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1.
BMC Med Inform Decis Mak ; 20(Suppl 1): 72, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32349764

RESUMO

BACKGROUND: Semantic textual similarity (STS) is a fundamental natural language processing (NLP) task which can be widely used in many NLP applications such as Question Answer (QA), Information Retrieval (IR), etc. It is a typical regression problem, and almost all STS systems either use distributed representation or one-hot representation to model sentence pairs. METHODS: In this paper, we proposed a novel framework based on a gated network to fuse distributed representation and one-hot representation of sentence pairs. Some current state-of-the-art distributed representation methods, including Convolutional Neural Network (CNN), Bi-directional Long Short Term Memory networks (Bi-LSTM) and Bidirectional Encoder Representations from Transformers (BERT), were used in our framework, and a system based on this framework was developed for a shared task regarding clinical STS organized by BioCreative/OHNLP in 2018. RESULTS: Compared with the systems only using distributed representation or one-hot representation, our method achieved much higher Pearson correlation. Among all distributed representations, BERT performed best. The highest Person correlation of our system was 0.8541, higher than the best official one of the BioCreative/OHNLP clinical STS shared task in 2018 (0.8328) by 0.0213. CONCLUSIONS: Distributed representation and one-hot representation are complementary to each other and can be fused by gated network.

2.
Eur Radiol ; 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385649

RESUMO

OBJECTIVES: To explore which preoperative clinical data and conventional MRI findings may indicate microvascular invasion (MVI) of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and have clinical significance. METHODS: The study enrolled 113 patients with histopathologically confirmed cHCC-CCA (MVI-positive group [n = 56], MVI-negative group [n = 57]). Two radiologists retrospectively assessed the preoperative MRI features (qualitative analysis of morphology and dynamic enhancement features), and each lesion was assigned according to the LI-RADS. Preoperative clinical data were also evaluated. Logistic regression analyses were used to assess the relative value of these parameters as potential predictors of MVI. Recurrence-free survival (RFS) rates after hepatectomy in the two groups were estimated using Kaplan-Meier survival curves and compared using the log-rank test. RESULTS: The majority of cHCC-CCAs were categorized as LR-M. On multivariate analysis, a higher serum AFP level (OR, 0.523; 95% CI, 0.282-0.971; p = 0.040), intratumoral fat deposition (OR, 14.368; 95% CI, 2.749-75.098; p = 0.002), and irregular arterial peritumoral enhancement (OR, 0.322; 95% CI, 0.164-0.631; p = 0.001) were independent variables associated with the MVI of cHCC-CCA. After hepatectomy, patients with MVI of cHCC-CCA showed earlier recurrence than those without MVI (hazard ratio [HR], 0.402; 95% CI, 0.189-0.854, p = 0.013). CONCLUSION: A higher serum AFP level and irregular arterial peritumoral enhancement are potential predictive biomarkers for the MVI of cHCC-CCA, while intratumoral fat detected on MRI suggests a low risk of MVI. Furthermore, cHCC-CCAs with MVI may have worse surgical outcomes with regard to early recurrence than those without MVI. KEY POINTS: • Higher serum levels of AFP combined with irregular arterial peritumoral enhancement are independent risk factors for the MVI of cHCC-CCA, while fat deposition might be a protective factor. • cHCC-CCA with MVI may have a higher risk of early recurrence after surgery. • Most cHCC-CCAs were categorized as LR-M in this study, and no significant difference was found in MVI based on LI-RADS category.

3.
Mol Med Rep ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32468070

RESUMO

Mechanical allodynia, which develops in patients of diabetes mellitus as a neuropathic manifestation, remains without an effective treatment. The aim of the present study was to investigate the effects and potential mechanisms underlying resveratrol (RES) in a rat model of streptozocin (STZ)­induced diabetic mechanical allodynia (DMA). The rat model of DMA was established by the administration of an intraperitoneal injection of STZ. From day 8 post­STZ injection, rats were administered with an intragastric injection of various doses of RES for 14 consecutive days. The von Frey filaments were applied to detect the paw withdrawal threshold and evaluate the analgesic effects of RES. Based on the dose­effect curve, the ED50 of RES was calculated. Immunofluorescence staining and western blotting were performed to detect the expression of purinergic receptor P2X3 (P2X3R) in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH) following RESED50 treatment. The results indicated that RES significantly alleviated mechanical allodynia in DMA model rats in a dose­dependent manner. Compared with the control group, the expression of P2X3R in DRG neurons and SDH terminals was markedly decreased following the administration of RESED50 (P<0.05). Collectively, the results indicated that RES displayed a dose­dependent analgesic effect on DMA model rats. Furthermore, P2X3R expression downregulation in the DRG and SDH may be a mechanism underlying the analgesic effects of RES on DMA­related behaviors.

4.
Environ Toxicol ; 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32469461

RESUMO

Epithelial-to-mesenchymal transition (EMT) is key to invasion and metastasis by oral squamous carcinoma (OSCC) cells. MicroRNAs (miRNAs) such as miRNA-146a are known to be upregulated in OSCC. However, it is unclear whether they are involved in driving EMT. Here, we investigated the effect of miR-146a overexpression on proliferation, migration, and EMT in OSCC cells. OSCC cells were transfected with a plasmid expressing miR-146a precursor. Cell lines that stably overexpressed miRNA-146a were assessed for proliferation, colony formation, and invasiveness in vitro. Expression of markers and regulators of EMT, cell motility, and invasion were measured by qRT-PCR and western blot. Potential miRNA-146a binding sites in the 3'UTR of ST8SIA4 were identified by bioinformatic analysis. To confirm that miRNA-146a binds to and regulates ST8SIA4, we transfected OSCC cell lines with miRNA-146a mimics and a luciferase reporter construct containing either the wild type or mutant 3'UTR of ST8SIA4. OSCC cell lines that overexpressed miR-146a displayed higher proliferation, colony formation, invasion, and MMP-2 activity than cells transfected with a control vector. Overexpression of miR-146a also decreased expression of the epithelial cell marker E-cadherin and increased expression of Twist1, a transcription factor that promotes EMT, as well as markers associated with mesenchymal cells (vimentin and N-cadherin) and tumor invasion (p-paxillin and p-cortactin). Luciferase expression was lower in OSCC cells transfected with miRNA-146a mimics or with luciferase constructs carrying the wild type, but not mutant, 3'UTR of ST8SIA4. Overexpression of miR-146a promotes EMT phenotypes and may drive tumorigenesis and progression in OSCC, making it a useful target for future OSCC treatments.

5.
Antiviral Res ; 179: 104789, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32353383

RESUMO

Human adenoviruses (HAdVs) often cause mild respiratory infections. These infections, however, can potentially become fatal in immunosuppressive patients. Unfortunately, there has been no specific anti-HAdV drug approved for treatment of HAdV infections. In this study, a time-course transcriptome of HAdV-infected human lung epithelial cells (A549 cells) was performed and compared with perturbation datasets of 890 drug-treated A549 cells from the library of integrated network-based cellular signatures (LINCS) database to predict previously unknown therapeutic drug-HAdV relationships using a characteristic direction (CD) algorithm. We performed experiments to validate a prediction for the anti-diabetic drug rosiglitazone as a candidate drug for treatment of anti-HAdV both in vivo and in vitro. The Type I interferon (IFNs) signaling pathway was negatively regulated during the course of HAdV infection and rosiglitazone increased STAT1 phosphorylation for antiviral IFN response induction. Taken together, this study confirmed the prospect for re-exploitation of this FDA-approved drug as a potential therapeutic for HAdV infections.

6.
J Ethnopharmacol ; 258: 112932, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32376368

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) has been widely used as an approach worldwide. Chinese Medicines (CMs) had been used to treat and prevent viral infection pneumonia diseases for thousands of years and had accumulated a large number of clinical experiences and effective prescriptions. AIM OF THE STUDY: This research aimed to systematically excavate the classical prescriptions of Chinese Medicine (CM), which have been used to prevent and treat Pestilence (Wenbing, Wenyi, Shiyi or Yibing) for long history in China, to obtain the potential prescriptions and ingredients to alternatively treat COVID-19. MATERIALS AND METHODS: We developed the screening system based on data mining, molecular docking and network pharmacology. Data mining and association network were used to mine the high-frequency herbs and formulas from ancient prescriptions. Virtual screening for the effective components of high frequency CMs and compatibility Chinese Medicine was explored by a molecular docking approach. Furthermore, network pharmacology method was used to preliminarily uncover the molecule mechanism. RESULTS: 574 prescriptions were obtained from 96,606 classical prescriptions with the key words to treat "Warm diseases (Wenbing)", "Pestilence (Wenyi or Yibing)" or "Epidemic diseases (Shiyi)". Meanwhile, 40 kinds of CMs, 36 CMs-pairs, 6 triple-CMs-groups existed with high frequency among the 574 prescriptions. Additionally, the key targets of SARS-COV-2, namely 3CL hydrolase (Mpro) and angiotensin-converting enzyme 2(ACE2), were used to dock the main ingredients from the 40 kinds by the LigandFitDock method. A total of 66 compounds components with higher frequency were docked with the COVID-19 targets, which were distributed in 26 kinds of CMs, among which Gancao (Glycyrrhizae Radix Et Rhizoma), HuangQin (Scutellariae Radix), Dahuang (Rhei Radix Et Rhizome) and Chaihu (Bupleuri Radix) contain more potential compounds. Network pharmacology results showed that Gancao (Glycyrrhizae Radix Et Rhizoma) and HuangQin (Scutellariae Radix) CMs-pairs could also interact with the targets involving in immune and inflammation diseases. CONCLUSIONS: These results we obtained probably provided potential candidate CMs formulas or active ingredients to overcome COVID-19. Prospectively, animal experiment and rigorous clinic studies are needed to confirm the potential preventive and treat effect of these CMs and compounds.

7.
Prostate ; 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32449814

RESUMO

INTRODUCTION: Prostate smooth muscle contraction is critical for etiology and treatment of lower urinary tract symptoms in benign prostatic hyperplasia (BPH). Integrins connect the cytoskeleton to membranes and cells to extracellular matrix, what is essential for force generation in smooth muscle contraction. Integrins are composed of different subunits and may cooperate with integrin-linked kinase (ILK). Here, we examined effects of inhibitors for different integrin heterodimers and ILK on contraction of human prostate tissues. METHODS: Prostate tissues were obtained from radical prostatectomy. Integrins and ILK were detected by Western blot, real-time polymerase chain reaction (RT-PCR), and double fluorescence staining. Smooth muscle contractions of prostate strips were studied in an organ bath. Contractions were compared after application of solvent (controls), the ILK inhibitor Cpd22 (N-methyl-3-(1-(4-(piperazin-1-yl)phenyl)-5-(4'-(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-1H-pyrazol-3-yl)propanamide), the integrin α2ß1 inhibitor BTT-3033 (1-(4-fluorophenyl)-N-methyl-N-[4[[(phenylamino)carbonyl]amino]phenyl]-1H-pyrazole-4-sulfonamide), or the integrin α4ß1/α9ß1 inhibitor BOP (N-(benzenesulfonyl)- l-prolyl- l-O-(1-pyrrolidinylcarbonyl)tyrosine sodium salt). RESULTS: Western blot analyses of prostate tissues using antibodies raised against integrins α2b, α4, α9, ß1, and ILK revealed bands matching the expected sizes of corresponding antigens. Expression of integrins and ILK was confirmed by RT-PCR. Individual variations of expression levels occurred independently from divergent degree of BPH, reflected by different contents of prostate-specific antigen. Double fluorescence staining of prostate sections using antibodies raised against integrins α2 and ß1, or against ILK resulted in immunoreactivity colocalizing with calponin, suggesting localization in prostate smooth muscle cells. Electric field stimulation (EFS) induced frequency-dependent contractions, which were inhibited by Cpd22 (3 µM) and BTT-3033 (1 µM) (inhibition around 37% by Cpd22 and 46% by BTT-3033 at 32 Hz). The thromboxane A2 analog U46619-induced concentration-dependent contractions, which were inhibited by Cpd22 and BTT-3033 (around 67% by Cpd22 and 39% by BTT-3033 at 30 µM U46619). Endothelin-1 induced concentration-dependent contractions, which were not affected by Cpd22 or BTT-3033. Noradrenaline and the α1 -adrenergic agonists methoxamine and phenylephrine-induced concentration-dependent contractions, which were not or very slightly inhibited by Cpd22 and BTT-3033. BOP did not change EFS- or agonist-induced contraction. CONCLUSIONS: Integrin α2ß1 and ILK inhibitors inhibit neurogenic and thromboxane A2 -induced prostate smooth muscle contraction in human BPH. A role for these targets for prostate smooth muscle contraction may appear possible.

8.
Cells ; 9(5)2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32375403

RESUMO

Coordinated actions of Rab and Rho are necessary for numerous essential cellular processes ranging from vesicle budding to whole cell movement. How Rab and Rho are choreographed is poorly understood. Here, we report a protein complex comprised of kalirin, a Rho guanine nucleotide exchange factor (GEF) activating Rac1, and RabGEF transport protein particle (TRAPP). Kalirin was identified in a mass spectrometry analysis of proteins precipitated by trappc4 and detected on membranous organelles containing trappc4. Acute knockdown of kalirin did not affect trappc4, but significantly reduced overall and membrane-bound levels of trappc9, which specifies TRAPP toward activating Rab11. Trappc9 deficiency led to elevated expression of kalirin in neurons. Co-localization of kalirin and Rab11 occurred at a low frequency in NRK cells under steady state and was enhanced upon expressing an inactive Rab11 mutant to prohibit the dissociation of Rab11 from the kalirin-TRAPP complex. The small RNA-mediated depletion of kalirin diminished activities in cellular membranes for activating Rab11 and resulted in a shift in size of Rab11 positive structures from small to larger ones and tubulation of recycling endosomes. Our study suggests that kalirin and TRAPP form a dual GEF complex to choreograph actions of Rab11 and Rac1 at recycling endosomes.

9.
Cell Mol Biol Lett ; 25: 27, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32336973

RESUMO

Objective: MicroRNA dysregulation occurs in many human diseases, including atherosclerosis. Here, we examined the serum expression and clinical significance of miR-186-5p in patients with atherosclerosis, and explored its influence on vascular smooth muscle cell (VSMC) proliferation and migration. Methods: Blood samples were collected from 104 patients with asymptomatic atherosclerosis and 80 healthy controls. Quantitative real-time PCR was applied to measure the miR-186-5p level. An ROC curve was established to assess the discriminatory ability of the serum miR-186-5p level for identifying atherosclerosis from controls. CCK-8 and Transwell assays were used to evaluate the impact of miR-186-5p on cell behaviors. Results: Serum expression of miR-186-5p was significantly higher in atherosclerosis patients than in the control group. The serum miR-186-5p level showed a positive correlation with CIMT and could be used to distinguish atherosclerosis patients from healthy controls, with an area under the curve (AUC) score of 0.891. In VSMCs, overexpression of miR-186-5p significantly promoted cell proliferation and migration, while the opposite results were observed when miR-186-5p was downregulated. Conclusion: Overexpression of miR-186-5p has a certain diagnostic significance for atherosclerosis. Upregulation of miR-186-5p stimulates VSMC proliferation and migration. Therefore, it is a possible target for atherosclerosis interventions.

10.
Macromol Rapid Commun ; 41(10): e2000064, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32307760

RESUMO

Three-dimensional (3D) printing of poly(dimethylsiloxane) (PDMS) is realized with a two-state curing strategy, i.e., photocuring for additively manufacturing high-precision architectures followed by thermal cross-linking for high-performance objects, taking Sylgard-184 as an example. In the mixture of base and curing agent of Sylgard-184, the photocuring ingredient methacrylated PDMS is incorporated to form hybrid inks with not only high-efficiency UV curing ability but also moderate rheological properties for 3D printing. The inks are then used to additively manufacture high-precision architectures by UV-assisted direct ink writing. Various architectures such as lattices and honeycombs, channels that can be used as microfluidics, and pressure-proof pipes with a feature size of ≈100 µm, can be readily printed. Thereafter, thermal cross-linking at elevated temperature is conducted to obtain the 3D PDMS objects with comparable properties to Sylgard-184. The facile, universal two-stage approach to 3D printing of PDMS can facilitate the development of microfluidics, flexible electronics, soft robots, and so on.

11.
Mol Biol Evol ; 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32324877

RESUMO

Goats are one of the most widespread farmed animals across the world; however, their migration route to East Asia and local evolutionary history remain poorly understood. Here, we sequenced 27 ancient Chinese goat genomes dating from the Late Neolithic period to the Iron Age. We found close genetic affinities between ancient and modern Chinese goats, demonstrating their genetic continuity. We found that Chinese goats originated from the eastern regions around the Fertile Crescent, and we estimated that the ancestors of Chinese goats diverged from this population in the Chalcolithic period. Modern Chinese goats were divided into a northern and a southern group, coinciding with the most prominent climatic division in China, and two genes related to hair follicle development, FGF5 and EDA2R, were highly divergent between these populations. We identified a likely causal de novo deletion near FGF5 in northern Chinese goats that increased to high frequency over time, whereas EDA2R harbored standing variation dating to the Neolithic. Our findings add to our understanding of the genetic composition and local evolutionary process of Chinese goats.

12.
J Anim Sci ; 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32303739

RESUMO

Improving feed efficiency is a primary goal in poultry breeding strategies. Residual feed intake (RFI) in chickens typically calculated at growing period is a measure of feed efficiency that independent of level of production. The objective of this study was to evaluate phenotypic correlations of growth performance, carcass traits, meat quality, and blood variables with RFI in growing native chickens. A total of 1008 chickens were selected for the experiment to derive RFI. After the RFI measurement period of 42 d, the 25 chickens with low RFI values, 25 chickens with medium RFI values, and 25 chickens with high RFI values were selected. The RFI was significantly positively correlated with FCR and ADFI, while it was not significantly correlated with initial BW, final BW, ADG, and MBW0.75. The abdominal fat weight and yield of high RFI group were significantly greater than those of medium and low RFI group. And the abdominal fat yield was significantly positively correlated with RFI. Moreover, the plasma IGF-1 content of low RFI group was significantly greater than those of high and medium RFI groups. The plasma concentrations of ACTH, T3, and cortisol of high RFI birds were significantly greater than that of low RFI birds. RFI was significantly positively correlated with plasma concentrations of T3 and cortisol, while it was significantly negatively correlated with plasma concentration of IGF-1. In addition, the serum levels of GLU and TG of high RFI birds were significantly lower than that of low RFI birds. The serum LDL-C content of high RFI group was significantly greater than that of medium and low RFI groups, and it was significantly positively correlated with RFI. Our data suggested that selection of chickens with low RFI values may be beneficial to reduce fat deposition in native chickens without affecting meat quality. Circulating IGF-1, T3, cortisol, and LDL-C concentrations can be used as indirect selection indicators of feed efficiency in native chickens. The effect of IGF-1, T3, cortisol, and LDL-C on feed efficiency of native chickens should be carefully examined and validated in future breeding programs.

13.
Sci Total Environ ; 719: 137517, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32120112

RESUMO

Global climate change and decreases in available land are significant challenges that humans are currently facing. Alternative management approaches for sugarcane fields have great potential to help mitigate these problems in China. We hypothesized that soybean intercropping with reduced nitrogen input could increase crop productivity and reduce the carbon footprint (CF) of sugarcane fields in China. Therefore, a long-term field experiment from 2009 to 2017 in the Pearl River Delta of China was chosen to test this hypothesis. The results showed that the energy yields of sugarcane/soybean intercropping systems were 17.8%-39.4% higher than those of sugarcane monocropping systems. The energy yields of the same cropping systems using conventional and reduced N inputs (525 kg ha-1 and 300 kg ha-1) did not show a significant difference. Additionally, the CF values of the unit yield (CFY) for sugarcane/soybean intercropping were 3.2%-30.4% lower than those of the monocropping systems, showing the higher CF efficiency of the intercropping pattern, although the difference was not significant. The CF of the unit area (CFA) and the CFY of all the cropping patterns at the conventional N level were 19.5%-62.0% higher than that at the reduced N level, demonstrating that reducing the nitrogen input could significantly lower the CF of the sugarcane fields. In addition, the high N level cased negative effects in terms of increasing the crop productivity and reducing the CF of the soybean/sugarcane intercropping pattern. In conclusion, sugarcane/soybean intercropping with reduced N input improved crop productivity while lowering the CF of sugarcane fields in China. The sugarcane/soybean (1:2) intercropping with 300 kg N ha-1 system showed the best benefits in the Pearl River Delta of China. These advanced agricultural practices contributed to improved farmland use efficiency and clean production in an agricultural system.


Assuntos
Saccharum , Soja , Agricultura , Pegada de Carbono , China , Fertilizantes , Nitrogênio
14.
Brief Bioinform ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32112084

RESUMO

As an important type of proteins, intrinsically disordered proteins/regions (IDPs/IDRs) are related to many crucial biological functions. Accurate prediction of IDPs/IDRs is beneficial to the prediction of protein structures and functions. Most of the existing methods ignore the fully ordered proteins without IDRs during training and test processes. As a result, the corresponding predictors prefer to predict the fully ordered proteins as disordered proteins. Unfortunately, these methods were only evaluated on datasets consisting of disordered proteins without or with only a few fully ordered proteins, and therefore, this problem escapes the attention of the researchers. However, most of the newly sequenced proteins are fully ordered proteins in nature. These predictors fail to accurately predict the ordered and disordered proteins in real-world applications. In this regard, we propose a new method called RFPR-IDP trained with both fully ordered proteins and disordered proteins, which is constructed based on the combination of convolution neural network (CNN) and bidirectional long short-term memory (BiLSTM). The experimental results show that although the existing predictors perform well for predicting the disordered proteins, they tend to predict the fully ordered proteins as disordered proteins. In contrast, the RFPR-IDP predictor can correctly predict the fully ordered proteins and outperform the other 10 state-of-the-art methods when evaluated on a test dataset with both fully ordered proteins and disordered proteins. The web server and datasets of RFPR-IDP are freely available at http://bliulab.net/RFPR-IDP/server.

15.
Neurol India ; 68(1): 176-178, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32129273

RESUMO

Understanding the pathogenesis and the typical imaging features of carotid artery web, and accurately diagnosing the carotid artery web will help to implement targeted intervention for cryptogenic stroke and reduce the recurrence of stroke events. Carotid web (CW) can be defined as an endoluminal shelf-like projection often noted at the origin of the internal carotid artery just beyond the bifurcation. It is recognized as a possible cause of ischemic stroke in young adults. We describe here a case of ischemic stroke caused by a CW in a healthy man. Detection of this vascular abnormality required the use of computed tomography angiography. CW is a specific anatomical structure. Its imaging and clinical manifestations are different from atherosclerosis. It's also is a latent etiology to cryptogenic stroke. CW should be considered in patients with otherwise cryptogenic stroke, otherwise healthy patients presenting with stroke and without the typical risk factors for atherosclerotic carotid disease and stroke.

16.
Cells ; 9(2)2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32075111

RESUMO

MicroRNAs play key roles during ovary development, with emerging evidence suggesting that miR-202-5p is specifically expressed in female animal gonads. Granulosa cells (GCs) are somatic cells that are closely related to the development of female gametes in mammalian ovaries. However, the biological roles of miR-202-5p in GCs remain unknown. Here, we show that miR-202-5p is specifically expressed in GCs and accumulates in extracellular vesicles (EVs) from large growth follicles in goat ovaries. In vitro assays showed that miR-202-5p induced apoptosis and suppressed the proliferation of goat GCs. We further revealed that miR-202-5p is a functional miRNA that targets the transforming growth factor-beta type II receptor (TGFßR2). MiR-202-5p attenuated TGF-ß/SMAD signaling through the degradation of TGFßR2 at both the mRNA and protein level, decreasing p-SMAD3 levels in GCs. Moreover, we verified that steroidogenic factor 1 (SF1) is a transcriptional factor that binds to the promoters of miR-202 and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) through luciferase reporter and chromatin immunoprecipitation (ChIP) assays. That contributed to positive correlation between miR-202-5p and CYP19A1 expression and estradiol (E2) release. Furthermore, SF1 repressed TGFßR2 and p-SMAD3 levels in GCs through the transactivation of miR-202-5p. Taken together, these results suggest a mechanism by which miR-202-5p regulates canonical TGF-ß/SMAD signaling through targeting TGFßR2 in GCs. This provides insight into the transcriptional regulation of miR-202 and CYP19A1 during goat ovarian follicular development.

17.
Eur J Pharmacol ; 873: 172985, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32017934

RESUMO

Prostate smooth muscle contraction and prostate enlargement contribute to lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Recent evidence demonstrated that inhibitors for polo-like kinases (PLKs) inhibit smooth muscle contraction of human prostate tissues. However, their additive effects to α1-blockers, and effects on prostate growth are unknown. Here, we examined effects of a novel and highly selective PLK1 inhibitor, onvansertib on prostate smooth muscle contraction alone and in combination with α1-blockers, and on proliferation and viability of prostate stromal cells (WPMY-1). Prostate tissues were obtained from radical prostatectomy. Contractions were studied in an organ bath. Proliferation and viability were assessed by plate colony, EdU, and CCK-8 assay. Electric field stimulation (EFS)-induced contractions of human prostate tissues were inhibited to 34% by 100 nM and 1 µM onvansertib at 32 Hz, and to 48% and 47% by the α1-blockers tamsulosin and silodosin. Combination of onvansertib with tamsulosin or silodosin further reduced EFS-induced contractions in comparison to α1-blockers alone (59% and 61% respectively), and to onvansertib alone (68% for both). Noradrenaline-, phenylephrine-, methoxamine-, endothelin-1-, and ATP-induced contractions were inhibited by onvansertib (100 nM) to similar extent. Viability and proliferation of WPMY-1 cells were reduced in a concentration- and time-dependent manner (24-72 h, 10-100 nM). Onvansertib inhibits neurogenic, adrenergic, and endothelin-1- and ATP-induced contractions of human prostate smooth muscle, and proliferation of stromal cells. Contractions are reduced not more than 50% by α1-blockers. Combination of α1-blockers with onvansertib provides additive inhibition of prostate contractions.

18.
Mol Ther Nucleic Acids ; 19: 1123-1133, 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-32059338

RESUMO

Myasthenia gravis (MG) is an autoimmune disorder resulting from antibodies against the proteins at the neuromuscular junction. Emerging evidence indicates that long non-coding RNAs (lncRNAs), acting as competing endogenous RNAs (ceRNAs), are involved in various diseases. However, the regulatory mechanisms of ceRNAs underlying MG remain largely unknown. In this study, we constructed a lncRNA-mediated ceRNA network involved in MG using a multi-step computational strategy. Functional annotation analysis suggests that these lncRNAs may play crucial roles in the immunological mechanism underlying MG. Importantly, through manual literature mining, we found that lncRNA SNHG16 (small nucleolar RNA host gene 16), acting as a ceRNA, plays important roles in the immune processes. Further experiments showed that SNHG16 expression was upregulated in peripheral blood mononuclear cells (PBMCs) from MG patients compared to healthy controls. Luciferase reporter assays confirmed that SNHG16 is a target of the microRNA (miRNA) let-7c-5p. Subsequent experiments indicated that SNHG16 regulates the expression of the key MG gene interleukin (IL)-10 by sponging let-7c-5p in a ceRNA manner. Furthermore, functional assays showed that SNHG16 inhibits Jurkat cell apoptosis and promotes cell proliferation by sponging let-7c-5p. Our study will contribute to a deeper understanding of the regulatory mechanism of MG and will potentially provide new therapeutic targets for MG patients.

19.
Sci Total Environ ; 715: 136377, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32014759

RESUMO

The deammonification process is a promising and energy efficient nitrogen removal technology. Since deammonification process has succeeded in high-strength ammonia nitrogen wastewater treatment (sidestream deammonification) but its application in treating low-strength ammonium nitrogen wastewater (mainstream deammonification) remains a great challenge. In this study, mainstream deammonification process in two reactors maintained stability with hydrazine (N2H4) addition. The two reactors consisted of a deammonification granular reactor and a mixed ammonia oxidizing bacteria (AOB) flocculent with anaerobic ammonia oxidizing bacteria (AnAOB) granular reactor. Deammonification granular reactor had a more efficient total nitrogen removal efficiency (TNRE, 80.5 ± 5.8%) and nitrogen removal rate (NRR, 0.33 ± 0.04 g/(L·day)). The advantage of retain biomass in granular sludge reactor lead to a more balanced ex-situ activity between AOB (0.37 mg N/(g VSS·h)) and AnAOB (0.43 mg N/(g VSS·h)). Candidatus Brocadia and Nitraspira were detected the dominant genus responsible for the observed AnAOB and nitrite oxidizing bacteria (NOB), respectively. The more obvious effect of N2H4 on enhancing AnAOB and suppressing NOB both in ex-situ activity and genus abundances in mixed sludge reactor were also founded may due to loose spatial distribution among species.


Assuntos
Microbiota , Amônia , Compostos de Amônio , Reatores Biológicos , Hidrazinas , Nitritos , Nitrogênio , Oxirredução , Esgotos
20.
Genes (Basel) ; 11(2)2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32069836

RESUMO

The aim of the study was to understand the internal relationship between milk quality and lipid metabolism in cow mammary glands. A serial of studies was conducted to assess the molecular mechanism of PRL/microRNA-183/IRS1 (Insulin receptor substrate) pathway, which regulates milk fat metabolism in dairy cows. microRNA-183 (miR-183) was overexpressed and inhibited in cow mammary epithelial cells (CMECs), and its function was detected. The function of miR-183 in inhibiting milk fat metabolism was clarified by triglycerides (TAG), cholesterol and marker genes. There is a CpG island in the 5'-flanking promoter area of miR-183, which may inhibit the expression of miR-183 after methylation. Our results showed that prolactin (PRL) inhibited the expression of miR-183 by methylating the 5' terminal CpG island of miR-183. The upstream regulation of PRL on miR-183 was demonstrated, and construction of the lipid metabolism regulation network of microRNA-183 and target gene IRS1 was performed. These results reveal the molecular mechanism of PRL/miR-183/IRS1 pathway regulating milk fat metabolism in dairy cows, thus providing an experimental basis for the improvement of milk quality.

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