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Biomedical subjects

Gang Xue

Publications and source records attributed to Gang Xue.

At least 19 recordsLinked to original sources

Apolipoprotein E promotes papillary thyroid carcinoma progression by activating PINK1/Parkin-mediated mitophagy.

BACKGROUND: Increasing evidence supports a progression-related role of apolipoprotein E (APOE) in papillary thyroid carcinoma (PTC), yet a clear mechanistic explanation for this association is still lacking. Considering the pivotal role of mitochondrial homeostasis in tumorigenesis, the potential role of APOE in promoting PTC progression through mitophagy regulation was investigated. Additionally, the involvement of the PINK1/Parkin-associated pathway in this process was examined to provide insights into its contribution to tumor progression. METHODS: APOE in thyroid carcinoma was characterized in terms of its expression profile, diagnostic relevance, and potential biological functions, based on integrative evidence derived from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. APOE and mitophagy-related protein expression were further examined in PTC tissues by immunohistochemistry. Further evaluation of APOE in PTC cell lines focused on its association with proliferation, apoptosis, and mitophagy, with bidirectional functional perturbation serving as the basis for assessment. Pharmacological inhibitors were used to assess the involvement of mitophagy-related signaling in the observed APOE-dependent phenotypes. Additionally, the in vivo impact of APOE on PTC tumor growth and mitophagy was further investigated through a nude mouse xenograft model, providing insight into its potential role in tumor progression. RESULTS: A significant upregulation of APOE was observed in thyroid carcinoma tissues and PTC cell lines, supporting its potential relevance as a diagnostic biomarker. The modulation of APOE expression significantly influenced PTC cell proliferation and apoptosis, with overexpression promoting cell proliferation and inhibiting apoptosis, while knockdown led to the opposite effects. Mechanistically, APOE overexpression increased AMP-activated protein kinase (AMPK) phosphorylation and decreased mammalian target of rapamycin (mTOR) phosphorylation, accompanied by increased PINK1 and Parkin expression and mitophagy-related changes, including altered mitochondrial membrane potential, reduced overall reactive oxygen species levels, and increased autophagosome formation. Pharmacological inhibition of mitophagy attenuated the proliferative and antiapoptotic effects of APOE. CONCLUSIONS: These findings demonstrate that APOE promotes PTC progression in association with PINK1/Parkin-related mitophagy and modulation of the AMPK/mTOR axis. The APOE-associated mitophagy axis may provide a rationale for future preclinical investigation in PTC.

Apolipoprotein E (APOE)↗

Acceptor or donor (diaryl B or N) substituted octupolar truxene: synthesis, structure, and charge-transfer-enhanced fluorescence.

Two diaryl B- and N-substituted truxene charge-transfer compounds B3 and N3 have been synthesized. The fluorescence intensities of several nonfunctionalized truxene compounds are 1 order of magnitude weaker than that of B3 and N3. To reveal the structure-property correlations, the X-ray structures of B3 and N3 and their precursors 3 and 4 have been determined. The extended molecular dimension, the especially shortened B-C bond, and the improved planarity of B3 can serve as direct structural evidence for the charge transfer.

Journal Article↗

The performance of BAF using natural zeolite as filter media under conditions of low temperature and ammonium shock load.

Natural zeolite and expanded clay were used as filter media for biological aerated filter (BAF) to treat municipal wastewater in parallel in whole three test stages. The stage one test results revealed that zeolite BAF and expanded clay BAF have COD and NH(3)-N removals in the range of 84.63-93.11%, 85.74-96.26%, 82.34-93.71%, and 85.06-93.2%, respectively, under the conditions of water temperature of 20-25 degrees C and hydraulic load of 2-3m(3)/(m(2)h). At the following stage two, the influent NH(3)-N concentration was increased to about double value of the stage one, and it was investigated that the effluent NH(3)-N of expanded clay BAF increased significantly and then gradually restored to normal condition in 2 weeks, while the effluent NH(3)-N of zeolite BAF kept stable. At stage three, the low reactor temperature has also different effects on these two BAFs, under conditions of water temperature of 7-10 degrees C, hydraulic load of 2-3m(3)/(m(2)h), zeolite BAF and expanded clay BAF have COD and NH(3)-N removals in the range of 74.5-88.47% (average of 81.57%), 71.73-88.49% (average of 81.06%), 71.91-87.76% (average of 80.49%), and 38.41-77.17% (average of 65.42%), respectively. Three stages test results indicated that the zeolite BAF has a stronger adaptability to NH(3)-N shock load and low temperature compared to expanded clay BAF. In addition, the detection of the amounts of heterobacteria and nitrobacteria of two biological aerated filters in three stages also showed the zeolite filter media was more suitable to the attached growth of nitrobacteria, which is helpful to the improvement of nitrification performance in zeolite BAF.

Bioreactors↗

Improving the performance of sequencing batch reactor (SBR) by the addition of zeolite powder.

Two types of operation means "SBR reactor alone (control reactor)" and "adding zeolite powder into SBR reactor (test reactor)" were used to treat municipal wastewater. The test results revealed that zeolite powder addition could improve the activity of the activated sludge. It was investigated the specific oxygen utilization rate (SOUR) of the tested zeolite sludge were about double times that of the control activated sludge, and the nitrification rate and settling property of zeolite-activated sludge were both improved. Due to the combination of zeolite adsorption for NH(4)(+)-N and enhanced simultaneous nitrification and de-nitrification (SND), a higher nitrogen removal was observed in test reactor compared to the control reactor, and the addition of zeolite powder is helpful to inhabit sludge bulking. In addition, through long-term parallel shock load test, it was found that the zeolite powder addition could enhance the ability of activated sludge in resisting the shock load of organics and ammonium. Compared to the control activated sludge, zeolite powder added activated sludge could remove COD, NH(4)(+)-N, TN and TP significantly in a shorter cycle time. At the same operational time period, the test SBR could treat wastewater quantity 1.22 times that treated in control SBR.

Environmental Restoration and Remediation↗

Minicircle-IFNgamma induces antiproliferative and antitumoral effects in human nasopharyngeal carcinoma.

PURPOSE: The aims of this work were to investigate the antitumor effect of IFNgamma gene transfer on human nasopharyngeal carcinoma (NPC) and to assess the potential of minicircle vector for antitumor gene therapy. EXPERIMENTAL DESIGN: We developed a recombinant minicircle vector carrying the human IFNgamma gene and evaluated the effects of minicircle-mediated IFNgamma gene transfer on NPC cell lines in vitro and on xenografts in vivo. RESULTS: Relative to p2PhiC31-IFNgamma, minicircle-mediated IFNgamma gene transfer in vitro resulted in 19- to 102-fold greater IFNgamma expression levels in transfected cells (293, NIH 3T3, CNE-1, CNE-2, and C666-1) and inhibited the growth of CNE-1, CNE-2, and C666-1 cells more efficiently, reducing relative growth rates to 7.1 +/- 1.6%, 2.7 +/- 1.0%, and 6.1 +/- 1.6%, respectively. Flow cytometry and caspase-3 activity assays suggested that the antiproliferative effects of IFNgamma gene transfer on NPC cell lines could be attributed to G(0)-G(1) arrest and apoptosis. Minicircle-mediated intratumoral IFNgamma expression in vivo was 11 to 14 times higher than p2PhiC31-IFNgamma in CNE-2- and C666-1-xenografted mice and lasted for 21 days. Compared with p2PhiC31-IFNgamma treatment, minicircle-IFNgamma treatment significantly increased survival and achieved inhibition rates of 77.5% and 83%, respectively. CONCLUSIONS: Our data indicate that IFNgamma gene transfer exerts antiproliferative effects on NPC cells in vitro and leads to a profound antitumor effect in vivo. Minicircle-IFNgamma is more efficient than corresponding conventional plasmids due to its capability of mediating long-lasting high levels of IFNgamma gene expression. Therefore, minicircle-mediated IFNgamma gene transfer is a promising novel approach in the treatment of NPC.

Animals↗

Activated sludge ozonation to reduce sludge production in membrane bioreactor (MBR).

Total experimental period was divided into two stages. At first stage, a series of batch studies were carried out to get an understanding of the effect of ozonation on sludge properties. At the following stages, three membrane bioreactors (MBRs) with different amounts of activated sludge to be ozonated were run in parallel for a long period to evaluate the influence of sludge ozonation on sludge yield and permeate quality. Through batch study, it was found that ozone could disrupt the cell walls and cause the release of plasm from the cells, then the amounts of soluble organics in the solution increased with ozonation time. With the rise of soluble organics, the amount of soluble organics to be mineralized increased as well, which would reduce the soluble organics content. For the counteraction between these two aspects, a pseudo-balance could be achieved, and soluble organics would vary in a limited range. Sludge ozonation also increased the contents of soluble nitrogen and phosphorus in the solution. On the basis of batch study, a suitable ozone dosage of 0.16 kg O(3)/kg MLSS was determined. Three systems were run in parallel for a total period of 120 days; it was demonstrated that a part of activated sludge ozonation could reduce sludge production significantly, and biological performance of mineralization and nitrification would not be inhibited due to sludge ozonation. Experimental results proved that the combination of ozonation unit with MBR unit could achieve an excellent quality of permeate as well as a small quantity of sludge production, and economic analysis indicated that an additional ozonation operating cost for treatment of both wastewater and sludge was only 0.096 Yuan (US$ 0.0115)/m(3) wastewater.

Bioreactors↗

In vitro effect of adenovirus-mediated human Gamma Interferon gene transfer into human mesenchymal stem cells for chronic myelogenous leukemia.

For developing gene therapy for chronic myelogenous leukemia (CML), we evaluated the feasibility of using autologous bone marrow stromal cells (BMSCs) of one CML patient as a target cell population and studied the efficiency of recombinant adenovirus-mediated human Gamma Interferon (hIFN-gamma) gene transfer into BMSCs. BMSCs can be readily obtained, expanded, and successfully transduced with adenoviral vectors in vitro. We studied the in vitro expression of hIFN-gamma in human BMSCs following transduction with Ad/hIFN-gamma. On transduction of BMSCs at a MOI of 50, the expression and secretion of hIFN-gamma were achieved as high as 5492 +/- 660 approximately 50647 +/- 4049 ng/10(6) cells per 24 h over the course of 3 weeks. We further studied the effects of hIFN-gamma produced by transduced BMSCs on the proliferation of the human leukemia cell line K562 cells in vitro, proliferation of K562 cells was markedly inhibited in the experimental groups as compared with the other two control groups after 5 days of coculture. We also found that the percentage of K562 cells in the G(1) phase of cell cycle can be increased by treatment of hIFN-gamma produced by Ad/hIFN-gamma transduced BMSCs, but the percentage of K562 cells in the S phase of cell cycle can be decreased in the same time. Apoptosis rate of K562 cells in the experimental groups was 30.8 +/- 8.5%, as compared with the other two control groups (5.6 +/- 1.3% and 5.5 +/- 0.8%, respectively) (p < 0.01). Our results indicate that hIFN-gamma gene engineered BMSCs of CML donors could be successfully established and that local production of hIFN-gamma is sufficiently to inhibit the proliferation of K562 cells and induce apoptosis of K562 cells in vitro, suggesting an important potential use in the clinical gene therapy of CML.

Adenoviridae↗

[Factors affecting biological removal of iron and manganese in groundwater].

Factors affecting biological process for removing iron and manganese in groundwater were analyzed. When DO and pH in groundwater after aeration were 7.0 - 7.5 mg/L and 6.8 - 7.0 respectively, not only can the activation of Mn2+ oxidizing bacteria be maintained, but also the demand of iron and manganese removal can be satisfied. A novel inoculating approach of grafting mature filter material into filter bed, which is easier to handle than selective culture media, was employed in this research. However, this approach was only suitable to the filter material of high-quality manganese sand with strong Mn2+ adsorption capacity. For the filter material of quartz sand with weak adsorption capacity, only culturing and domesticating Mn2+ oxidizing bacteria by selective culture media can be adopted as inoculation in filter bed. The optimal backwashing rate of biological filter bed filled with manganese sand and quartz sand should be kept at a relatively low level of 6 - 9 L/(m2 x s) and 7 -11 L/( m2 x s), respectively. Then the stability of microbial phase in filter bed was not disturbed, and iron and manganese removal efficiency recovered in less than 5h. Moreover, by using filter material with uniform particle size of 1.0 - 1.2 mm in filter bed, the filtration cycle reached as long as 35 - 38h.

Bacteria↗

[Construction of recombinant adenovirus carrying human IFNgamma gene by in vitro ligation and its expression].

BACKGROUND & OBJECTIVE: Interferon-gamma (IFNgamma) can promote directly the apoptosis of some kinds of tumor cells and regulate cellular immunity, therefore, it may play an important role in gene therapy for tumors. This study was to construct recombinant adenovirus carrying human IFNgamma cDNA, and detect its expression profile in eukaryotic cells. METHODS: IFNgamma cDNA was amplified by reverse transcription-polymerase chain reaction (RT-PCR) from human peripheral blood mononuclear cells, and cloned into adenoviral shuttle plasmid pShuttle to construct recombinant adenovirus carrying human IFNgamma cDNA (Ad-IFNgamma) by in vitro ligation. Hepatocellular carcinoma cell line HepG2 was infected with Ad-IFNgamma, and the expression of IFNgamma was detected by RT-PCR and immunohistochemistry. RESULTS: The sequence of the cloned IFNgamma cDNA was completely consistent with that reported in GenBank. PCR analysis confirmed the existence of IFNgamma gene in Ad-IFNgamma without wild adenovirus contamination, and the genome of Ad-IFNgamma showed the predicted map of restricted endonuclease enzymes analysis. IFNgamma mRNA and protein were detected in HepG2 cells infected with Ad-IFNgamma. CONCLUSIONS: In vitro ligation is a simple and convenient method for construction of recombination adenovirus vector. We have constructed a functional recombinant adenovirus expressing human IFNgamma, which could be a potential antivirus and antitumor agent in vitro or in vivo.

Adenoviridae↗

Role of extracellular exopolymers on biological phosphorus removal.

Three sequencing batch reactors supplied with different carbon sources were investigated. The system supplied with glucose gained the best enhanced biological phosphorus removal although all of the three reactors were seeded from the same sludge. With the measurement of poly-beta-hydroxyalkanoate (PHA) concentration, phosphorus content in sludge and extracellular exopolymers (EPS) with scanning electron microscopy (SEM) combined with energy dispersive spectrometry (EDS), it was found that the biosorption effect of EPS played an important role in phosphorus removal and that the amount of PHA at the end of anaerobic phase was not the only key factor to determine the following phosphorus removal efficiency.

Adsorption↗

Poly[[di-mu2-aqua-di-mu5-croconato(2-)-nickel(II)dipotassium(I)] tetrahydrate].

In the title compound, [[K2Ni(C5O5)2(H2O)2].4H2O]n, the Ni atom lies on an inversion centre. Two inversion-related croconate [4,5-dihydroxy-4-cyclopentene-1,2,3-trionate(2-)] ligands and an Ni(II) ion form a near-planar symmetrical [Ni(C5O5)2]2- moiety. The near-square coordination centre of the moiety is then extended to an octahedral core by vertically bonding two water molecules in the [Ni(C5O5)2(H2O)2]2- coordination anion. The crystal structure is characterized by a three-dimensional network, involving strong K...O...K binding, K...O-Ni binding and hydrogen bonding.

Journal Article↗

Dynamic distribution and expression in vivo of human endostatin gene delivered by adenoviral vector.

Endostatin, a 20-kDa carboxyl-terminal fragment of collagen XVIII, is a potent inhibitor of endothelial cell proliferation and tumor angiogenesis. We have constructed replication-deficient recombinant adenovirus (Ad-rhE), which encoded secreted human endostatin, and our previous studies showed that Ad-rhE had a potent suppression of tumor growth in vivo. In the present study, we investigated the dynamic distribution and expression of human endostatin gene in vivo using fluorogenic real-time quantitative PCR and enzyme-linked immunosorbent assay(ELISA), respectively, with an injection of 2.0 x10(9)pfu of Ad-rhE. After injection, the Ad-rhE DNAs decreased sharply, but lasted a relative long-term at low concentration (10,000--20,000 copies/mg tissues). Whereas the expressed endostatin rose up rapidly, and reached to the top on day 5 after injection of Ad-rhE, and then decreased sharply, but endostatin in tumors sustained to over 9 days at a certain level. Both Ad-rhE DNAs and endostatin mainly enriched in tumors in vivo, and then in livers. These results suggest that endostatin gene delivered by adenoviral vector can generate a high expression in vivo, and both the metabolism pathways of Ad-rhE DNAs and endostatin in vivo are through the systems of livers.

Adenoviridae↗

[Study on the encapsulation technique of high purity gamma-linolenic acid, part 1--saponification reaction and saponification value].

OBJECTIVE: To measure the saponification value and fatty acid formation of evening primrose oil, to study the effects of pH value on production yield and fatty acid formation during the saponification reaction, and to provide rationales for the selection of raw material, the enhancement of production yield of saponification, and the encapsulation of gamma-linolenic acid with urea. METHOD: To measure fatty acid's formation with gas chromatographic method and to measure the saponification value. RESULT: The content of gamma-linolenic acid is 7%-10% in evening primrose oil. The content of gamma-linolenic acid is inversely correlated with that of unsaturated fatty acid. The saponification value, the amount of KOH for saponification of evening primrose oil, and the pH value for subsequent isolations of oils are determined. From the measurement of fatty acids of evening primrose oil in two different cultivation locations, the content of gamma-linolenic acid is determined to be 7%-10%, unsaturated oils account for 90%. CONCLUSION: The saponification value of evening primrose oil is between 180-200, pH value of isolated oil is 1.5-2.0 after saponification reaction. Fatty acids mainly include palmitic acid, stearic acid, oleic acid, linolic acid and gamma-linolenic acid.

Fatty Acids, Essential↗

[Study on the encapsulation technique of high purity gamma-linolenic acid, part 1--Single factor, and two-factor tests for encapsulation process].

OBJECTIVE: To study the effects of all factors during the process of urea encapsulation of gamma-linolenic acid on the purity and yield. METHOD: To observe the material proportions, time, temperature and purity using single-factor and two-factor tests. RESULT: Single-factor test showed that the optimal ratio of all materials (oil, urea and 95% ethanol) was 1:3:8. A 30% purity after single encapsulation process was obtained, at the best temperature range was - 15 degrees C-20 degrees C, for 24 hours. Two-factor test showed that the optimal ratio of oil, urea and ethanol was 1:3:8, where the concentration of ethanol was 90%-95%. The purity reached 90% or higher, with three-time encapsulation process. CONCLUSION: An optimized process was identified where material ratios, encapsulation time, temperature, and ethanol concentrations were determined using single-factor and two-factor tests.

Ethanol↗

Automated peak tracking for comprehensive impurity profiling in orthogonal liquid chromatographic separation using mass spectrometric detection.

The presence and quantity of impurities in pharmaceutical drugs can have a significant impact on their quality and safety. With the continuous pressure for increased industry productivity, there is urgent need for a systematic and comprehensive drug impurity profiling strategy. We report here our development of the fully automated Comprehensive Orthogonal Method Evaluation Technology (COMET) system. The system includes five columns, seven orthogonal HPLC methods, and hyphenated UV-MS detections, which provides automated generic impurities screening for any drug sample. An automated MS peak tracking approach by program-based mass spectral interpretation is devised to unambiguously track impurities among all orthogonal HPLC methods. The program passes electro-spray ionization mass spectra (ESI-MS) through four sequential decision-making mass ion tests and determines molecular weights for every peak. The system reduces the time required to obtain impurity profile from weeks to days, while the automated MS peak tracking takes only minutes to interpret all MS spectral data of interest. Up-to-date, impurity contents of 56 in-development drug candidate samples have all been successfully illustrated by COMET, which contained more than 500 chemical entities. The program is able to track more than 80% of the compounds automatically with majority of the failure due to insufficient ionization for some impurities by ESI. This system is well suited for efficient drug development and ensuring the quality and safety of drug products.

Algorithms↗

Inhibition of tumor growth in xenografted nude mice with adenovirus-mediated endostatin gene comparison with recombinant endostatin protein.

BACKGROUND: Inhibition of tumor growth by endostatin has been shown to be an effective strategy in cancer therapy in mice. However, its widespread application has been hampered by difficulties in a large-scale production of the recombinant endostatin protein, rapid loss bioactivity of the protein, and the cumbersome daily administration. These limitations could be resolved by in vivo delivery and expression of the endostatin gene. In this study, we observed the effect and advantage of endostatin gene therapy mediated by a recombinant adenoviral vector (Ad/hEndo) on the growth of hepatocellular carcinoma BEL-7402 xenografted tumors, comparison with recombinant endostatin protein. METHODS: Hepatocellular carcinoma BEL-7402 cells were inoculated subcutaneously in the flank of Balb/c nude mice. Nine days after tumor cell inoculation, animals were given a cycle of four courses of intra-tumoral injections of Ad/hEndo of 5 x 10(8) pfu (low-dose group) and 1 x 10(9) pfu (high-dose group) at intervals of six days, respectively. Recombinant human endostatin protein (rhEndo) was administrated daily subcutaneously at a dose of 10 mg.kg(-1).d(-1) at a site nearby the tumor for ten days. The expression of endostatin mRNA in tumor tissue was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) after Ad/hEndo injection. Dynamic changes of concentration of endostatin protein in tumor tissue were quantitated by enzyme-linked immunosorbent assay (ELISA). RESULTS: After 4 courses of treatment, the tumor growth rates of high-dose treated group with 1 x 10(9) pfu of Ad/hEndo were inhibited by 42.26% compared with the Ad/LacZ control group (P = 0.001) and by 46.26% compared with the NIH buffer control group (P = 0.003), respectively. However, in this study, Ad/hEndo at low dose of 5 x 10(8) pfu failed to demonstrate significant inhibition of tumor growth, compared with control groups. After daily administration of recombinant human endostatin protein (rhEndo) for 9 days, the ratio of T/C (rhEndo group versus PBS group) was less than 47%. However, two days after rhEndo treatment ceased, the ratio of T/C was more than 50%. The peak of expression of endostatin mRNA in tumor tissue was at 2 or 3 days after administration intratumorally with Ad/hEndo of 1 x 10(9) pfu and gradually dropped undetectable by day 7. Dynamic analysis of endostatin concentration in tumor tissue showed that the highest level of mRNA is up at the third day after injection, and dropped to basal level three weeks later. CONCLUSIONS: Endostatin gene therapy mediated by a recombinant adenoviral vector had significantly inhibited the growth of hepatocellular carcinoma BEL-7402 xenografted tumors at a high dose of 1 x 10(9) pfu compared with other groups. The analysis of dynamic expression of endostatin in vivo indicated that Ad/hEndo had acquired a high-level, relatively long-term expression in vivo and bioactivity capability.

Adenoviridae↗

4,5-propylenedithio-1,3-dithiole-2-thione and 4,5-propylenedithio-1,3-dithiol-2-one.

4,5-Propylenedithio-1,3-dithiole-2-thione, C(6)H(6)S(5), (I), crystallizes in the centrosymmetric space group P2(1)/c. The molecular packing is characterized by pairs of S.S intermolecular contacts between neighbouring molecules, which may account for the rather high thermal stability of the crystal. 4,5-Propylenedithio-1,3-dithiol-2-one, C(6)H(6)OS(4), (II), in which an O atom replaces the terminal S atom of (I), crystallizes in the non-centrosymmetric polar space group Cc. The packing pattern of (II) indicates that the macropolarization direction is along [101]. Although the packing patterns are qualitatively significantly different, the molecular structures of (I) and (II) are similar, each exhibiting a chair conformation.

Journal Article↗