TUNEL-positive cells, whereas Müller cell processes were p75 immunopositive. Thus, it was most unlikely that p75 induced apoptosis of RGCs in the rat retina.

Aging↗

Stealth polycyanoacrylate nanoparticles as tumor necrosis factor-alpha carriers: pharmacokinetics and anti-tumor effects.

The objective of this study was to investigate the pharmacokinetics and in vivo anti-tumor effect of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) encapsulated in poly(methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles. Our experimental results showed that PEG-PHDCA nanoparticles could extend the half-life of rHuTNF-alpha to 7.42 h and obviously change the protein biodistribution in tissues, and in particular, increase accumulation of rHuTNF-alpha in tumor. Compared with PHDCA nanoparticles and free rHuTNF-alpha, PEG-PHDCA nanoparticles loaded with rHuTNF-alpha showed higher antitumor potency at the same dose, which might be related to its higher accumulation in tumor tissues and longer plasma circulation time. Therefore, PEG-PHDCA nanoparticles could be an effective carrier for rHuTNF-alpha.

Animals↗

PEGylated recombinant human tumor necrosis factor alpha: pharmacokinetics and anti-tumor effects.

The aim of the present work was to investigate and assess the merit of PEGylated recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) following our previous work. The rHuTNF-alpha was modified using activated polyethylene glycol (PEG), N-succinimidyl succinnate monomethoxy polyethylene glycol (SS-PEG). The pharmacokinetics and anti-tumor effect were investigated. The experimental results showed that PEGylated rHuTNF-alpha could obviously alter in vivo behavioral characteristics of rHuTNF-alpha. Among the synthesized PEG-rHuTNF-alphas with different PEG molecules, PEG20000-rHuTNF-alpha demonstrated the longest circulating half-life (24.8 h) which was about 50 times longer than that of rHuTNF-alpha (28.8 min). In addition, there was much more PEG20000-rHuTNF-alpha distributed into tumor tissues than other PEG-rHuTNF-alphas or rHuTNF-alpha with time, and PEG20000-rHuTNF-alpha also showed the highest anti-tumor potency. These results indicated that PEG20000-rHuTNF-alpha was a useful long circulating molecule with selective localization in tumor tissues and enhanced anti-tumor activity of rHuTNF-alpha.

Animals↗

Behavioral effects of ivermectin in a freshwater oligochaete, Lumbriculus variegatus.

Ivermectin is a potent antiparasitic drug against nematode and arthropod parasites. In this study, we examined the lethal and sublethal effects of ivermectin in a freshwater oligochaete, Lumbriculus variegatus. The median lethal concentration (LC50) at 72 h after ivermectin exposure was 560 nM. Sublethal endpoints focused on several stimulus-evoked locomotor behaviors: escape reflexes controlled by giant interneuron pathways, swimming and reversal, and crawling. Swimming, reversal, and crawling are controlled by nongiant interneuron pathways. Ivermectin inhibited swimming, reversal, crawling frequency, and crawling speed in a time- and concentration-dependent manner with a mean inhibitory concentration (IC50) at 3 h of 1.1, 16, 91, and 51 nM, respectively. Ivermectin at 0.3 nM also significantly decreased the frequency of helical swimming waves. Picrotoxin, a Cl- channel blocker, antagonized the ivermectin-induced decrease in swimming frequency, crawling frequency, and crawling speed. There were no adverse effects on escape reflex 3 h after exposure to 300 nM ivermectin. Electrophysiological recordings showed that ivermectin had no effects on the conduction velocity of giant fiber systems. The results indicated that locomotor behaviors controlled by nongiant locomotor pathways were more sensitive to ivermectin than pathways controlled by giant interneurons and that Cl- channels may be involved in mediating ivermectin's inhibitory effects.

Animals↗

Preparation of single chain variable fragment of MG(7) mAb by phage display technology.

AIM: To develop the single chain variable fragment of MG MG(7)murine anti-human gastric cancer monoclonal antibody using the phage display technology for obtaining a tumor-targeting mediator. METHODS: mRNA was isolated from MG MG(7) producing murine hybridoma cell line and converted into cDNA. The variable fragments of heavy and light chain were amplified separately and assembled into ScFv with a specially constructed DNA linker by PCR. The ScFvs DNA was ligated into the phagmid vector pCANTAB5E and the ligated sample was transformed into competent E. Coli TG1. The transformed cells were infected with M13K07 helper phage to form MG MG(7) recombinant phage antibody library. The volume and recombinant rate of the library were evaluated by means of bacterial colony count and restriction analysis. After two rounds of panning with gastric cancer cell line KATO III of highly expressing MG(7)-binding antigen, the phage clones displaying ScFv of the antibody were selected by ELISA from the enriched phage clones. The antigen-binding affinity of the positive clone was detected by competition ELISA. HB2151 E. Coli was transfected with the positive phage clone demonstrated by competition ELISA for production of a soluble form of the MG(7) ScFv. ELISA assay was used to detect the antigen-binding affinity of the soluble MG(7) ScFv. Finally, the relative molecular mass of soluble MG(7) ScFv was measured by SDS-PAGE. RESULTS: The V(H), V(L) and ScFv DNAs were about 340bp, 320bp and 750bp, respectively. The volume of the library was up to 2 X 10(6) and 8 of 11 random clones were recombinants. Two phage clones could strongly compete with the original MG(7) antibody for binding to the antigen expressed on KATO III cells. Within 2 strong positive phage clones, the soluble MG(7) ScFv from one clone was found to have the binding activity with KATO III cells. SDS-PAGE showed that the relative molecular weight of soluble MG(7) ScFv was 32. CONCLUSION: The MG(7) ScFv was successfully produced by phage antibody technology, which may be useful for broadening the scope of application of the antibody.

Animals↗

[Relationship between eutrophication control and reservoir operation].

Choosing Miyun Reservoir as a research background, the spatial distribution characteristics of water quality in the reservoir were analyzed, and the relationship between reservoir operation and-eutrophication control was discussed. With the assistance of water quality model and the monitored data, measures that wiping off the nutrients combined with the flood prevention operation was proposed. At last, the feasibility of the measure was also discussed.

Phosphorus↗

PEGylated recombinant human tumor necrosis factor alpha: preparation and anti-tumor potency.

AIM: To assess the merits of polyethylene glycol-modified recombinant human tumor necrosis factor alpha (PEG-rHuTNF-alpha). METHODS: The rHuTNF-alpha was modified with N-succinimidyl succinate monomethoxy polyethylene glycol (SS-PEG) of three different molecular weights. The PEG-rHuTNF-alpha was separated into fractions of various molecular weights by gel filtration chromatography. In vitro activities of various fractions were determined with L929 cell assay and in vivo anti-tumor potencies of main fractions were studied with respect to necrosis of S-180 solid tumor. RESULTS: The rHuTNF-alpha could be modified using SS-PEG under mild conditions. The main fraction of PEG5000-rHuTNF-alpha contained four PEG molecules, and PEG12000-rHuTNF-alpha and PEG20000-rHuTNF-alpha contained two PEG molecules, respectively. There was a higher activity when rHuTNF-alpha was coupled to less numbers of the same molecular weight PEG molecules. When PEG-rHuTNF-alpha was of the same molecular weight, rHuTNF-alpha modified with bigger molecular weight PEG molecules had a higher activity. PEG-rHuTNF-alpha was resistant to proteolysis, and over 70 % activity remained after 8 h, but the activity of rHuTNF-alpha was time-dependently diminished by incubation with bovine trypsin. PEG5000-rHuTNF-alpha (1500 IU per mouse) had a similar anti-tumor potency compared with rHuTNF-alpha (3000 IU per mouse). PEG12000-rHuT NF-alpha (1500 IU per mouse) had an increased anti-tumor potency compared with rHuTNF-alpha (3000 IU per mouse). In particular, PEG20000-rHuTNF-alpha at a dose of 1500 IU per mouse had a higher anti-tumor potency than rHuTNF-alpha at a dose of 6000 IU per mouse. CONCLUSION: PEG-modified rHuTNF-alpha could be more suitable for therapeutic use

Animals↗

DNA topoisomerase II as the primary cellular target for salvicine in Saccharomyces cerevisiae.

AIM: To identify whether DNA topoisomerase II (Topo II) is the primary cellular target of salvicine in Saccharomyces cerevisiae (S cerevisiae) and the action mode of salvicine. METHODS: The catalytic activity of Topo II was determined by Topo II mediated supercoiled pBR322 relaxation. The effects of salvicine on the growth of four strains of S cerevisiae were assessed by clone forming assay. RESULTS: Salvicine inhibited Topo II mediated supercoiled pBR322 relaxation in cell-free system. Cytotoxicities of salvicine to parent (JN394) and TOP1 deleted (JN394top1-) yeast cells were at the same level, suggesting Topo I might not be the cellular target of salvicine. Salvicine displayed high activity against JN394t2-1 cells at 25 degrees C, while no growth inhibition was observed at 30 degrees C in the concentration range of interest. Furthermore, JN394t2-5 cells which expressed top2-5 mutant allele were highly resistant to salvicine and etoposide (VP16). CONCLUSION: Topo II was the primary cellular target of salvicine in vivo and salvicine killed yeast cells mainly by trapping the DNA-Topo II cleavage complex. Salvicine and VP16 might share some similar action locus on Topo II.

Cytotoxicity, Immunologic↗

[Effect of Shajiang black soil amended by coal fly ash on ecological factors and residue of heavy metal in wheat field].

The effect of Shajiang black soil amended by coal fly ash on ecological factors in wheat field and residua of Cd, Cr, Pb, Hg and As were studied by pot experiment. The results showed that applying coal fly ash into Shajiang black soil could decrease soil density, soil proportion and clay content, but increase soil porosity, filtration coefficient and soil temperature. Moreover, it could promote water evaporating when soil moisture was high and keep soil water when lower than 10%. It also could facilitate activity of soil micro-organism and promote soil nutrient transforming. With (6-18) x 10(4) kg.hm-2 coal fly ash applied in Shajiang black soil, the accumulated quantity of Cd, Cr, Pb, Hg and As in soil and in wheat grain were lower than international standard index of pollution. Therefor, Shajiang black soil amended by coal fly ash was safe and reliable within the above range.

Coal↗

[Significance of lung perfusion scanning with technetium labeled macroaggregated albumin and pulmonary function assay for diagnosis of early hepatopulmonary syndrome].

OBJECTIVE: To evaluate the values of pulmonary function assay and dynamic pulmonary perfusion imaging with technetium labeled macroaggregated albumin ((99m)TcMAA) in the early diagnosis of hepatopulmonary syndrome (HPS). METHODS: The pulmonary function assay and (99m)TcMAA scans were performed in 28 patients with HPS, 30 cirrhotic patients (CP) without HPS, and 21 healthy controls (HC). RESULTS: In the patients with HPS, PaO(2), SaO(2) and diffusion capacity for carbon monoxide of lungs (DLco) was significantly lower than that in CP (P<0.01) and HC (P<0.01), and alveolar-arterial gradient [P((A-a))O(2)] was significantly increased (P<0.001). Results from (99m)TcMAA scans showed that the radionuclides were distributed over the spleen, kidney, liver and brain, and the ratios of arterivenous shunt were significantly higher than that in CP (P<0.001) and NC (P<0.001). In cirrhotic patients, DLco significantly decreased (P<0.05), P((A-a))O(2) and shunt ratios increased (P<0.01 and 0.001). CONCLUSIONS: Pulmonary function assay and dynamic pulmonary perfusion imaging with (99m)TcMAA are sensitive methods for diagnosis of the early HPS.

Hepatopulmonary Syndrome↗

[A clinical and pathological analysis of 41 patients with anti-glomerular basement membrane antibody related diseases].

OBJECTIVE: To investigate the clinical and pathological characteristics of anti-glomerular basement membrane (GBM) antibody associated diseases with different clinical patterns. METHODS: The clinical and pathological data of 41 patients with anti-GBM antibody associated diseases, screened in our institute in recent six years, were retrospectively analyzed. RESULTS: 22 of the 41 patients presented as Goodpasture syndrome, 2 of them having normal renal function. 32 of the 41 patients had anti-GBM antibody positive only (single positive). 31 of the 32 single positive patients were male with an average age of (26.8 +/- 9.7) years. The remaining 9 patients were both anti-GBM antibody and antineutrophil cytoplasmic antibody (ANCA) positive (double positive); 7 of the 9 were female with an average age of (44.5 +/- 19.6) years. There was significant difference in gender and age between the single and double positive groups (P < 0.05). 30 of the 32 patients with renal biopsy had crescentic glomerulonephritis and the remaining two with normal renal function had mild mesangial proliferative glomerulonephritis only. 24 of the 30 (80%) crescentic glomerulonephritis patients had all glomeruli affected by crescents with severe glomerular capillary loop and Bowman's capsule damage. With immunofluorescence examination, 16 of the 23 cases had typical IgG and C(3) linear deposition along glomerular capillary walls, but the remaining 7 had fine granular IgG and/or C(3) deposition. In a few cases, granular deposition was found even in mesangium. There was no correlation between the immunofluorescence patterns and the severity of glomerular damage (P > 0.05). All patients had anemia, hematuria and proteinuria, 7 of the 41 cases presented as nephrotic syndrome. After intensive immunosuppressive therapy, only four patients, including the two patients with normal renal functions, achieved remission, the remaining patients either were in renal replacement therapy or died. CONCLUSIONS: Anti-GBM antibody associated diseases are not rare in China. Single positive patients are mainly young male, while double positive patients are mainly middle-aged female. Most of the patients with anti-GBM antibody associated diseases have crescentic glomerulonephritis (rapidly progressive glomerulonephritis, RPGN) with a bad prognosis. However, not all the patients have typical linear deposition of IgG and C(3) along glomerular capillary walls. Only a few non-oliguric patients with normal renal function or mild renal damage may achieve remission.

Adolescent↗

[Detection of neuroendocrine differentiation in NSCLC and its clinical significance].

OBJECTIVE: To study differentiation of neuroendocrine (NE) in non-small cell lung carcinoma (NSCLC) and its effect on the responsiveness to chemotherapy. METHODS: Neuron-specific enolase (NSE), chromogranin A (CgA) and synaptophysin (SYN) were detected in 42 cases of NSCLC by using Western blot and immunohistochemistry. Electron microscopy was also used to observe the ultrastructure of NE granule in above specimens. The relationship between the chemotherapeutic responsiveness and the differentiation of NE in carcinoma tissues was evaluated. RESULTS: (1) The positive rate of NE detected by Western blot is higher than that detected by immunohistochemistry and electron microscopy. (2) There is no relationship between the expression of NE and the type of lung carcinoma as well as the differentiated degree of carcinoma. (3) The positive rate of three markers detected by immunohistochemistry and Western blot methods in the group of responsive to chemotherapy is higher than that in non-responsive group (P < 0.05). CONCLUSIONS: There is a high rate of NE differentiation in NSCLC, of which NSE's rate is highest, SYN takes second place, and CgA's rate is lowest. Immunohistochemistry and Western blot method are both very useful for the diagnosis of NE differentiation in NSCLC. The sensitivity of Western blot is higher than immunohistochemistry. The differentiation of NE may be one of the factors effected the chemotherapy in NSCLC.

Aged↗

[Clinical analysis of 62 cases laryngeal papilloma in children].

OBJECTIVE: To investigate the clinical features of laryngeal papilloma in children. METHOD: In a group of 62 patients with laryngeal papilloma in children, the tumors of 28 patients were cut under the direct laryngoscope, 34 patients were treated with laryngeal micro-laser operation. RESULT: The post-operation followup ranged from 2 to 5 years, the cure rate of 2 years was 51.61%. CONCLUSION: The clinical features of this disease include rapid development, a large lesion, and it is often found in the infraglottic cavity. Furthermore, we believe that in order to eliminate the tumors more accurately and decrease recurrence, micro-laser surgery and the use of interferon is very necessary.

Adolescent↗