Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.571
Filtrar
1.
J Cell Physiol ; 235(1): 221-231, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31187497

RESUMO

The motility of mesenchymal stem cells (MSCs) is highly related to their homing in vivo, a critical issue in regenerative medicine. Our previous study indicated copper (Cu) might promote the recruitment of endogenous MSCs in canine esophagus defect model. In this study, we investigated the effect of Cu on the motility of bone marrow mesenchymal stem cells (BMSCs) and the underlying mechanism in vitro. Cu supplementation could enhance the motility of BMSCs, and upregulate the expression of hypoxia-inducible factor 1α (Hif1α) at the protein level, and upregulate the expression of rho family GTPase 3 (Rnd3) at messenger RNA and protein level. When Hif1α was silenced by small interfering RNA (siRNA), Cu-induced Rnd3 upregulation was blocked. When Rnd3 was silenced by siRNA, the motility of BMSCs was decreased with or without Cu supplementation, and Cu-induced cytoskeleton remodeling was neutralized. Furthermore, overexpression of Rnd3 also increased the motility of BMSCs and induced cytoskeleton remodeling. Overall, our results demonstrated that Cu enhanced BMSCs migration through, at least in part, cytoskeleton remodeling via Hif1α-dependent upregulation of Rnd3. This study provided an insight into the mechanism of the effect of Cu on the motility of BMSCs, and a theoretical foundation of applying Cu to improve the recruitment of BMSCs in tissue engineering and cytotherapy.

2.
Methods Mol Biol ; 2084: 269-282, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31729667

RESUMO

Untargeted lipidomics aims to comprehensively measure and characterize all lipid species in biological systems. Ion mobility-mass spectrometry (IM-MS) has showed a great potential for untargeted lipidomic analysis. Coupling with liquid chromatography and data-independent tandem MS techniques, acquired IM-MS data set contains four-dimensional information for lipid identification, including m/z of MS1 ion, retention time (RT), collision cross section (CCS), and MS/MS spectra. In this protocol, we introduced a data processing workflow using an integrative web server, namely, LipidIMMS Analyzer, to support accurate lipid identification. The protocol demonstrated the integration of all four dimensional information to achieve unambiguous identifications of lipids in complex biological samples.

3.
Chemosphere ; 238: 124603, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31442773

RESUMO

Environmental pollution is a risk factor for kidney dysfunction. However, the combined toxicity of air pollutants on kidney function is scarce. We estimated the relationship between combined toxicity of air pollutants and kidney function among adult women (n = 7071, 18-65 years old) in Mianyang City, Southwest China. We measured serum concentrations of uric acid, urea, creatinine, and cystatin C, and we calculated the individual estimated glomerular filtration rate (eGFR) using a cystatin C-based equation developed specifically for Chinese patients with CKD equation. Air pollution data were collected to calculate the individual average daily dose (ADD) of pollutants based on the air quality complex index (AQCI). Mean AQCI was higher in winter and lower in summer, and followed the monthly and seasonal trends of air pollutants. Concomitantly, individual ADD was also higher in winter and lower in summer, and the seasonal differences were reflected in the levels of kidney biomarkers (including uric acid, urea, creatinine, cystatin C, and eGFR). With an interquartile range (IQR: 1.04-1.50 m3/day/kg) increases of ADD, the serum concentrations of uric acid, urea, creatinine, and cystatin C increase [B (95%CI): 1.774 (0.318, 3.231) umol/L, 0.218 (0.1888, 0.247) mmol/L, 1.501 (1.016, 1.986) umol/L, and 0.006 (0.003, 0.009) mg/L, respectively], whereas eGFR decreases [B (95%CI): -0.776 (-1.106, -0.446) mL/min/1.73 m2]. Totally, the relationship between combined toxicity of air pollutants and kidney function in Chinese adult women suggests that the toxicity of combined air pollutants inversely affects kidney function, which might accelerate the risk of CKD.

4.
Anim Biotechnol ; : 1-9, 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31680615

RESUMO

Aquaporin 9 plays critical roles in aspects of energy homeostasis, metabolism, gluconeogenesis, fat synthesis and even the individual growth and development. So the Aquaporin 9 (AQP9) gene is a potential candidate gene for bovine growth traits. In this study, we detected the polymorphism of the bovine AQP9 gene including all exons by PCR-SSCP and DNA sequencing methods with six pairs of PCR primers in 555 individuals from three cattle breeds. Three novel SNPs (NC_007308:g.47575 C > T, 47615 C > T, 47690A > G) were detected using P6 primer. The linkage disequilibrium analysis indicated that the three SNPs were completely linked (r2 = 1), which constructed three genotypes (AA, AB, BB). The genotype AB was dominant in all three breeds. The frequencies of haplotype A and haplotype B were almost equivalent between each other. The individuals with genotype AB were significantly higher than those individuals with genotype BB in body weight (p < 0.01), chest circumference (p < 0.05) and rump length (p < 0.05). Moreover, individuals with genotype AA were significantly higher than those of individuals with genotype BB in body height (p < 0.01). These results suggested that the novel SNPs could be a perfect molecular marker for marker-assisted selection (MAS) breeding.

5.
Medicine (Baltimore) ; 98(44): e17519, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689753

RESUMO

BACKGROUND: Accumulated evidence has indicated the associations between single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) and the susceptibility to diabetes mellitus (DM), but the conclusions remain controversial. This study was to investigate the true contribution of miRNA SNPs to the risk of DM by using a meta-analysis of all the published studies. METHODS: Relevant studies were identified in the databases of PubMed and the Cochrane Library databases. The strength of associations between miRNA polymorphisms and DM risk was assessed by odds ratios (ORs) and 95% confidence intervals (95% CIs) under five genetic models using the STATA software. RESULTS: Six studies, containing 2773 cases and 2632 controls, were enrolled, 5 of which evaluated miR-146a (rs2910164), 4 for miR-27a (rs895819), and 3 for miR-124 (rs531564) and 2 for miR-375 (rs6715345), miR-128a (rs11888095), miR-194a (rs3820455). The meta-analysis indicated that the G allele or GG genotype of miR-146a rs2910164 was associated with a significantly increased risk for DM compared with C allele or GC/CC genotype in Latin American population; CC genotype of miR-27a rs895819 polymorphism was associated with a significantly decreased risk for DM in Asian population compared with the TT genotype; patients carrying with CC genotype of miR-124 rs531564 had a lower probability to develop DM regardless of ethnicity; no associations were identified between polymorphisms in miR-375, miR-128a, miR-194a and the susceptibility to DM. CONCLUSION: Our study suggests that miR-146a/miR-27a and miR-124 polymorphisms may be ethnicity-dependent or -independent susceptibility factors to DM, respectively.

6.
Cancer Sci ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31691433

RESUMO

Capn4, also known as CapnS1, is a member of the Calpain family, which plays a crucial role in maintaining the activity and function of calpain. We have previously reported that Capn4 also plays an essential role in the migration of nasopharyngeal carcinoma (NPC) cells through the regulation of matrix metalloproteinase 2 (MMP2) via nuclear factor-κB (NF-κB) activation. EBV latent membrane protein 1 (LMP1) is closely related to the malignant behaviors of NPC; however, the relationship between LMP1 and Capn4 in NPC remain unclear. Immunohistochemical studies showed that the level of LMP1 and Capn4 expression was high in both primary and metastatic NPC tissues, with a significantly positive correlation. We further found that LMP1 was able to up-regulate the Capn4 promoter in a dose-dependent manner through the CTAR1 and CTAR2 domains to activate AP-1. Moreover, we also found that LMP1 activated AP-1 through ERK/JNK phosphorylation. These findings indicate that Capn4 coordination with LMP1 promotes actin rearrangement and ultimately, cellular migration. These results reveal that Capn4 coordination with LMP1 enhances NPC migration via increasing actin rearrangement involving ERK/JNK/AP-1 signaling. Therapeutically, additional and more-specific LMP1 and Capn4 targeted inhibitors could be exploited to treat NPC.

7.
Opt Express ; 27(19): 26295-26306, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31674514

RESUMO

In this paper, by adaptively partitioning and precoding the subcarriers, we proposed a practical and effective entropy loading (EL) scheme for single sideband discrete multi-tone (SSB-DMT) systems. To reveal the practical performance, information bits per symbol (IBPS) is used to identify the optimal probabilistically shaped quadrature amplitude modulation (PS-QAM). Under the constraint of normalized generalized mutual information (NGMI) of the off-the-shelf forward error correction (FEC), we obtain the PS-QAMs that achieve the maximum IBPS using different constellations for different signal-to-noise ratio (SNR). Based on the result, we proposed two adaptively partitioning methods, equally partitioned precoding (EPP) and optimally partitioned precoding (OPP), to perform hybrid constellation entropy loading (HCEL). The HCEL with OPP significantly reduces the number of distribution matcher to 3 from generally several hundred of conventional EL with negligible loss of net data rate (NDR). As demonstrated by experiments, the HCEL with OPP achieves 4.4 dB receiver sensitivity gain compared to conventional bit and power loading, Levin-Campello (LC), and 1.2 dB receiver sensitivity gain compared to HCEL with EPP at the NDR of 60 Gb/s after 80 km standard single mode fiber transmission, making it a competitive and practical solution for EL in the short-to-medium reach transmission systems.

8.
Free Radic Biol Med ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31669348

RESUMO

Postmenopausal osteoporosis (OP) is one of the most common bone diseases that affects millions of aging women. Reduced osteogenesis and increased oxidative stress have been implicated in bone marrow mesenchymal stem cells (BMMSCs) derived from OP patients. Melatonin has shown positive effects on osteoblast differentiation and bone formation; however, it was unknown whether melatonin could restore OP-impaired osteogenic potential of BMMSCs and what the underlying mechanisms entailed. The objective of this study is to investigate (1) whether melatonin can restore the impaired osteogenic potential of OP BMMSCs by preserving their antioxidant functions, and if so, (2) whether intravenous administration of melatonin can prevent OP-induced bone loss in ovariectomized (OVX) rats. Ovariectomies were performed in female rats and BMMSCs were isolated from the osteoporotic rats 3 months later. In vitro treatment with melatonin successfully improved the osteogenic differentiation of OP BMMSCs, as evidenced by increased levels of matrix mineralization and osteoblast-specific genes. In melatonin-treated OP BMMSCs, intracellular oxidative stress was significantly attenuated, while levels of intracellular antioxidant enzymes were noticeably up-regulated - particularly superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPX1). Silent information regulator type 1 (SIRT1) was involved in the melatonin-mediated recovery of osteogenesis and antioxidant functions. Meanwhile, in vivo injections of melatonin via the tail vein successfully ameliorated the bone micro-architecture in ovariectomized rat femurs. Further experiments confirmed that BMMSCs derived from melatonin-treated OVX rats exerted well-preserved antioxidant properties and osteogenic potential. Our findings demonstrate that the administration of melatonin is a promising strategy for treating patients with postmenopausal OP by preserving the antioxidant properties and osteogenic potential of their BMMSCs.

9.
Med Sci Monit ; 25: 8297-8305, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31682593

RESUMO

BACKGROUND Obesity has become a global public health problem. Obesity increases the risk of several lethal diseases. This study aimed to assess whether the obesity susceptibility was associated with genetic variation in vitamin D receptor (VDR) gene by conducting a meta-analysis. MATERIAL AND METHODS PubMed, EMBASE and Cochrane Library databases were screened for all relevant articles published up to October 2018. The pooled odds ratios (OR) were calculated using STATA 13.0 software for 4 polymorphisms in the VDR gene (ApaI, BsmI, FokI and TaqI). RESULTS Seven case-control studies, including 1188 obese patients and 1657 healthy controls, were recruited. The pooled findings showed that there were no associations between obesity risk and the VDR polymorphisms in ApaI, BsmI and TaqI loci overall. However, VDR TaqI polymorphism was associated with the risk of obesity in Asian under homozygous [TT versus tt: odds ratio (OR)=0.26, 95% confidence interval (CI)=0.14-0.49; P<0.001], heterozygous (Tt versus tt: OR=0.34, 95% CI=0.18-0.64; P=0.001), and dominant (TT+Tt versus tt: OR=0.30, 95% CI=0.17-0.52; P<0.001) models; FokI variant was related with increased risk of obesity only under dominant model (FF+Ff versus ff: OR=1.54, 95% CI=1.15-2.06; P=0.004). CONCLUSIONS Our meta-analysis results suggest that the T allele of TaqI may have a protective effect, while the F allele of FokI is proposed as a risk factor related to obesity.

10.
Opt Express ; 27(21): 29916-29923, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684246

RESUMO

We demonstrate the transmission of a 30-GBd polarization-multiplexed probabilistically shaped 4096-ary quadrature amplitude modulation (QAM) signal over 50.9-km standard signal-mode fiber (SSMF), with a net single-carrier bit rate of 484.4 Gb/s carrying 16.1 information bits per symbol (a potential spectral efficiency of 15.9 bits/s/Hz when taking into account a 0.01 spectral roll-off). The signal is generated from 28-nm complementary metal-oxide-semiconductor (CMOS) digital-to-analog converters (DACs) with 8-bit nominal resolution and is received by an intradyne coherent receiver with a laser that has a linewidth of ∼1 kHz.

11.
J Virol ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666372

RESUMO

Follicular helper T (TFH) cells have been shown to support productive human immunodeficiency virus-1 (HIV-1) replication and to serve as a key component of the latent viral reservoir. However, the viral characteristics of this latent reservoir and the clinical relevance of this reservoir remain unclear. In this study, we assessed the tropic composition of latent viruses from peripheral TFH (pTFH), non-TFH memory and naïve CD4+ T cells from individuals with HIV-1-infections on suppressive combined antiretroviral therapy (cART). X4-tropic latent HIV-1 was preferentially enriched in pTFH cells compared to the other two subsets. Interestingly, the ratio of X4-tropic latent HIV-1 in pTFH cells was not only robustly and inversely correlated with blood CD4+ T cell counts across patients but was also prognostic of CD4+ T cell recovery in individuals on long-term cART. Moreover, patients with higher X4-tropic latent HIV-1 ratios in pTFH cells showed greater risks of opportunistic coinfections. These findings reveal the characteristics of latent HIV-1 in TFH cells and suggest that the ratio of X4-tropic latent HIV-1 in pTFH cells is a valuable indicator for disease progression and cART efficacy.Importance TFH cells have been shown to harbor a significant amount of latent HIV-1; however, the viral characteristics of this reservoir and its clinical relevance remain largely unknown. In this study, we demonstrate that X4-tropic latent HIV-1 is preferentially enriched in pTFH cells, which also accurately reflects the viral tropism shift. The ratio of X4-tropic proviruses in pTFH cells but not in other memory CD4+ T cell subsets is inversely and closely correlated with blood CD4+ T cell counts and CD4+ T cell recovery rates with cART. Our data suggest that the ratio of X4-tropic provirus in peripheral TFH cells can be easily measured and reflects disease progression and treatment outcomes during cART.

12.
Theranostics ; 9(24): 7325-7344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695771

RESUMO

Metastasis is one of the most threatening aspects of cervical cancer. We developed a method to intraoperatively map the primary tumor, metastasis and metastatic sentinel lymph nodes (SLNs), providing real-time intraoperative guidance in cervical cancer. Methods: TMTP1, a tumor metastasis targeting peptide, was employed to modify the indocyanine green (ICG)-loaded poly (ethylene glycol)- poly (lactic-co-glycolic acid) (PEG-PLGA) micelles. The cervical cancer subcutaneous tumor model and lung metastasis model were established to determine the active targeting of ICG-loaded TMTP1-PEG-PLGA micelles (ITM) for the primary tumor and occult metastasis of cervical cancer. Human cervical cancer HeLa cells engineered by firefly luciferase were injected into the right hocks of BALB/c nude mice to develop the SLN metastasis model. The ITM and control ICG-loaded PEG-PLGA micelles (IM) were injected into the right hind footpads in the SLN metastasis model, and the migration and retention of micelles were recorded under near-infrared fluorescence. K14-HPV16 transgenic mice were also used to detect the image capability of ITM to target cancerous lesions. Results: ITM could actively target imaging of the primary tumor and cervical cancer metastasis. ITM quickly diffused from the injection site to SLNs along lymphatic capillaries and remained in the SLNs for 12 h. Moreover, ITM specifically accumulated in the tumor metastatic SLNs (T-SLNs), which could be successfully distinguished from normal SLNs (N-SLNs). Conclusion: ITM could achieve active targeting of the primary tumor, metastasis and T-SLNs, providing precise and real-time intraoperative guidance for cervical cancer.

13.
Comput Biol Med ; 116: 103519, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31710870

RESUMO

BACKGROUND: Understanding the biomechanical effects of cervical disc degeneration (CDD) on the cervical spine is fundamental for understanding the mechanisms of spinal disorders and improving clinical treatment. While the biomechanical effects of CDD on segmental flexibility and the posterior facets have been reported, a clear understanding of the effect of the motion loading method on facet joint forces after CDD is still lacking. Therefore, the objective of this study was to determine the effect of the motion loading method on facet joint forces after CDD. METHODS: A three-dimensional nonlinear finite element (FE) model of the cervical spine (C3-C7) was developed and validated to represent normal conditions. This normal model was modified to create six degenerative models simulating mild, moderate, and severe grades of disc degeneration at C5-C6. While under a follower compressive preload (73.6 N), a 1-Nm moment was applied to all models to determine range of motion (ROM). A displacement load was applied to all degenerative models under the same follower load, making the C5-C6 degeneration segment motion same to the ROM of C5-C6 in normal model, and facet joint forces were computed. RESULTS: Compared with the normal model, ROM of the C5-C6 degenerative segments dramatically declined in all postures with increasing degenerative pathologies in the disc. The ROM in the adjacent normal segments of the degenerative segments also declined, with the exception of C4-C5 during extension. Under a 1-Nm moment load, there were not obvious changes in facet joint forces in the C5-C6 degenerative segment with increasing grades of degeneration, but facet joint forces in the adjacent normal segments did increase. Under a displacement load, the facet joint forces of the C5-C6 degenerative segment increased with increasing grades of degeneration. CONCLUSIONS: Facet joint forces were positively correlated with the ROM of the degenerative segment, demonstrating that the motion loading method had a significant effect on facet joint forces after CDD. Loading conditions must be strictly controlled in future finite element analysis studies to improve the comparability between models built by different units.

14.
Mol Plant ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31706032

RESUMO

Symbiotic microorganisms improve nutrient uptake by plants. To initiate mutualistic symbiosis with arbuscular mycorrhizal (AM) fungi, plants perceive Myc factors, including lipochitooligosaccharides (LCOs) and short-chain chitooligosaccharides (CO4/CO5), secreted by AM fungi. However, the molecular mechanism of Myc factors perception remains elusive. Here, we identified a heteromer of LysM receptor-like kinases, OsMYR1/OsLYK2 and OsCERK1, that mediates perception of AM fungi in rice. CO4 directly binds to OsMYR1, promoting the dimerization and phosphorylation of this receptor complex. Compared to control plants, Osmyr1 and Oscerk1 mutant rice plants are less sensitive to Myc factors and show decreased AM colonization. We engineered transgenic rice by expressing chimeric receptors that respectively replaced the ectodomains of OsMYR1 and OsCERK1 with those from the homologous Nod factor receptors MtNFP and MtLYK3 of Medicago truncatula. Transgenic plants displayed increased calcium oscillations in response to Nod factors compared to control rice. Our findings reveal a mechanism for mycorrhizal symbiotic signal perception in rice, and the ectopic expression of chimeric Nod/Myc receptors achieves a potentially important step towards generating cereals that host nitrogen-fixing bacteria.

15.
Int Immunopharmacol ; 77: 105911, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31671330

RESUMO

Liver fibrosis results from sustained liver injury and is characterized by inflammation, hepatic stellate cell (HSC) activation, extracellular matrix (ECM) accumulation and liver structure destruction. The Farnesoid-X receptor (FXR) antagonizes toxic liver injury and fibrosis, yet the mechanism in liver fibrosis remains unclear. We investigated the effects of FXR agonist obeticholic acid (OCA) on liver fibrosis in mice. Mice were injected with carbon tetrachloride (CCl4) for 3 weeks or 6 weeks to induce liver fibrosis. OCA (5 mg/kg) or PBS is administered daily during CCl4-treatment. At sacrifice, biochemical parameters and fibrosis were assessed. Pretreatment with OCA alleviated hepatic injury in 6 weeks group but not in 3 weeks group of CCl4 liver cirrhosis. At same time, pretreatment with OCA exhibit a dramatic protection of liver fibrosis in both 3 weeks group and 6 weeks group. Further experiments found that OCA pretreatment inhibited α-SMA expression and the activation of hepatic pSmad3 in 3 weeks group and 6 weeks group of CCl4-induced liver cirrhosis. Moreover, OCA activated FXR nuclear translocation and increased the interaction between liver FXR and pSmad3. This led to the discovery of a novel role for FXR in regulating fibrosis through interaction with pSmad3. Our data suggest that CCl4-induced liver fibrosis is protected by OCA through interaction between farnesoid X receptor and Smad3.

16.
J Inorg Biochem ; 203: 110909, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31689591

RESUMO

Glioma stem cells (GSCs) are thought to be responsible for the recurrence and invasion of glioblastoma multiform (GBM), which have been evaluated and exploited as the therapeutic target for GBM. Cyclometalated iridium(III) complexes have been demonstrated as the potential anticancer agents, however, their antitumor efficacies against GSCs are still unknown. Herein, we investigated the antitumor activity of two cyclometalated iridium(III) complexes [Ir(ppy)2L](PF6) (Ir1) and [Ir(thpy)2L](PF6) (Ir2) (ppy = 2-phenylpyridine, thpy = 2-(2-thienyl)pyridine and L = 4,4'-Bis(hydroxymethyl)-2,2'-bipyridine) against GSCs. The results clearly indicate that Ir1 and Ir2 kill GSCs selectively with IC50 values ranging from 5.26-9.05 µM. Further mechanism research display that Ir1 and Ir2 can suppress the proliferation of GSCs, penetrate into GSCs efficiently, localize to mitochondria, and induce mitochondria-mediated apoptosis, including the loss of mitochondrial membrane (MMP), elevation of intracellular reactive oxygen species (ROS) and caspases activation. Moreover, Ir1 and Ir2 can destroy the GSCs self-renewal and unlimited proliferation capacity by affecting the GSCs colony formation. According our knowledge, this is the first study to investigate the anti-GSCs properties of cyclometalated iridium(III) complexes.

17.
Sci Rep ; 9(1): 16205, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31700033

RESUMO

Angiotensin II type-1 receptor-neprilysin inhibitor (ARNi) is consisted of Angiotensin II type-1 receptor (AT1) antagonist and neprilysin (NEP) inhibitor, which could simultaneously increase the vasodilators of the natriuretic peptides and antagonize vasoconstrictors of Ang II. ARNi has been proved a superior effect and lower risks of death on chronic heart failure (CHF) and hypertension. In this paper, ARNi from Traditional Chinese Medicines (TCM) was discovered based on target combination of AT1 and NEP by virtual screening, biological assay and molecular dynamics (MD) simulations. Two customized strategies of combinatorial virtual screening were implemented to discover AT1 antagonist and NEP inhibitor based on pharmacophore modeling and docking computation respectively. Gyrophoric acid (PubChem CID: 135728) from Parmelia saxatilis was selected as AT1 antagonist and assayed with IC50 of 29.76 µM by calcium influx assay. And 3,5,3'-triiodothyronine (PubChem CID: 861) from Bos taurus domesticus was screened as NEP inhibitor and has a dose dependent inhibitory activity by biochemistry fluorescence assay. Combined with MD simulations, these compounds can generate interaction with the target, key interactive residues of ARG167, TRP84, and VAL108 in AT1, and HIS711 in NEP were also identified respectively. This study designs the combinatorial strategy to discover novel frames of ARNi from TCM, and gyrophoric acid and 3,5,3'-triiodothyronine could provide the clues and revelations of drug design and therapeutic method of CHF and hypertension for TCM clinical applications.

18.
Sci Total Environ ; 702: 135030, 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31715394

RESUMO

Trichloroethylene (TCE) has serious threat to ecosystem. Fe-Pd nanoparticles (NPs) are good materials for catalytic degradation of TCE but still face severe challenges including easy fouling, agglomeration, deactivation and difficult separation and reuse etc. To overcome these drawbacks, we have constructed a novel structured PVDF/Fe-Pd NPs composite membrane with nanosized surface pores to execute the TCE degradation. Results indicate the degradation shows pseudo first-order reaction kinetics and high degradation rate in the static state degradation. Furthermore, the degradation ability can be enhanced by increasing Fe and Pd contents, the degradation temperature or decreasing the degradation pH value. However, the degradation is essentially limited by the diffusion. Thus, the cross-flow degradation is further applied to promote the diffusion. By this operating model, the degradation ability of the composite membrane can be greatly improved. More importantly, the reactants always keep the purity in the membrane surface side and can be controlled to enter the membrane pore for catalytic degradation. Thus, products can be timely discharged via the membrane pores and the side reactions between reactants and products can be largely reduced. In addition, the nanosized surface pores can also prevent the Fe-Pd NPs from being fouled. In a word, the novel composite membrane shows strong degradation ability, good stability and convenient operating ability for the TEC catalytic degradation.

19.
Nat Neurosci ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719672

RESUMO

The importance of neuronal ensembles, termed engram cells, in storing and retrieving memory is increasingly being appreciated, but less is known about how these engram cells operate within neural circuits. Here we tagged engram cells in the ventral CA1 region of the hippocampus (vCA1) and the core of the nucleus accumbens (AcbC) during cocaine conditioned place preference (CPP) training and show that the vCA1 engram projects preferentially to the AcbC and that the engram circuit from the vCA1 to the AcbC mediates memory recall. Direct activation of the AcbC engram while suppressing the vCA1 engram is sufficient for cocaine CPP. The AcbC engram primarily consists of D1 medium spiny neurons, but not D2 medium spiny neurons. The preferential synaptic strengthening of the vCA1→AcbC engram circuit evoked by cocaine conditioning mediates the retrieval of cocaine CPP memory. Our data suggest that the vCA1 engram stores specific contextual information, while the AcbC D1 engram and its downstream network store both cocaine reward and associated contextual information, providing a potential mechanism by which cocaine CPP memory is stored.

20.
BMC Genomics ; 20(1): 856, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31726968

RESUMO

BACKGROUND: Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long ncRNAs (lncRNAs) and circular RNAs (circRNAs), accomplish remarkable variety of biological functions. However, the composition of ncRNAs and their interactions with coding RNAs in modulating and controlling of cellular process in plants is largely unknown. Using a diverse group of high-throughput sequencing strategies, the mRNA, miRNA, lncRNA and circRNA compositions of tobacco (Nicotiana tabacum) roots determined and their alteration and potential biological functions in response to topping treatment analyzed. RESULTS: A total of 688 miRNAs, 7423 non-redundant lncRNAs and 12,414 circRNAs were identified, among which, some selected differentially expressed RNAs were verified by quantitative real-time PCR. Using the differentially expressed RNAs, a co-expression network was established that included all four types of RNAs. The number of circRNAs identified were higher than that of miRNAs and lncRNAs, but only two circRNAs were present in the co-expression network. LncRNAs appear to be the most active ncRNAs based on their numbers presented in the co-expression network, but none of them seems to be an eTM (endogenous Target Mimicry) of miRNAs. Integrated with analyses of sequence interaction, several mRNA-circRNA-miRNA interaction networks with a potential role in the regulation of nicotine biosynthesis were uncovered, including a QS-circQS-miR6024 interaction network. In this network miR6024 was significantly down-regulated, while the expression levels of its two targets, circQS and its host gene QS, were sharply increased following the topping treatment. CONCLUSIONS: These results illustrated the transcriptomic profiles of tobacco roots, the organ responsible for nicotine biosynthesis. mRNAs always play the most important roles, while ncRNAs are also expressed extensively for topping treatment response, especially circRNAs are the most activated in the ncRNA pool. These studies also provided insights on the coordinated regulation module of coding and non-coding RNAs in a single plant biological sample. The findings reported here indicate that ncRNAs appear to form interaction complex for the regulation of stress response forming regulation networks with transcripts involved in nicotine biosynthesis in tobacco.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA