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1.
Mater Sci Eng C Mater Biol Appl ; 106: 110251, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753346

RESUMO

In this work, a versatile folic acid (FA) decorated reductive-responsive ε-poly-l-Lysine (ε-PL)-based microcapsules (FA-ε-PLMCs) were designed and facilely assembled by using sonochemical technique. Cellular uptake experiment of FA-ε-PLMCs loaded with Coumarin 6 (C6) as a model of hydrophobic drugs implied that hydrophobic drugs encapsulated inside FA-ε-PLMCs could be delivered selectively into Hela cells via folate-receptor (FR)-mediated endocytosis due to FA decorated on microcapsules. Furthermore, the shells of FA-ε-PLMCs cross-linked by disulfide bonds were derived from sulfhydryl groups (-SH) under ultrasonication. Under reductive environment, the hydrophobic drugs loaded in FA-ε-PLMCs would be easily released due to the cleavage of disulfide bonds. Benefiting from their suitable particle size, good loading capacity for hydrophobic drugs, remarkable targetability and reductive-triggered release, the obtained FA-ε-PLMCs could be a promising hydrophobic drugs carrier for the cancer treatment.

2.
J Cell Biochem ; 121(1): 609-620, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31353638

RESUMO

MicroRNAs (miRNAs) take part in a variety of biological processes by regulating target genes. Transforming growth factor ß receptor 1 (TGFBR1) and TGFBR2 are crucial members of the TGF-ß family and are serine/threonine kinase receptors. The aim of this study was to explore the functions of ssc-miR-204 in porcine preadipocyte differentiation and apoptosis with regard to the TGFß/Smad pathway. We identified miRNAs predicted to target TGFBR1 and TGFBR2 using a database and selected ssc-miR-204 as a candidate miRNA. ssc-miR-204 overexpression dramatically reduced the levels of TGFBR1 and TGFBR2. However, after transfection with ssc-miR-204 inhibitor, TGFBR1 and TGFBR2 levels were dramatically increased. ssc-miR-204 overexpression dramatically promoted porcine preadipocyte differentiation and apoptosis. After transfection with ssc-miR-204 inhibitor, porcine preadipocyte differentiation and apoptosis were dramatically inhibited. After transfection with ssc-miR-204 mimics, Smad2, Smad3, Smad4, p-Smad2, and p-Smad3 protein levels significantly decreased, and adipogenesis was regulated by inhibiting the TGF-ß/Smad3 signaling pathway. Taken together, these results verified that ssc-miR-204 regulates porcine preadipocyte differentiation and apoptosis by targeting TGFBR1 and TGFBR2.

3.
Chemosphere ; 238: 124650, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31472347

RESUMO

Arsenic (As) has become a major problem in maintaining the environment and human health due to its wide application in the production of agriculture and industry. Many studies indicate that As can affect spermatogenesis process and lower sperm quality. However, the undergoing molecular mechanism is unclear. For this, forty-eight 8-week old adult male mice were divided into four groups of twelve each, which were administrated to 0, 0.2, 2, 20 ppm As2O3 in their drinking water respectively for six months. The results showed that As treatment reduced sperm counts and increased the sperm malformation ratio of mice. Interestingly, both the amounts of round and elongated spermatids, and the ratios of spermatids elongation were decreased significantly by As exposure. Furthermore, the structure of Chromatoid Body (CB) which presents a typical nebulous shape in round spermatids after spermatogenesis arrested, and the mRNA expression levels of gene TDRD1, TDRD6 and TDRD7 related to CB were changed by arsenic. Again, the mRNA and protein expression levels of the markers DDX25 and CRM1 in haploid periods of spermatogenesis and the associated proteins HMG2, PGK2, and H4 with DDX25 regulation were declined significantly with As treatment. Taken together; it reveals that As interferes with spermatogenesis by disorganizing the elongation of spermatids. H4, HMG2 and PGK2 are regulated by DDX25 which interacts with CRM1 and may play a vital role in spermatogenesis disorder induced by As exposure, which maybe provides one of the underlying mechanisms for As-induced male reproductive toxicity.

4.
Chemosphere ; 240: 124937, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31574441

RESUMO

Nowadays, silica nanoparticles (SiNPs) as one of the most productive nano-powder, has been extensively applied in various filed. The potential harm of SiNPs has previously received severe attention. A bulk of researches have proven the adverse effect of SiNPs on the health of ecological organisms and human. However, neurotoxic impacts of SiNPs, still remain in the stage of exploration. The potential neurotoxic effects of SiNPs need to be further explored. And the toxic mechanism needs comprehensive clarification. Herein, the neurotoxicity of SiNPs of various concentrations (100, 300, 1000 µg/mL) on adult zebrafish was determined by behavioral phenotyping and confirmed by molecular biology techniques such as qPCR. Behavioral phenotype revealed observable effects of SiNPs on disturbing light/dark preference, dampening exploratory behavior, inhibiting memory capability. Furthermore, the relationship between neurotoxic symptom and the transcriptional alteration of autophagy- and parkinsonism-related genes was preliminarily assessed. Importantly, further investigations should be carried out to determine the effects of SiNPs to cause neurodegeneration in the brain as well as to decipher the specific neurotoxic mechanisms. In sum, this work comprehensively evaluated the neurotoxic effect of small-sized SiNPs on overall neurobehavioral profiles and indicated the potential for SiNPs to cause Parkinson's disease, which will provide a solid reference for the research on the neurotoxicity of SiNPs.

5.
Talanta ; 207: 120283, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594573

RESUMO

A flame photometric detector with a silicon photodiode assembly instead of a photomultiplier tube for sulfur detection was developed and evaluated. The photosensitive area of photodiode, the optical design, and band-pass filters, were optimized. It was found that the optimal photosensitive area of the photodiode was 100 (mm)2, and three focus lenses combined with a broad band-pass filter of 378/52 nm and a QB21 glass yielded the best result. This design fully utilized the wide emission spectrum of S2*, the response characteristics of silicon photodiode, and effective absorption of strong emission spectrums of OH* at wavelength around 310 nm by QB21 glass. The limits of detection for nine kinds of sulfur containing compounds were between 5.8 × 10-12 to 9.5 × 10-12 g s-1. This mode provided a linear response of 3 orders of magnitude for compounds being tested and a selectivity of sulfur over carbon of 105. It is demonstrated for the first time that the overall performance of the flame photometric detector integrated with a silicon photodiode assembly work at room temperature was comparable to a conventional detector coupled with a photomultiplier tube, with advantages of short equilibration time, robust to electromagnetic interference and vibration, and low cost. The new detector can find wide application in gas chromatography and on-line monitoring instruments for sulfur measurement.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31786832

RESUMO

BACKGROUND: In this study, we evaluated the diagnostic potential and clinical impact of an automated multiplex PCR platform (the FilmArray Respiratory Panel; FA-RP), specially designed for pathogen detection in respiratory tract infections in adults with unexplained pneumonia (UP). METHODS: A total of 112 UP patients in Shanghai, China, were enrolled prospectively and assessed using the FA-RP from October 2016 to March 2018. We examined the test results and their influence on clinical decisions. Furthermore, as a control group, we retrospectively obtained the clinical data of 70 UP patients between October 2014 and March 2016 (before the FA-RP was available). The two patient groups were compared with respect to factors, including general antimicrobial use and defined daily dose (DDD) numbers. RESULTS: Between October 2016 and March 2018, the positive rate obtained using FA-RP for UP was 76.8%. The primary pathogens in adults with UP were Influenza A/B (47.3%, 53/112). Compared with the patients before FA-RP was available, patients who underwent FA-RP testing had higher rates of antiviral drug use and antibiotic de-escalation during clinical treatment. FA-RP significantly decreased the total DDDs of antibiotic or antifungal drugs DDDs by 7 days after admission (10.6 ± 2.5 vs 14.1 ± 8.8, P < .01). CONCLUSIONS: The FA-RP is a rapid and sensitive nucleic acid amplification test method for UP diagnosis in adults. The application of FA-RP may lead to a more accurately targeted antimicrobial treatment and reduced use of antibiotic/antifungal drugs.

8.
Comput Methods Programs Biomed ; 184: 105106, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31670178

RESUMO

BACKGROUND AND OBJECTIVE: The process of nanoparticles (NPs) entering blood circulation to actively target tumor cells involves four stages-the transport of NPs in blood vessels, transvascular transport of NPs, transport of NPs in the tumor interstitial matrix and entry of NPs into tumor cells. These four stages are a complex process involving mechanical, physical, biochemical, and biophysical factors, the tumor microenvironment (TME) and properties of NPs play important roles in this process. Because this process involves a large number of factors and is very complex, it is difficult to study with conventional methods. METHODS: Using mathematical models for simulation is suitable for addressing this complex situation and can describe the complexity well. RESULTS: This work focuses on the theoretical simulation of NPs that target tumor cells to illustrate the effects of the abnormal microenvironment of tumors and properties of NPs on the transport process. Mathematical models constructed by different methods are enumerated. Through studying these mathematical models, different methods to overcome nanoparticle (NP) transport obstacles are illustrated. CONCLUSIONS: It is necessary to construct a theoretical model of active targeting nanodrug delivery under the coupling of micro-flow field and specific binding force field, and to simulate and analyze the delivery process at mesoscopic scale using computational fluid dynamics (CFD) method, so as to reveal the law and characteristics of drug delivery and cell uptake in the micro-environment of tumors in vivo. The methods and techniques discussed can serve as the basis for systematic studies of active targeting of functional nanoparticles to tumor cells.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31683467

RESUMO

OBJECTIVE: This study aimed to investigate the effects of dexmedetomidine on cerebral oxygen saturation [Sct(O2)] and postoperative cognitive function in elderly patients undergoing minimally invasive coronary artery bypass graft surgery. METHODS: Sixty elderly patients who received minimally invasive coronary artery bypass graft surgery were randomly equally divided into dexmedetomidine group (group D) and control group (group N). The patients in group D were pumped with 1 µg/kg dexmedetomidine for 15 min before incision, followed by continuous pumping at 0.3-0.5 µg/(kg·h) till the end of the operation. The patients in group N received same dose of normal saline during the operation. Sct(O2) was monitored at pre-induction (T0), post-induction (T1), 30 min (T2) after single-lung ventilation, and after surgery (T3). Mini-mental state examination (MMSE) was used to assess the cognitive function at 1 day before, 72 hour and 7 days after surgery. RESULTS: Sct(O2) level in group D was significantly higher than that in group N at T2 (P < 0.05). Sct(O2) level was statistically lower at T2 than that at T0, T1 and T3 in the same group N (P < 0.05). At 72 h and 7d after operation, the incidence of cognitive dysfunction in group D was markedly lower than that in group N (P < 0.05), the MMSE score in group D was markedly higher than those in group N, but was significantly lower than that before surgery (P < 0.05). CONCLUSION: Dexmedetomidine can alleviate the decrease of Sct(O2) during single-lung ventilation, improve postoperative cognitive function, and reduce the incidence of POCD in elderly patients with minimally invasive coronary artery bypass surgery.

10.
Opt Express ; 27(21): 29949-29961, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684250

RESUMO

Atomically thin layer transition metal dichalcogenides have been intensively investigated for their rich optical properties and potential applications on nano-electronics. In this work, we study the incoherent phonon and exciton population dynamics in monolayer WS2 by time-resolved Resonance Raman scattering spectroscopy. Upon excitation of the exciton transition, both Stokes and anti-Stokes scattering strength of the optical and the longitudinal acoustic two phonon modes exhibit large reduction. Based on the assumption of quasi-equilibrium distribution, the hidden phonon population dynamics is retrieved, which shows an instant build-up and a relaxation lifetime of ∼4 ps at the exciton density ∼1012cm-2. A phonon temperature rises of ∼20 K was identified due to the exciton excitation and relaxation. The exciton relaxation dynamics extracted from the transient vibrational Raman response shows strong excitation density dependence, signaling an important bi-molecular contribution to the decay. These results provide significant knowledge on the thermal dynamics after optical excitation, enhance the understanding of the fundamental exciton dynamics in two-dimensional transition metal materials, and demonstrate that time-resolved Resonance Raman scattering spectroscopy is a powerful method for exploring quasi-particle dynamics in optical materials.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31763754

RESUMO

Tiara[5]arenes (T[5]s), a new class of five-fold symmetric oligophenolic macrocycles, which are not accessible from the addition of formaldehyde to phenol, were synthesized for the first time. These pillar[5]arene-derived structures display both unique conformational freedom, differing from that of pillararenes, with a rich blend of solid-state conformations, and excellent host-guest interactions in solution. Finally we show how this novel macrocyclic scaffold can be functionalized in a variety of ways and used as functional crystalline materials to distinguish uniquely between benzene and cyclohexane.

12.
J Agric Food Chem ; 67(48): 13307-13317, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31679333

RESUMO

Epidemiological studies have demonstrated that hypercholesterolemia is associated with an elevated risk of atherosclerosis and cardiovascular diseases. In addition to the available cholesterol-lowering drugs, nutritionally balanced diets containing functional foods have attracted much interest as potential candidates to improve hypercholesterolemia. In the study, we demonstrated that dietary succinoglycan riclin effectively alleviated diet-induced hypercholesterolemia. Compared with the high-cholesterol-diet (HCD) group, the high-riclin group significantly decreased levels of the serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), and hepatic cholesterol (34, 40, and 51%, respectively), consequently improving hepatic steatosis and reducing proinflammatory cytokine expressions. 1H nuclear magnetic resonance (NMR)-based lipidomics and metabolomics analyses revealed that the riclin group partially reversed metabolic profile changes induced by the HCD, approaching that of the normal diet (ND) group. Riclin has no direct effects on cholesterol metabolism-related gene expression among the three HCD model groups. Basically, riclin increased the solution viscosity and interfered in the process of bile acid-cholesterol emulsification, decreasing cholesterol digestion and promoting cholesterol and bile acid excretion in the feces. These results suggested potential therapeutic utility of succinoglycan riclin as a food additive for people suffering from hypercholesterolemia and related diseases.

13.
BMC Infect Dis ; 19(1): 1006, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779590

RESUMO

BACKGROUND: Monocytes are the predominant innate immune cells at the early stage of Mycobacterium tuberculosis (M. tb) infection as the host defense against intracellular pathogens. Understanding the profile of different monocyte subpopulations and the dynamics of monocyte-related biomarkers may be useful for the diagnosis and prognosis of tuberculosis. METHODS: We enrolled 129 individuals comprising patients with pulmonary tuberculosis (PTB) (n = 39), tuberculous pleurisy (TBP) (n = 28), malignant pleural effusion (MPE) (n = 21), latent tuberculosis infection (LTBI) (n = 20), and healthy controls (HC) (n = 21). Surface expression of CD14, CD16, and CD163 on monocytes was detected using flow cytometry. In addition, soluble CD163 (sCD163) was determined by enzyme linked immunosorbent assay. RESULTS: Higher frequency of CD14+CD16+ (15.7% vs 7.8%, P < 0.0001) and CD14-CD16+ (5.3% vs 2.5%, P = 0.0011) monocytes and a decreased percentage of CD14+CD16- (51.0% vs 70.4%, P = 0.0110) cells was observed in PTB patients than in HCs. Moreover, PTB patients displayed a higher frequency of CD163+ cells in CD16+ monocytes than those in the HC group (40.4% vs 11.3%, P < 0.0001). The level of sCD163 was elevated in TBP patients and was higher in pleural effusion than in plasma (2116.0 ng/ml vs 1236.0 ng/ml, P < 0.0001). sCD163 levels in pleural effusion and plasma could be used to distinguish TBP from MPE patients (cut-off values: 1950.0 and 934.7 ng/ml, respectively; AUCs: 0.8418 and 0.8136, respectively). Importantly, plasma sCD163 levels in TBP patients decreased significantly after anti-TB treatment. CONCLUSIONS: Higher expression of membrane and soluble CD163 in active tuberculosis patients might provide insights regarding the pathogenesis of tuberculosis, and sCD163 may be a novel biomarker to distinguish TBP from MPE and to predict disease severity.

14.
J Fish Biol ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721203

RESUMO

In this study, we cloned the complementary (c)DNA sequences of tumour necrosis factor receptor (TNFR)-associated factor 3 (traf3) in Nile tilapia, Oreochromis niloticus. The expression patterns of the traf3 gene were investigated and preliminary functional analyses were performed. In healthy fish, traf3 transcript was broadly expressed in all examined tissues, with the highest expression level in the blood and the lowest in the liver. The traf3 gene reached its highest expression at 8 days post-fertilisation (dpf) during embryonic development. Moreover, we found that expression of traf3 was clearly altered following stimulation with Streptococcus agalactiae in vivo and that traf3 could be induced by lipopolysaccharides (LPS), Poly I: C and S. agalactiae WC1535 in Nile tilapia macrophages. Overexpression in 293T cells showed that Traf3 protein was mainly distributed in the cytoplasm and could significantly increase nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. Taken together, these results implied that traf3 could play important roles in the immune response to pathogen invasion.

15.
Int J Mol Med ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31746376

RESUMO

Ovarian cancer has a high rate of recurrence, with M2 macrophages having been found to be involved in its progression and metastasis. To examine the relationship between macrophages and ovarian cancer in the present study, M0 macrophages were stimulated with apoptotic SKOV3 cells and it was found that these macrophages promoted tumor proliferation and migration. Subsequently, the mRNAs and proteins expressed at high levels in these M2 macrophages were examined by RNA­Seq and quantitative proteomics, respectively, which revealed that M0 macrophages stimulated by apoptotic SKOV3 cells also expressed M2 markers, including CD206, interleukin­10, C­C motif chemokine ligand 22, aminopeptidase­N, disabled homolog 2, matrix metalloproteinase 1 and 5'­nucleotidase. The abundance of phosphorylated Erk1/2 in these macrophages was increased. The results indicate that apoptotic SKOV3 cells stimulate M0 macrophages to differentiate into M2 macrophages by activating the ERK pathway. These results suggest possible treatments for patients with ovarian cancer who undergo chemotherapy; inhibiting M2 macrophage differentiation during chemotherapy may reduce the rate of tumor recurrence.

16.
Exp Cell Res ; : 111742, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31759056

RESUMO

Protein kinase D (PKD) plays an important role in the development of cardiac hypertrophy induced by pressure overload. However, the mechanism involved is unclear. This study, using primary cardiomyocyte culture, PKD knockdown and overexpression, and other molecular techniques, tested our hypothesis that PKD pathway mediates cardiac hypertrophy by negatively regulating autophagy in cardiomyocyte. Neonatal cardiomyocytes were isolated from Wistar rats and cell hypertrophy was induced by norepinephrine treatment (PE, 10-4 mol/L), and divided into the following groups: (1) Vehicle; (2) PE; (3) PE + control siRNA; (4) PE + Rapamycin (100 nM); (5) PE + PKD-siRNA (2 × 108 U/0.1 ml); (6) PE + PKD siRNA + 3 MA (10 mM). The results showed that PE treatment induced cardiomyocyte hypertrophy, which were confirmed by cell size and biomarkers of cardiomyocyte hypertrophy including increased ANP and BNP mRNA. PKD knockdown or Rapamycin significantly inhibited PE-induced cardiomyocyte hypertrophy. In addition, PKD siRNA increased autophagy activity determined by electron microscopy, increased biomarkers of autophagy by Western blot, accompanied by down-regulated AKT/mTOR/S6K pathway. All the effects of PKD knockout were inhibited by co-treatment with 3-MA, an autophagy inhibitor. Oppositely, the autophagy in cardiomyocytes was inhibited by PKD overexpression. These results suggest that PKD participates in the development of cardiac hypertrophy by regulating autophagy via AKT/mTOR/S6K pathway.

17.
Acta Trop ; 202: 105253, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678234

RESUMO

This study aimed to investigate the effects of programmed cell death protein 10 (PCDP10) on the female reproductive system of Schistosoma japonicum, one of the major infectious agents of schistosomiasis. We found that PCDP10 was widely distributed in the integument, the worm parenchymal area, and the vitellarium of the female worm, but was localized to a lesser extent in the ovary and testicles. RNAi experiments successfully achieved gene knockdown, and the ultrastructural morphology of the adult reproductive organs was observed. The results demonstrated that, compared with those of the negative control group, the number of cortical granules around oocytes decreased and the number of immature oocyte cells increased. Fusion of yolk globules occurred, and the number and the diameter of yolk droplets decreased significantly. Real-time PCR showed that the expression of yolk glands reached its peak before ovulation and then decreased. The TUNEL assay results showed that apoptosis in the RNAi group was significantly higher than that in the negative control group. These results suggested that SjPCDP10 plays an important role in the female reproductive system. In conclusion, PCD10 is involved in oocyte growth and development, especially in eggshell formation, which may provide a reference for further elucidating the molecular mechanism of PCDP10 involved in egg formation and embryo development in Schistosoma japonicum.

18.
Front Immunol ; 10: 2430, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681314

RESUMO

Background: Previously, we have found that blockade of PD-1/PD-Ls pathway could enhance CD4+ T cells-mediated protective immunity in patients with active tuberculosis (ATB). However, the mechanism of PD-1/PD-Ls pathway involved in negative regulation of anti-TB immunity has been still unclear. Recently, the study of human immunodeficiency virus (HIV) infection demonstrated that PD-1 could induce the expression of basic leucine zipper ATF-like transcription factor (BATF) to inhibit CD8+ T cell function. While the mechanism of immune regulation of BATF in Mycobacterium tuberculosis (M. tb) infection has not yet been elucidated. Methods: We enrolled 104 participants including ATB patients (n = 66), latent tuberculosis infection (LTBI) (n = 16) and healthy control (HC) (n = 22). The expressions of BATF in peripheral blood CD4+ and CD8+ T cells from enrolled subjects were determined using flow cytometry. Intervention with PD-1/PD-Ls pathway was performed by using blocking antibodies or human PD-L1 fusion protein. Silencing BATF in peripheral blood mononuclear cells (PBMCs) by electroporation with siRNA. Real-time quantitative PCR, CFSE dilution assay and enzyme linked immunosorbent assay (ELISA) were employed to test T cell functions after BATF knockdown. Results: The percentages of BATF+CD4+ (P = 0.0003 and P < 0.0001, respectively) and BATF+CD8+ (P = 0.0003 and P = 0.0003, respectively) cells were significantly increased in ATB patients compared with LTBI and HC. BATF-expressing PD-1+ T cells in CD4+ and CD8+ T cells were much higher in ATB group than those in LTBI group (P = 0.0426 and 0.0104, respectively) and HC group (P = 0.0133 and 0.0340, respectively). There was a positive correlation between BATF expression and PD-1 expression in ATB patients (for CD4+ T cells, r = 0.6761, P = 0.0158; for CD8+ T cells, r = 0.6104, P = 0.0350). BATF knockdown could enhance IL-2 and IFN-γ secretions (P = 0.0485 and 0.0473, respectively) and CD4+ T cells proliferation (P = 0.0041) in vitro. Conclusions: In the context of tuberculosis, BATF mediates negative regulation of PD-1/PD-Ls pathway on T cell functions. BATF knockdown can improve cytokine secretion and cells proliferation in vitro.

19.
Math Biosci Eng ; 16(6): 6231-6241, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31698559

RESUMO

RNA modification plays an indispensable role in the regulation of organisms. RNA modification site prediction offers an insight into diverse cellular processing. Regarding different types of RNA modification site prediction, it is difficult to tell the most relevant feature combinations from a variant of RNA properties. Thereby, the performance of traditional machine learning based predictors relied on the skill of feature engineering. As a data-driven approach, deep learning can detect optimal feature patterns to represent input data. In this study, we developed a predictor for multiple types of RNA modifications method called DeepMRMP (Multiple Types RNA Modification Sites Predictor), which is based on the bidirectional Gated Recurrent Unit (BGRU) and transfer learning. DeepMRMP makes full use of multiple RNA site modification data and correlation among them to build predictor for different types of RNA modification sites. Through 10-fold cross-validation of the RNA sequences of H. sapiens, M. musculus and S. cerevisiae, DeepMRMP acted as a reliable computational tool for identifying N1-methyladenosine (m1A), pseudouridine (Ψ), 5-methylcytosine (m5C) modification sites.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31744785

RESUMO

OBJECTIVE: This study aimed to investigate the effect of long non-coding RNA (lncRNA) DLGAP1 antisense RNA 1 (DLGAP1-AS1) on vascular endothelial cell (VEC) injury via the phosphoinositide 3-kinase (PI3K)/Akt pathway in rat models of acute lower limb ischaemia-reperfusion (I/R). METHODS: Differentially expressed lncRNAs related to I/R were screened using the gene expression omnibus database. Acute lower limb I/R models were induced in male Wistar rats, in which the regulatory mechanisms of DLGAP1-AS1 silencing were analysed after the treatment of small interfering RNA (siRNA) against DLGAP1-AS1 or an inhibitor of the PI3K/Akt pathway. The relationship between DLGAP1-AS1 and the PI3K/Akt pathway was analysed. The levels of tumour necrosis factor (TNF)-α and vascular cell adhesion molecule-1 (VCAM-1), as well as malondialdehyde (MDA) concentration and creatine kinase (CK) activity, were measured. The number of circulating endothelial cells (CECs) and apoptosis of VECs were identified. RESULTS: Microarray based analysis indicated that DLGAP1-AS1 was highly expressed in I/R, which was further confirmed by detection of expression in rat models of acute lower limb I/R. Notably, the treatment of siRNA against DLGAP1-AS1 led to the activation of the PI3K/Akt pathway. In response to siRNA against DLGAP1-AS1, the levels of TNF-α and VCAM-1 were decreased, and MDA concentration and CK activity was downregulated. Reduced CEC numbers and suppressed VEC apoptosis were also observed. CONCLUSION: DLGAP1-AS1 silencing could further suppress the oxidative stress, exert an anti-apoptosis effect, and reduce inflammatory reaction, whereby VEC injury is alleviated by activation of the PI3K/Akt pathway in rats with acute lower limb I/R.

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