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1.
Nano Lett ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31573819

RESUMO

We present experimental results confirming extreme quantum confinement in GaN/AlxGa1-xN (x = 0.65 and 1.0) nanowire and planar heterostructures, where the GaN layer thickness is of the order of a monolayer. The results were obtained from temperature- and excitation-dependent and time-resolved photoluminescence measurements. In the GaN/AlN nanowire heterostructure array sample, the measured emission peak at 300 K is ∼5.18-5.28 eV. This is in excellent agreement with the calculated optical gap of 5.23 eV and 160-260 meV below the calculated electronic gap of 5.44 eV, suggesting that the observed emission is excitonic in nature with an exciton binding energy of ∼160-260 meV. Similarly, in the monolayer GaN/Al0.65Ga0.35N planar heterostructure, the measured emission peak at 300 K is 4.785 eV and in good agreement with the calculated optical gap of 4.68 eV and 95 meV below the calculated electronic gap of 4.88 eV. The estimated exciton binding energy is 95 meV and in close agreement with our theoretical calculations. Excitation-dependent and time-resolved photoluminescence data support the presence of excitonic transitions. Our results indicate that deep-ultraviolet excitonic light sources and microcavity devices can be realized with heterostructures incorporating monolayer-thick GaN.

2.
Arch Virol ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31598844

RESUMO

In this study, we report a novel double-stranded RNA (dsRNA) virus, Beauveria bassiana partitivirus 3 (BbPV-3), derived from the entomogenous fungus Beauveria bassiana isolate RCEF5853 from China. The genome of BbPV-3, whose sequence was determined by metagenomic sequencing, RT-PCR, and RACE cloning, comprises two dsRNA genome segments that are 1,856 and 1,719 bp long. The first segment contains a single ORF (ORF-1) encoding a 584-amino-acid-long protein (66.05 kDa) with a conserved RNA-dependent RNA polymerase (RdRp) motif. The second segment also has a single ORF (ORF-2) encoding a 500-amino-acid-long coat protein (CP) (55.9 kDa). The CP and RdRp sequences showed highest identity of 43.4% and 60.2%, respectively, to those of Colletotrichum eremochloae partitivirus 1. Phylogenetic analysis of the RdRp domain of the polyprotein revealed that BbPV-3 grouped together with the members of the genus Epsilonpartitivirus. Hence, we proposed that Beauveria bassiana partitivirus 3 is a novel member of the proposed genus Epsilonpartitivirus.

3.
Ear Nose Throat J ; : 145561319869608, 2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31566002

RESUMO

BACKGROUND: With the extensive development of endoscopic sinus surgery, iatrogenic medial rectus muscle injury should be treated with caution. Traditional methods to repair a ruptured medial rectus need an anterior orbitotomy approach, with more injury and difficulty in finding the posterior end of the ruptured medial rectus. OBJECTIVE: To explore a new method to repair a ruptured medial rectus. METHODS: Eight cases of iatrogenic medial rectus rupture after endoscopic sinus surgery were reviewed from July 2015 to January 2019. Assisted by image-guided navigation, the ruptured medial rectus was sutured under an endoscopic endonasal orbital approach. Two methods were designed to suture the ruptured medial rectus. Optic nerve and orbital decompression were performed in 5 cases with visual impairment. The extent of exotropia and diplopia were followed up for 5 to 33 months after surgery. RESULTS: With the help of image guidance, the posterior and anterior ends of the ruptured medial rectus of all patients were pinpointed, and operations using medial rectus anastomosis were successfully completed in 7 patients. The exotropia of these patients was corrected, and they have recovered. The vision of 2 patients recovered. There were no minor or major complications intraoperatively or postoperatively. CONCLUSION: Assisted by image-guided navigation, medial rectus anastomosis under an endoscopic endonasal orbital approach is a feasible method. The key to preventing orbital complications is strict professional training, including identification of the Onodi air cell and correct application of powered instrumentation.

4.
Exp Cell Res ; : 111653, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31574286

RESUMO

Acute myeloid leukemia (AML) is a group of highly aggressive malignancies with a 5-year overall survival of less than 40%. Cell overgrowth with defective apoptosis is a hallmark of AML, but little is known about how it occurs. Here, we show that aberrant activation of the largest subunit of RNA polymerase II (RPB1) encoded by POLR2A gene is critically involved in this hallmark. We retrospectively analyzed the expression profiles of POLR2A and RPB1 in a panel of AML cell lines, primary AML patients and peripheral blood samples. Meanwhile, correlation analysis was used to explore the correlation between the expression of RPB1 with tumor burden and overall survival time in untreated AML samples. RNA-Seq approach was performed to identify the differentially expressed genes between RPB1 silencing AML cells with control cells after knocking out RPB1. Furthermore, orthotopic AML models were established with RPB1 silencing and control cells to investigate the effects of RPB1 protein level on leukemia cell growth. In most AML patients, RPB1 was aberrantly activated and closely associated with poor prognosis, but not in normal hematopoietic cells. Global transcriptomic analysis revealed that POLR2A knockout strongly impaired growth of AML cells by selectively depleting a substantial set of AML-related oncogenic and anti-apoptosis genes such as MYC, RUNX2, MEIS1, CDC25A and BCL-2. Silencing RPB1 by genetic technology led to a potent regression of human refractory AML in mouse models. These findings reveal that dysregulated RPB1 is a central oncogenic hub that drives overgrowth by hijacking an array of oncogenic and anti-apoptosis factors. Targeting RPB1 is a potential therapeutic for treating AML.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31580705

RESUMO

Objectives: Large sample and high-quality evidence to evaluate the preliminary safety of the mobilizations and massage for cervical vertigo are not yet available. Thus, the present study aimed to investigate the comparative effectiveness and preliminary safety of Shi-style cervical mobilizations (SCM) compared with traditional massage (TM) in cervical vertigo patients. Design: A prospective, multicenter, open-label, randomized, controlled clinical trial with a 1:1 allocation ratio. Settings: Five academic medical centers. Subjects: A total of 360 adult patients with a diagnosis of cervical vertigo. Interventions: The patients were randomly allocated to either an SCM (n = 180) or TM (n = 180) group. The patients were treated during six sessions over 2 weeks. The primary outcome was the Dizziness Handicap Inventory (DHI) total scale score, and secondary outcomes included the DHI subscales, Chinese version of the Short-Form 36 Health Survey (CSF-36), and adverse events (AEs). Outcomes were assessed in the short term at 2 weeks, 1 month, and 3 months, and in the intermediate term at 6 months after randomization. Results: Significant changes were observed from the baseline in the DHI total scale and subscales at 2 weeks and 1, 3, and 6 months in both groups (all p < 0.05). However, the differences between the two groups were not significant (all p > 0.05). Furthermore, we noted significant changes from the baseline in SF-36 scores at 2 weeks in both groups (all p < 0.05), whereas CSF-36 scores were not significantly higher in the SCM group (all p > 0.05) compared with the TM group. No serious AEs were reported in either of the two groups. Conclusions: No differences in outcomes were detected between the SCM and TM groups in terms of treatment of cervicogenic dizziness. Efficacy trials are required to determine whether the improvement observed for each treatment was causally related to the interventions.

6.
Med Sci Monit ; 25: 7557-7566, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31592001

RESUMO

BACKGROUND Owing to the increased incidence of photodermatosis caused by ultraviolet light in recent years, it is necessary to clarify the mechanisms potential photodamage to the skin and reveal possible therapeutic targets. Heat shock protein 27 (Hsp27) is well known for suppressing apoptosis. The aim of present study was to elucidate possible photoprotective mechanism between Hsp27 and p21 on ultraviolet B (UVB)-induced photodamage. MATERIAL AND METHODS The Hsp27 gene was interfered to assess the expression of its downstream effectors, cell apoptosis, and cell proliferation ability. The cell apoptosis was tested using flow cytometry method. The cell proliferation ability was tested using Cell Counting Kit-8 (CCK-8) assay. The expression of protein was tested using western-blotting method. The expression of mRNA was detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The subcellular localization was elucidated using immunofluorescence. RESULTS Hsp27 knockdown decreased cell viability and increased the incidence of UVB-induced apoptosis. Compared with control group, activation of phosphorylated-Akt (p-Akt)-dependent pathway resulted in the nuclear accumulation of p21 and suppression of cell proliferation, while promoting apoptosis in Hsp27 knockdown group. In addition, Hsp27 knockdown increased p53 expression and the Bax: Bcl-2 ratio, which further accelerated the apoptotic process. CONCLUSIONS These findings complemented the mechanism of skin photodamage and demonstrated the photoprotective mechanisms of Hsp27 in HaCaT cells, which might implicate a potential therapeutic target of photodamage and photodermatosis.

7.
Chin Med J (Engl) ; 132(19): 2292-2299, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31567375

RESUMO

BACKGROUND: The dose and time point for switching from clopidogrel to ticagrelor remain controversial, especially for Chinese acute coronary syndrome (ACS) patients with complicated coronary artery disease (CAD). Hence, the purpose of this study was to further explore the optimal dose and time point for the switching strategy to balance the increase in platelet inhibition and the decrease in adverse events in Chinese ACS patients with complicated CAD managed by percutaneous coronary intervention (PCI). METHODS: From July 2017 to December 2017, the prospective, randomized, open-label study (the SwitcHIng from clopidogrel to ticagrelor study) assigned the eligible Chinese ACS patients with complicated CAD managed by PCI (n = 102) for 90 mg of ticagrelor at 12 h (T-90 mg-12 h), 90 mg of ticagrelor at 24 h (T-90 mg-24h) or 180 mg ticagrelor at 24 h (T-180 mg-24 h) after the last dose of clopidogrel. The primary endpoint was the comparison of maximal platelet aggregation (MPA) values at 2 h after switching strategies among the three groups. In addition, the MPA values at baseline, 8 h and before discharge and the rates of high on-treatment platelet reactivity were evaluated, the incidences of bleeding episodes and dyspnea during hospitalization and at 30-day follow-up in our study were also recorded. The MPA was measured by light transmittance aggregometry in our study. A repeated-measures analysis of variance (ANOVA) model and one-way ANOVA were used to compare data for the primary endpoint. RESULTS: The MPA values were significantly decreased in the T-180 mg-24 h group compared with the T-90 mg-12 h group (P = 0.017) and decreased numerically compared with the T-90 mg-24 h group (P = 0.072) at 2 h. In particular, the MPA values were markedly reduced in the T-90 mg-24 h group compared with the T-90 mg-12 h group at 8 h after switching treatment (P = 0.002). There was no significant difference among the three groups in all bleedings and dyspnea events. CONCLUSIONS: The optimal treatment strategy recommended in this study for Chinese ACS patients with complicated CAD managed by PCI is 180 or 90 mg of ticagrelor at 24 h after the last dose of clopidogrel. In addition, a negative interaction was detected in this study between the overlap for clopidogrel and ticagrelor at 12 h after the last dose of clopidogrel. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03577652; http://clinicaltrials.gov/ct2/show/NCT03577652.

8.
Pathol Oncol Res ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31489573

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma with high metastatic rate and high mortality rate, needing to find potential therapeutic targets and develop new therapy methods. The bioinformatics analysis was used in this study to find the targets. Firstly, the expression profile of ccRCC obtained from The Cancer Genome Atlas (TCGA) database and GSE53757 dataset were used to identify the significant up-regulated genes. IL20RB, AURKB and KIF18B with the top efficiency of capable of diagnosis ccRCC from para cancer tissue, were over-expressed in ccRCC samples, and expressed increasedly with the development of ccRCC. There was the closest correlation between AURKB and KIF18B in these three over-expressed genes. AURKB (high) or KIF18B (high) were all significantly correlated with higher T, N, M stage, G grade and shorter overall survival (OS) of ccRCC patients. Furthermore, the ccRCC patients with AURKB (high) + KIF18B (high) showed worse clinical characteristics and prognosis. Multivariate COX regression analysis indicated AURKB (high) and KIF18B (high) were all the independent prognostic risk factor without considering the interaction of AURKB and KIF18B. Moreover, considering the combination of each other, only AURKB (high) + KIF18B (high) expression was an independent prognostic risk factor for ccRCC patients, but not other situations. Collectively, AURKB was closely associated with KIF18B, and the combined expression of AURKB and KIF18B may be of great significance in ccRCC.

9.
Kaohsiung J Med Sci ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31483087

RESUMO

The current study aims to investigate the effect of rhein lysinate (RHL) on neuromotor function in rats with spinal cord injury (SCI) and to explore the underlying mechanism. A total of 63 adult male SD rats were randomly divided into the sham group, SCI group and RHL group (SCI-RHL group), with 21 rats in each group. Basso Beattie Bresnahan (BBB) scoring and the inclined plate test were used to evaluate the changes in motor function after SCI. Then, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) contents were quantified. Caspase-3-positive cells in spinal cord tissue were detected by immunohistochemical (IHC) staining, and protein expression was detected by Western blots. Here, our data showed that compared with the SCI group, the BBB score and inclined plate test score of the SCI-RHL group were significantly higher than those of the SCI group 7 days after the RHL intervention. After 7 days of RHL treatment, the activities of SOD and GSH-Px in the spinal cord increased significantly. At the same time, RHL reduced the MDA content in spinal cord tissue of SCI rats. Moreover, cleaved-caspase-3-positive cells and apoptotic cells were significantly lower in the SCI-RHL group than in the SCI group. More importantly, p38 mitogen-activated protein kinase (p38 MAPK) was significantly decreased in the SCI-RHL group compared with the SCI group. In summary, RHL can inhibit the activation of the p38 MAPK pathway after SCI, thereby reducing the apoptosis of spinal cord neurons and improving the neuromotor function of SCI rats.

10.
J Card Fail ; 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31541741

RESUMO

AIMS: Metabolomic profiling may have diagnostic and prognostic value in heart failure. This study investigated whether targeted blood and urine metabolomics reflects disease severity in non-ischemic dilated cardiomyopathy (DCM) patients and compared its incremental value on top of NT-proBNP. METHODS AND RESULTS: A total of 149 metabolites were measured in plasma and urine samples of 273 DCM patients with different stages of disease (DCM patients with LVRR (normal LVEF), n=70; asymptomatic DCM, n=72 and symptomatic DCM, n=131). Acylcarnitines, sialic acid, and glutamic acid are the most distinctive metabolites associated with disease severity, as repeatedly revealed by uni-biomarker linear regression, sPLSDA, Random Forest and conditional Random Forest analyses. However, the absolute difference of the metabolic profile among groups was marginal. A decision tree model based on the top metabolites did not surpass NT-proBNP in classifying stages. However, a combination of NT-proBNP and the top metabolites improved the decision tree to distinguish DCM patients with LVRR from symptomatic DCM (AUC 0.813±0.138 versus 0.739±0.114; p=0.02). CONCLUSION: Functional cardiac recovery is reflected in metabolomics. These alterations reveal potential alternative treatment targets in advanced symptomatic DCM. The metabolic profile can complement NT-proBNP in determining disease severity in non-ischemic DCM.

12.
FASEB J ; : fj201900803R, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31557058

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignant epithelial cancer of the head and neck with high prevalence in southern China, which is accompanied by notable invasiveness and metastasis. Long noncoding RNAs (lncRNAs) participate in the progression of various cancers including NPC. Microarray-based analysis identified highly expressed lncRNA mothers against decapentaplegic homolog 5 (SMAD5)-antisense RNA 1 (AS1) related to NPC. Interestingly, it is found that SMAD5-AS1 competitively bound to microRNA (miR)-106a-5p to regulate SMAD5. Herein, the study aimed to clarify the role of SMAD5-AS1/miR-106a-5p/SMAD5 axis in the process of epithelial mesenchymal transition (EMT) in NPC. SMAD5-AS1 was highly expressed and miR-106a-5p was poorly expressed in NPC tissues and cell lines. The NPC cells were treated with a series of small interfering RNAs, mimics, or inhibitors to explore the effects of SMAD5-AS1, SMAD5, and miR-106a-5p on EMT, cell proliferation, migration, and invasion in NPC. Of note, SMAD5-AS1 silencing or miR-106a-5p overexpression reduced expression of N-cadherin, matrix metallopeptidase 9, Snail, and Vimentin while elevating E-cadherin expression, thus inhibiting EMT, cell proliferation, migration, and invasion in NPC by down-regulation of SMAD5. Moreover, SMAD5 silencing could reduce the ability of EMT induced by SMAD5-AS1 up-regulation. SMAD5-AS1 silencing or miR-106a-5p elevation inhibited tumorigenesis in nude mice. Taken together, SMAD5-AS1 silencing suppressed EMT, cell proliferation, migration, and invasion in NPC by elevating miR-106a-5p to down-regulate SMAD5, which provided a novel therapeutic target for NPC treatment.-Zheng, Y.-J., Zhao, J.-Y., Liang, T.-S., Wang, P., Wang, J., Yang, D.-K., Liu, Z.-S. Long noncoding RNA SMAD5-AS1 acts as a microRNA-106a-5p sponge to promote epithelial mesenchymal transition in nasopharyngeal carcinoma.

13.
Pathol Res Pract ; : 152598, 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31562019

RESUMO

MicroRNA (miRNA) plays a significant role in suppressing the occurrence and development of tumor by inhibiting the translation of target proteins. Although previous researches have verified many miRNAs' functions in bladder cancer (BC), the function of miR-188-5p and miR-141-3p in BC still remains unknown. Our experiment manifested that miR-188-5p and miR-141-3p were highly expressed in BC tissues and cells, which indicated a poor prognosis. In vitro functional assays suggested that down-regulated miR-188-5p and miR-141-3p inhibited the proliferation, migration and invasion of BC cells, while a combination of half dose down-regulated miR-188-5p and half dose down-regulated miR-141-3p demonstrated a more obvious inhibition effect. All results indicated that miR-188-5p and miR-141-3p promoted BC respectively and synergistically. Therefore, miR-188-5p and miR-141-3p will not only assist the diagnosis of BC, but also serve as more effective joint markers to predict the progression of BC.

14.
Bioelectrochemistry ; 131: 107352, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31494386

RESUMO

The designed synthesis of efficient materials can significantly enhance the performance of electrochemical immunoassay in the detection of diseases, pesticide residues and environmental pollutants. The hollow AgPt@Pt core-shell nanoparticles (AgPt@Pt HNs) have exhibited high catalytic efficiency to the hydrogen peroxide (H2O2) reduction for its high mass activity from their hollow structure. Their limitation of instability can be overcome by loading on polypyrrole nanosheet (PPy NS). Besides, PPy NS exhibits good conductivity, and there exists environmentally-friendly method for its synthetic. Thus, AgPt@Pt HNs loaded on PPy NS (AgPt@Pt HNs/PPy NS) exhibits high catalytic efficiency to the reduction of H2O2 and good stability. Furthermore, the quick electron transfer of AgPt@Pt HNs/PPy NS modified glassy carbon electrode has been evidenced by the finding that the large constant of apparent electron transfer rate has also enlarged the current signal when the amount of electron is invariant. The modified electrode has fabricated a label-free amperometric immunosensor to detect sensitively prostate-specific antigen (PSA) with H2O2 as the electroactive material. The immunosensor in hollow core-shell nanosheet structure exhibiting good detection performance of PSA shows its promising applications in the clinical diagnosis.

15.
Phys Rev Lett ; 123(5): 050603, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31491311

RESUMO

Correlations of fluctuations are the driving forces behind the dynamics and thermodynamics in quantum many-body systems. For qubits embedded in a quantum bath, the correlations in the bath are key to understanding and combating decoherence-a critical issue in quantum information technology. However, there is no systematic method for characterizing the many-body correlations in quantum baths beyond the second order or the Gaussian approximation. Here we present a scheme to characterize the correlations in a quantum bath to arbitrary order. The scheme employs a weak measurement of the bath via the projective measurement of a central system. The bath correlations, including both the "classical" and the "quantum" parts, can be reconstructed from the correlations of the measurement outputs. The possibility of full characterization of many-body correlations in a quantum bath forms the basis for optimizing quantum control against decoherence in realistic environments, for studying the quantum characteristics of baths, and for the quantum sensing of correlated clusters in quantum baths.

16.
Pathol Res Pract ; 215(10): 152609, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31488317

RESUMO

BACKGROUND: Breast cancer is the most frequent carcinoma in females, which could be classified to 4 subtypes and the current treatment is still far from satisfactory. In this study, we explored the effects of autophagy inhibition on certain subtypes of breast cancer and the molecular mechanism underlying the different response for breast cancer subtypes initially. METHODS: Autophagy inhibitor hydroxychloroquine (HCQ) was used to identify the sensitivity of breast cancer subtypes to autophagy inhibition in the present study. Cell proliferation and cell invasion were assessed by Cell Counting Kit-8 assay (CCK-8) and transwell assay, respectively. Immunofluorescence staining and western blotting were applied to evaluate cell autophagy. In addition, levels of Ras/Raf/ERK signaling pathway were evaluated by western blotting. RESULTS: Our results showed that HCQ treatment suppressed breast cancer cell proliferation and migration in especially SUM-190 cells, which was most sensitive. Furthermore, HCQ inhibited cell autophagy in breast cancer cells by regulating levels of p62, LC3-I and LC3-II. Moreover, the expression of Ras was significant lower than other breast cancer cells. HCQ treatment markedly inhibited the activation of Ras/Raf/ERK signaling in SUM190 cells. CONCLUSION: To conclude, basal-like breast cancer represented by SUM-190 cells may be most sensitive to HCQ induced autophagy inhibition and the mechanism might be relative to Ras/Raf/ERK signaling pathway.

17.
Toxins (Basel) ; 11(10)2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31547122

RESUMO

In order to remove zearalenone (ZEA) detriment-Bacillus subtilis, Candida utilis, and cell-free extracts from Aspergillus oryzae were used to degrade ZEA in this study. The orthogonal experiment in vitro showed that the ZEA degradation rate was 92.27% (p < 0.05) under the conditions that Candida utilis, Bacillus subtilis SP1, and Bacillus subtilis SP2 were mixed together at 0.5%, 1.0%, and 1.0%. When cell-free extracts from Aspergillus oryzae were combined with the above probiotics at a ratio of 2:1 to make mycotoxin-biodegradation preparation (MBP), the ZEA degradation rate reached 95.15% (p < 0.05). In order to further investigate the MBP effect on relieving the negative impact of ZEA for pig production performance, 120 young pigs were randomly divided into 5 groups, with 3 replicates in each group and 8 pigs for each replicate. Group A was given the basal diet with 86.19 µg/kg ZEA; group B contained 300 µg/kg ZEA without MBP addition; and groups C, D, and E contained 300 µg/kg ZEA added with 0.05%, 0.10%, and 0.15% MBP, respectively. The results showed that MBP addition was able to keep gut microbiota stable. ZEA concentrations in jejunal contents in groups A and D were 89.47% and 80.07% lower than that in group B (p < 0.05), indicating that MBP was effective in ZEA biodegradation. In addition, MBP had no significant effect on pig growth, nutrient digestibility, and the relative mRNA abundance of estrogen receptor alpha (ERα) genes in ovaries and the uterus (p > 0.05).

18.
Brain Res ; 1724: 146442, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31513790

RESUMO

Prostaglandin E2 (PGE2) and proton are typical inflammatory mediators. They play a major role in pain processing and hypersensitivity through activating their cognate receptors expressed in terminals of nociceptive sensory neurons. However, it remains unclear whether there is an interaction between PGE2 receptors and proton-activated acid-sensing ion channels (ASICs). Herein, we show that PGE2 enhanced the functional activity of ASICs in rat dorsal root ganglion (DRG) neurons through EP1 and EP4 receptors. In the present study, PGE2 concentration-dependently increased ASIC currents in DRG neurons. It shifted the proton concentration-response curve upwards, without change in the apparent affinity of proton for ASICs. Moreover, PGE2 enhancement of ASIC currents was partially blocked by EP1 or EP4 receptor antagonist. PGE2 failed to enhance ASIC currents when simultaneous blockade of both EP1 and EP4 receptors. PGE2 enhancement was partially suppressed after inhibition of intracellular PKC or PKA signaling, and completely disappeared after concurrent blockade of both PKC and PKA signaling. PGE2 increased significantly the expression levels of p-PKCε and p-PKA in DRG cells. PGE2 also enhanced proton-evoked action potentials in rat DRG neurons. Finally, peripherally administration of PGE2 dose-dependently exacerbated acid-induced nocifensive behaviors in rats through EP1 and EP4 receptors. Our results indicate that PGE2 enhanced the electrophysiological activity of ASICs in DRG neurons and contributed to acidosis-evoked pain, which revealed a novel peripheral mechanism underlying PGE2 involvement in hyperalgesia by sensitizing ASICs in primary sensory neurons.

19.
Proc Natl Acad Sci U S A ; 116(39): 19626-19634, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31488712

RESUMO

Doxorubicin is a widely used chemotherapeutic agent that causes dose-dependent cardiotoxicity in a subset of treated patients, but the genetic determinants of this susceptibility are poorly understood. Here, we report that a noncanonical tumor suppressor activity of p53 prevents cardiac dysfunction in a mouse model induced by doxorubicin administered in divided low doses as in the clinics. While relatively preserved in wild-type (p53 +/+ ) state, mice deficient in p53 (p53 -/- ) developed left ventricular (LV) systolic dysfunction after doxorubicin treatment. This functional decline in p53 -/- mice was associated with decreases in cardiac oxidative metabolism, mitochondrial mass, and mitochondrial genomic DNA (mtDNA) homeostasis. Notably, mice with homozygous knockin of the p53 R172H (p53 172H/H ) mutation, which like p53 -/- state lacks the prototypical tumor suppressor activities of p53 such as apoptosis but retains its mitochondrial biogenesis capacity, showed preservation of LV function and mitochondria after doxorubicin treatment. In contrast to p53-null state, wild-type and mutant p53 displayed distinct mechanisms of transactivating mitochondrial transcription factor A (TFAM) and p53-inducible ribonucleotide reductase 2 (p53R2), which are involved in mtDNA transcription and maintenance. Importantly, supplementing mice with a precursor of NAD+ prevented the mtDNA depletion and cardiac dysfunction. These findings suggest that loss of mtDNA contributes to cardiomyopathy pathogenesis induced by doxorubicin administered on a schedule simulating that in the clinics. Given a similar mtDNA protection role of p53 in doxorubicin-treated human induced pluripotent stem cell (iPSC)-derived cardiomyocytes, the mitochondrial markers associated with cardiomyopathy development observed in blood and skeletal muscle cells may have prognostic utility.

20.
Ying Yong Sheng Tai Xue Bao ; 30(9): 2973-2982, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31529872

RESUMO

Ant nesting can modify soil physicochemical conditions in the tropical forest, exerting a crucial effect on spatiotemporal variation in soil microbial biomass carbon and quotient. In this study, the chloroform fumigation method was used to measure the spatiotemporal dynamics of microbial biomass carbon and quotient in ant nests and the reference soils in Syzygium oblatum community of tropical Xishuangbanna. The results were as following: 1) Microbial biomass carbon and quotient were significantly higher in ant nests (1.95 g·kg-1, 6.8%) than in the reference soils (1.76 g·kg-1, 5.1%). The microbial biomass carbon in ant nests and the reference soils showed a signifi-cantly unimodal temporal variation, whereas the temporal dynamics of microbial biomass quotient presented a distribution pattern of "V" type. 2) The microbial biomass carbon and quotient showed significant vertical changes in ant nests and the reference soils. The microbial biomass carbon decreased, and microbial biomass quotient increased significantly along the soil layers. The vertical variations in microbial biomass carbon and quotient were more significant in ant nests than in refe-rence soils. 3) Ant nesting significantly changed the spatiotemporal distributions of soil water and temperature in ant nests, which in turn affected spatiotemporal dynamics of soil microbial biomass carbon and quotient. Soil water content could explain 66%-83% and 54%-69% of the variation of soil microbial biomass carbon and quotient, respectively. Soil temperature could explain 71%-86% and 67%-76% of the variation of soil microbial biomass carbon and quotient in ant nests and the reference soils, respectively. 4) Changes in soil physicochemical properties induced by ant nesting had significant effect on the soil microbial biomass carbon and quotient. There were positive correlations of soil microbial biomass carbon to soil organic carbon, soil temperature, total nitrogen and soil water content, and to bulk density, nitrate nitrogen and hydrolyzed nitrogen; whereas a negative correlation of them was observed with soil pH. Soil pH was positively and other soil physicochemical properties were negatively correlated with microbial biomass quotient. Total organic carbon, total nitrogen and soil temperature had greater contribution to microbial biomass carbon, while total organic carbon and total nitrogen had the least negative effect on microbial biomass quotient. Therefore, ant nesting could modify microhabitats (e.g., soil water and soil temperature) and soil physicochemical properties (e.g., total organic carbon and total nitrogen), thereby regulating the spatiotemporal variation in soil microbial biomass carbon and quotient in tropical forests.


Assuntos
Formigas , Florestas , Microbiologia do Solo , Solo , Animais , Biomassa , Carbono , China , Nitrogênio
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