Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.343
Filtrar
1.
Aging (Albany NY) ; 13(17): 21497-21512, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491904

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a highly malignant gastrointestinal cancer with a high recurrence rate and poor prognosis. Although N6-methyladenosine (m6A), the most abundant epitranscriptomic modification of mRNAs, has been implicated in several cancers, little is known about its participation in ESCC progression. We found reduced expression of ALKBH5, an m6A demethylase, in ESCC tissue specimens with a more pronounced effect in T3-T4, N1-N3, clinical stages III-IV, and histological grade III tumors, suggesting its involvement in advanced stages of ESCC. Exogenous expression of ALKBH5 inhibited the in vitro proliferation of ESCC cells, whereas depletion of endogenous ALKBH5 markedly enhanced ESCC cell proliferation in vitro. This suggests ALKBH5 exerts anti-proliferative effects on ESCC growth. Furthermore, ALKBH5 overexpression suppressed tumor growth of Eca-109 cells in nude mice; conversely, depletion of endogenous ALKBH5 accelerated tumor growth of TE-13 cells in vivo. The growth-inhibitory effects of ALKBH5 overexpression are partly attributed to a G1-phase arrest. In addition, ALKBH5 overexpression reduced the in vitro migration and invasion of ESCC cells. Altogether, our findings demonstrate that the loss of ALKBH5 expression contributes to ESCC malignancy.

2.
Adv Mater ; : e2104126, 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510589

RESUMO

The nontrivial band structure of semimetals has attracted substantial research attention in condensed matter physics and materials science in recent years owing to its intriguing physical properties. Within this class, a group of nontrivial materials known as nodal-line semimetals is particularly important. Nodal-line semimetals exhibit the potential effects of electronic correlation in nonmagnetic materials, whereas they enhance the contribution of the Berry curvature in magnetic materials, resulting in high anomalous Hall conductivity (AHC). In this study, two ferromagnetic compounds, namely ZrMnP and HfMnP, are selected, wherein the abundance of mirror planes in the crystal structure ensures gapped nodal lines at the Fermi energy. These nodal lines result in one of the largest AHC values of 2840 Ω-1 cm-1 , with a high anomalous Hall angle of 13.6% in these compounds. First-principles calculations provide a clear and detailed understanding of nodal line-enhanced AHC. The finding suggests a guideline for searching large AHC compounds.

3.
Trans GIS ; 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34512105

RESUMO

COVID-19 maps convey hazard and risk information to the public, which play an important role in the risk communication for individual protection. The aim of this study is to improve the effectiveness and efficiency of communicating the specific risk of COVID-19 maps. By testing 71 subjects from Wuhan, China, this study explored how color schemes (cool, warm, and mixed colors) and data presentation forms (choropleth maps, graduated symbol maps) influence visual cognition patterns, risk perception, comprehension, and subjective satisfaction. The results indicated that the warm scheme (yellow/red) has significant strengths in visual cognition and understanding, and the choropleth map (vs. the graduated symbol map) has significant strengths in risk expression. On subjective satisfaction, the combination of the mixed scheme (blue/yellow/red) and the choropleth map scored highest mean value. These results have implications for enhancing the focused functions of COVID-19 maps that fit different terms: in the early and medium terms of disease transmission, choropleth maps with warm or cool colors should be considered as a priority design for their better risk perception. When the epidemic conditions are on the upturn, a better reading experience combination of choropleth maps with mixed colors can be considered.

4.
Front Endocrinol (Lausanne) ; 12: 690784, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512545

RESUMO

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. Long non-coding RNAs (lncRNAs) are regulators in DN progression. However, the regulatory mechanisms of multiple lncRNAs in DN remain to be determined. Our aim was to investigate the function and molecular mechanism of lncRNA RNA component of mitochondrial RNAase P (Rmrp) in DN. Here, we observed that the expression of Rmrp was up-regulated in the kidney of db/db DN mice and high glucose induced glomerular mesangial cells (MC). More importantly, the abnormal transcription of Rmrp was induced by nuclear transcription factor Sp1, which promotes the proliferation and production of fibrotic markers in MC. Subsequently, we screened the miRNAs related to Rmrp and found that Rmrp and miR-1a-3p are co-localized at the subcellular level of MC, and Rmrp could directly binds to miR-1a-3p. Further mechanism research demonstrated that the elevated miR-1a-3p significantly attenuated the proliferation and fibrosis-promoting effects induced by up-regulation of Rmrp. At the same time, we also investigated that miR-1a-3p can directly bind to Jun D proto-oncogene (JunD), thereby regulating the protein level of JunD. Rmrp-induced proliferation and fibrogenesis were reversed by co-transfection with JunD siRNA. In summary, Sp1 induced lncRNA Rmrp could drive the expression of JunD via sponging miR-1a-3p in DN progression.

5.
Sci Total Environ ; 804: 150054, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34509839

RESUMO

The deep-sea mussel Gigantidas platifrons is a representative species that relies on nutrition provided by chemoautotrophic endosymbiotic bacteria to survive in both hydrothermal vent and methane seep environments. However, vent and seep habitats have distinct geochemical features, with vents being more harsh than seeps because of abundant toxic chemical substances, particularly hydrogen sulfide (H2S). Until now, the adaptive strategies of G. platifrons in a heterogeneous environment and their sulfide detoxification mechanisms are still unclear. Herein, we conducted 16S rDNA sequencing and metatranscriptome sequencing of G. platifrons collected from a methane seep at Formosa Ridge in the South China Sea and a hydrothermal vent at Iheya North Knoll in the Mid-Okinawa Trough to provide a model for understanding environmental adaption and sulfide detoxification mechanisms, and a three-day laboratory controlled Na2S stress experiment to test the transcriptomic responses under sulfide stress. The results revealed the active detoxification of sulfide in G. platifrons gills. First, epibiotic Campylobacterota bacteria were more abundant in vent mussels and contributed to environmental adaptation by active oxidation of extracellular H2S. Notably, a key sulfide-oxidizing gene, sulfide:quinone oxidoreductase (sqr), derived from the methanotrophic endosymbiont, was significantly upregulated in vent mussels, indicating the oxidization of intracellular sulfide by the endosymbiont. In addition, transcriptomic comparison further suggested that genes involved in oxidative phosphorylation and mitochondrial sulfide oxidization pathway played important roles in the sulfide tolerance of the host mussels. Moreover, transcriptomic analysis of Na2S stressed mussels confirmed the upregulation of oxidative phosphorylation and sulfide oxidization genes in response to sulfide exposure. Overall, this study provided a systematic transcriptional analysis of both the active bacterial community members and the host mussels, suggesting that the epibionts, endosymbionts, and mussel host collaborated on sulfide detoxification from extracellular to intracellular space to adapt to harsh H2S-rich environments.

6.
ACS Chem Neurosci ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524791

RESUMO

The pathological amyloid plaques in Alzheimer's disease (AD) patients contain not only the wild-type ß-amyloid (wt-Aß) peptide sequences but also a variety of post-translationally modified variants. The pyroglutamate-3 Aß (pyroE3-Aß), which is generated from its truncated precursors ΔE3-Aß, shows the highest abundance among all modified Aß variants. Previous works have shown that pyroE3-Aß and/or ΔE3-Aß, compared with the wild-type sequences, led to a more rapid fibrillation process and final fibrils with higher neuronal cytotoxicity levels. However, much less is known about how the formation of pyroE3/ΔE3-Aß fibrils would affect the amyloid deposition of wt-Aß peptides, which are the main pathological events in AD. We show in the present work that the pyroE3/ΔE3-Aß40 fibrils differ significantly from the wt-Aß40 fibrils in terms of their molecular structures. When added into monomeric wt-Aß40 peptides, these variant fibrils can cross-seed the formation of wt-Aß40 fibrils with fibrillation kinetics that are greater than the self-seeded fibrillation of wt-Aß40. Furthermore, the cross-seeding process modulates the molecular structures of the yielded wt-Aß40 fibrils, which show similar features as their variant seeds. The cross-seeded fibrillation process also induces higher cytotoxicity levels compared with the self-seeded fibrillation of wt-Aß40. Overall, our results support the hypothesis that pyroE3 and ΔE3-Aß40 variants may serve as triggering factors of the pathological amyloid aggregation of wt-Aß40 and may underlie the pathological significance of pyroE3/ΔE3-Aß40 variants on the structural polymorphism of Aß deposits.

7.
ACS Chem Neurosci ; 12(18): 3387-3396, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34469122

RESUMO

Quercitrin (Qc) is a well-known flavonoid compound that exerts anti-inflammation effects on various diseases. The present study aimed to investigate the antidepressant-like response of Qc and its underlying mechanisms concerning neuroinflammation and neuroplasticity in mice with lipopolysaccharide (LPS)-induced depression-like behaviors. The results showed a single dose of Qc (10 mg/kg) produced an antidepressant-like effect at 2 h postadministration and lasted for at least 3 days. The expressions of neuroplasticity signaling molecules of pCREB/BDNF/PSD95/Synapsin1 were upregulated at 2 h, and ERK signaling was upregulated for 3 days in the hippocampus after a single administration of Oc or ketamine. A 5-day treatment of LPS led to depression-like behaviors, including reduced sucrose preference and increased immobility in the tail suspension test or forced swim test, which were all reversed by a single dose of Qc. In LPS-treated mice, Qc reduced the levels of inflammation-related factors including IL-10, IL-1ß, and TNF-α in serum, as well as the activations of PI3K/AKT/NF-κB and MEK/ERK pathways in the hippocampus. Moreover, Qc restored the expressions of pCREB/BDNF/PSD95/Synapsin1 signaling in the hippocampus that were impaired by LPS. LY294002, a PI3K inhibitor, but not PD98059, a MEK inhibitor, produced effects similar to Qc. LY294002 also restored the expressions of pCREB/BDNF/PSD95/Synapsin1 signaling in the hippocampus impaired by LPS. Additionally, subeffective doses of Qc and LY294002 induced behavioral and molecular synergism. Together, the depression-like behaviors in LPS-treated mice were alleviated by a single dose of Qc likely via inhibition of the activations PI3K/AKT/NF-κB inflammation signaling and subsequent improvement of neuroplasticity.

8.
Biosens Bioelectron ; 194: 113600, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34481242

RESUMO

A sensitive electrogenerated chemiluminescence (ECL) biosensor for glucose was developed based on in situ growth of TiO2 nanowires on Ti3C2 MXenes (TiO2-Ti3C2) as the nanoplatform. Via tuning the alkaline oxidation time, different amount of TiO2 nanowires can be found on MXenes. An ECL biosensor for glucose was constructed by covalent immobilization of glucose oxidase (GODx) on the glycine functional TiO2-Ti3C2 surface, with the ECL signal depending on the in-situ formation of H2O2 via the specifically catalysis of glucose by GODx, resulting in the apparent increase of ECL signal. The TiO2-Ti3C2 can also act as the catalyst for the oxidation of H2O2 into O2 to enhance the ECL of luminol. Based on this strategy, a highly sensitive ECL biosensor for glucose was obtained in wide concentration range of 20 nM-12 mM with a low detection limit of 1.2 nM (S/N = 3). The synergistic effects of large surface area, excellent conductivity, and high catalytic activity of the TiO2-Ti3C2 make the sensor highly sensitive toward glucose; the specific enzyme catalysis reaction promises excellent selectivity of the ECL sensor. The proposed biosensor has been employed to detect glucose in human serum, fruits, and sweat samples with excellent performance, providing a universal approach for glucose in various samples, which shows great prospect in clinical diagnostics and wearable sensors.

9.
Plant Physiol Biochem ; 167: 665-677, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34488152

RESUMO

Acetic acid priming may mitigate salt stress to plants by modulating lipid metabolism. Carex rigescens is a stress-tolerant turfgrass species with a widespread distribution in north China. The objective of this study was to figure out whether modification of lipid profiles, including the contents, compositions and saturation levels of leaf lipids, may contribute to acetic acid modulated salt tolerance in C. rigescens. Plants of C. rigescens were primed with or without acetic acid (30 mM) and subsequently exposed to salt stress (300 mM NaCl) for 15 days. Salt stress affected the physiological performance of C. rigescens, while acetic acid-primed plants showed significantly lower malondialdehyde content, proline content, and electrolyte leakage than non-primed plants under salt stress. Acetic acid priming enhanced the contents of phospholipids and glycolipids involved in membrane stabilization and stress signaling (phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, digalactosyl diacylglycerol, monogalactosyl diacylglycerol, and sulfoquinovosyldiacylglycerol), reduced the content of toxic lipid intermediates (free fatty acids) during subsequent exposure to salt stress. Furthermore, expression levels of genes involved in lipid metabolism such as CK and PLDα changed due to acetic acid priming. These results demonstrated that acetic acid priming could enhance salt tolerance of C. rigescens by regulating lipid metabolism. The lipids could be used as biomarkers to select for salt-tolerant grass germplasm.

10.
Nat Commun ; 12(1): 4087, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471112

RESUMO

We utilized forebrain organoids generated from induced pluripotent stem cells of patients with a syndromic form of Autism Spectrum Disorder (ASD) with a homozygous protein-truncating mutation in CNTNAP2, to study its effects on embryonic cortical development. Patients with this mutation present with clinical characteristics of brain overgrowth. Patient-derived forebrain organoids displayed an increase in volume and total cell number that is driven by increased neural progenitor proliferation. Single-cell RNA sequencing revealed PFC-excitatory neurons to be the key cell types expressing CNTNAP2. Gene ontology analysis of differentially expressed genes (DEgenes) corroborates aberrant cellular proliferation. Moreover, the DEgenes are enriched for ASD-associated genes. The cell-type-specific signature genes of the CNTNAP2-expressing neurons are associated with clinical phenotypes previously described in patients. The organoid overgrowth phenotypes were largely rescued after correction of the mutation using CRISPR-Cas9. This CNTNAP2-organoid model provides opportunity for further mechanistic inquiry and development of new therapeutic strategies for ASD.

11.
Chin Med J (Engl) ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34483254

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with loss of motor neurons. Our objective was to explore the epidemiology, clinical features, and survival factors of 1809 patients with ALS. METHODS: We analyzed 1809 ALS patients, who were recruited from the Peking University Third Hospital from January 2005 to December 2015. Demographic data and disease-related parameters were collected. Kaplan-Meier curves were used to compare survival time. Cox proportional hazards function and the hazard ratio were used to identify adjusted prognostic predictors. RESULTS: The results showed that the average annual incidence in Beijing alone was 0.38 cases/100,000 person-years and the mean age of onset was 48.88 ±â€Š11.35 (95% confidence interval [CI]: 48.17-49.85) years. The median survival time from onset to death/tracheostomy was 58.89 ±â€Š33.03 (95% CI: 51.46-63.84) months. In the adjusted Cox proportional hazard model, age of onset, diagnosis delay, rate of disease progression (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised decline [points/month]), and body mass index all had an independent effect on survival in ALS. CONCLUSIONS: Our study provides information on epidemiology, clinical features, and survival factors of patients with ALS in China. These results can be helpful in clinical practice, clinical trial design, and validation of new tools to predict disease progression.

12.
Anal Chim Acta ; 1180: 338880, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34538324

RESUMO

We present a direct injection mass spectrometry (DI-MS) platform that accurately, precisely, and quickly quantitates global levels of DNA cytidine methylation (5 mC) and hydroxymethylation (5hmC). Our platform combines an Advion TriVersa NanoMate coupled online to a Thermo Scientific Orbitrap Fusion Lumos. Following digestion to nucleosides, the DNA samples are analyzed at the rate of <1 min per injection with comparable detection limits of 0.63 ng/µL and 0.31 ng/µL, respectively. In contrast, the detection limits for 5 mC and 5hmC in state-of-art nano liquid chromatography (LC) coupled to online mass spectrometry (nLC-MS) are notably different (0.04 ng/µL and 2.5 ng/µL, respectively). The high sensitivity of DI-MS is achieved by optimizing sample buffer composition, the source fragmentation energy, and the radio frequency of the instrument ion funnel. DI-MS accurately reports the relative abundance of 5 mC and 5hmC over a range of 1%-7% (R2 > 0.98) and 0.13%-1.75% (R2 > 0.99), respectively. Accurate measurement of C, 5 mC and 5hmC is achieved by optimizing in-source fragmentation to obtain a population of up to 93% of just the nucleoside base. This protocol minimizes base dimer formation and partial base-deoxyribose dissociation in gas phase and greatly improves modified base quantitation. We also demonstrate that DI-MS overcomes biases in differential chromatographic retention and issues of sample degradation in the autosampler due to its high throughput. Finally, we present an application of our workflow to quantify DNA modifications on a batch of 81 samples in about 1.5 h.

13.
Vet Parasitol ; 299: 109566, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34509125

RESUMO

Toxoplasma gondii, an intracellular apicomplexan protozoan parasite, can infect all warm-blooded animals. Infected swine are considered one of the most important sources of T. gondii infection in humans. Rapidly and effectively diagnosing T. gondii infection in swine is essential. PCR-based diagnostic tests have been fully developed, and very sensitive and specific PCR is crucial for the diagnosis of swine toxoplasmosis. In this study, we used the T. gondii dense granule protein 14 (GRA14) gene as a target to design specific primers and established a high-specificity and high-sensitivity PCR detection method for swine toxoplasmosis. Notably, this PCR method could detect T. gondii tachyzoite DNA in the acute infection phase. The GRA14 gene PCR assay detected a minimum of 2.35 tachyzoites of T. gondii and can be used for T. gondii detection in blood, tissue, semen, urine and waste feed specimens. A total of 5462 blood specimens collected from pigs in 5 provinces and autonomous regions in southern China during 2016-2017 were assessed by the newly established GRA14 gene PCR method. The overall T. gondii infection rate was 18.9 % (1033/5462). According to the statistical analysis of different regions in China, the positive rates of swine toxoplasmosis from 2016 to 2017 were highest in the Shaanxi, Fujian and Guangdong areas, at 31.7 % (44/139), 21.9 % (86/391) and 18.8 % (874/4645), respectively. Specimens collected in 2017 had a higher positive rate (19.1 %) than those collected in 2016 (16.1 %). In addition, specimens collected in autumn (39.4 %), spring (22.8 %) and winter (18.2 %) had higher positive rates than those collected in summer (3.8 %). These results indicate that the new PCR method based on the T. gondii GRA14 gene has utility for the diagnosis of swine toxoplasmosis and can facilitate the diagnosis of toxoplasmosis in clinical laboratories.

14.
BMC Genom Data ; 22(1): 30, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34482817

RESUMO

BACKGROUND: Preterm birth (< 37 weeks' gestation) is a common outcome of pregnancy that has been associated with increased risk of cardiovascular disease for women later in life. Little is known about the physiologic mechanisms underlying this risk. To date, no studies have evaluated if differences in DNA methylation (DNAm) among women who experience preterm birth are short-term or if they persist and are associated with subsequent cardiovascular sequelae or other health disorders. The purpose of this study was to examine long-term epigenetic effects of preterm birth in African American mothers (n = 182) from the InterGEN Study (2014-2019). In this study, we determine if differences in DNAm exist between women who reported a preterm birth in the last 3-5 years compared to those who had full-term births by using two different approaches: epigenome-wide association study (EWAS) and genome-wide co-methylation analyses. RESULTS: Though no significant CpG sites were identified using the EWAS approach, we did identify significant modules of co-methylation associated with preterm birth. Co-methylation analyses showed correlations with preterm birth in gene ontology and KEGG pathways. Functional annotation analysis revealed enrichment for pathways related to central nervous system and sensory perception. No association was observed between DNAm age and preterm birth, though larger samples are needed to confirm this further. CONCLUSIONS: We identified differentially methylated gene networks associated with preterm birth in African American women 3-5 years after birth, including pathways related to neurogenesis and sensory processing. More research is needed to understand better these associations and replicate them in an independent cohort. Further study should be done in this area to elucidate mechanisms linking preterm birth and later epigenomic changes that may contribute to the development of health disorders and maternal mood and well-being.

15.
Echocardiography ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34505316

RESUMO

Preexcitation cardiomyopathy is a rare cardiac anomaly but it can be life threatening. It may occur in type B preexcitation syndrome. A patients with this condition typically has an enlarged left ventricle and reduced systolic function without tachycardia-associated cardiomyopathy. Echocardiography plays an important role in diagnosis in identifying this condition by revealing the "rebounce" movement of the inter-ventricular septum (IVS). We report echocardiographic findings of five pediatric patients with preexcitation cardiomyopathy. All of them had a radiofrequency catheter ablation (RFCA) and recovered during the follow-up.

16.
Bioengineered ; 12(1): 5655-5663, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34470571

RESUMO

The purpose of this study was to evaluate the function and possible mechanism of miR-212-3p in fetal growth restriction (FGR) and to demonstrate the relationship between miR-212-3p and placental growth factor (PGF). First, we used qRT-PCR to detect the expression of miR-212-3p and PGF in placental tissues of normal delivery (HC group) and FGR, as well as in human trophoblast cell HTR-8/Svneo. The results revealed that miR-212-3p expression was significantly upregulated and PGF was significantly downregulated in placental tissue in the FGR group compared with the HC group. In addition, interference with miR-212-3p expression increased the proliferation, invasion, and migration of HTR-8/SVneo cells and decreased apoptosis of cells. Meanwhile, Western blot results showed that miR-212-3p expression downregulation promoted the phosphorylated protein expression of Phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), which in turn activated the PI3K/AKT signaling pathway. And the results of dual luciferase reporter further showed that miR-212-3p could target PGF, and the expression of both was negatively correlated in FGR group tissues. In addition, downregulation of miR-212-3p expression reversed the inhibitory effect of PGF downregulation on HTR-8/SVneo cells. In conclusion, miR-212-3p can target and inhibit the PGF expression and regulate the PI3K/AKT signaling pathway to regulate trophoblast cell invasion, migration, proliferation and cell apoptosis. This provides a potential biomarker for the development of FGR.

17.
Proc Natl Acad Sci U S A ; 118(36)2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34470826

RESUMO

Netrin-1, a secreted protein recently characterized as a relevant cancer therapeutic target, is the antiapoptotic ligand of the dependence receptors deleted in colorectal carcinoma and members of the UNC5H family. Netrin-1 is overexpressed in several aggressive cancers where it promotes cancer progression by inhibiting cell death induced by its receptors. Interference of its binding to its receptors has been shown, through the development of a monoclonal neutralizing antinetrin-1 antibody (currently in phase II of clinical trial), to actively induce apoptosis and tumor growth inhibition. The transcription factor p53 was shown to positively regulate netrin-1 gene expression. We show here that netrin-1 could be a target gene of the N-terminal p53 isoform Δ40p53, independent of full-length p53 activity. Using stable cell lines, harboring wild-type or null-p53, in which Δ40p53 expression could be finely tuned, we prove that Δ40p53 binds to and activates the netrin-1 promoter. In addition, we show that forcing immortalized human skeletal myoblasts to produce the Δ40p53 isoform, instead of full-length p53, leads to the up-regulation of netrin-1 and its receptor UNC5B and promotes cell survival. Indeed, we demonstrate that netrin-1 interference, in the presence of Δ40p53, triggers apoptosis in cancer and primary cells, leading to tumor growth inhibition in preclinical in vivo models. Finally, we show a positive correlation between netrin-1 and Δ40p53 gene expression in human melanoma and colorectal cancer biopsies. Hence, we propose that inhibition of netrin-1 binding to its receptors should be a promising therapeutic strategy in human tumors expressing high levels of Δ40p53.

18.
Int J Nurs Pract ; : e13011, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34472156

RESUMO

AIM: This study was conducted to identify and compare the levels of compassion fatigue and job satisfaction among haemodialysis nurses in public and private hospitals in China and explore explanatory factors based on sociodemographic and occupational characteristics. METHODS: A descriptive study was conducted using a self-designed demographic questionnaire, the Professional Quality of Life Scale and the Minnesota Satisfaction Questionnaire, with responses from 283 haemodialysis nurses working at six public and private hospitals in China between June and November 2018. RESULTS: The compassion fatigue score of public hospital nurses was significantly higher than that of private hospital nurses. Univariate analysis showed that there were significant differences in compassion fatigue among nurses based on the number of years worked, nature of employment, and education level. Correlational analysis showed a negative correlation between overall job satisfaction and compassion fatigue in both public and private hospitals. Multiple regression analysis showed that compassion fatigue among haemodialysis nurses in public hospitals was associated with years worked, type of employment, and intrinsic and extrinsic satisfaction, whereas in private hospitals, education level, years worked, and intrinsic and extrinsic satisfaction were significant. CONCLUSION: Haemodialysis nurses in public hospitals are more likely to develop compassion fatigue than those in private hospitals.

19.
Bioengineered ; 12(1): 6759-6770, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34519627

RESUMO

Atherosclerosis is a fatal disorder that is fundamental to various cardiovascular diseases and severely threatens people's health worldwide. Several studies have demonstrated the role of circular RNAs (circRNAs) in the pathogenesis of atherosclerosis. circUSP36 acts as a key modulator in the progression of atherosclerosis, but the molecular mechanism underlying this role is as yet unclear. This study aimed to elucidate the mechanism by which circUSP36 exerts its function in an in vitro cell model of endothelial cell dysfunction, which is one of pathological features of atherosclerosis. The circRNA traits of circUSP36 were confirmed, and we observed high expression of circUSP36 in endothelial cells exposed to oxidized low-density lipoprotein (ox-LDL). Functional assays revealed that overexpression of circUSP36 suppressed proliferation and migration of ox-LDL-treated endothelial cells. In terms of its mechanism, circUSP36 adsorbed miR-637 by acting as an miRNA sponge. Moreover, enhanced expression of miR-637 abated the impact of circUSP36 on ox-LDL-treated endothelial cell dysregulation. Subsequently, the targeting relationship between miR-637 and WNT4 was predicted using bioinformatics tools and was confirmed via luciferase reporter and RNA pull-down assays. Notably, depletion of WNT4 rescued circUSP36-mediated inhibition of endothelial cell proliferation and migration. In conclusion, circUSP36 regulated WNT4 to aggravate endothelial cell injury caused by ox-LDL by competitively binding to miR-637; this finding indicates circUSP36 to be a promising biomarker for the diagnosis and therapy of atherosclerosis.

20.
J Exp Bot ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34338731

RESUMO

Phytophthora root and stem rot in soybean [Glycine max (L.) Merr.] is a destructive disease worldwide. Improving soybean resistance to the causal pathogen, Phytophthora sojae, is a major target for breeders; however, it remains largely unclear how the pathogen regulates the various affected signaling pathways in the host, which consist of complex networks including key transcription factors and their targets. We previously demonstrated that GmBTB/POZ enhances soybean resistance to P. sojae and associated defense response. Here, we report that GmBTB/POZ interacts with transcription factor GmAP2 and promotes the ubiquitination of GmAP2. The GmAP2-RNAi transgenic soybean hairy roots exhibited an enhanced resistance to P. sojae, whereas GmAP2-overexpressing hairy roots showed P. sojae hypersensitivity. Subsequently, GmWRKY33 was identified as a target of GmAP2, which represses its expression by directly binding to the GmWRKY33 promoter. GmWRKY33 acts as a positive regulator in the response of soybean to P. sojae. Additionally, the overexpression of GmBTB/POZ released the GmAP2-regulated suppression of GmWRKY33 expression in the GmAP2-OE soybean hairy roots and increased their resistance to P. sojae. Taken together, these results indicate a novel regulatory mechanism, the GmBTB/POZ-GmAP2 modulation of the P. sojae resistance response, which putatively regulates the downstream target gene GmWRKY33 in soybean.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...