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1.
Metallomics ; 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32202275

RESUMO

All cells require Cu as a cofactor, but Cu2+ induces toxicity and oxidative damage. A strict system is thus needed to maintain Cu homeostasis. Using the ZFL zebrafish liver cell line as a model, we studied the cellular responses after exposure to Cu2+, using whole-transcriptome shotgun sequencing (RNA-seq) to screen nearly all transcriptomes in cell samples and identify changes in gene expression. ZFL cells were treated with 100, 200, or 400 µM CuCl2 and harvested after 4 and 24 h. RNA was then extracted and subjected to RNA-Seq and qPCR validation. Exposure to 400 µM CuCl2 for 4 h and 24 h led to the regulation of 5993 and 4235 genes, respectively. In a gene ontology enrichment analysis, Cu2+ exposure enriched the nitrogen compound metabolic process and antioxidant activity but did not significantly affect cellular copper, zinc, iron and calcium ion homeostasis. In a KEGG pathway enrichment analysis, anti-oxidative stress induced the glutathione metabolism pathway. Furthermore, Cu2+ also induced genes related to apoptosis and arrested the cell cycle in the G2 phase. This study was based on the full gene expression profile combined with pathway analysis details, providing a full cellular response picture for Cu.

2.
Transl Stroke Res ; 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32221863

RESUMO

Some researchers have previously shown that RNAi knockdown of arginyl-tRNA synthetase (ArgRS) before or after a hypoxic injury can rescue animals from death, based on the model organism, C. elegans. However, there has been no study on the application of arginyl-tRNA synthetase knockdown in treating mammalian ischemic stroke, and its potential mechanism and effect on ischemic brain damage are still unknown. Here, we focused on the Rars gene, which encodes an arginyl-tRNA synthetase, and examined the effects of Rars knockdown in a permanent middle cerebral artery occlusion model in rats. To achieve this aim, adult male Sprague-Dawley (SD) rats were given right cerebral cortex injections of short hairpin RNA (shRNA) adenovirus (AV) particles to knock down arginyl-tRNA synthetase, and a non-targeting control (NTC) vector or phosphate-buffered solution served as the controls. After 4 days, the rats were exposed to permanent middle cerebral artery occlusion (pMCAO). Then, the right cerebral cortex level of arginyl-tRNA synthetase was examined, and the effects of the Rars knockdown were evaluated by differences in infarction volume, oxidative stress, blood-brain barrier, mitochondrial function, and glucose metabolism at 1 day and 3 days after MCAO. The injection of shRNA adenovirus particles successfully suppressed the expression of arginyl-tRNA synthetase in the cerebral cortex. We observed an improvement in oxidative stress, mitochondrial function, and glucose utilization and a reduction in brain edema compared with the non-targeting control rats with suppressed expression of arginyl-tRNA synthetase mRNA in the ipsilateral ischemic cortex of the brain. Our findings indicate that knockdown of arginyl-tRNA synthetase in the cerebral cortex exerted neuroprotective effects, which were achieved not only by the improvement of oxidative stress and glucose utilization but also by the maintenance of mitochondrial morphological integrity and the preservation of mitochondrial function. Knockdown of ArgRS administration could be a promising approach to protect ischemic stroke.

3.
Eur J Pharmacol ; 873: 172992, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32035144

RESUMO

Hesperetin, a flavonoid from citrus fruits, possess various pharmacological properties, including anti-inflammatory, anti-oxidative, anti-tumor potentials. However, the role and its mechanism in ulcerative colitis (UC) remains unclear. This study aimed to investigate the protective effects and mechanisms of hesperetin on dextran sodium sulfate (DSS) -induced colitis. Our results showed that hesperetin significantly relieved the symptoms of DSS -induced colitis and increased the expressions of zonula occludens-1 (ZO-1), occludin and mucin2 (MUC-2) as well as the decrease of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-18, HMGB1 and IL-6. Of note, results from immunohistochemistry (IHC) and western blotting indicated that hesperetin inhibited the expressions of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), the two key proteins of necroptosis pathway, and inactivated RIPK3/MLKL necroptosis signalling. Meanwhile, in the cell-coculture system between Caco-2 and RAW264.7 cells, hesperetin treatment significantly ameliorated the decrease of trans epithelial electric resistance (TEER) value while HS-173 (necroptosis inducer) could obviously influence the effect of hesperetin. In addition, hesperetin attenuated the LPS-induced increasing in 4-kDa fluorescein isothiocyanate-dextran (FD4) permeability while HS-173 could weaken the protective effect of hesperetin. Meanwhile, HS-173 reduced the changes in the expressions of phosphorylated RIPK3, phosphorylated MLKL, ZO-1, occludin and MUC-2 as well as TNF-α, IL-1ß. These findings demonstrated hesperetin ameliorated DSS-induced colitis by maintaining the epithelial barrier via blocking the intestinal epithelial necroptosis.

4.
J Proteomics ; : 103691, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32068187

RESUMO

Acute myocardial infarction (AMI) is an acute heart disease. Cycloastragenol, as a natural product, inhibits inflammation and protects cardiomyocytes. Cycloastragenol (Y006) modulates inflammation in AMI is not known. To explore the function of Cycloastragenol in AMI, this study investigated the effect of Y006 and its mechanisms both in vitro and in vivo. Y006 influences the concentration of 11 proteins, as shown by a proteomics analysis, immunohistochemistry and western blotting. Among these 11 proteins, Erk1/2, PLCG1, IKBKG, and ZEB1 are related to inflammatory regulation. BAX, COX2, and GSK3ß are involved in modulating cardiomyocyte apoptosis, and RhoA and DSC2 are directly associated with myocardial function. However, the functions of ARHGAP17 and Rit2 in heart are less well established. Additionally, Y006 suppressed TNF-α, IFN-γ and IL-17 production in PBMCs (peripheral blood monocytes) from patients with acute myocardial infarction and enhanced IL-10 and IL-4 expression. Similar results were obtained in a rat model of AMI by flow cytometry detection and ELISA. Our findings indicate that Y006 protects rats from AMI through direct or indirect inhibition of inflammation and cardiomyocyte apoptosis. However, the specific mechanism of Y006's protective function requires further study. Nonetheless, this research revealed a novel aspect for the treatment of myocardial infarction. SIGNIFICANCE: In the present study, we undertook the first proteomic evaluation of Cycloastragenol (Y006) function in acute myocardial infarction (AMI). Y006 significantly improved myocardial function in vivo by regulating multiple molecular expressions. Hypoxia is a direct reason for AMI. And our data support a role of Y006 in gene expression, cell apoptosis under hypoxia. The conclusions of this research assist to explain the potential molecular mechanism in Cycloastragenol treating AMI and supply a new method for ameliorating AMI.

5.
Aquat Toxicol ; 220: 105402, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31927065

RESUMO

The increasing quantities of insecticides that leach into water bodies severely affect the health of the aquatic environment. Juvenile hormone analogue (JHA) insecticides are endocrine disrupters that interfere with hormonal activity in insects by mimicking juvenile hormones (JHs). Because the structure and functions of methyl farnesoate in crustaceans are similar to the insect JHs, exogenous JHA insecticides may cause adverse effects on the growth and reproduction in crustaceans similar to those observed in insects. This study examined the toxic effects of two JHA insecticides, methoprene and fenoxycarb, on the water flea Moina macrocopa. The 24-h and 48-h LC50 values for fenoxycarb and methoprene were 0.53 and 0.32 mg/L and 0.70 and 0.54 mg/L, respectively. Chronic exposure to the two JHAs caused a series of toxic effects in M. macrocopa, including shortening of life expectancy, repression of body growth, reduction in fecundity, and disturbed the expression of genes involved in the JH signaling pathway, in cuticle development, and in the carbohydrate, amino acid, and ATP metabolic processes. Moreover, JHA exposure impaired the growth and reproduction of the offspring of M. macrocopa exposed to JHAs, even when the neonates were not exposed to the chemicals. In addition, changes in the expression of genes related to histone methylation indicate that epigenetic changes may promote transgenerational impairment in M. macrocopa. These results demonstrate the toxic effects of fenoxycarb and methoprene on non-target aquatic organisms. The damages done by these JHA insecticides to the aquatic environment is worthy of our attention and further studies.

6.
J Hazard Mater ; 386: 121662, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31771885

RESUMO

The catalytic performance of Fe3O4/reduced graphene oxide (Fe3O4/rGO) nanocomposite makes it attractive for the removal of emerging pollutants from water, but the combination of its efficient adsorption and degradation of per- and polyfluoroalkyl substances has not been studied. Here we report the optimal granular Fe3O4/rGO with high thermal and acid resistance stability through controlling its self-assembly for the adsorption and degradation of sodium p-perfluorous nonenoxybenzene sulfonate (OBS) from water. The maximum adsorption capacity for OBS was calculated to be 362.4 µmol/g according to Langmuir fitting. Electrostatic, π-π and hydrogen bonding interactions were involved in OBS adsorption, and the quaternary N in Fe3O4/rGO was a key adsorption site. The efficiency of the utilization of free radicals generated in Fenton-like and persulfate (PS) systems increased with the increase of OBS adsorbed onto the Fe3O4/rGO, while the increase of OBS amount adsorbed on Fe3O4/rGO would casue a slow OBS removal in the adsorption-degradation process due to the slow adsorption process. The Fenton-like oxidation was more efficient for OBS removal than PS oxidation. The spent Fe3O4/rGO was able to be reused in the Fenton-like system at least ten times, while the OBS removal in the PS reaction system was reduced to 47.8 % after six reuse cycles.

7.
Acta Pharmacol Sin ; 41(3): 319-326, 2020 Mar.
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.

8.
Int J Biol Macromol ; 144: 615-623, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31843600

RESUMO

The structural modification of polysaccharides directly affects their physicochemical properties and applications. Dextran, a chained polysaccharide, consists of multiple d-glucose molecules with repetitive structures. In this study, the physicochemical properties of oxidized dextran (DO) at different concentrations of NaClO/NaBr and H2O2 were compared. The results showed that NaClO/NaBr oxidation is more conducive to the formation of carboxyl groups. Oxidized dextran with NaClO/NaBr (DOB) showed good iron (III) chelating ability, and the DOB­iron (III) complex (DOBIC) had an iron content of 28.31%. According to structural analysis, NaClO/NaBr (2 g/100 g of active chlorine) and H2O2 (4 g/100 g), respectively, oxidize the C1 and C2 hydroxyl groups of dextran to carboxyl groups and open the ring when DO and iron have the strongest chelation ability. The complex is indeed a chelate iron complex, and iron core is composed of iron oxyhydroxide or the ß-FeOOH mineral polymorph. These results indicate that DOBIC is expected to be a good iron supplement or food additive to strengthen iron.

9.
Front Microbiol ; 10: 2601, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31787964

RESUMO

[This corrects the article DOI: 10.3389/fmicb.2019.01416.].

10.
World J Pediatr ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31686366

RESUMO

BACKGROUND: Pulmonary hemorrhage (PH) is a life-threatening respiratory complication of extremely low-birth-weight infants (ELBWIs). However, the risk factors for PH are controversial. Therefore, the purpose of this study was to analyze the perinatal risk factors and short-term outcomes of PH in ELBWIs. METHODS: This was a retrospective cohort study of live born infants who had birth weights that were less than 1000 g, lived for at least 12 hours, and did not have major congenital anomalies. A logistic regression model was established to analyze the risk factors associated with PH. RESULTS: There were 168 ELBWIs born during this period. A total of 160 infants were included, and 30 infants were diagnosed with PH. Risk factors including gestational age, small for gestational age, intubation in the delivery room, surfactant in the delivery room, repeated use of surfactant, higher FiO2 during the first day, invasive ventilation during the first day and early onset sepsis (EOS) were associated with the occurrence of PH by univariate analysis. In the logistic regression model, EOS was found to be an independent risk factor for PH. The mortality and intraventricular hemorrhage rate of the group of ELBWIs with PH were significantly higher than those of the group of ELBWIs without PH. The rates of periventricular leukomalacia, moderate-to-severe bronchopulmonary dysplasia and severe retinopathy of prematurity, and the duration of the hospital stay were not significantly different between the PH and no-PH groups. CONCLUSIONS: Although PH did not extend hospital stay or increase the risk of bronchopulmonary dysplasia, it increased the mortality and intraventricular hemorrhage rate in ELBWIs. EOS was the independent risk factor for PH in ELBWIs.

11.
World J Gastroenterol ; 25(40): 6116-6128, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31686767

RESUMO

BACKGROUND: For periampullary adenocarcinoma, the histological subtype is a better prognostic predictor than the site of tumor origin. Intestinal-type periampullary adenocarcinoma (IPAC) is reported to have a better prognosis than the pan-creatobiliary-type periampullary adenocarcinoma (PPAC). However, the classification of histological subtypes is difficult to determine before surgery. Apparent diffusion coefficient (ADC) histogram analysis is a noninvasive, non-enhanced method with high reproducibility that could help differentiate the two subtypes. AIM: To investigate whether volumetric ADC histogram analysis is helpful for distinguishing IPAC from PPAC. METHODS: Between January 2015 and October 2018, 476 consecutive patients who were suspected of having a periampullary tumor and underwent magnetic resonance imaging (MRI) were reviewed in this retrospective study. Only patients who underwent MRI at 3.0 T with different diffusion-weighted images (b-values = 800 and 1000 s/mm2) and who were confirmed with a periampullary adenocarcinoma were further analyzed. Then, the mean, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC values and ADCmin, ADCmax, kurtosis, skewness, and entropy were obtained from the volumetric histogram analysis. Comparisons were made by an independent Student's t-test or Mann-Whitney U test. Multiple-class receiver operating characteristic curve analysis was performed to determine and compare the diagnostic value of each significant parameter. RESULTS: In total, 40 patients with histopathologically confirmed IPAC (n = 17) or PPAC (n = 23) were enrolled. The mean, 5th, 25th, 50th, 75th, 90th, and 95th percentiles and ADCmax derived from ADC1000 were significantly lower in the PPAC group than in the IPAC group (P < 0.05). However, values derived from ADC800 showed no significant difference between the two groups. The 75th percentile of ADC1000 values achieved the highest area under the curve (AUC) for differentiating IPAC from PPAC (AUC = 0.781; sensitivity, 91%; specificity, 59%; cut-off value, 1.50 × 10-3 mm2/s). CONCLUSION: Volumetric ADC histogram analysis at a b-value of 1000 s/mm2 might be helpful for differentiating the histological subtypes of periampullary adenocarcinoma before surgery.


Assuntos
Adenocarcinoma/diagnóstico , Neoplasias do Sistema Biliar/diagnóstico , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Duodenais/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Ampola Hepatopancreática/diagnóstico por imagem , Ampola Hepatopancreática/patologia , Ampola Hepatopancreática/cirurgia , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/cirurgia , Diagnóstico Diferencial , Neoplasias Duodenais/patologia , Neoplasias Duodenais/cirurgia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos
12.
Anesthesiology ; 131(5): 1125-1147, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31567367

RESUMO

BACKGROUND: Cancer pain is a pervasive clinical symptom impairing life quality. Vascular endothelial growth factor A has been well studied in tumor angiogenesis and is recognized as a therapeutic target for anti-cancer treatment. This study tested the hypothesis that vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 contribute to bone cancer pain regulation associated with spinal central sensitization. METHODS: This study was performed on female rats using a metastatic breast cancer bone pain model. Nociceptive behaviors were evaluated by mechanical allodynia, thermal hyperalgesia, spontaneous pain, and CatWalk gait analysis. Expression levels were measured by real-time quantitative polymerase chain reaction, western blot, and immunofluorescence analysis. Excitatory synaptic transmission was detected by whole-cell patch-clamp recordings. The primary outcome was the effect of pharmacologic intervention of spinal vascular endothelial growth factor A/vascular endothelial growth factor receptor 2-signaling on bone cancer pain behaviors. RESULTS: The mRNA and protein expression of vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 were upregulated in tumor-bearing rats. Spinal blocking vascular endothelial growth factor A or vascular endothelial growth factor receptor 2 significantly attenuated tumor-induced mechanical allodynia (mean ± SD: vascular endothelial growth factor A, 7.6 ± 2.6 g vs. 5.3 ± 3.3 g; vascular endothelial growth factor receptor 2, 7.8 ± 3.0 g vs. 5.2 ± 3.4 g; n = 6; P < 0.0001) and thermal hyperalgesia (mean ± SD: vascular endothelial growth factor A, 9.0 ± 2.4 s vs. 7.4 ± 2.7 s; vascular endothelial growth factor receptor 2, 9.3 ± 2.5 s vs. 7.5 ± 3.1 s; n = 6; P < 0.0001), as well as spontaneous pain and abnormal gaits. Exogenous vascular endothelial growth factor A enhanced excitatory synaptic transmission in a vascular endothelial growth factor receptor 2-dependent manner, and spinal injection of exogenous vascular endothelial growth factor A was sufficient to cause pain hypersensitivity via vascular endothelial growth factor receptor 2-mediated activation of protein kinase C and Src family kinase in naïve rats. Moreover, spinal blocking vascular endothelial growth factor A/vascular endothelial growth factor receptor 2 pathways suppressed protein kinase C-mediated N-methyl-D-aspartate receptor activation and Src family kinase-mediated proinflammatory cytokine production. CONCLUSIONS: Vascular endothelial growth factor A/vascular endothelial growth factor receptor 2 contributes to central sensitization and bone cancer pain via activation of neuronal protein kinase C and microglial Src family kinase pathways in the spinal cord.

14.
Antiviral Res ; 172: 104619, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31600533

RESUMO

Hepatitis B virus (HBV) infection remains an important public health problem worldwide. Covalently closed circular DNA (cccDNA) exhibits as an individual minichromosome and is the molecular basis of HBV infection persistence and antiviral treatment failure. In the current study, we demonstrated that histone deacetylase 11 (HDAC11) inhibits HBV transcription and replication in HBV-transfected Huh7 cells. By using an HBV in vitro infection system, HDAC11 was found to affect the transcriptional activity of cccDNA but did not affect cccDNA production. Chromatin immunoprecipitation (ChIP) assays were utilized to analyze the epigenetic modifications of cccDNA. The results show that HDAC11 specifically reduced the acetylation level of cccDNA-bound histone H3 but did not affect that of histone H4. Furthermore, HDAC11 overexpression decreased the levels of cccDNA-bound acetylated H3K9 (H3K9ac) and H3K27 (H3K27ac). In conclusion, HDAC11 restricts HBV replication through epigenetic repression of cccDNA transcription. These findings reveal the novel role of HDAC11 in HBV infection, further broadening our knowledge regarding the functions of HDAC11 and the roles of HDACs in the epigenetic regulation of HBV cccDNA.

15.
J Colloid Interface Sci ; 557: 655-663, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31561082

RESUMO

Per- and polyfluoroalkyl substances (PFASs) are widely used and co-exist in various aquatic environments, but their co-removal is not clear. In this study, the competitive adsorption behavior and mechanism of six traditional and emerging PFASs on anion-exchange resin IRA67 in the bisolute and mixed systems were studied. The adsorption equilibrium of the long-chain PFASs was at least 96 h whereas 48 h was required for the short-chain PFASs. When the PFASs were co-removed in the bisolute system, their competition was not obvious at low PFAS concentration of 0.01597 mmol/L due to the relatively adequate adsorption sites. When the concentrations of PFASs were increased to 0.07666 mmol/L, the removal of perfluorobutanoic acid (PFBA) and perfluorobutane sulfonate (PFBS) decreased by 77.78% and 72.09%, respectively. The competitive experiments showed that the adsorbed short-chain PFASs could be replaced by the long-chain ones, which was closely related to their hydrophobicity, backbone and functional groups. With the increase of solution pH from 3 to 7, the polyamine groups on the resin IRA67 were transferred to the base forms and the effective adsorption sites decreased, resulting in a more obvious competitive replacement behavior. This study suggested that the PFASs with long chain could be more effectively removed from the coexisting PFASs solution by the anion-exchange resins, and the short-chain PFASs in water may be removed when high dosage of anion-exchange resins is applied or the solution pH is decreased.

16.
Virus Res ; 273: 197758, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31541668

RESUMO

The baculovirus expression vector system (BEVS) is one of the most powerful eukaryotic expression systems. Recombinant protein expression is usually controlled by promoters of the baculovirus very late genes (i.e., polyhedrin and p10); therefore, identifying novel regulatory factors for these promoters is key to increasing BEVS productivity. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is the viral vector most frequently used in BEVS. VP39 is the major nucleocapsid protein of AcMNPV and plays a pivotal role in nucleocapsid assembly in the nucleus. In this study, we found that knocking out vp39 from the AcMNPV genome resulted in decreased protein abundance of polyhedrin and P10. Further assays revealed that the mRNA transcripts and the promoter activities of polyhedrin and p10 were decreased in the absence of vp39, suggesting that VP39 contributes to the activity of the very late viral gene promoters and may represent a means of optimizing the current BEVS.

17.
J Pain ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31494272

RESUMO

Orofacial pain is characterized by its easy spread to adjacent areas, thus presenting with primary hyperalgesia (hypersensitivity at the site of injury) and secondary hyperalgesia (extraterritorial hypersensitivity outside the injured zone). However, the mechanisms behind the secondary hyperalgesia are poorly understood. In the present study, we used a mouse model of partial transection of the infraorbital nerve (pT-ION) to study whether calcium channel subunit α2δ1 (Cavα2δ1) and its downstream signaling contributes to the development of secondary hyperalgesia in the orofacial area. pT-ION caused primary (V2 skin) and secondary (V3 skin) hyperalgesia, which was reversed by the Cavα2δ1 antagonist gabapentin and by the expression of Cavα2δ1-targeting interfering RNA in trigeminal ganglion (TG)-V3 neurons. pT-ION induced increased expression of PKC and TRPA1, which was reversed by Cavα2δ1-targeting interfering RNA, and PKC inhibition reversed the upregulation of TRPA1 and gap junction (GJ) proteins induced by pT-ION. Cavα2δ1 overexpression in TG-V2 neurons induced the upregulation of PKC, TRPA1, and the GJ proteins in the TG and trigeminal subnucleus caudalis and induced hypersensitivity in the V3 skin area, which was reversed by TRPA1, GJ, or PKC blockade. Thus, we conclude that Cavα2δ1 contributes to the development of secondary hyperalgesia through its downstream PKC-TRPA1/GJ signaling pathways. PERSPECTIVE: This study demonstrates that the activation of Cavα2δ1 and the downstream PKC-TRPA1/GJ signaling pathway contributes greatly to trigeminal nerve injury-induced secondary mechanical and cold hyperalgesia. This suggests that inhibitors of Cavα2δ1, TRPA1, or GJs might be effective treatments for nerve injury-induced spreading of orofacial pain.

18.
J Ovarian Res ; 12(1): 74, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399035

RESUMO

BACKGROUND: The mechanism of the pathological change of polycystic ovary syndrome (PCOS) is still unclear. Previous studies have shown that PCOS is a chronic nonspecific low-grade inflammatory condition, and that heat shock protein (HSP)70 has a potent anti-inflammatory property. So the aim of this study is to investigate the correlation between HSP70 and the hormones and inflammatory factors and to find out the role of HSP70 in the pathogenesis of PCOS. METHODS: Twenty female Sprague-Dawley (SD) rats (aged 23 days and weighted 80-90 g) were randomly divided into two groups (n = 10 per group), PCOS group and control group. PCOS group were subcutaneously injected with 6 mg/100 g dehydro-epiandrosterone (DHEA) for 20 consecutive days, the control group were subcutaneously injected with a solvent of equivalent amount. All the samples were collected in the morning fasting state, 12 h after the last administration. Histological examinations of ovarian tissues were analyzed. Hormone levels and inflammatory factors levels were measured by enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Serum concentrations of testosterone (T) and luteinizing hormone (LH) were significantly higher in the PCOS group than the control group (P < 0.001), but the concentrations of estradiol (E2), follicle stimulating hormone (FSH) and insulin didn't show significant difference between these two groups. All the concentrations of inflammatory factors including C-reactive protein (CRP), interleukin (IL)-6, IL-18, and tumor necrosis factor (TNF)-α. were significantly higher in PCOS group than the control group (P < 0.001). The expressions of HSP70 were significantly lower in serum but higher in ovarian tissues in the PCOS group than the control group. Spearman rank correlation analysis showed strong negative correlation of serum HSP70 levels with T, LH and all the detected inflammatory factors. CONCLUSION: The abnormal expression of HSP70 correlated with testosterone and inflammatory factors, which indicates that HSP70 may play an important role in PCOS pathology.


Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Síndrome do Ovário Policístico/etiologia , Síndrome do Ovário Policístico/metabolismo , Animais , Biomarcadores , Citocinas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas de Choque Térmico HSP70/genética , Hormônios/metabolismo , Mediadores da Inflamação/metabolismo , Ovário/metabolismo , Ovário/patologia , Síndrome do Ovário Policístico/sangue , Ratos , Ratos Sprague-Dawley
19.
Ann Vasc Surg ; 61: 203-211, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31381999

RESUMO

BACKGROUND: Willis covered stents are used in clinical practice for some complex cerebrovascular diseases. However, the performance of the Willis covered stent requires further investigation. In this study, we investigate the safety and efficacy of Willis covered stents for the treatment of complex vascular diseases of the internal carotid artery (ICA). METHODS: Thirteen patients with complex ICA diseases treated with the Willis covered stent system at our institution from October 2016 to January 2018 were analyzed retrospectively. Follow-up observation and digital subtraction angiography (DSA) examination were conducted at about 6-10 months after the treatment. RESULTS: The complex vascular diseases of the ICA were successfully treated in 12 patients. The technical success rate was 92.3%. Pathologically, 13 lesions included blood blister-like aneurysm (n = 7), traumatic pseudoaneurysm (n = 1), traumatic carotid artery rupture (n = 1), and aneurysm with arteriovenous fistula (n = 4). Thirteen patients with complex vascular diseases of the ICA were treated with 15 Willis covered stents. The release sites of Willis covered stents were the C7 (n = 2), C6 (n = 1), C5 and/or C4 (n = 9), and the C2 (n = 3) segment of the ICA. DSA performed immediately after stent deployment revealed that complete occlusion of the lesion was achieved in 11 patients and endoleak was observed in 2 patients. Of the 11 patients, postoperative DSA examination indicated that the lesions were occluded completely. Among 2 patients, who had a second stent implantation at the break of the ICA, the traumatic ICA rupture was essentially completely obstructed in 1 patient. The endoleak remained in 1 patient with carotid cavernous sinus fistula because the placement of the second stent system was difficult with his ICA tortuosity. No recurrence of aneurysms, hemorrhagia, and other lesions was observed, and the patients' parent arteries were patent without stenosis. No procedure-related complications or deaths occurred during follow-up. CONCLUSIONS: For the treatment of complex vascular diseases in the ICA, Willis covered stent implantation is safe and effective. However, longer follow-up, large-sample controlled studies, and multicenter studies are needed for further confirmation.

20.
Ying Yong Sheng Tai Xue Bao ; 30(7): 2181-2190, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31418220

RESUMO

We used the mean annual temperature and mean annual precipitation data during 1961 and 2017 of 101 national meteorological stations in Yunnan Province to calculate three climate-induced potential productivity in Yunnan Province by Miami model and the Thornthwaite Memorial model. The abrupt test was carried out by Mann-Kendell method. The spatial and temporal distribution characteristics and future trends of the three climate-induced potential productivities were analyzed. Results showed that the average values of the temperature potential productivity (Yt), precipitation potential productivity (Yr) and evapotranspiration potential productivity (Ye) during the study period was 1968, 1477 and 1434 g·m-2·a-1, respectively. The value of Yt was rising in Yunnan Province. For the value of Yr /Yt, there was a large difference in water-heat ratio among regions, as well as the binding conditions. There was an abrupt change in climate-induced potential productivity, with Yt began to abrupt change significantly in 2001. There was no abrupt change in Yr, but Ye had abrupt change in 2002-2004. The spatial distribution of climate production potential and climate tendency were uneven. The annual average value of Yt, Yr and Ye was 1030-2465, 927-2341 and 832-1995 g·m-2·a-1, respectively. The climate-induced potential productivity was the lowest in the northwestern and northeastern Yunnan and the highest in the southwestern and southern Yunnan. Most of the climatic propensity rates of Yt, Yr and Ye showed increase, decrease and increase trends respectively. Eight schemes simulating future climate change (i.e., temperature increased by 1 ℃, precipitation increased by 10%, temperature decreased by 1 ℃, precipitation decreased by 10%, temperature increased by 1 ℃ and precipitation decreased by 10%, temperature increased by 1 ℃ and precipitation increased by 10%, the temperature decrease by 1 ℃ and the precipitation increased by 10%, the temperature decrease by 1 ℃ and precipitation decreased by 10%) would lead to Ye changes of 6-45, 13-77.2, 15-67, -87 to -17, -74-46, 58-96, -54-57, -101 to -59 g·m-2·a-1, respectively. On the whole, if the climate tends to be "warm and wet" in the future, it will be beneficial for crop production. However, if it tends to be "cold and dry", it will be unfavorable to crop production in the study area.


Assuntos
Mudança Climática , Ecossistema , China , Temperatura Ambiente , Água
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