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Biomedical subjects

Q Qiu

Publications and source records attributed to Q Qiu.

At least 19 recordsLinked to original sources

Reversible flocculation of silica across the phase boundary of poly(vinyl caprolactam) in aqueous solution.

The colloid stability of silica dispersions in water in the presence of poly(vinyl caprolactam) (PVCAP) has been studied below and above the lower consolute temperature (LCT) of its solutions. The dispersion sediments slowly without PVCAP in the temperature range studied (26-40 degrees C) or with PVCAP below the LCT ( approximately 30 degrees C). In contrast, with PVCAP above the LCT, rapid flocculation occurs at acid pH, with re-dispersal on cooling. Reversible flocculation is also obtained above the LCT by cycling the pH from alkaline to acid and back. The flocculation observed above the LCT may also be regarded as heterocoagulation between the silica particles and the aggregates of the polymer.

Journal Article↗

Sustained antiproliferative mechanisms by RB24, a targeted precursor of multiple inhibitors of epidermal growth factor receptor and a DNA alkylating agent in the A431 epidermal carcinoma of the vulva cell line.

Recently, with the purpose of enhancing the potency of epidermal growth factor receptor (EGFR)-based therapies, we designed a novel strategy termed 'Cascade-release targeting' that seeks to develop molecules capable of degrading to multiple tyrosine kinase (TK) inhibitors and highly reactive electrophiles, in a stepwise fashion. Here we report on the first prototype of this model, RB24, a masked methyltriazene, that in addition to being an inhibitor on its own was designed to degrade to RB14, ZR08, RB10+a DNA alkylating methyldiazonium species. The cascade degradation of RB24 requires the generation of two reactive electrophiles: (a) an iminium ion and (b) a methyldiazonium ion. Thus, we surmise that these species could alkylate the active site of EGFR, thereby irreversibly blocking its action and that DNA damage could be induced by the methyldiazonium. Using the EGFR-overexpressing human epidermoid carcinoma of the vulva cell line, A431, we demonstrate herein that (a) RB24 and its derived species (e.g. RB14, ZR08) irreversibly inhibit EGFR autophosphorylation, (b) RB24 induced significant levels of DNA strand breaks, (c) sustained inhibition of EGFR by RB24 was associated with blockade of MAPK activation and c-fos gene expression, (d) RB24 induced irreversible cell growth inhibition with a 100-fold greater potency than Temodaltrade mark, a clinical methyltriazene. The pronounced growth inhibitory potency of RB24 was attributed to its ability to simultaneously damage DNA and irreversibly block EGFR TK activity.

Alkylating Agents↗

EGF-induced trophoblast secretion of MMP-9 and TIMP-1 involves activation of both PI3K and MAPK signalling pathways.

Epidermal growth factor (EGF) is present in the maternal-fetal environment and has an important role in placental development. Matrix metalloproteinase-9 (MMP-9) expression/activation is a pre-requisite in extravillous trophoblast invasion. Whereas EGF up-regulates MMP-9 activity in a variety of cell types, there is no direct evidence for the stimulation of MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) secretion by EGF in extravillous trophoblasts. In addition, the signalling pathways involved in this regulation are not clear. In the present study, we have examined the possible involvement of the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in the regulation of the MMP-9/TIMP-1 system by EGF in vitro. We used a well-established invasive extravillous trophoblast cell line (HTR8/Svneo) and measured gene and protein expression by semi-quantitative RT-PCR and western analysis respectively. MMP activity was determined by zymography. We showed for the first time that EGF activated both PI3K/Akt and MAPK/extracellular-signal regulated kinase (ERK) signalling in HTR8/SVneo, and increased both MMP-9 and TIMP-1 mRNAs and protein concentrations. Interfering with either signalling pathway via PI3K inhibitor LY294002 or MEK inhibitor U0126 in EGF-stimulated HTR8/SVneo cells blocked the induction of MMP-9 and TIMP-1. LY294002 inhibited Akt phosphorylation, but had no effect on ERK phosphorylation; U0126 suppressed ERK phosphorylation without interfering with the phosphorylation of Akt. In addition, expression of constitutively active Akt (Myr-Akt1, Myr-Akt2, Myr-Akt3) was not sufficient to induce proMMP-9 and TIMP-1 secretion. Our results suggest that the activation of both PI3K and MAPK pathways in extravillous trophoblasts is necessary for the up-regulation of MMP-9 and TIMP-1 expression by EGF.

Blotting, Western↗

Complexation between poly(maleic acid/octyl vinyl ether) and poly(vinyl caprolactam) in aqueous solution and at the alumina/water interface.

Solution and interfacial properties of binary polymer mixtures of poly(maleic acid/octyl vinyl ether) (PMAOVE) and poly(vinyl caprolactam) (PVCAP) have been studied for the alumina/water system. To test the hydrophobic effect, mixtures of poly(maleic acid/methyl vinyl ether) (PMAMVE) and PVCAP are also investigated and compared to the behavior of PMAOVE/PVCAP. At low pH, both polymer mixtures become turbid upon mixing. The turbidity increases at low mixing ratios of PVCAP to the vinyl ether component, reaches a maximum, and then decreases at higher mixing ratios. Upon shifting the pH to the alkaline range, i.e., pH 7.5 and above, the turbid solution becomes clear for both the polymer mixtures. Cloud point measurements indicate the absence of complexation of PVCAP with PMAMVE under the alkaline conditions, but strong interaction with PMAOVE. This is attributed to the different forces involved in the complexation among the polymers: H bonding for PVCAP/PMAMVE and both H bonding and hydrophobic effects for PVCAP/PMAOVE. At the alumina/water interface, the normally nonadsorbing PVCAP is triggered to adsorb by PMAOVE, attributed to the hydrophobic complexation between the two. However, the adsorption of PVCAP shows a maximum as a function of the concentration of PMAOVE. At concentrations of PMAOVE above the onset of its own plateau adsorption, the amount of PVCAP triggered to adsorb is reduced possibly due to the polymer complex formation in solution.

Journal Article↗

CDS1 and promoter single nucleotide polymorphisms of the CTLA-4 gene in human myasthenia gravis.

The cytotoxic T lymphocyte associated protein 4 (CTLA-4) gene (Ctla-4) is a candidate gene for autoimmune disease. We here report results of two single nucleotide polymorphisms (SNPs) in the Ctla-4, a +49 A/G SNP in CDS1 and a C/T promoter SNP at position -318. There were no differences in these two SNPs between patients and healthy individuals. The frequency of allele G and genotype G/G at position +49 in CDS1 was increased in patients with thymoma when compared with patients with normal and hyperplastic thymic histopathology. Patients with the G/G genotype had signs of immune activation manifested as higher levels of serum IL-1beta and higher percentage of CD28(+) T lymphocytes. There was a strong linkage between the 86bp allele in the 3'-UTR and the A(+49) allele in CDS1. Our results suggest that the SNP at position +49 in CDS1 might be associated with the manifestations of MG.

3' Untranslated Regions↗

X-linked inhibitor of apoptosis protein expression and the regulation of apoptosis during human placental development.

In this study, we have examined the expression and potential role of X-linked inhibitor of apoptosis protein (XIAP), Fas, and Fas ligand (FasL) in the regulation of apoptosis throughout placental development. Protein expression was determined by Western blot analysis and immunohistochemistry, whereas apoptotic cell death was assessed by DNA fragmentation analysis and TUNEL. The XIAP was present in trophoblast throughout placental development, but its content significantly decreased during late pregnancy, when apoptosis was maximal. The FasL content was low during early placental development but increased coincidentally to the decrease in XIAP during the third trimester. Our data also suggest that placental apoptosis is the culmination of the relative expression of these cell-death and -survival proteins, a phenomenon that is cell type-specific and dependent on cytodifferentiation and the stage of placental development. Moreover, the induction of syncytiotrophoblast apoptosis may involve the concomitant up-regulation of FasL for Fas activation and the removal of downstream inhibition of the apoptotic cascade by XIAP.

Apoptosis↗

Influence of maternal smoking on trophoblast apoptosis throughout development: possible involvement of Xiap regulation.

Maternal smoking is associated with severe perinatal complications and significant placental pathologies with underlying ultrastructural changes. In this study, we examined the influence of maternal smoking on trophoblast apoptosis throughout development and correlated those findings with changes in expression of X-linked inhibitor of apoptosis protein (Xiap) as well as Fas and Fas ligand (FasL). Trophoblast apoptosis was determined by DNA fragmentation and TUNEL. Protein expression was assessed by Western blotting and immunohistochemistry. Maternal smoking was associated with increased trophoblast apoptosis in the first trimester but decreased trophoblast apoptosis near term. Placental Xiap levels decreased significantly throughout development in nonsmokers (P < 0.05) but remained elevated in smokers. Fas and FasL levels did not vary significantly throughout development nor between groups. However, procaspase-3 levels were significantly increased in smokers at term. Our results suggest that maternal smoking has different effects at different stages of trophoblast differentiation and that this is regulated in part through modulations in placental Xiap expression.

Apoptosis↗

Gap junction assembly: PTX-sensitive G proteins regulate the distribution of connexin43 within cells.

Cells expressing connexin43 are able to upregulate gap junction (GJ) communication by enhancing the assembly of new GJs, apparently through increased connexin trafficking. Because G proteins are known to regulate different aspects of protein trafficking, we examined the effects of pertussis toxin (PTX; a specific inhibitor of certain G proteins) on GJ assembly. Dissociated Novikoff hepatoma cells were reaggregated for 60 min to form nascent junctions. PTX inhibited GJ assembly, as indicated by a reduction in dye transfer. Electron microscopy also revealed a 60% decrease in the number of GJ channels per cell interface. Importantly, PTX blocked the twofold enhancement in GJ assembly found in the presence of low-density lipoprotein. Two G(i alpha) proteins (G(i alpha 2) and G(i alpha 3)), which have been implicated in the control of membrane trafficking, reacted with PTX in ADP-ribosylation studies. PTX and/or the trafficking inhibitors, brefeldin A and monensin, inhibited GJ assembly to comparable degrees. In addition, assays for GJ hemichannels demonstrated reduced plasma membrane levels of connexin43 following PTX treatment. These results suggest that PTX-sensitive G proteins regulate connexin43 trafficking, and, as a result of inhibition with PTX, the number of plasma membrane hemichannels available for GJ assembly is reduced.

Adenosine Diphosphate Ribose↗

Assembly and activation of HK-PK complex on endothelial cells results in bradykinin liberation and NO formation.

Prekallikrein (PK) activation on human umbilical endothelial cells (HUVEC) presumably leads to bradykinin liberation. On HUVEC, PK activation requires the presence of cell-bound high-molecular-weight kininogen (HK) and Zn(2+). We examined the Zn(2+) requirement for HK binding to and the consequences of PK activation on endothelial cells. Optimal HK binding (14 pmol/10(6) HUVEC) is seen with no added Zn(2+) in HEPES-Tyrode buffer containing gelatin versus 16--32 microM added Zn(2+) in the same buffer containing bovine serum albumin. The affinity and number of HK binding sites on HUVEC are a dissociation constant of 9.6 +/- 1.8 nM and a maximal binding of 1.08 +/- 0.26 x 10(7) sites/cell (means +/- SD). PK is activated to kallikrein by an antipain-sensitive mechanism in the presence of HK and Zn(2+) on HUVEC, human microvascular endothelial cells, umbilical artery smooth muscle cells, and bovine pulmonary artery endothelial cells. Simultaneous with kallikrein formation, bradykinin (5.0 or 10.3 pmol/10(6) HUVEC in the absence or presence of lisinopril, respectively) is liberated from cell-bound HK. Liberated bradykinin stimulates the endothelial cell bradykinin B2 receptor to form nitric oxide. Assembly and activation of PK on endothelial cells modulates their physiological activities.

Animals↗

[A pilot study on the value of duplex polymerase chain reaction method in early diagnosis of Legionella pneumonia].

OBJECTIVE: To investigate the value of duplex polymerase chain reaction (DPCR) in early diagnosis of Legionella pneumonia by detecting Legionella DNA in sputum and bronchoalveolar lavage fluid(BALF). METHODS: During the process of DPCR, two different sets of oligonucleotide primers were simultaneously used to amplify 386bp 16SrRNA gene fragment and 206bp mip gene fragment. These two primers were designed according to the sequences of 16SrRNA gene and mip gene of Legionella. The sputum and BALF of patients from two groups, including a Legionella pneumonia group (n = 15) and an ordinary pneumonia group (n = 31) were collected at early course of the disease. All of the samples were detected with DPCR for Legionella DNA. Simulated samples were also detected to investigate the sensitivity of the method for testing clinical samples. RESULTS: All the samples collected from the Legionella pneumonia patients, including 25 of sputum,and 8 of BALF showed positive DPCR. The results of DPCR, which could distinguish Legionella pneumophila from non-pneumophila Legionella spp. to some degree, were in good accordance with those of the specific serum antibodies. All of the samples from the ordinary pneumonia group including 40 of sputum and 16 of BALF demonstrated negative DPCR. Different samples of the same patient showed the same DPCR results. The lowest detection level of simulated sputum sample was the same as that of simulated BALF sample, being 1 x 10(3) cfu/ml. CONCLUSIONS: This preliminary study showed that DPCR had satisfactory sensitivity, specificity and stability for detecting Legionella DNA in sputum and BALF. The method is of value in early diagnosis of Legionella pneumonia. Its wide use for clinical work requires further investigation.

Adult↗

[GC-MS analysis of volatile oil from Atractylodes chinensis].

OBJECTIVE: To determine chemical constituents of volatile oil from Atractylodes chinensis(D. C.) Koidz by quantitative with qualitative analysis. METHODS: By GC and GC/MS/DS analytical technology and SE-54 capillary column, the chemical constituents of volatile oil from Atractylodes chinensis(D. C.) Kiodz were systematically analyzed. RESULTS: 68 peaks were separated, which occupied over 90% of the total area of all chromatographic peaks. The 55 components were identified. CONCLUSION: The number of compoments of volatile oil from Atractylodes chinensis(D. C.) Koidz determined in this analysis, are two times as many as those reported in some literatures.

Asteraceae↗

[Observation on the changes in nasopharyngeal carcinoma patients' olfactory before and after radiotherapy].

OBJECTIVE: Detecting nasopharyngeal carcinoma (NPC) patients' olfactory before and after radiotherapy for investigating the infection of radiotherapy on these patients' olfactory. METHOD: 100 NPC patients' olfactory were detected before the start of radiotherapy and after the termination of therapy in 3, 6, 12, 24 and 36 months. RESULT: Patients' smell acuity decreased sharply 3 months after therapy, but varying degrees of recovery were noted in 6 and 12 months. However their smell acuity became worse in the following time. CONCLUSION: NPC patients' smell acuity can be profoundly affected by radiotherapy. And after radiotherapy, their smell acuity will decrease wave-likely and cannot fully recover.

Adult↗

[Experimental study on oncogenicity of Aristolochia manshuriensis in rats].

OBJECTIVE: To observe the oncogenetic process, biological behavior, pathological and immunohistochemical features of tumor induced by Aristolochia manshuriensis (AM) in rats. METHODS: Acute renal injury model was established with AM docoction in different dosages by gastrogavage to observe the histomorphologic and immunohistochemical features dynamically. RESULTS: (1) At month 0, 1 and 3, the occurrence of renal tumor or tumor-like proliferation was not observed; (2) At month 6, the occurrence of renal tumor-like proliferation in all the three AM dosage groups (50 g/kg, 30 g/kg and 20 g/kg) was 100.0%. Immunohistochemical examination conducted in 2 rats showed that the short spindle-shaped interstitial cells were expressed positively both by vimentin and proliferative cell nuclear antigen (PCNA), but were shown negative for smooth muscle actin (SMA) and p53; (3) At month 6, the occurrence of renal tumor in the three dosage groups was 42.8%, 25.0% and 0% respectively, including 4 cases of renal mesenchymal tumor and 1 case of nephroblastoma. Immunohistochemical examination conducted in 3 cases of renal mesenchymal tumor showed that the short spindle-shaped tumor cells expressed both by vimentin and PCNA, and SMA and p53 were positive for well-differentiated tumor cells. (4) The occurrence of extrarenal tumor in the three dosage groups was 14.3%, 12.5% and 12.5% respectively, 1 case of mammary duct epithelial tumor, 1 thyroid follicle epithelial tumor and 1 skin appendicular epithelial tumor. No tumor occurred in the control group. CONCLUSION: Large dosage of AM is oncogenic. The occurrence of renal tumor was relatively high, and the histological type is mainly mesenchymal. Vimentin, SMA, PCNA and p53 positive expression was shown for well-differentiated renal mesenchymal tumor. The occurrence of extrarenal tumor is rather low.

Animals↗

Plasminogen activator inhibitor-1 fused with erythropoietin (EPO) mimetic peptide (EMP) enhances the EPO activity of EMP.

Erythropoietin (EPO) mimetic peptide (EMP) encoding sequence was inserted into the gene of plasminogen activator inhibitor-1 (PAI-1) between Ala348 and Pro349 (P2'-P3'), generating a novel gene, PAI-1/EMP (PMP). This was cloned into pET32a expression vector, fused with TrxA peptide in the vector, and a 63-kDa protein was expressed in inclusion bodies with an expression level >50%. The TrxA/PMP protein was purified by Ni-NTA-agarose metal-ligand affinity chromatography to a purity >90%, showing a single, silver-stained band on SDS-PAGE. Using a reticulocyte counting assay, the EPO activity of PMP was determined to be 5,000 IU/mg, 2,500-fold that of EMP.

Amino Acid Sequence↗

Long-term outcome of acute renal injury induced by Aristolochia manshuriensis Kom in rats.

AIM: To investigate the long-term functional and morphological changes of the kidney induced by acute intoxication of Aristolochia manshuriensis Kom in rats. METHODS: Experimental model of acute renal injury was established in the Sprague-Dawley rats with oral administration of decoctions of Chinese herb, Aristolochia manshuriensis Kom, at dosages of 50 g.kg-1.d-1 and 30 g.kg-1.d-1 for 7 consecutive days, and 20 g.kg-1.d-1 for 15 consecutive days. Renal function was assayed at months 0 (right after treatment), 1, 3, and 6 of the experiment. Renal histological examination was also performed. RESULTS: 1) At month 0, the renal functional changes of acute renal injury included azotemia, low molecular weight proteinuria, glycosuria, hypoosmotic urine, and NAG enzymuria. Histopathological changes showed acute tubular necrosis, predominantly at the corticomedullary junction. 2) At months 1 and 3, the renal function of rats of the experiment was gradually restored and histopathologic examination suggested that the tubular lesions gradually recovered. In HE sections, basophilic deposits were observed in the tubular cytoplasm. And interstitial infiltration of inflammatory cells was not prominent. 3) At months 6, renal preneoplastic lesions, renal tumors, and extrarenal tumors occurred in rats. The occurrence of renal preneoplastic lesions at dosages of 50 g.kg-1.d-1, 30 g.kg-1.d-1, and 20 g.kg-1.d-1 were 100.0% at all three doses, renal tumors 42.8%, 25.0%, and 0%, respectively, extrarenal tumors 14.4%, 12.5%, and 12.5%, respectively, and systemic tumors 57.2%, 37.5%, and 12.5%, respectively. The occurrence of basophilic deposits, renal preneoplastic lesions, renal tumors, and extrarenal tumors in normal control group was nil. CONCLUSIONS: 1) Administration of large dosage of Aristolochia manshuriensis Kom induces acute renal failure in rats. 2) The long-term renal function and histopathologic changes of acute renal injury induced by Aristolochia manshuriensis Komrecover spontaneously. 3) Aristolochia manshuriensis Kom has been proved to be oncogenic for the first time.

Acute Kidney Injury↗

[Study on chemical constituents of essential oil of Biota orientalis by GC-MS].

The essential oil was extracted from Biota orientalis (L) Endl by using steam distillery, analyzed with SE-54(30 m x 0.25 mm I.d) fused silica capillary column. The optimum separate and analytical conditions were researched. The amount of the components from the essential oil was determinated by monoliration method. The separated components were identified by GC-MS. There are 33 components which are make up 80% of the total essential oil were separated and identified.

Alkenes↗

Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function.

Surface reactivity is one of the common characteristics of bone bioactive ceramics. It contributes to their bone bonding ability and their enhancing effect on bone tissue formation. During implantation, reactions occur at the material-tissue interface that lead to time-dependent changes in the surface characteristics of the implant material and the tissues at the interface. This review describes some of the current concepts regarding the surface reactivity of bone bioactive materials and its effect on attachment, proliferation, differentiation and mineralization of bone cells.

3T3 Cells↗