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1.
J Autoimmun ; : 102336, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31601476

RESUMO

Excessive inflammatory cytokines play crucial roles in the pathogenesis of rheumatoid arthritis (RA), however, the underlying mechanism remains unclear. In this study, we demonstrated that pentaxin 3 (PTX3), an essential component of innate immunity, was elevated in RA and preferentially bound to CD14+ monocytes. C1q promoted the binding and resulted in increased cell proliferation, activation and caspase-1-related late apoptotic cells (7-AAD+annexin V+), as well as enhanced release of inflammatory cytokines including TNF-α, IL-1ß and IL-6. Serum from RA patients, compared with healthy controls, induced gasdermin D (GSDMD)-dependent pyroptosis in monocytes, and this ability was associated with disease activity. Moreover, PTX3 synergized with C1q to promote pyroptosis in RA-serum pre-incubated monocytes by coordinately enhancing NLRP3 inflammasome over-activation and inducing GSDMD cleavage, cell swelling with large bubbles, caspase-1-dependent cell death and inflammatory cytokine release including IL-6. On the other hand, IL-6 promoted PTX3 plus C1q-induced pyroptosis in both normal and RA serum pre-incubated monocytes. These findings collectively implicated an important role of IL-6 in driving PTX3 plus C1q-mediated pyroptosis in RA and shed lights on a potential new treatment strategy targeting pyroptosis-mediated persistent inflammatory cytokine release.

2.
J Cell Physiol ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31549412

RESUMO

Diabetic nephropathy (DN) is a common clinically relevant complication of diabetes that is associated with damage to the capillaries, yet the etiology of this condition remains unclear. Nuclear factor-kappa B (NF-κB) activation is known to be associated with DN-related inflammation and disease progression. Recent work indicated that microRNAs are diagnostic biomarkers of DN progression associated with inflammation in the progression of DN. miR-218 is known to play key regulatory roles in certain cancers in humans, while its influence on DN pathology remains uncertain. The present study, therefore, sought to assess how miR-218 influences the progression of disease in both a rat streptozotocin-induced model of DN and as well as an in vitro model system in which mouse podocytes were stimulated with high glucose levels. We found miR-218 to be markedly downregulated in both model systems relative to appropriate controls, and this downregulation was associated with IKK-ß upregulation. In DN rat model, overexpressing miR-218 was sufficient to reduce renal injury. We further determined that podocyte proliferation was markedly impaired by glucose treatment, leading to the apoptotic death of these cells, and miR-218 mimics were able to reduce these phenotypes. Overexpressing miR-218 also significantly dampened inflammatory responses in this model system, as evidenced by reduced tumor necrosis factor-α, interleukin-6 (IL-6), IL-1ß, and MCP-1 levels. We then confirmed that miR-218 targeting the messenger RNA encoding IKK-ß using a dual-luciferase reporter assay. Together, our results provide clear evidence that miR-218 regulate NF-κB-mediated inflammation, which is central to DN progression.

3.
Environ Pollut ; 255(Pt 1): 113147, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31522002

RESUMO

This study investigated the spatial and temporal distributions of particulate and gaseous air pollutants in a primary school in Beijing and assessed their health impact on the children. The results show that air quality inside the classroom was greatly affected by the input of outdoor pollutants; high levels of pollution were observed during both the heating and nonheating periods and indicate that indoor and outdoor air pollution posed a threat to the children's health. Traffic sources near the primary school were the main contributors to indoor and outdoor pollutants during both periods. Moreover, air quality in this primary school was affected by coal combustion and atmospheric reactions during the heating and nonheating periods, respectively. Based on the estimation by exposure-response functions and the weighting of indoor and outdoor pollutants during different periods, the levels of PM2.5, PM 10 and O3 at school had adverse respiratory health effects on children. Longer exposures during the nonheating period contributed to higher health risks. These results emphasized that emission sources nearby had a direct impact on air quality in school and children's respiratory health. Therefore, measures should be taken for double control on air pollution inside and outside the classroom to protect children from it.

4.
J Comput Biol ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31526187

RESUMO

This study was aimed to identify novel miRNA biomarkers and explore the cooperative function of multi-RNAs in the progress of primary melanoma. The miRNA expression profile GSE62370 generated from 9 congenital nevi and 92 primary melanoma samples was downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs between primary melanoma and congenital nevi were compared and the target genes of them were selected. Pathway enrichment analysis and protein/protein interaction (PPI) network of miRNA target genes were performed. In addition, the differential expression of miRNAs to identify the tumor stage-dependent differences in miRNA expression was analyzed. Differentially expressed miRNAs, including 6 upregulated and 23 downregulated, were found in primary melanoma. Besides, the miRNA-associated gene regulatory network revealed 274 nodes, including miR-142-5p and miR-125b, and 307 miRNA-target pairs. miRNA-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, such as melanoma, was found. Target genes in the PPI module were mainly enriched in cancer-related pathways. Finally, the melanoma stage-related overexpressed miR-142-5p and the downregulated miR-550, miR-1826, miR-1201, miR-205, and miR-125b were identified. Some validated miRNAs, including miR-125a/b, let-7a/b, and miR-205, were found and illustrated the reliability of our study. Four novel miRNAs, including miR-142-5p, miR-550a, miR-1826, and miR-1201, were considered to have potential prognostic values for primary melanoma.

5.
Plant J ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31529523

RESUMO

The nutritional traits of maize kernels are important for human and animal nutrition, and these traits undergone selection to meet the diverse nutritional needs of humans. However, our knowledge of the genetic basis of selecting for kernel nutritional traits is limited. Here, we identified both single and epistatic QTLs contributing to the differences of oil and carotenoid traits between maize and teosinte. Over half of teosinte alleles of single QTLs increased the values of the detected oil and carotenoid traits. Based on the pleiotropism or linkage information of the identified single QTLs, we constructed a trait-locus network to help clarify the genetic basis of correlations among oil and carotenoid traits. Furthermore, the selection features and evolutionary trajectories of the genes or loci underlying variations in oil and carotenoid traits revealed that these nutritional traits occurred diverse selection events during maize domestication and improvement. To deeply illustrate, a mutator distance-relative transposable element (TE) in intron one of DXS2, encoding a rate-limiting enzyme in the methylerythritol phosphate pathway, was identified to increase carotenoid biosynthesis by enhancing DXS2 expression. The TE exists in teosinte, underwent selection during maize domestication and improvement, and is nearly fixed in yellow maize. Our findings not only provide important insights into evolutionary changes in nutritional traits, but also highlight the feasibility of reintroducing nutritionally important genes hidden in the wild relative back into commercial agricultural germplasm.

6.
Water Environ Res ; 2019 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-31544306

RESUMO

There are noteworthy problems in current strategies to calculate river water environmental capacity(WEC), including the generalization of tributaries and water intakes, which results in inaccurate calculation results of the WEC, and the difficulty in adapting to dynamic changes of demands and hydrological conditions in terms of practical application. To address these flaws, the subsection summation model(SSM) was built for river WEC calculation. The SSM increases the number of control sections according to drain outlets, water intakes, and tributaries and acquires the WEC of the functional area section-by-section. The Wei River was taken as the study area for verification and application of the SSM. Supported by a comprehensive integration platform, the WEC simulation system of the Wei River was constructed. The results show that the SSM enhances the accuracy of the WEC calculation, and the results are closer to the actual situation. The simulation system could obtain the WEC according to the demands and changes in the hydrological conditions, thus providing technical means for policy-makers.

7.
PLoS One ; 14(9): e0222091, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509561

RESUMO

Quantitative analysis of the contribution rate of China's hydraulic science and technology and analysis of the underlying reasons behind changes provide an important foundation upon which the government can formulate water policies. This paper abandons the assumption of a scale economy and separates the changes of benefits brought about by the scale from scientific and technological progress, thus changing the C-D production function from linear to nonlinear. Based on a feedforward neural network, it calculates the coefficient of the output elasticity, the economic contribution rate of China's hydraulic science and technology and the scale economies for each year using relevant data from 1981 to 2016. The results show that (1) the average contribution rate of capital investment from 1981 to 2016 was 47.3%, and the average contribution rate of labor from 1981 to 2016 was 9.1%. It is not obvious that the significant increase in the labor force has contributed to the growth of China's water conservancy industry. (2) The average contribution rate of scale economies in 1981-2016 was 26.7%, and the contribution rate of scale economies is negatively correlated with the capital contribution rate. (3) The average contribution rate of China's hydraulic science and technology was 43.6% from 1981 to 2016, and the average contribution rate of the total factor productivity after removing scale economies from 1981 to 2016 was 16.9%. During the period of the 6th Five-Year Plan(1981~1985), the contribution rate of water conservancy science and technology was relatively high. Since that time, it has remained at 40%. In recent years, as water conservancy reforms in key areas have made positive progress, scientific and technological progress has increased the growth of water conservancy benefits annually.

8.
Small ; : e1902842, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31483576

RESUMO

Over the past several decades, lattice materials have been developed and used as engineering materials for lightweight and stiff industrial structures. Recent advances in additive manufacturing techniques have prompted the emergence of architected materials with minimum characteristic sizes ranging from several micrometers to hundreds of nanometers. Taking advantage of the topological design, structural optimization, and size effects of nanomaterials, various 3D micro-/nanolattice materials composed of different materials exhibit combinations of superior mechanical properties, such as low density, high strength (even approaching the theoretical limits), large deformability, good recoverability, and flaw tolerance. As a result, some micro-/nanolattices occupy an unprecedented area in Ashby charts with a combination of different material properties. Here, recent advances in the fabrication and mechanics of micro-/nanolattices are described. First, various design principles and advanced techniques used for the fabrication of micro-/nanolattices are summarized. Then, the mechanical behaviors and properties of micro-/nanolattices are further described, including the compressive Young's modulus, strength, energy absorption, recoverability, and tensile behavior, with an emphasis on mechanistic insights and origins. Finally, the main challenges in the fabrication and mechanics of micro-/nanolattices are addressed and an outlook for further investigations and potential applications of micro-/nanolattices in the future is provided.

9.
Nat Commun ; 10(1): 3921, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477723

RESUMO

Over the last decade, researchers have endeavored to mimic the naturally motile microorganisms and develop artificial nano/microswimmers, which propel themselves in aqueous media. However, most of these nano/microswimmers are propelled by the self-electrophoretic mechanism, which has one critical incompetency: the inability to operate in a high concentration electrolyte solution, such as the most important body fluid, blood. This ionic quenching behavior is well backed by the classical Helmholtz-Smoluchowski theory and seems to be an insurmountable challenge which has shadowed the otherwise promising biomedical applications for artificial nano/microswimmers. Here, we propose that the active nano/microswimmer's self-electrophoresis is fundamentally different from the passive nanoparticle electrophoresis. By significantly increasing the Dukhin number with polyelectrolyte coating and geometry optimization, a favorable deviation from the Helmholtz-Smoluchowski behavior can be realized, and ion tolerance is enhanced by over 100 times for a visible light-powered self-electrophoretic microswimmer.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31486716

RESUMO

Geminiviruses cause severe damage to agriculture worldwide. The replication protein (Rep) is the indispensable viral protein for viral replication. Although various functional domains of Rep protein in geminivirus have been characterized, the most carboxyl-terminus of Rep was not available. We have reported the first cassava-infected geminivirus-Sri Lankan cassava mosaic virus (SLCMV-HN7 strain) in China. In this study, we reported the second Chinese SLCMV strain, SLCMV-Col and conducted comparative genomic analysis between these two SLCMV strains. The virulence of SLCMV-Col is much stronger than SLCMV-HN7, indicated by the higher virus titer, severer symptoms and more extent host defense. We functionally characterized that Rep protein, a 7-amino-acid motif at the most carboxyl-terminus, is essential for Rep protein accumulation and virulence of SLCMV. We also provided evidences suggesting that motif could also enhance triggering of salicylic acid (SA) defense against SLCMV infection in Nicotiana benthamiana. The significance of the balance between virulence and host SA defense responses in expanding invasion of SLCMV is also discussed. .

11.
Artigo em Inglês | MEDLINE | ID: mdl-31486761

RESUMO

A novel bacterial strain, C3212T, was isolated from a marine alga collected from the sea shore of Yantai, China. The strain was Gram-stain-negative, rod-shaped, aerobic, non-motile, and oxidase- and catalase-positive. Growth was observed at 8-37 °C (optimum, 28 °C), at pH 6.0-9.0 (optimum, pH 7.0) and in the presence of 1.0-7.0 % (w/v) NaCl (optimum, 4.0 %). The major respiratory quinone was ubiquinone-8 (Q-8). The polar lipids of strain C3212T consisted of diphosphatidylglycerol (cardiolipin), phosphatidylglycerol, phosphatidylethanolamine, an unidentified aminophospholipid, an unidentified phospholipid and an unidentified polar lipid. The major fatty acids were C16 : 1ω6c and/or C16 : 1ω7c, and C18 : 1ω6c and/or C18 : 1ω7c. The DNA G+C content of strain C3212T was 44.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that the novel strain was related most closely to Leucothrix pacifica XH122T, Leucothrix arctica IMCC 9719T and Leucothrix mucor DSM 2157T with similarities of 98.0, 97.5 and 94.3 %, respectively. Estimated DNA-DNA hybridization values were 14.2, 20.7 and 13.9 % between strain C3212T and L. pacifica XH122T, L. arctica IMCC 9719T and L. mucor DSM 2157T, respectively. Phenotypic, phylogenetic and genomic analyses revealed that strain C3212T represents a novel species of the genus Leucothrix, for which the name Leucothrix sargassi sp. nov. is proposed. The type strain is C3212T (=MCCC 1K03600T=KCTC 72121T).

12.
Neuro Oncol ; 2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31563962

RESUMO

BACKGROUND: The ligands of mitochondrial translocator protein (TSPO) have been widely used as diagnostic biomarkers for glioma. However, the true biological actions of TSPO in vivo and its role in glioma tumourigenesis remain elusive. METHODS: TSPO knockout xenograft and spontaneous mouse glioma models were employed to assess the roles of TSPO in the pathogenesis of glioma. A Seahorse Extracellular Flux Analyzer was used to evaluate mitochondrial oxidative phosphorylation and glycolysis in TSPO knockout and wild-type glioma cells. RESULTS: TSPO deficiency promoted glioma cell proliferation in vitro in mouse GL261 cells and patient-derived stem cell-like GBM1B cells. TSPO knockout increased glioma growth and angiogenesis in intracranial xenografts and a mouse spontaneous glioma model. Loss of TSPO resulted in a greater number of fragmented mitochondria, increased glucose uptake and lactic acid conversion, decreased oxidative phosphorylation and increased glycolysis. CONCLUSION: TSPO serves as a key regulator of glioma growth and malignancy by controlling the metabolic balance between mitochondrial oxidative phosphorylation and glycolysis.

13.
J Sep Sci ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503388

RESUMO

"Dogel ebs" was known as Sophora flavescens Ait., a classical traditional Chinese Mongolian herbal medicine, which had the effects on damp-heat dysentery, scrofula, and syndrome of accumulated dampness toxicity. Although the chemical constituents have been clarified by our previous studies, the metabolic transformation of "Dogel ebs" in vivo was still unclear. To explore the mechanism of "Dogel ebs," the metabolites in plasma, bile, and urine samples were investigated. A fast positive and negative ion switching technology was used for the simultaneous determination of flavonoids and alkaloids in "Dogel ebs" in a single run. And a target-group-change coupled with mass defect filtering strategy was utilized to analyze the collected data. 89 parent compounds and 82 metabolites were characterized by high-performance liquid chromatography with quadrupole exactive Orbitrap mass spectrometry. Both phase I and phase II metabolites were observed and the metabolic pathways involved in oxidation, demethylation, acetylation, and glucuronidation. 69 metabolites of "Dogel ebs," including three hydroxyls bonding xanthohumol, formononetin-7-O-glucuronide, 2'-hydroxyl-isoxanthohumol decarboxylation metabolite, oxysophocarpine dehydrogen, 9α-hydroxysophoramine-O-glucuronide, etc. were reported for the first time.

14.
Mol Microbiol ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31515877

RESUMO

The flagellated eukaryote Trypanosoma brucei alternates between the insect vector and the mammalian host and proliferates through an unusual mode of cell division. Cell division requires flagellum motility-generated forces, but flagellum motility exerts distinct effects between different life cycle forms. Motility is required for the final cell abscission of the procyclic form in the insect vector, but is necessary for the initiation of cell division of the bloodstream form in the mammalian host. The underlying mechanisms remain elusive. Here we carried out functional analyses of a flagellar axonemal inner-arm dynein complex in the bloodstream form and investigated its mechanistic role in cytokinesis initiation. We showed that the axonemal inner-arm dynein heavy chain TbIAD5-1 and TbCentrin3 form a complex, localize to the flagellum, and are required for viability in the bloodstream form. We further demonstrated the interdependence between TbIAD5-1 and TbCentrin3 for maintenance of protein stability. Finally, we showed that depletion of TbIAD5-1 and TbCentrin3 arrested cytokinesis initiation and disrupted the localization of multiple cytokinesis initiation regulators. These findings identified the essential role of an axonemal inner-arm dynein complex in cell division, and provided molecular insights into the flagellum motility-mediated cytokinesis initiation in the bloodstream form of T. brucei.

15.
Int Immunopharmacol ; 76: 105845, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31470266

RESUMO

BACKGROUND: Extracellular matrix (ECM) comprising the environments of multicellular society has a dynamic network structure. Collagen is one of the ubiquitous components of ECM. Collagen affects the inflammatory response by regulating the release of pro-inflammatory cytokines from cells. Gelatin, denatured collagen found temporally in tissues, is supposed to be pathophysiologically involved in tissue remodeling, inflammation caused by tissue damage. Previous reports indicate that, phorbol myristate (PMA)-stimulated human U937 (lymphoma cell line) cells that are often used as macrophage-like cells, show cell aggregations when cultured on type I collagen (col I) or gelatin-coated dishes, accompanying the changes of production and release of proinflammatory factors. However, it still remains to be examined whether collagen and gelatin affects normal macrophages as well. AIM: This study aims to investigate the effect of col. I, the main component of collagenous protein and its denatured product, gelatin, on mouse peritoneal macrophages (MPMs). METHODS: MTT assay, flow cytometric analysis of ROS, biochemical detection of antioxidant levels, ELISA assay, and western blot were used. RESULTS: MPMs formed multicellular aggregates on col. I - and gelatin-coated dishes with a concentration- and time-dependent manner. Further studies showed that the culture on col. I and gelatin up-regulated the protein expression and secretion of pro-inflammatory molecules such as IL-1ß, TNFα and prostaglandin E2 (PGE2) in MPMs. The levels were higher in the cells on gelatin than those on col. I. ROS levels are significantly increased in the cells cultured on both col. I- and gelatin-coated dishes, accompanying decreased levels of antioxidant enzyme catalase (CAT) and anti-oxidant glutathione (GSH), and enhanced nuclear translocation of NF-κB. CONCLUSION: Col I - or gelatin-coated culture induced the formation of multicellular aggregates and increased production of NF-κB-associated pro-inflammatory molecules in MPMs through up-regulation of ROS levels.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31394804

RESUMO

Particulate matter (PM) was collected in three different areas, SY-1, SY-2, and SY-3, in Shenyang, China, during the warm and cold seasons from 2012 to 2014. SY-1 was located beside a thermal power plant, far from the central area. SY-2 was near a coal heating boiler on the main road, close to the central area. SY-3 was on the main road, without fixed emission sources. Nine PM-bound polycyclic aromatic hydrocarbons (PAHs) were analyzed. The results showed that the mean concentration of total PAHs was higher in the cold season (92.6-316 ng m-3) than in the warm season (18.4-32.2 ng m-3). Five- and six-ring PAHs occupied a large percentage at all sites in the warm season, and four-ring PAHs were the dominant components in the cold season. Several diagnostic PAH ratios indicated that the main sources of PAHs in Shenyang in the warm and cold seasons were not only coal burning but also vehicle emission. In this study, we suggest that a benzo[a]pyrene/benzo[ghi]perylene ratio ([BaP]/[BgPe]) of 0.6 was a useful indicator to speculate the relative significance of coal burning and vehicle exhaust. Although the Shenyang government has undertaken actions to address air pollution, the PM and PAH concentrations did not decrease significantly compared to those in our previous studies. The cancer risk calculated from the BaP equivalent total concentration at all three sites in the warm and cold seasons exceeded the acceptable limit established by the US EPA.

17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(8): 844-847, 2019 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-31400143

RESUMO

Congenital lipodystrophic diabetes (CLD) is a rare genetic disease characterized by generalized or topical subcutaneous fat loss combined with various metabolic disorders such as insulin resistance, dyslipidemia, and impaired glucose tolerance. Recent studies have discovered genes underlying the disease. Mutations of such genes are associated with adipogenic anomaly, especially regulational function of peroxisome proliferators-activated receptor γ (γPPAR) for lipid. This paper has provided a review for the main clinical symptoms, classification, pathogenic genes, molecular mechanism and the relationship between PPARγ and fat loss.


Assuntos
Diabetes Mellitus/genética , Lipodistrofia Generalizada Congênita/genética , PPAR gama/genética , Diferenciação Celular , Humanos , Resistência à Insulina , Fatores de Transcrição
18.
J Comput Biol ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31424282

RESUMO

Melanoma is the most deadly type of skin cancer. This study aimed at uncovering the molecular mechanisms underlying melanoma progression. This study used the microarray dataset GSE46517, downloaded from the Gene Expression Omnibus database, including eight normal tissue samples, nine nevus tissue samples, 31 primary melanoma samples, and 73 metastatic melanoma tissue samples. Differentially expressed genes (DEGs) in nevus, primary melanoma, and metastatic melanoma were identified, with which a reactome functional interaction (FI) network was constructed, and pathway enrichment analysis of the network modules was performed. The common DEGs in primary and metastatic melanoma were identified by venn diagram analysis, followed by Gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and a protein-protein interaction (PPI) network. The study identified 130 DEGs in nevus, 539 DEGs in primary melanoma, and 1170 DEGs in metastatic melanoma. The reactome FI network modules 10, 14, and 15 were significantly enriched in the transforming growth factor (TGF)-ß signaling pathway. EDNRB, MITF, and LEF1 were the common upregulated DEGs in nevus, primary, and metastatic melanoma, and they were significantly enriched in the melanogenesis pathway. In the PPI network with the common DEGs in primary and metastatic melanoma, EGFR, ERBB2, CD8A, and MMP9 were the hub genes. EDNRB, MITF, LEF1, EGFR, ERBB2, CD8A, MMP9, melanogenesis pathway, and TGF-ß signaling pathway might be involved in the molecular mechanism of melanoma. These genes may be recommended as promising molecular targets for development of melanoma therapeutics.

19.
Xenotransplantation ; : e12550, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31435990

RESUMO

BACKGROUND: In vivo pig liver xenotransplantation preclinical trials appear to have poor efficiency compared to heart or kidney xenotransplantation because of xenogeneic rejection, including coagulopathy, and particularly thrombocytopenia. In contrast, ex vivo pig liver (wild type) perfusion systems have been proven to be effective in "bridging" liver failure patients until subsequent liver allotransplantation, and transgenic (human CD55/CD59) modifications have even prolonged the duration of pig liver perfusion. Despite the fact that hepatocyte cell lines have also been proposed for extracorporeal blood circulation in conditions of acute liver failure, porcine hepatocyte cell lines, and the GalT-KO background in particular, have not been developed and applied in this field. Herein, we established immortalized wild-type and GalT-KO porcine hepatocyte cell lines, which can be used for artificial liver support systems, cell transplantation, and even in vitro studies of xenotransplantation. METHODS: Primary hepatocytes extracted from GalT-KO and wild-type pigs were transfected with SV40 LT lentivirus to establish immortalized GalT-KO porcine hepatocytes (GalT-KO-hep) and wild-type porcine hepatocytes (WT). Hepatocyte biomarkers and function-related genes were assessed by immunofluorescence, periodic acid-Schiff staining, indocyanine green (ICG) uptake, biochemical analysis, ELISA, and RT-PCR. Furthermore, the tumorigenicity of immortalized cells was detected. In addition, a complement-dependent cytotoxicity (CDC) assay was performed with GalT-KO-hep and WT cells. Cell death and viability rates were assessed by flow cytometry and CCK-8 assay. RESULTS: GalT-KO and wild-type porcine hepatocytes were successfully immortalized and maintained the characteristics of primary porcine hepatocytes, including albumin secretion, ICG uptake, urea and glycogen production, and expression of hepatocyte marker proteins and specific metabolic enzymes. GalT-KO-hep and WT cells were confirmed as having no tumorigenicity. In addition, GalT-KO-hep cells showed less apoptosis and more viability than WT cells when exposed to complement and xenogeneic serum. CONCLUSIONS: Two types of immortalized cell lines of porcine hepatocytes with GalT-KO and wild-type backgrounds were successfully established. GalT-KO-hep cells exhibited higher viability and injury resistance against a xenogeneic immune response.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31444521

RESUMO

Because of the emergence of antibiotic resistance, we must investigate new antibiotical agents. The present study was designed to find new compounds with antibacterial activity from metabolites of Bacillus pumilus. We found that the concentrated fermentation broth of Bacillus pumilus has antibacterial property. By high-performance liquid chromatography (HPLC), three compounds with antibacterial activity were first isolated from the ethyl acetate layer of fermentation broth of Bacillus pumilus. And then their structures were identified by nuclear magnetic resonance (NMR) and mass spectrometry (MS) analysis. According to the data, the compound 1, compound 2, and compound 3 were determined to be 3,4-dipentylhexane-2,5-diol, 1,1'-(4,5-dibutylcyclohexane-1,2-diyl)bis(ethan-1-ol), and 1,1'-(4,5-dibutyl-3,6-dimethylcyclohexane-1,2-diyl)bis(ethan-1-one). And all of them exhibited potent inhibitory effects against a panel of pathogenic bacteria including Staphylococcus aureus ATCC6538, Micrococcus luteus CMCC28001, Variant Salmonella gallinarum CVCC79207, Pasteurella multocida CVCC474, Swine Salmonella, Salmonella enterica ATCC13076, Swine Escherichia coli K88, Chicken Escherichia coli O78. Given its antibacterial activity, 3,4-dipentylhexane-2,5-diol, 1,1'-(4,5-dibutylcyclohexane-1,2-diyl)bis(ethan-1-ol), 1,1'-(4,5-dibutyl-3,6-dimethylcyclohexane-1,2-diyl)bis(ethan-1-one) are assumed to be promising agents for further development as antibacterial agents.

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