Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 425
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Sci Total Environ ; 715: 136949, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-32041051

RESUMO

This study investigated the chemical profiles of PM2.5 from open burning of electronic waste (E-waste), household garbage, wheat residue, and outdoor barbeque in a combustion chamber. Carbonaceous fractions, including polycyclic aromatic hydrocarbons (PAHs), and water-soluble ions and elements in PM2.5 were quantified. A PM2.5 exposure study was performed to detect PM2.5-induced bioreactivities in vascular smooth muscle cells (VSMCs). Among all fractions, organic carbon (OC) exhibited the highest mass contribution to PM2.5-ranging from 39.9% ±â€¯0.82% to 53.1% ±â€¯8.76%. Proportions of total water-soluble ions and total elements both followed the sequence E-waste > wheat straw > outdoor barbeque > household garbage. Because of the high burning temperature, outdoor barbeque PM2.5 exhibited the highest total quantified PAHs (29.7‰). E-waste PM2.5 exhibited the highest heavy metal contents, derived mainly from the materials in printed circuit boards. The coefficients of divergence among the four source profiles ranged from 0.47 to 0.75, indicating that the collinear problems could be avoided in source apportionment in receptor models. The induced production of reactive oxygen species exhibited a significant dose-dependent increase and followed the sequence E-waste > household garbage > outdoor barbeque > wheat residue. Similar patterns and sequence among the four sources were observed in monocyte chemoattractant protein 1 (MCP-1) and interleukin 1ß (IL-1ß) production. The data indicated that PM2.5 emitted from E-waste has the highest cytotoxicity and special protections should be aimed at mitigating it. The Pearson correlation coefficient demonstrated that elemental carbon, heavy metals, and nitrated PAHs were strongly correlated with VSMC bioreactivity. Light elements exhibited moderate negative correlations with bioreactivities, implying that light elements (e.g., Ca) could mitigate heavy metal-induced cytotoxicity. This study summarized the chemical profiles of PM2.5 from four typical open burning sources and demonstrated their high cytotoxicity to the cardiovascular system.

2.
Neuropharmacology ; 167: 107980, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32014448

RESUMO

Brain glioma is one of the most common brain tumors in the central nervous system (CNS). The blood-brain tumor barrier (BTB) restricts the delivery of anti-tumor drugs into tumor tissue in the brain. Therefore, improving the transportation of antineoplastic drugs across the BTB is essential to ameliorate treatment of brain tumors. The present study was performed to explore the effect and mechanism of salvianolic acid A (Sal A) on transportation of doxorubicin (Dox) across the BTB in vivo and in vitro. By creating a brain C6 glioma model in rats, we demonstrated that Sal A significantly increased the level of Dox in brain tumor tissue as shown by liquid chromatograph mass spectrometry. Interestingly, we found that Sal A increased transendothelial electrical resistance (TEER) values of the BTB and decreased the permeability of FITC-Dextran (4kD) across the BTB in vitro. Furthermore, the expression of tight junction proteins (TJs) in glioma endothelial cells (GECs) and brain tumor microvessels were also increased, suggesting that Sal A enhanced delivery of Dox across the BTB independent of the paracellular pathway. Next, we detected that Sal A had an effect on transcellular transport of compounds across the BTB. The accumulation of FITC-labeled bovine serum albumin (FITC-BSA) was significantly increased in GECs after treatment with Sal A (10 µM) for 6h, which was inhibited after pre-treatment with methyl-ß-cyclodextrin (MßCD) for 30 min. The increased delivery of Dox across the BTB was also reduced after treatment with MßCD. In addition, phosphorylation levels of protein kinase B (PKB) and tyrosine protein kinase-Src family (Src) were increased in the Sal A treatment group. Sal A up-regulated the expression level of the phosphorylation of Caveolin-1 (pCaveolin-1), and this effect was reversed by a PKB or Src inhibitor. Taken together, our study showed for the first time that Sal A facilitated the delivery of antitumor drugs into brain tumor tissues by targeting the PKB/Src/Caveolin-1 signaling pathway.

3.
FASEB J ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32057145

RESUMO

Liver regeneration after injury requires fine-tune regulation of connective tissue growth factor (Ctgf). It also involves dynamic expression of hepatocyte nuclear factor (Hnf)4α, Yes-associated protein (Yap), and transforming growth factor (Tgf)-ß. The upstream inducers of Ctgf, such as Yap, etc, are well-known. However, the negative regulator of Ctgf remains unclear. Here, we investigated the Hnf4α regulation of Ctgf post-various types of liver injury. Both wild-type animals and animals contained siRNA-mediated Hnf4α knockdown and Cre-mediated Ctgf conditional deletion were used. We observed that Ctgf induction was associated with Hnf4α decline, nuclear Yap accumulation, and Tgf-ß upregulation during early stage of liver regeneration. The Ctgf promoter contained an Hnf4α binding sequence that overlapped with the cis-regulatory element for Yap and Tgf-ß. Ctgf loss attenuated inflammation, hepatocyte proliferation, and collagen synthesis, whereas Hnf4α knockdown enhanced Ctgf induction and liver fibrogenesis. These findings provided a new mechanism about fine-tuned regulation of Ctgf through Hnf4α antagonism of Yap and Tgf-ß activities to balance regenerative and fibrotic signals.

4.
Pharmacol Res ; 152: 104605, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31863866

RESUMO

Ferulin C, a natural sesquiterpene coumarin, isolated from the roots of Ferula ferulaeoides (Steud.) Korov, displaying potent antiproliferatory activity against breast cancer cells. This study aimed to elucidate the underlying molecular mechanisms of Ferulin C-induced breast cancer cells death in vitro and in vivo. Ferulin C presented potent antiproliferatory activity against MCF-7 and MDA-MB-231 cells and remarkable tubulin polymerization inhibitory activity (IC50 = 9.2 µM). Meanwhile, we predicted Ferulin C bind to the Colchicine site of tubulin through CETSA assay, molecular docking and molecular dynamics (MD) simulations. In immunofluorescence assay, Ferulin C disturbed the microtubule integrity and structure. Furthermore, Ferulin C stimulated significant cell cycle arrest in the G1/S period via p21Cip1/Waf1 - CDK2 signaling, induced classic cell apoptosis, impaired metastasis via down-regulating Ras-Raf-ERK and AKT-mTOR signaling. Intriguingly, Ferulin C treatment induced autophagy by ULK1 signaling to synergize with the inhibition of proliferation and metastasis. Based upon the RNAseq analysis, PAK1, as a novel essential modulator, was involved in the signaling regulated by Ferulin C -induced α/ß-tubulin depolymerization. Additionally, Ferulin C displayed an acceptable antiproliferatory activity in an MCF-7 xenograft model without inducing obvious weight loss in the Ferulin C treated mice. Summarily, our findings substantiated that Ferulin C was a potent, colchicine site binding microtubule-destabilizing agent with anti-proliferation and anti-metastasis activity via PAK1 and p21-mediated signaling in breast cancer cells.

5.
Biotechnol Bioeng ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31803933

RESUMO

Phenylpropionic acids are commonly used in the synthesis of pharmaceuticals, cosmetics, and fine chemicals. However, the synthesis of phenylpropionic acids faces the challenges of high cost of substrates and a limited range of products. Here, we present an artificially designed amino-group-transformation biocatalytic process, which uses simple phenols, pyruvate, and ammonia to synthesize diverse phenylpropionic acids. This biocatalytic cascade comprises an amino-group-introduction module and three amino-group-transformation modules, and operates in a modular assembly manner. Escherichia coli catalysts coexpressing enzymes from different modules achieve whole-cell simultaneous one-pot transformations of phenols into the corresponding phenylpropionic acids including (S)-α-amino acids, α-keto acids, (R)-α-amino acids, and (R)-ß-amino acids. With cofactor recycling, protein engineering, and transformation optimization, four (S)-α-amino acids, four α-keto acids, four (R)-α-amino acids, and four (R)-ß-amino acids are synthesized with good conversion (68-99%) and high enantioselectivities (>98%). Therefore, the amino-group-transformation concept provides a universal and efficient tool for synthesizing diverse products.

6.
Opt Express ; 27(24): 35203-35215, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31878693

RESUMO

Conventional optofluidic lens usually has only one interface, which means that the zoom range is small, and the ability to correct aberrations is poor. In this paper, we propose a hybrid driving variable-focus optofluidic lens. It has one water-oil interface shifted by an applied voltage and one tunable Polydimethylsiloxane (PDMS) lens deformed by pumping liquid in or out of the cavity. The proposed lens combines the advantages of electrowetting lens and mechanical lens. Therefore, it can provide a large focal length tuning range with good image quality. The shortest positive and negative focal length are ∼6.02 mm and ∼-11.15 mm, respectively. The maximum resolution of our liquid lens can be reached 18 lp/mm. We also designed and fabricated a zoom system using the hybrid driving variable-focus optofluidic lens. In the experiment, the zoom range of the system is 14 mm∼30 mm and the zoom ratio is ∼2.14× without any mechanical moving parts. Its applications for zoom telescope system and zoom microscope and so on are foreseeable.

7.
Cell Commun Signal ; 17(1): 167, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842906

RESUMO

BACKGROUND: Loss of monoubiquitination of histone H2B (H2Bub1) was found to be associated with poor differentiation, cancer stemness, and enhanced malignancy of non-small cell lung cancer (NSCLC). Herein, we investigated the biological significance and therapeutic implications of ubiquitin-specific protease 22 (USP22), an H2Bub1 deubiquitinase, in non-small cell lung cancer (NSCLC). METHODS: USP22 expression and its clinical relevance were assessed in NSCLC patients. The effects of USP22 knockout on sensitivity to cisplatin and irradiation, and growth, metastasis of NSCLC xenografts, and survival of cancer-bearing mice were investigated. The underlying mechanisms of targeting USP22 were explored. RESULTS: Overexpression of USP22 was observed in 49.0% (99/202) of NSCLC tissues; higher USP22 immunostaining was found to be associated with enhanced angiogenesis and recurrence of NSCLC. Notably, USP22 knockout dramatically suppressed in vitro proliferation, colony formation; and angiogenesis, growth, metastasis of A549 and H1299 in mouse xenograft model, and significantly prolonged survival of metastatic cancer-bearing mice. Furthermore, USP22 knockout significantly impaired non-homologous DNA damage repair capacity, enhanced cisplatin and irradiation-induced apoptosis in these cells. In terms of underlying mechanisms, RNA sequencing and gene ontology enrichment analysis demonstrated that USP22 knockout significantly suppressed angiogenesis, proliferation, EMT, RAS, c-Myc pathways, concurrently enhanced oxidative phosphorylation and tight junction pathways in A549 and H1299 NSCLC cells. Immunoblot analysis confirmed that USP22 knockout upregulated E-cadherin, p16; reduced ALDH1A3, Cyclin E1, c-Myc, and attenuated activation of AKT and ERK pathways in these cells. CONCLUSIONS: Our findings suggest USP22 plays critical roles in the malignancy and progression of NSCLC and provide rationales for targeting USP22, which induces broad anti-cancer activities, as a novel therapeutic strategy for NSCLC patient.

8.
J Affect Disord ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31780136

RESUMO

BACKGROUND: Previous neuroimaging studies have showed that imbalanced functional integration of distributed large-scale brain networks is associated with pathophysiological characteristics of major depressive disorder (MDD). However, the association between network integrative disturbances and clinical features and cognitive functions remains largely unclear in adolescent MDD. This study investigated the neural correlates of abnormal functional connectivity networks with clinical and cognitive characteristics in adolescent MDD. METHODS: Twenty-eight first-episode, treatment-naive adolescents with MDD and 24 well-matched healthy controls (HCs) underwent functional magnetic resonance imaging (fMRI) and a battery of cognitive tests. A seed-based functional connectivity (FC) approach was used to depict connectivity patterns of the cognitive control network (CCN), affective network (AN) and default mode network (DMN), whose between-group differences were correlated with clinical variables and cognitive functions in the patients. RESULTS: Compared with the HCs, the MDD patients exhibited impaired executive functions. The FC analysis revealed lower CCN FC with the temporal, parietal and frontal regions and the limbic system, higher AN FC with the temporal and occipital regions and the cerebellum, and lower DMN FC with the cerebellum and insula. Interestingly, the decreased CCN FC was related to disease severity (with the inferior frontal gyrus) and executive dysfunctions (with the middle cingulate gyrus and supramarginal gyrus) in the patients. LIMITATIONS: The main limitations were the relatively small sample size and suboptimal imaging parameters. CONCLUSION: Functional alteration of CCN during the developmentally sensitive period may be important in the neurobiology of adolescent MDD.

9.
Commun Biol ; 2: 406, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31701034

RESUMO

Menopause is a critical window of susceptibility for its sensitivity to endocrine disrupting chemicals due to the decline of endogenous estrogen. Using a surgical menopausal (ovariectomized) mouse model, we assessed how mammary tissue was affected by both 17ß-estradiol (E2) and polybrominated diphenyl ethers (PBDEs). As flame retardants in household products, PBDEs are widely detected in human serum. During physiologically-relevant exposure to E2, PBDEs enhanced E2-mediated regrowth of mammary glands with terminal end bud-like structures. Analysis of mammary gland RNA revealed that PBDEs both augmented E2-facilitated gene expression and modulated immune regulation. Through single-cell RNA sequencing (scRNAseq) analysis, E2 was found to induce Pgr expression in both Esr1 + and Esr1 - luminal epithelial cells and Ccl2 expression in Esr1 + fibroblasts. PBDEs promote the E2-AREG-EGFR-M2 macrophage pathway. Our findings support that E2 + PBDE increases the risk of developing breast cancer through the expansion of estrogen-responsive luminal epithelial cells and immune modulation.

10.
Adv Sci (Weinh) ; 6(20): 1901051, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31637162

RESUMO

The rapid development of microelectronics has equally rapidly increased the demand for miniaturized energy storage devices. On-chip microsupercapacitors (MSCs), as promising power candidates, possess great potential to complement or replace electrolytic capacitors and microbatteries in various applications. However, the areal capacities and energy densities of the planar MSCs are commonly limited by the low voltage window, the thin layer of the electrode materials and complex fabrication processes. Here, a new-type three-dimensional (3D) tubular asymmetric MSC with small footprint area, high potential window, ultrahigh areal energy density, and long-term cycling stability is fabricated with shapeable materials and photolithographic technologies, which are compatible with modern microelectronic fabrication procedures widely used in industry. Benefiting from the novel architecture, the 3D asymmetric MSC displays an ultrahigh areal capacitance of 88.6 mF cm-2 and areal energy density of 28.69 mW h cm-2, superior to most reported interdigitated MSCs. Furthermore, the 3D tubular MSCs demonstrate remarkable cycling stability and the capacitance retention is up to 91.8% over 12 000 cycles. It is believed that the efficient fabrication methodology can be used to construct various integratable microscale tubular energy storage devices with small footprint area and high performance for miniaturized electronics.

11.
Acta Pharmacol Sin ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645662

RESUMO

Pyroptosis is a form of inflammatory cell death that could be driven by the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation following myocardial infarction (MI). Emerging evidence suggests the therapeutic potential for ameliorating MI-induced myocardial damages by targeting NLRP3 and pyroptosis. In this study, we investigated the myocardial protection effect of a novel anthraquinone compound (4,5-dihydroxy-7-methyl-9,10-anthraquinone-2-ethyl succinate) named Kanglexin (KLX) in vivo and in vitro. Male C57BL/6 mice were pre-treated either with KLX (20, 40 mg· kg-1per day, intragastric gavage) or vehicle for 7 consecutive days prior to ligation of coronary artery to induce permanent MI. KLX administration dose-dependently reduced myocardial infarct size and lactate dehydrogenase release and improved cardiac function as compared to vehicle-treated mice 24 h after MI. We found that MI triggered NLRP3 inflammasome activation leading to conversion of interleukin-1ß (IL-1ß) and IL-18 into their active mature forms in the heart, which could expand the infarct size and drive cardiac dysfunction. We also showed that MI induced pyroptosis, as evidenced by increased DNA fragmentation, mitochondrial swelling, and cell membrane rupture, as well as increased levels of pyroptosis-related proteins, including gasdermin D, N-terminal GSDMD, and cleaved caspase-1. All these detrimental alterations were prevented by KLX. In hypoxia- or lipopolysaccharide (LPS)-treated neonatal mouse ventricular cardiomyocytes, we showed that KLX (10 µM) decreased the elevated levels of terminal deoxynucleotidyl transferase dUTP nick end labeling- and propidium iodide-positive cells, and pyroptosis-related proteins. We conclude that KLX prevents MI-induced cardiac damages and cardiac dysfunction at least partly through attenuating NLRP3 and subsequent cardiomyocyte pyroptosis, and it is worthy of more rigorous investigations for its potential for alleviating ischemic heart disease.

12.
Sci Rep ; 9(1): 13062, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506551

RESUMO

The conventional electrowetting lens usually has one tunable liquid-liquid (L-L) interface. The shape of L-L interface is deformed to get variable focal length due to electrowetting effect. However, contact angle saturation of the L-L interface is an unavoidable problem which prevents focal length from further changing. Here, we demonstrate an optofluidic lens based on electrowetting liquid piston. The proposed lens has two connected chambers, the piston chamber and the lens chamber to form a closed-loop fluidic system. The electrowetting liquid piston can generate clockwise and counter-clockwise liquid flows, which can make the L-L interface convex and concave. To prove the concept, we fabricate an optofluidic device whose shortest negative and positive focal lengths are ~-17.9 mm and ~18 mm with 5 mm aperture, respectively. The proposed optofluidic lens has large tunable focal length range. Widespread application of such an adaptive lens is foreseeable.

13.
Front Cell Dev Biol ; 7: 181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552246

RESUMO

The trans-Golgi network (TGN) and endosomes are essential protein sorting stations in the secretory transport pathway. Protein sorting is fundamentally a process of spatial segregation, but the spatial relationships among the proteins that constitute the sorting machinery have not been systematically analyzed at high resolution in mammalian cells. Here, using two-color STORM imaging, we show that the TGN/endosome-localized cargo adaptors, AP-1, GGA2 and epsinR, form elongated structures of over 250 nm in length at the juxta-nuclear Golgi area. Many of these structures are associated with clathrin. We found that AP-1 is spatially segregated from AP-3 and GGA2, whereas a fraction of AP-1 and GGA2 punctae are associated with epsinR. Moreover, we observed that the planar cell polarity cargo proteins, Vangl2 and Frizzled6 associate with different cargo adaptors-AP-1 and GGA2 or epsinR, respectively-when exiting the TGN. Knockdown analysis confirms the functional significance of this segregation. Our data indicates that TGN/endosome-localized cargo adaptors have distinct spatial relationships. The spatially segregated cargo adaptors GGA2 and AP-1 regulate sorting of Frizzled6 and Vangl2, respectively and spatially associated cargo adaptors can cooperatively regulate a specific sorting process.

14.
Am J Cancer Res ; 9(8): 1650-1663, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31497348

RESUMO

Liver kinase B1 (LKB1), a serine/threonine kinase, is frequently inactivated in several types of human cancers. To date, inactivation of LKB1 tumor suppressor has rarely been reported in glioblastoma. In this study, we investigated LKB1 status, biological significance, and therapeutic implications in glioblastoma. Loss of LKB1 immunostaining was identified in 8.6% (5/58), while decrease of LKB1 immunostaining was found in 29.3% (17/58) of glioblastoma tissues. Notably, mining TCGA database of LKB1 expression in glioblastoma revealed that lower mRNA level of LKB1 was associated with shorter survival in glioblastoma. We found that knockdown of LKB1 significantly promoted in vitro proliferation, adhesion, invasion, and metformin-induced apoptosis, and simultaneously enhanced activation of ERK and mammalian-target of rapamycin (mTOR) signaling pathways in LKB1-compenent U87 and T98 glioblastoma cells. Moreover, global transcriptional profiling revealed that adhesion and cytoskeletal proteins such as Vinculin, Talin and signaling pathways including focal adhesion kinase (FAK), extracellular martrix (ECM) receptor interaction, and cellular motility were significantly enriched in U87 and T98 glioblastoma cells upon LKB1 knockdown. Additionally, we demonstrated that the enhanced activation of FAK by LKB1 knockdown was dependent on differentially expressed cytoskeletal proteins in these glioblastoma cells. Importantly, we further found that mTOR1 inhibitor rapamycin dominantly inhibited in vitro cellular proliferation, while FAK inhibitor PF-573288 drastically decreased invasion of LKB1-attenuated glioblastoma cells. Therefore, downregulation of LKB1 may contribute to the pathogenesis and malignancy of glioblastoma and may have potential implications for stratification and treatment of glioblastoma patients.

15.
J Psychiatr Res ; 118: 44-65, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31493709

RESUMO

Anxiety is presumably driven by fear memory. The nucleus accumbens involves emotional regulation. Molecular profiles in the nucleus accumbens related to stress-induced fear memory remain elucidated. Fear memory in mice was induced by a paradigm of social defeat. Physical and psychological stress was delivered to an intruder that was attacked by an aggressive resident. Meanwhile, an observer experienced psychological stress by seeing aggressor attacks. The nucleus accumbens tissues from intruder and observer mice that appear fear memory and anxiety as well as control mice were harvested for analyses of mRNA and miRNA profiles by high throughput sequencing. In the nucleus accumbens of intruders and observers with fear memory and anxiety, genes encoding AdrRα, AChRM2/3, GluRM2/8, HrR1, SSR, BDNF and AC are upregulated, while genes encoding DR3/5, PR2, GPγ8 and P450 are downregulated. Physical and/or psychological stress leads to fear memory and anxiety likely by molecules relevant to certain synapses. Moreover, there are differential expressions in genes that encode GABARA, 5-HTR1/5, CREB3, AChRM2, RyR, Wnt and GPγ13 in the nucleus accumbens from intruders versus observers. GABAergic, serotonergic and cholinergic synapses as well as calcium, Wnt and CREB signaling molecules may be involved in fear memory differently induced by psychological stress and physical/psychological stress. The data from analyzing mRNA and miRNA profiles are consistent. Some molecules are validated by qRT-PCR and dual luciferase reporter assay. Fear memory and anxiety induced by the mixture of physical and psychological stress or psychological stress appear influenced by complicated molecular mechanisms in the nucleus accumbens.

16.
Transbound Emerg Dis ; 66(6): 2605-2610, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31402584

RESUMO

Wild and domestic aquatic birds are the natural reservoirs of avian influenza viruses (AIVs). All subtypes of AIVs, including 16 hemagglutinin (HA) and nine neuraminidase (NA), have been isolated from the waterfowls. The H5 viruses in wild birds display distinct biological differences from their highly pathogenic H5 counterparts. Here, we isolated seven H5N3 AIVs including three from wild birds and four from domestic ducks in China from 2015 to 2018. The isolation sites of all the seven viruses were located in the region of the East Asian-Australasian Migratory Flyway. Phylogenetic analysis indicated that the surface genes of these viruses originated from the wild bird H5 HA subtype and the N3 Eurasian lineage. The internal genes of the seven H5N3 isolates are derived from the five gene donors isolated from the wild birds or ducks in Eastern-Asia region. They were also divided into five genotypes according to their surface genes and internal gene combinations. Interestingly, two of the seven H5N3 viruses contributed their partial internal gene segments (PB1, M and NS) to the newly emerged H7N4 reassortants, which have caused first human H7N4 infection in China in 2018. Moreover, we found that the H5N3 virus used in this study react with the anti-serum of the H5 subtype vaccine isolate (Re-11 and Re-12) and reacted well with the Re-12 anti-serum. Our findings suggest that worldwide intensive surveillance and the H5 vaccination (Re-11 and Re-12) in domestic ducks are needed to monitor the emergence of novel H5N3 reassortants in wild birds and domestic ducks and to prevent H5N3 viruses transmission from the apparently healthy wild birds and domestic ducks to chickens.

17.
Front Pharmacol ; 10: 789, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396081

RESUMO

Liraglutide (Lir) is a glucagon-like peptide-1 receptor agonist that lowers blood sugar and reduces myocardial infarct size by improving endothelial cell function. However, its mechanism has not yet been clarified. Unfolded protein response (UPR) plays an important role in the pathogenesis of myocardial ischemia-reperfusion injury. It determines the survival of cells. Endoplasmic reticulum position protein homologue 2 (CNPY2) is a novel initiator of UPR that also participates in angiogenesis. To this extent, the current study further explored whether Lir regulates angiogenesis through CNPY2. In our article, a hypoxia/reoxygenation (H/R) injury model of human umbilical vein endothelial cells (HUVECs) was established and the effect of Lir on HUVECs was first evaluated by the Cell Counting Kit-8. Endothelial tube formation was used to analyze the ability of Lir to induce angiogenesis. Subsequently, the effect of Lir on the concentrations of hypoxia-inducible factor 1α (HIF1α), vascular endothelial growth factor (VEGF), and CNPY2 was detected by enzyme-linked immunosorbent assay. To assess whether Lir regulates angiogenesis through the CNPY2-initiated UPR pathway, the expression of UPR-related pathway proteins (CNPY2, GRP78, PERK, and ATF4) and angiogenic proteins (HIF1α and VEGF) was detected by reverse transcription-polymerase chain reaction and Western blot. The results confirmed that Lir significantly increased the expression of HIF1α and VEGF as well as the expression of CNPY2-PERK pathway proteins in HUVECs after H/R injury. To further validate the experimental results, we introduced the PERK inhibitor GSK2606414. GSK2606414 was able to significantly decrease both the mRNA and protein expression of ATF4, HIF1α, and VEGF in vascular endothelial cells after H/R injury. The effect of Lir was also inhibited using GSK2606414. Therefore, our study suggested that the CNPY2-PERK pathway was involved in the mechanism of VEGF expression after H/R injury in HUVECs. Lir increased the expression of VEGF through the CNPY2-PERK pathway, which may promote endothelial cell angiogenesis and protect HUVEC from H/R damage.

18.
Dalton Trans ; 48(42): 15906-15916, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31441474

RESUMO

In order to improve the remarkable performance of a mononuclear tricarbonyl rhenium(i) complex (ReL1) that exhibits rare aggregation-induced phosphorescence enhancement (AIPE) behavior, two new complexes (ReL3 and ReL4) were prepared and investigated. They incorporate a 2-pyridyl-1,2,4-triazole (pyta) ligand connected to a 2-phenylbenzoxazole (PBO) moiety. Complex ReL3 differs from ReL1 by the presence of a bulky tert-butyl substituent, and ReL4 is an isomer where the PBO group is linked to the pyta ligand by its phenyl group. Theoretical calculations were in congruence with electrochemical and spectroscopic properties in solutions. Both new compounds exhibited strong AIPE and much better solid-state emission efficiency than ReL1, with photoluminescence quantum yields up to 55% for ReL4. Crystallographic data indicate that this increase in emission efficiency is due to optimum packing that prevents quenching. This work shows that minor structural changes may have major effects upon the solid-state spectroscopic properties and it provides a rational basis for accessing AIPE-active strongly emissive rhenium(i) complexes.

19.
Clin Chim Acta ; 498: 68-75, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31421121

RESUMO

BACKGROUND: Platelet antibodies can lead to clinical diseases such as platelet transfusion refractoriness (PTR), fetal/neonatal alloimmune thrombocytopenia (FNAIT), etc. This study is aimed at understanding CD36 expression, platelet alloantibody distribution in different populations in Northern China, and effects of platelet alloantibodies on pregnancy. STUDY DESIGN AND METHODS: Whole blood samples of 612 subjects including hematological patients, pregnant women, and blood donors were collected at a single center, then CD36 expressions were determined, followed by platelet antibody screening and characterization of platelet antibody specificity. A retrospective analysis was performed in 1552 pregnant women admitted to Department of Obstetrics, in order to investigate FNAIT occurrence. RESULTS: Rate of CD36 deficiency expression was 2.12% (13/612), all cases exhibited type II deficiency without type I deficiency being detected, and such rate is lower than that in Southern China (3.43%), Japanese (4.87%) and in the black people (4.18%), and higher than that in the White people (0.09%). Positive rates of platelet antibody screening in hematological patient group (6.86%, 14/204) and in pregnant women group (6.31%, 13/206) are higher than that in blood donor group (0.49%, 1/202), P < .01. Out of 1552 pregnant women, there were not children with FNAIT. CONCLUSION: The frequency of CD36 deficiency in northern China was low, all of them were type II deficiency, and no CD36 antibody was detected. It is speculated that the risk of immune-related thrombocytopenia caused by CD36 deficiency in this population is very low. Platelet antibodies should be monitored early in patients with hematological and multiple miscarriages pregnant.

20.
Biol Blood Marrow Transplant ; 25(12): 2517-2521, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31445185

RESUMO

Clonal hematopoiesis (CH), characterized by the accumulation of acquired somatic mutations in the blood, is associated with an elevated risk of aging-related diseases and premature mortality in non-cancer populations. Patients who undergo autologous hematopoietic cell transplantation (HCT) are also at high risk of premature onset of aging-related conditions. Therefore, we examined the association between pretreatment CH and late-occurring (≥1 year) nonrelapse mortality (NRM) after HCT. We evaluated pathogenic and likely pathogenic CH variants (PVs) in 10 patients who developed NRM after HCT and in 29 HCT recipient controls matched by age at HCT ± 2 years (median, 64.6 years; range, 38.5 to 74.7 years), sex (79.5% male), diagnosis (61.5% with non-Hodgkin lymphoma, 18.0% with Hodgkin lymphoma, and 20.5% with multiple myeloma), and duration of follow-up. We analyzed mobilized hematopoietic stem cell DNA in samples collected before HCT using a custom panel of amplicons covering the coding exons of 79 myeloid-related genes associated with CH. PVs with allele fractions >2% were used for analyses. Cases were significantly more likely than controls to have CH (70% versus 24.1%; P = .002), to have ≥2 unique PVs (60% versus 6.9%; P < .001), and to have PVs with allelic fractions ≥10% (40% versus 3.4%; P = .003). Here we provide preliminary evidence of an association between pre-HCT CH and NRM after HCT independent of chronologic age. Integration of CH analyses may improve the accuracy of existing pre-HCT risk prediction models, setting the stage for personalized risk assessment strategies and targeted treatments to optimally prevent or manage late complications associated with HCT.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA