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1.
Hematology ; 25(1): 79-84, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32019476

RESUMO

Objectives: To explore the clinical features and prognosis of normal karyotype acute myeloid leukemia (NK-AML) pediatric patients with WT1 mutations.Methods: The clinical data and prognostic information of 220 NK-AML pediatric patients were selected from target-AML project of The Cancer Genome Atlas (TCGA) database. Survival analyses were performed for NK-AML pediatric patients with different combinations of mutations.Results: We found that 28(12.7%) NK-AML patients harbored WT1 mutations. The positive rate of FLT3-ITD in the WT1-mutated group was higher than that in the WT1 wild-type group (P = 0.002). In contrast, WT1 mutation and NPM1 mutation were mutually exclusive (P = 0.013). Furthermore, the WT1-mutated group suffered lower rates of complete remission (CR) (P < 0.001 and P < 0.001, respectively) but higher rates of minimal residual disease (MRD) (P = 0.003 and P = 0.021, respectively) after both one and two courses of induction chemotherapy. Patients with WT1 mutations had significantly worse overall survival (OS) and event-free survival (EFS) in both univariate (P < 0.001 and P = 0.007, respectively) and multivariate survival analyses (P < 0.001 and P < 0.001, respectively). The stratification analysis showed that for FLT3-ITD positive patients, WT1 mutations predicted shorter OS (P = 0.003) and EFS (P < 0.001).Conclusion: WT1 mutations conferred an independent poor prognosis for NK-AML pediatric patients.

2.
Biol Res ; 53(1): 5, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046779

RESUMO

BACKGROUND: LincRNAs have been revealed to be tightly associated with various tumorigeneses and cancer development, but the roles of specific lincRNA on tumor-related angiogenesis was hardly studied. Here, we aimed to investigate whether linc-OIP5 in breast cancer cells affects the angiogenesis of HUVECs and whether the linc-OIP5 regulations are involved in angiogenesis-related Notch and Hippo signaling pathways. METHODS: A trans-well system co-cultured HUVECs with linc-OIP5 knockdown breast cancer cell MDA-MB-231 was utilized to study the proliferation, migration and tube formation abilities of HUVECs and alterations of related signaling indicators in breast cancer cells and their conditioned medium through a series of cell and molecular experiments. RESULTS: Overexpressed linc-OIP5, YAP1, and JAG1 were found in breast cancer cell lines MCF7 and MDA-MB-231 and the expression levels of YAP1 and JAG1 were proportional to the breast cancer tissue grades. MDA-MB-231 cells with linc-OIP5 knockdown led to weakened proliferation, migration, and tube formation capacity of co-cultured HUVECs. Besides, linc-OIP5 knockdown in co-cultured MDA-MB-231 cells showed downregulated YAP1 and JAG1 expression, combined with a reduced JAG1 level in conditioned medium. Furthermore, a disrupted DLL4/Notch/NRP1 signaling in co-cultured HUVECs were also discovered under this condition. CONCLUSION: Hence, linc-OIP5 in MDA-MB-231 breast cancer cells may act on the upstream of the YAP1/Notch/NRP1 signaling circuit to affect proliferation, migration, and tube formation of co-cultured HUVECs in a non-cellular direct contact way through JAG1 in conditioned medium. These findings at least partially provide a new angiogenic signaling circuit in breast cancers and suggest linc-OIP5 could be considered as a therapeutic target in angiogenesis of breast cancers.

3.
Cell Res ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32047270

RESUMO

The pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1R) belongs to the secretin receptor family and is widely distributed in the central neural system and peripheral organs. Abnormal activation of the receptor mediates trigeminovascular activation and sensitization, which is highly related to migraine, making PAC1R a potential therapeutic target. Elucidation of PAC1R activation mechanism would benefit discovery of therapeutic drugs for neuronal disorders. PAC1R activity is governed by pituitary adenylate cyclase-activating polypeptide (PACAP), known as a major vasodilator neuropeptide, and maxadilan, a native peptide from the sand fly, which is also capable of activating the receptor with similar potency. These peptide ligands have divergent sequences yet initiate convergent PAC1R activity. It is of interest to understand the mechanism of PAC1R ligand recognition and receptor activity regulation through structural biology. Here we report two near-atomic resolution cryo-EM structures of PAC1R activated by PACAP38 or maxadilan, providing structural insights into two distinct ligand binding modes. The structures illustrate flexibility of the extracellular domain (ECD) for ligands with distinct conformations, where ECD accommodates ligands in different orientations while extracellular loop 1 (ECL1) protrudes to further anchor the ligand bound in the orthosteric site. By structure-guided molecular modeling and mutagenesis, we tested residues in the ligand-binding pockets and identified clusters of residues that are critical for receptor activity. The structures reported here for the first time elucidate the mechanism of specificity and flexibility of ligand recognition and binding for PAC1R, and provide insights toward the design of therapeutic molecules targeting PAC1R.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32041882

RESUMO

The pathogenesis of bipolar disorder (BD) has remained enigmatic, largely because genetic animal models based on identified susceptible genes have often failed to show core symptoms of spontaneous mood cycling. However, pedigree and induced pluripotent stem cell (iPSC)-based analyses have implicated that dysfunction in some key signaling cascades might be crucial for the disease pathogenesis in a subpopulation of BD patients. We hypothesized that the behavioral abnormalities of patients and the comorbid metabolic abnormalities might share some identical molecular mechanism. Hence, we investigated the expression of insulin/synapse dually functioning genes in neurons derived from the iPSCs of BD patients and the behavioral phenotype of mice with these genes silenced in the hippocampus. By these means, we identified synaptotagmin-7 (Syt7) as a candidate risk factor for behavioral abnormalities. We then investigated Syt7 knockout (KO) mice and observed nocturnal manic-like and diurnal depressive-like behavioral fluctuations in a majority of these animals, analogous to the mood cycling symptoms of BD. We treated the Syt7 KO mice with clinical BD drugs including olanzapine and lithium, and found that the drug treatments could efficiently regulate the behavioral abnormalities of the Syt7 KO mice. To further verify whether Syt7 deficits existed in BD patients, we investigated the plasma samples of 20 BD patients and found that the Syt7 mRNA level was significantly attenuated in the patient plasma compared to the healthy controls. We therefore concluded that Syt7 is likely a key factor for the bipolar-like behavioral abnormalities.

5.
Sci Rep ; 10(1): 2225, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32042041

RESUMO

Paulownia species are important ecological, economic and ornamental species, but their phylogenetic relationship remains unclear, which seriously affects the development and utilization of these important resources. The complete chloroplast genomes of six Paulownia species were assembled by next-generation sequencing data. By adding two known Paulownia chloroplast genomes to these six assembled genomes, we performed the comparative analysis and phylogenetic tree reconstruction of Paulownia. The results indicated that the chloroplast genomes of Paulownia species ranged in size from 154,107 to 154,694 bp. These chloroplast genomes contained 117 unique functional genes, including 80 protein-coding genes, four rRNA genes, and 33 tRNA genes. Twelve hotspot regions, five protein-coding genes and seven noncoding regions, were identified in the chloroplast genomes that showed high levels of sequence variation. Additionally, positive selection was observed in three genes, rps2, rbcL and ndhG. The maximum likelihood (ML) and Bayesian (BI) analysis strongly supported the monophyletic origin of Paulownia species, which clustered into two major clades: One clade included P. coreana, P. tomentosa and P. kawakamii, while the other clade comprised the 5 other species including P. fargesii and P. australis. This study provides useful genetic information for phylogenetic reconstruction, taxonomic discrepancies, and studying species evolution and phylogeography in Paulownia.

6.
J Clin Lab Anal ; : e23241, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32052899

RESUMO

BACKGROUND: Blast transformation of chronic myelogenous leukemia (CML) to T lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is rare, and the molecular mechanism is still unclear. CASE REPORT: A 28-year-old woman who developed T-ALL with coexpressing both p210 and p190 BCR-ABL transcripts five years after the initial diagnosis of CML in chronic phase. The proliferation of bone marrow was extremely active with blast cells over 20%. Chromosome analysis revealed t(9;22)(q34;q11) and t(10;11)(q25;p15). Flow immunophenotyping showed that blasts expressed CD4, CD7, CD11b, CD38, CD34, CD33, and cCD3. CONCLUSION: It is the first T-cell blast of CML case with coexisting p210 and p190 as well as additional chromosome translocations. Through review this case and previous reports, we will reveal that CML patients with T-lymphocyte transformation depend on potential molecular and pathological mechanism.

7.
Bioengineered ; 11(1): 209-218, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32065044

RESUMO

MicroRNAs have been implicated as critical regulatory molecules in many cerebrovascular diseases. Recent studies demonstrated miR-22 might provide a potential neuroprotective effect. However, the neuroprotective effect of miR-22 in ischemia/reperfusion (I/R) injury has not been thoroughly elucidated. In this study, the PC12 cells were subjected to 4 h oxygen and glucose deprivation (I) and 24 h reoxygenation (R). The PC12 cells were pre-transfected with miR-22 or anti-miR-22 or siRNA-mediated downregulation of p53-upregulated-modulator-of-apoptosis (PUMA)(PUMA siRNA) or their controls at 24 h prior to exposure to I/R. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot were employed to analyze mRNA and protein expression. PI and Annexin V assays and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay were used to quantify the rate of apoptosis. We found that miR-22 expression was significantly downregulated in the PC12 cells subjected to I/R. Loss of function of miR-22 increased PC12 apoptosis after I/R, and overexpression of miR-22 decreases PC12 apoptosis after I/R. PUMA protein was upregulated in the I/R group as compared with the sham group. The increased PUMA protein expression and apoptosis induced by I/R was reversed by transfection with PUMA siRNA. We concluded that I/R enhanced apoptosis and PUMA expression in PC12 cells via downregulation of miR-22. Enhanced miR-22 expression reversed both PUMA expression and apoptosis induced by I/R in PC12 cells. miR-22/PUMA axis has important implications for their clinical applications.

8.
Clin Cancer Res ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31988198

RESUMO

PURPOSE: Copy number changes and translocations have been studied extensively in many datasets with long term follow-up. The impact of mutations remains debated given the short time to follow-up of most datasets. METHODS: we performed targeted panel sequencing covering 125 myeloma-specific genes and the loci involved in translocations in 223 newly diagnosed myeloma samples recruited into one of the Total Therapy Trials (TT). RESULTS: As expected, the most commonly mutated genes were NRAS, KRAS, and BRAF making up 44% of patients. Double-Hit, BRAF and DIS3 mutations had an impact on outcome alongside classical risk factors in the context of an intensive treatment approach. We were able to identify both V600E and non-V600E BRAF mutations, 58% of which were predicted to be hypoactive or kinase dead. Interestingly, 44% of the hypoactive/kinase dead BRAF mutated patients showed co-occurring alterations in KRAS, NRAS or activating BRAF mutations suggesting they play a role in the oncogenesis of multiple myeloma (MM) by facilitating MAPK activation and may lead to chemo resistance. CONCLUSION: Overall, these data highlight the importance of mutational screening to better understand newly diagnosed MM (NDMM) and may lead to patient specific mutation-driven treatment approaches.

9.
Biol Trace Elem Res ; 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31983054

RESUMO

The role of pro-inflammatory cytokines in the toxicity of fluoride to tumor cells was investigated by culturing Hepa1-6 cells in medium containing gradient concentrations of fluoride (0, 0.5, 1, 1.5, 2, 3, 4, and 5 mmol/L). The viability of Hepa1-6 cells was detected via MTT assay. Interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-α, and IL-1ß levels in the supernatant were determined via an enzyme-linked immunosorbent assay, and the protein expression levels of these enzymes in Hepa1-6 cells were evaluated by immunofluorescence staining. Results showed that the viability of Hepa1-6 cells remarkably decreases after fluoride exposure, especially at concentration of 3, 4, and 5 mmol/L fluoride. Levels of IL-2, TNF-α, and IL-1ß in the supernatant markedly decreased when cells were exposed to fluoride at concentrations of 1 mmol/L or higher. However, levels of TNF-α and IL-1ß substantially increased and IL-2 showed no remarkable change when the fluoride concentration was 0.5 mmol/L. The content of IL-6 remarkably increased with increasing fluoride concentrations up to 2 mmol/L, and then markedly decreased at 3, 4, and 5 mmol/L fluoride; the decreasing trend of IL-6 content under high fluoride exposure is consistent with the decrease in Hepa1-6 cell viability observed at the same concentration. The protein expression levels of IL-2, IL-6, TNF-α, and IL-1ß were in accordance with their contents in the supernatant. In summary, our study demonstrated that fluoride inhibits Hepa1-6 cell growth and results in disorders in the expression and secretion pro-inflammatory cytokines.

10.
BMC Surg ; 20(1): 16, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31952490

RESUMO

BACKGROUND: The present study aimed to compare the perioperative safety and long-term survival of patients with synchronous colorectal liver metastases undergoing sequential resection (SeR), delayed resection (DeR) and simultaneous resection (SiR). METHODS: From January 2007 to December 2016, data from patients undergoing surgery at Peking University Cancer Hospital for synchronous colorectal liver metastases were retrospectively collected. The above three different surgical strategies were compared. RESULTS: A total of 233 cases were included, with 49 in the SeR group, 98 in the DeR group and 86 in the SiR group. The incidence of severe complications was 26.7% in the SiR group, higher than that in the DeR group (11.2%, P = 0.007) and the SeR group (16.3%, P = 0.166). The overall survival at 1 and 3 years in the SeR group (93.9 and 50.1%) was lower than that in the DeR group (94.9 and 64.8%, P = 0.019), but not significantly different from that in the SiR group (93.0 and 55.2%, P = 0.378). Recurrence-free survival at 1 and 3 years in the SeR group (22.4 and 18.4%) was lower than that in the DeR group (43.9 and 24.2%, P = 0.033) but not significantly different from that in the SiR group (31.4 and 19.6%, P = 0.275). Cox multivariate analysis indicated that T4, lymph node-positive primary tumour, liver metastases > 30 mm and SiR (compared with DeR) were correlated with poor prognosis. CONCLUSION: Simultaneous resection has a relatively higher incidence of severe complications, and with a staged resection strategy, the prognosis of delayed resection was better than that of sequential resection.

11.
Nat Commun ; 11(1): 541, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992713

RESUMO

The fast development of high-resolution electron microscopy (EM) demands a background-noise-free substrate to support the specimens, where atomically thin graphene membranes can serve as an ideal candidate. Yet the preparation of robust and ultraclean graphene EM grids remains challenging. Here we present a polymer- and transfer-free direct-etching method for batch fabrication of robust ultraclean graphene grids through membrane tension modulation. Loading samples on such graphene grids enables the detection of single metal atoms and atomic-resolution imaging of the iron core of ferritin molecules at both room- and cryo-temperature. The same kind of hydrophilic graphene grid allows the formation of ultrathin vitrified ice layer embedded most protein particles at the graphene-water interface, which facilitates cryo-EM 3D reconstruction of archaea 20S proteasomes at a record high resolution of ~2.36 Å. Our results demonstrate the significant improvements in image quality using the graphene grids and expand the scope of EM imaging.

12.
Medicine (Baltimore) ; 99(4): e18789, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977870

RESUMO

Clinical features of extremity fractures (EFs) in patients presenting with traumatic spinal fractures (TSFs) and spinal cord injury (SCI) have not been investigated. To investigate the clinical features and risk factors for EFs in patients presenting with TSFs and SCI.Data from 1392 patients presenting with TSFs and SCI in our hospitals between 2001 and 2010 were retrospectively reviewed, among which 165 patients (129 males and 36 females, 37.5 ±â€Š10.6 years old) presented with EFs. The clinical features of EFs have been investigated.The frequencies of upper limb fractures were significantly higher in the motor vehicle collisions (MVCs) group than in the high-fall group (P = .012) and the struck-by-object group (P = .002). The frequencies of lower limb fractures were significantly higher in the struck-by-object group (P = .019) and the high-fall group (P = .011) than the MVCs group. Univariate logistic regression analysis show that being in the 19 to 39 age group (P = .001), having a lumbar spinal fracture (P < .001) and experiencing a high fall (P < .001) were risk factors for EFs. Multivariate logistic regression analysis showed that we should focus on the factors that having a lumbar spinal fracture and experiencing a high fall.High fall and MVCs were the most common aetiologies for EFs. Having a lumbar spinal fracture and experiencing a high fall were significant risk factors for EFs. We should make early diagnoses and initiate timely treatment according to different patterns of extremity fractures in patients with TSFs and SCI.


Assuntos
Fraturas Ósseas/epidemiologia , Extremidade Inferior/lesões , Fraturas da Coluna Vertebral/epidemiologia , Extremidade Superior/lesões , Acidentes/estatística & dados numéricos , Adulto , Fatores Etários , Feminino , Fraturas Ósseas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fraturas da Coluna Vertebral/etiologia
13.
Life Sci ; 242: 117240, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31891722

RESUMO

Lycium barbarum polysaccharides (LBP) are derived from Wolfberry and have antioxidant activities. This study aimed to evaluate the efficacy of LBP for kidney injury in a rat model of sepsis. Male rats were divided randomly to control group (Con), LPS group (LPS), ulinastatin group (ULI), low dose LBP group (LBP-1), middle dose LBP group (LBP-2) and high dose LBP group (LBP-3). After intraperitoneal injection of LPS (5 mg/kg) to make sepsis model (LPS group), 10,000 U/kg ulinastatin were given in ULI group, and 200, 400 and 800 mg/kg LBP was given in LBP-1, -2, -3 group, respectively. Serum IL-1ß, IL-6, IL-8, TNF-α and NF-κB levels were measured by ELISA. Nrf2, Keap1, NF-κB, HO-1 and NQO1 expression levels were detected by PCR and Western blot analysis. We found that LBP decreased the levels of NF-κB and pro-inflammatory cytokines while attenuated kidney injury. In addition, LBP regulated Keap1-Nrf2/ARE signaling pathway in the kidney. In conclusion, LBP attenuates inflammation injury in the kidney via possible regulation of Keap1-Nrf2/ARE signaling.


Assuntos
Lesão Renal Aguda/prevenção & controle , Elementos de Resposta Antioxidante/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Sepse/complicações , Transdução de Sinais/efeitos dos fármacos , Animais , Western Blotting , Citocinas/metabolismo , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
14.
Phys Chem Chem Phys ; 22(4): 2372-2378, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31934697

RESUMO

The subtle variation of metallic bonding, induced by external influence, plays an essential role in determining physical, mechanical, and chemical properties of metals. However, it is extremely difficult to describe this variation because of the delocalization nature of metallic bonding. Here, we utilize the reduced density gradient and topological analysis of electron density to capture the local metallic bonding variations (LMBV) caused by lattice distortion and carrier injection in many face-centered cubic (fcc) metals. We find that the LMBV determines the traits of fcc metals such as strength, malleability, and ductility. Moreover, the fcc metals can become more flexible/stronger with the electron/hole injection, providing an important guidance to tune metals for desired mechanical properties.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31940862

RESUMO

Exposure to polycyclic aromatic hydrocarbons (PAHs) may lead to adverse health risks. To understand the potential sources and carcinogenic risks of PAHs in Tangshan, 40 PM2.5 samples were collected for analysis of eighteen PM2.5-bound PAHs during non-heating period and heating period. The results display a significant variation. The median concentration of ∑18PAHs during the heating period (282 ng/m3) was higher than during the non-heating period (185 ng/m3). Especially, the median concentration of Benzopyrene (BaP) during the heating period (61.6 ng/m3) was 16.9-fold that during the non-heating period (3.64 ng/m3). It exceeded BaP annual average limit of China (1 ng/m3). Diagnostic ratios (DRs) and principal component analysis (PCA) both indicated that vehicle emissions and coal and biomass combustion were the dominant contributors of PAHs pollution in Tangshan. The incremental lifetime cancer risk (ILCR) of three age groups (children, teenagers, and adults) ranged from 2.56 × 10-6 to 5.26 × 10-5 during the entire sampling periods. The 95% risk values of adults exceeded 10-4 during the heating periods, indicating a potential health risk from PAHs.

16.
Theor Appl Genet ; 133(3): 917-933, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31897512

RESUMO

KEY MESSAGE: Eight environmentally stable QTL for grain yield-related traits were detected by four RIL populations, and two of them were validated by a natural wheat population containing 580 diverse varieties or lines. Yield and yield-related traits are important factors in wheat breeding. In this study, four RIL populations derived from the cross of one common parent Yanzhan 1 (a Chinese domesticated cultivar) and four donor parents including Hussar (a British domesticated cultivar) and three semi-wild wheat varieties in China were phenotyped for 11 yield-related traits in eight environments. An integrated genetic map containing 2009 single-nucleotide polymorphism (SNP) markers generated from a 90 K SNP array was constructed to conduct quantitative trait loci (QTL) analysis. A total of 161 QTL were identified, including ten QTL for grain yield per plant (GYP) and yield components, 49 QTL for spike-related traits, 43 QTL for flag leaf-related traits, 22 QTL for plant height (PH), and 37 QTL for heading date and flowering date. Eight environmentally stable QTL were validated in individual RIL population where the target QTL was notably detected, and six of them had a significant effect on GYP. Furthermore, Two QTL, QSPS-2A.4 and QSL-4A.1, were also validated in a natural wheat population containing 580 diverse varieties or lines, which provided valuable resources for further fine mapping and genetic improvement in yield in wheat.

17.
Dalton Trans ; 49(5): 1388-1392, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31942596

RESUMO

A noncentrosymmetric (NCS) alkali-metal borophosphate CsBP2O6(OH)2 (CBPO) containing a unique borophosphate anionic partial structure has been obtained through a mixed-solvent thermal method. Its structure could be regarded as a 1-D chain that is built by Cs+ cations and a unique anionic chain [BP2O6(OH)2]∞n- composed of BO4 and PO3(OH) groups. CBPO possesses a wide UV-vis transparent range and shows a strong SHG response. Moreover, we have well explored and established the origin of the SHG effect by dipole moment and PDOS calculations. This work will help inspire and stimulate scientists to discover more such excellent NLO materials.

18.
Cell Calcium ; 86: 102151, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31954234

RESUMO

Accumulating evidence obtained over the last three decades has revealed a neuroendocrine system in the brain that mediates long term increases in blood pressure. The system involves distinct ion transport pathways including the alpha-2 isoform of the Na,K pump and epithelial sodium channels, as well as critical hormone elements such as angiotensin II, aldosterone, mineralocorticoid receptors and endogenous ouabain. Activation of this system either by circulating or central sodium ions and/or angiotensin II leads to a cascading sequence of events that begins in the hypothalamus and involves the participation of several brain nuclei including the subfornical organ, supraoptic and paraventricular nuclei and the rostral ventral medulla. Key events include heightened aldosterone synthesis and mineralocorticoid receptor activation, upregulation of epithelial sodium channels, augmented synthesis and secretion of endogenous ouabain from hypothalamic magnocellular neurons, and sustained increases in sympathetic outflow. The latter step depends upon increased production of angiotensin II and the primary amplification of angiotensin II type I receptor signaling from the paraventricular nucleus to the rostral ventral lateral medulla. The transmission of sympathetic traffic is secondarily amplified in the periphery by increased short- and long-term potentiation in sympathetic ganglia and by sustained actions of endogenous ouabain in the vascular wall that augment expression of sodium calcium exchange, increase cytosolic Ca2+ and heighten myogenic tone and contractility. Upregulation of this multi-amplifier system participates in forms of hypertension where salt, angiotensin and/or aldosterone are elevated and contributes to adverse outcomes in heart failure.

19.
Sci Total Environ ; 704: 135318, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31780162

RESUMO

The level of eutrophication in reservoirs is dependent on their internal and external P loads. Identifying the P pollution characteristics and its fractional composition in sediments is therefore necessary to determine the potential bioavailability and dominant sources of P for effective water pollution control. In this study, we investigated the P pollution characteristics in the overlying water and sediment in a chain of reservoirs (the Panjiakou (PJK), Daheiting (DHT) and Yuqiao (YQ) Reservoirs) in North China. Our results showed that the P concentrations in the overlying water of the YQ Reservoir was higher than that of the PJK and DHT Reservoirs, but the sediment P loading and P bio-availability were lower than the PJK and DHT Reservoirs. However, the sediment P release risk in the YQ Reservoir was higher than the DHT and PJK Reservoirs. The YQ Reservoir was mainly polluted by internal sediment P release and external sources predominantly derived from the inflowing polluted Sha River Basin. Various forms of P in the DHT Reservoir decreased with depth, and the P in the overlying water column was mainly sourced from internal P release due to sediment accumulation of excess P from human activities. In recent years, the proportion of bio-available P (BAP) in the PJK and YQ Reservoirs had increased, and the proportion of the more inert Al-P and Ca-P in the PJK Reservoir decreased. Ca-P in the YQ Reservoir had also decreased, indicating that inert P has been gradually transformed into active P in the PJK and YQ Reservoirs in recent years. The observed differences in P loading and sedimentary P fractions indicate different pollution characteristics and sources between the three reservoirs. We therefore recommend site-specific remediation strategies for effective control on P pollution in the three eutrophic reservoirs.

20.
Chemosphere ; 241: 125099, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629238

RESUMO

Our previous study showed that excessive fluoride (F) intake can induce liver dysfunction. The aim of this study was to investigate the mechanisms of F-induced mitochondrial damage resulting in liver dysfunction. Damaged mitochondrial ultrastructure and state of liver cells were estimated by TEM, TUNEL staining and BrdU measurement. The ROS level and ATP content in the liver tissue were measured by ELISA kit. Meanwhile, optic atrophy (OPA1), mitofusin-1 (Mfn1), NDUFV2, SDHA, CYC1, and COX Ⅳ expression levels were measured through real-time PCR and Western-blot. Results showed that the ROS level increased, thereby resulting in mitochondrial ultrastructure damage and abundant liver cells presented evident apoptotic characteristics after F treatment. Decreased ATP content and the abnormal expression of OPA1, Mfn1, NDUFV2, SDHA, CYC1, and COX Ⅳ of the liver tissue were observed. In conclusion, excessive F-induced mitochondrial respiratory chain damaged and mitochondrial fusion disorder resulted in liver dysfunction.

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