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1.
Toxicol Lett ; 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32234357

RESUMO

Traditional Chinese Medicines (TCMs)-containing aconitine are popular and indispensable home remedies in Asia for thousands of years due to its excellent pharmaceutical effects. Accumulating evidence has identified that repeated-dose of aconitine could cause polymorphic ventricular arrhythmias. However, underlying molecular mechanisms are still not fully understood. Hence, the present study firstly investigated the potential role of Notch1 signaling in aconitine-induced cardiotoxicity, aiming to elaborate possible molecular mechanisms involved in aconitine triggered ventricular arrhythmias. Our results showed that aconitine increased Notch1 signaling and downstream KDM5A expression in human and rat cardiomyocytes at non-detectable cytotoxic doses. Furthermore, aconitine promoted the formation of a new regulatory complex containing NICD and KDM5A in a CK2αHI regime, which then targeted to HCN4 promoter and induced re-expression of HCN4 in mature cardiomyocytes. Ultimately, HCN4-mediated If current contributed to aconitine-caused alterations in beating rate of rat cardiomyocytes. All changes aforementioned were significantly ameliorated by Notch1 inhibitor, suggesting that Notch1-mediated epigenetic regulation of HCN4 contributes to aconitine-induced ventricular myocardial dysrhythmia. Thus, our findings provide a novel toxic mechanism and position Notch1/NICD/KDM5A/HCN4 toxicity pathway as a potential target for the treatments of repeated-dose of medicine containing aconitine induced ventricular arrhythmias.

2.
Zhongguo Zhong Yao Za Zhi ; 45(1): 85-91, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237415

RESUMO

Polygonatum cyrtonema belongs to the plant family Liliaceae, and its dried rhizome is one of the sources of Chinese traditional medicine of Polygonati Rhizoma. It possesses the dual function as both medicine and food. Its main chemical components are polysaccharides and saponins. In order to understand the biosynthesis pathway of polysaccharides and diosgenin in P. cyrtonema, the corresponding transcriptomic data were obtained by extracting and sequencing the RNA of four parts of P. cyrtonema, namely, leaves, stems, rhizomes and roots. By adopting BGISEQ-500 sequencing platform, 42.03 Gb data were retrieved. Subsequently, the de novo assembly was carried out by Trinity software to obtain 137 233 transcripts, of which 68.13% of unigenes were annotated in seven databases including KEGG, GO, NR, NT, SwissProt, Pfam and KOG. Transcripts that may be involved in the biosynthesis of polysaccharides and diosgenin were analyzed by data mining. With help of qPCR, we validated expression data of four genes that were possibly involved in the biosynthesis of target metabolites. This experiment provides data for the study of biosynthetic pathways of P. cyrtonema secondary metabolites and the clarification of related structural gene functions.

3.
Neuroreport ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32168099

RESUMO

Postoperative cognitive dysfunction is a well-recognized complication after major surgery in the elderly, but its pathophysiological mechanism is not fully understood. In the present study, we used liquid chromatography-tandem mass spectrometry combined with tandem mass tags to identify differentially expressed proteins and perform further functional studies on protein of interest. Here, we showed that hippocampal complement C3 was significantly upregulated after surgery, which was accompanied by marked decreases in synaptic related proteins and density. In aged patients undergoing gastrointestinal surgery, we also found significantly increased plasma level of C3b postoperatively and were negatively associated with cognitive performance. Notably, selective inhibition of complement C3 by compstatin was able to rescue synaptic and cognitive impairments induced by surgery in aged mice. Collectively, our study confirms that surgery can induce cognitive impairments, and the possible mechanisms might be related to abnormal complement signaling and synaptic disruption.

4.
ACS Appl Mater Interfaces ; 12(12): 13698-13708, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32129070

RESUMO

Recent emerged metal-organic frameworks (MOFs), as superior drug carriers, provide novel strategies to combat pathogenic bacterial infections. Although various antibacterial metal ions can be easily introduced in MOFs for chemical bacterial ablation, such a single-model bactericidal method suffers from high-dose use, limited antibacterial efficiency, and slow sterilization rate. Hence, developing a dual bactericidal system is urgently required. Herein, we report an MOF/Ag-derived nanocomposite with efficient metal-ion-releasing capability and robust photo-to-thermal conversion effect for synergistic sterilization. The MOF-derived nanocarbon consisting of metallic zinc and a graphitic-like carbon framework is first synthesized, and then Ag nanoparticles (AgNPs) are evenly introduced via the displacement reaction between Zn and Ag+. Upon near-infrared irradiation, the fabricated nanoagents can generate massive heat to destroy bacterial membranes. Meanwhile, abundant Zn2+ and Ag+ ions are released to make chemical damage to bacterial intracellular substances. Systematic antibacterial experiments reveal that such dual-antibacterial effort can endow the nanoagents with nearly 100% bactericidal ratio for highly concentrated bacteria at a very low dosage (0.16 mg/mL). Furthermore, the nanoagents exhibit less cytotoxicity, which provides potential possibilities for the applications in the biological field. In vivo assessment indicates that the nanocomposites can realize rapid and safe wound sterilization and are expected to be an alternative to antibiotics. Overall, we present an easily fabricated structure-engineered nanocomposite with chemical and photothermal effects for broad-spectrum bacterial sterilization.

6.
Paediatr Anaesth ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32162448

RESUMO

BACKGROUND: A recent consensus statement in Europe has suggested that the fasting time for clear liquid in children can be shortened to 1 hour before a surgery. However, the study to show that 1-hour fasting time for clear fluids is safe in young children is still lacking. This study aimed to investigate the gastric emptying time for carbohydrate-rich drink and regular 5% glucose solution in children aged 3-7 years. METHODS: After overnight fasting, individuals were randomly assigned to ingest 5 mL kg-1 of either carbohydrate-rich drink or 5% glucose solution. One week later, the same subjects were asked to ingest the other one. Ultrasonography was performed to examine the gastric contents. Gastric antral cross-sectional area was measured, and the gastric fluid volume was calculated before and after fluid ingestion within 120 minutes. The primary outcome was the gastric emptying time for both the clear fluids calculated using the antral cross-sectional area and logarithms of gastric fluid volume. The degrees of thirst and hunger of two drinks were evaluated using a visual analogue scale as the secondary outcomes. RESULTS: Data from 16 individuals were analyzed. In the glucose solution group, the antral cross-sectional area and logarithms of gastric fluid volume returned to baseline at 30 minutes after ingestion. However, in the carbohydrate-rich drink group, the median [interquartile range; range] antral cross-sectional area (3.69 [2.64-5.15; 1.83-8.93] cm2 vs 2.41 [2.10-2.96; 1.81-4.37] cm2 , P < .001) and mean (95% confidence interval) logarithms of gastric fluid volume (2.54 [2.30-2.79] mL vs 2.12 [1.94-2.30] mL, P = .048) were still higher than at 60 minutes and returned to the baseline values at 90 minutes after ingestion, respectively. The degree of thirst was lower in the glucose solution group than that in the carbohydrate-rich drink group. CONCLUSIONS: Gastric emptying of carbohydrate-rich drink is slower than that of 5% glucose solution but the residual gastric fluid volume is low one hour after ingestion of 5 mL kg-1 of either fluid.

7.
Mol Plant ; 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32017998

RESUMO

Improved soybean cultivars have been adapted to grow at a wide range of latitudes, enabling expansion of cultivation worldwide. However, the genetic basis of this broad adaptation is still not clear. Here, we report the identification of GmPRR3b as a major flowering time regulatory gene that has been selected during domestication and genetic improvement for geographic expansion. Through a genome-wide association study of a diverse soybean landrace panel consisting of 279 accessions, we identified 16 candidate quantitative loci associated with flowering time and maturity time. The strongest signal resides in the known flowering gene E2, verifying the effectiveness of our approach. We detected strong signals associated with both flowering and maturity time in a genomic region containing GmPRR3b. Haplotype analysis revealed that GmPRR3bH6 is the major form of GmPRR3b that has been utilized during recent breeding of modern cultivars. mRNA profiling analysis showed that GmPRR3bH6 displays rhythmic and photoperiod-dependent expression and is preferentially induced under long-day conditions. Overexpression of GmPRR3bH6 increased main stem node number and yield, while knockout of GmPRR3bH6 using CRISPR/Cas9 technology delayed growth and the floral transition. GmPRR3bH6 appears to act as a transcriptional repressor of multiple predicted circadian clock genes, including GmCCA1a, which directly upregulates J/GmELF3a to modulate flowering time. The causal SNP (Chr12:5520945) likely endows GmPRR3bH6 a moderate but appropriate level of activity, leading to early flowering and vigorous growth traits preferentially selected during broad adaptation of landraces and improvement of cultivars.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32076794

RESUMO

Dendritic cell (DC) based immunotherapy is a promising approach to clinical cancer treatment. miRNAs are a class of small non-coding RNA molecules that bind to RNAs to mediate multiple events which are important in diverse biological processes. miRNA mimics and antagomirs may be potent agents to enhance DC-based immunotherapy against cancers. miRNA array analysis was used to identify a representative miR-5119 potentially regulating PD-L1 in DCs. We evaluated levels of ligands of immune cell inhibitory receptors (IRs) and miR-5119 in DCs from immunocompetent mouse breast tumor-bearing mice, and examined the molecular targets of miR-5119. We report that miRNA-5119 was downregulated in spleen DCs from mouse breast cancer-bearing mice. In silico analysis and qPCR data showed that miRNA-5119 targeted mRNAs encoding multiple negative immune regulatory molecules, including ligands of IRs such as PD-L1 and IDO2. DCs engineered to express a miR-5119 mimic downregulated PD-L1 and prevented T cell exhaustion in mice with breast cancer homografts. Moreover, miR-5119 mimic-engineered DCs effectively restored function to exhausted CD8+ T cells in vitro and in vivo, resulting in robust anti-tumor cell immune response, upregulated cytokine production, reduced T cell apoptosis, and exhaustion. Treatment of 4T1 breast tumor-bearing mice with miR-5119 mimic-engineered DC vaccine reduced T cell exhaustion and suppressed mouse breast tumor homograft growth. This study provides evidence supporting a novel therapeutic approach using miRNA-5119 mimic-engineered DC vaccines to regulate inhibitory receptors and enhance anti-tumor immune response in a mouse model of breast cancer. miRNA/DC-based immunotherapy has potential for advancement to the clinic as a new strategy for DC-based anti-breast cancer immunotherapy.

9.
Bioorg Med Chem Lett ; 30(7): 126996, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32033852

RESUMO

Bioactive oxazolopyridine unit was used in the synthesis of fluorescent markers for specific organelles in this paper. The compounds 1a-c are linked with double bond between oxazolopyridine ring and photogenic precursors (3a-c). Compound 1a showed higher fluorescence yield (0.86 in THF), compounds 1b-c showed larger stokes shifts in DMSO. In lipid vesicles environment, they also showed good optical properties. In addition, the three compounds are biomarkers with lower cytotoxicity. Among them, compound 1a based on oxazolopyridine and coumarin unit is a dual targetable fluorescent marker for mitochondria and lipid droplets; while the other two compounds 1b-c are only biomarkers for lipid droplets.

10.
Insect Sci ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32101381

RESUMO

Bumblebees play an important role in maintaining the balance of natural and agricultural ecosystems, and the characteristic gut microbiota of bumblebees exhibit significant mutualistic functions. China has the highest diversity of bumblebees; however, gut microbiota of Chinese bumblebees has mostly been investigated through culture-independent studies. Here, we analyzed the gut communities of bumblebees from Sichuan, Yunnan, and Shaanxi provinces in China through 16S rRNA amplicon sequencing and bacterial isolation. It revealed that the bumblebees examined in this study harbored two gut enterotypes as previously reported: one is dominated by Gilliamella and Snodgrassella, and the other is distinguished by prevalent environmental species. The gut compositions obviously varied among different individual bees. We then isolated 325 bacterial strains and the comparative genomic analysis of Gilliamella strains revealed that galactose and pectin digestion pathways were conserved in strains from bumblebees, while genes for the utilization of arabinose, mannose, xylose, and rhamnose were mostly lost. Only two strains from the Chinese bumblebees possess the multidrug resistant gene emrB, which is phylogenetically closely related to that from the symbionts of soil entomopathogenic nematode. In contrast, tetracycline-resistant genes were uniquely present in three strains from USA. Our results illustrate the prevalence of strain-level variations in the metabolic potentials and the distributions of antibiotic resistant genes in Chinese bumblebee gut bacteria. This article is protected by copyright. All rights reserved.

11.
Ultrasound Med Biol ; 46(5): 1169-1178, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32063394

RESUMO

This study was aimed at investigating the value of shear wave elastography (SWE) in quantitative evaluation of keloids. A total of 87 patients with 139 keloids were enrolled. Vancouver scar scale (VSS) scores were recorded. Thickness and blood flow grade were evaluated using high-frequency ultrasound. Skin stiffness (mean speed of shear wave, Cmean) was evaluated using SWE in both transverse and longitudinal sections. All measurements were performed in both keloids and site-matched unaffected skin (normal controls). The reliability of measurements was evaluated using intra- and inter-class correlation coefficients by two observers. Inter- and intra-observer repeatability was excellent (correlation coefficient > 0.99, p < 0.01). The SWE results revealed a significant increase in Cmean in keloids (p < 0.001) compared with the normal controls. Cmean in the longitudinal section was greater than that in the transverse section for keloids (p < 0.001). Cmean was highly positively correlated with VSS score (r = 0.904, p < 0.001), moderately positively correlated with thickness (r = 0.490, p < 0.001) and less positively correlated with blood flow (r = 0.231, p < 0.01). This non-invasive, tolerable and convenient imaging technique could be an effective tool for objectively evaluating keloid stiffness in the future, thus laying a foundation for the treatment and evaluation of keloids.

12.
Mol Ther ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32053770

RESUMO

Caspase-8, a well-characterized initiator of apoptosis, has also been found to play non-apoptotic roles in cells. In this study, we reveal that caspase-8 can induce cell death in a special way, which does not depend on activation of caspases and mitochondrial initiation. Instead, we prove that caspase-8 can cause lysosomal deacidification and thus lysosomal membrane permeabilization. V-ATPase is a multi-subunit proton pump that acidifies the lumen of lysosome. Our results demonstrate that caspase-8 can bind to the V0 domain of lysosomal Vacuolar H+-ATPase (V-ATPase), but not the V1 domain, to block the assembly of functional V-ATPase and alkalinize lysosomes. We further demonstrate that the C-terminal of caspase-8 is mainly responsible for the interaction with V-ATPase and can suffice to inhibit survival of cancer cells. Interestingly, regardless of the protein level, it is the expression rate of caspase-8 that is the major cause of cell death. Taken together, we identify a previously unrevealed caspase-8-mediated cell death pathway different form typical apoptosis, which could render caspase-8 a particular physiological function and may be potentially applied in treatments for apoptosis-resistant cancers.

13.
Sci Rep ; 10(1): 1375, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992783

RESUMO

The purpose of this study was to investigate the performance of high-frequency ultrasound (HFUS) and shear wave elastography (SWE) in the quantitative evaluation of therapeutic responses of keloids. 43 patients with 76 keloids were recruited into this study. In keloids and symmetrical sites, the skin thickness was measured using HFUS and skin stiffness expressed as elastic moduli (Young's modulus and shear wave velocity) was measured using SWE. The coefficient of variation values were calculated by using difference values of skin elastic moduli and skin thickness. A significant increase of both skin stiffness and thickness appeared in pre-treated keloids compared with post-treated keloids (P < 0.001) and normal controls (P < 0.001), respectively. Stiffness in post-treated keloids and normal skins was significantly different (P < 0.001), while the difference in thickness measurements showed no significance (P = 0.56, >0.05). The coefficient of variation of Young's modulus was the highest when compared between (i) pre-treated keloids and theirs site-matched areas; (ii) pre-treated and post-treated keloids. SWE, which showed greater ability in determining the extent of keloids recovery, may provide an ideal tool to assess the stiffness of keloids and theirs therapeutic response.

14.
Molecules ; 25(2)2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31941038

RESUMO

(1) Background: Flavonoids are the primary medicinal ingredient of Saussurea involucrate, which have significant antioxidant capacity. Optimizing the extraction of Saussurea involucrate flavonoids (SIFs) and exploring the ability to block melanin deposition caused by reactive oxygen can greatly promote the development of S. involucrate whitening products. (2) Methods: Ultrasonic extraction process was optimized using the Box-Behnken design (BBD) and response surface methodology (RSM). Then, the effect of SIFs on antioxidant activity and anti-deposition of melanin, and genes related to the melanin synthesis are studied. (3) Results: The optimal extraction procedures are as follows: the extraction time, ethanol content, and solvent ratio (v/w) are 64 min, 54%, and 54:1, respectively. The reducing activity and scavenging rates of 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion, hydroxyl radical, and ABTS+ were promoted as more S. involucrate flavonoid extract was added. The SIFs extract induced a decrease in the melanin synthesis by inhibiting the human melanoma A375 cell tyrosinase activity. SIFs also depress expression of melanin synthesis related genes. (4) Conclusions: the highest SIFs content was obtained by using 54% ethanol and 54:1 solvent ratio (v/w) for 64 min. The extract of SIFs exhibited good ability of antioxidant and anti-deposition of melanin in human melanocytes.

15.
J Insect Sci ; 20(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31927595

RESUMO

Bactrocera dorsalis (Hendel) is a notorious insect pest that attacks diverse vegetables and fruits worldwide. The sterile insect technique has been developed as an environmentally friendly and effective control method that depends on the mass production of target flies. Because dietary yeast (protein) and sucrose (carbohydrate) are important in adult diets, yeast:sucrose (Y:S) mixtures are crucial for the mass-rearing of B. dorsalis. In this study, we found adult diets with different ratios of yeast to sucrose-influenced fecundity, and an extremely high or low Y:S ratios significantly decreased egg production of B. dorsalis. Additionally, the maximum oviposition efficiency was realized at dietary yeast to sucrose ratios of 1:1 and 1:3, suggesting their potential use to produce more eggs for the mass production of B. dorsalis. Here, new gel diets having different yeast concentrations (g/L water) were also assessed for rearing B. dorsalis larvae. Gel diets containing 20 g/L yeast led to a higher pupation, pupal weight and adult eclosion rate, and a shorter developmental time than other yeast concentrations. Moreover, the present gel diet also resulted in greater pupal production and adult emergence rates than previously used liquid and solid artificial diets, revealing that it is suitable for rearing B. dorsalis larvae. This research provides a useful reference on artificial diets mixtures for mass rearing B. dorsalis, which is critical for employing the sterile insect technique.


Assuntos
Ração Animal/análise , Criação de Animais Domésticos/métodos , Oviposição , Tephritidae/fisiologia , Animais , Dieta , Feminino , Fertilidade/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/fisiologia , Masculino , Oviposição/efeitos dos fármacos , Pupa/efeitos dos fármacos , Pupa/crescimento & desenvolvimento , Pupa/fisiologia , Sacarose/administração & dosagem , Tephritidae/efeitos dos fármacos , Tephritidae/crescimento & desenvolvimento , Fermento Seco/administração & dosagem
16.
Nat Mater ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959952

RESUMO

Self-assembled monolayers (SAMs) are widely used to engineer the surface properties of metals. The relatively simple and versatile chemistry of metal-thiolate bonds makes thiolate SAMs the preferred option in a range of applications, yet fragility and a tendency to oxidize in air limit their long-term use. Here, we report the formation of thiol-free self-assembled mono- and bilayers of glycol ethers, which bind to the surface of coinage metals through the spontaneous chemisorption of glycol ether-functionalized fullerenes. As-prepared assemblies are bilayers presenting fullerene cages at both the substrate and ambient interface. Subsequent exposure to functionalized glycol ethers displaces the topmost layer of glycol ether-functionalized fullerenes, and the resulting assemblies expose functional groups to the ambient interface. These layers exhibit the key properties of thiolate SAMs, yet they are stable to ambient conditions for several weeks, as shown by the performance of tunnelling junctions formed from SAMs of alkyl-functionalized glycol ethers. Glycol ether-functionalized spiropyrans incorporated into mixed monolayers lead to reversible, light-driven conductance switching. Self-assemblies of glycol ethers are drop-in replacements for thiolate SAMs that retain all of their useful properties while avoiding the drawbacks of metal-thiolate bonds.

17.
Behav Brain Res ; 383: 112509, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-31987933

RESUMO

Systemic inflammation induces cognitive impairments via unclear mechanisms. Accumulating evidence has demonstrated that a subset of neurons that express parvalbumin (PV) play a critical role in regulation of cognitive and emotional behavior. Thus, the aim of the present study was to test whether disruption of PV interneuron mediates systemic inflammation-induced depression-like behavior and working memory impairment by lipopolysaccharide (LPS) challenge. Here we showed that LPS induces depression-like behavior and working memory impairment, coinciding with increased PV expression, enhanced GABAergic transmission, and impaired long-term potentiation (LTP) in the hippocampus. Notably, systemic administration of NMDA (N-methyl-D-aspartate) receptor (NMDAR) antagonist ketamine was able to interfere with PV expression and reverse depression-like behavior and working memory impairment, which is probably mediated by reversing impaired LTP. In addition, flumazenil, a competitive antagonist acting at the benzodiazepine binding site of the GABAA receptor, also ameliorated these abnormal behaviors. Collectively, our study added growing evidence to the limited studies that overinhibition mediated by PV interneurons might play a critical role in LPS-induced depression-like behavior and working memory impairment.

18.
Small ; 16(8): e1906005, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31971660

RESUMO

In this work, a phosphine-based covalent organic framework (Phos-COF-1) is successfully synthesized and employed as a template for the confined growth of broad-scope nanoparticles (NPs). Ascribed to the ordered distribution of phosphine coordination sites in the well-defined pores, various stable and well-dispersed ultrafine metal NPs including Pd, Pt, Au, and bimetallic PdAuNPs with narrow size distributions are successfully prepared as determined by transmission electron microscopy, X-ray photoelectron spectroscopy, inductively coupled plasma, and powder X-ray diffraction analyses. It is also demonstrated that the as-prepared Phos-COF-1-supported ultrafine NPs exhibit excellent catalytic activities and recyclability toward the Suzuki-Miyaura coupling reaction, reduction of nitro-phenol and 1-bromo-4-nitrobenzene, and even tandem coupling and reduction of p-nitroiodobenzene. This work will open many new possibilities for preparing COF-supported ultrafine NPs with good dispersity and stability for a broad range of applications.

19.
FEBS Open Bio ; 10(3): 351-361, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901223

RESUMO

Lung adenocarcinoma (LUAD) accounts for ~40% of lung cancer cases, and the 5-year relative survival rate is no more than 1%. Dysregulation of components of striatin-interacting phosphatase and kinase (STRIPAK) complexes is associated with various diseases, including cancer. Striatin-interacting protein 2 (STRIP2), also called Fam40b, has been reported to regulate tumor cell growth and migration. Here, we investigated the role of STRIP2 in LUAD growth, migration and the underlying mechanisms. Analysis of data from The Cancer Genome Atlas database revealed that STRIP2 is highly expressed and predicted poor outcomes in patients with LUAD. Moreover, quantitative RT-PCR (qRT-PCR) analysis revealed that the mRNA expression of STRIP2 is greater in all tested LUAD cells than in a normal lung cell line. To investigate the function of STRIP2, we overexpressed STRIP2 in SPC-A1 cells and depleted STRIP2 in Calu-3 cells. Cell proliferation was evaluated by Cell Counting Kit-8 and colony-forming assays, and Transwell assay was employed to test cell invasion and migration. Our results indicate that STRIP2 depletion suppressed cell proliferation, invasion and migration in Calu-3 cells, and overexpression of STRIP2 had the opposite effects in SPC-A1 cells. Moreover, we discovered that STRIP2 depletion reduced the protein levels of p-Akt and phosphorylated-mammalian target of rapamycin (p-mTOR) in Calu-3 cells, whereas STRIP2 overexpression increased levels of these proteins in SPC-A1 cells. Furthermore, we found that silencing of STRIP2 clearly enhanced protein levels of E-cadherin and reduced levels of N-cadherin, Vimentin and matrix metalloproteinase-9 in Calu-3 cells, whereas overexpression of STRIP2 had the opposite effect in SPC-A1 cells. Our data indicate that STRIP2 promotes the proliferation and motility of LUAD cells, and this may be mediated through the regulation of the Akt/mTOR pathway and epithelial-mesenchymal transition. These results may facilitate the development of therapeutic strategies to treat LUAD.

20.
J Neuroinflammation ; 17(1): 23, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31948437

RESUMO

BACKGROUND: Postoperative cognitive decline (POCD) is a recognized clinical phenomenon characterized by cognitive impairments in patients following anesthesia and surgery, yet its underlying mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity, learning, and memory via activation of TrkB-full length (TrkB-FL) receptors. It has been reported that an abnormal truncation of TrkB mediated by calpain results in dysregulation of BDNF/TrkB signaling and is associated with cognitive impairments in several neurodegenerative disorders. Calpains are Ca2+-dependent proteases, and overactivation of calpain is linked to neuronal death. Since one source of intracellular Ca2+ is N-methyl-d-aspartate receptors (NMDARs) related and the function of NMDARs can be regulated by neuroinflammation, we therefore hypothesized that dysregulation of BDNF/TrkB signaling mediated by NMDAR/Ca2+/calpain might be involved in the pathogenesis of POCD. METHODS: In the present study, 16-month-old C57BL/6 mice were subjected to exploratory laparotomy with isoflurane anesthesia to establish the POCD animal model. For the interventional study, mice were treated with either NMDAR antagonist memantine or calpain inhibitor MDL-28170. Behavioral tests were performed by open field, Y maze, and fear conditioning tests from 5 to 8 days post-surgery. The levels of Iba-1, GFAP, interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), NMDARs, calpain, BDNF, TrkB, bax, bcl-2, caspase-3, and dendritic spine density were determined in the hippocampus. RESULTS: Anesthesia and surgery-induced neuroinflammation overactivated NMDARs and then triggered overactivation of calpain, which subsequently led to the truncation of TrkB-FL, BDNF/TrkB signaling dysregulation, dendritic spine loss, and cell apoptosis, contributing to cognitive impairments in aging mice. These abnormities were prevented by memantine or MDL-28170 treatment. CONCLUSION: Collectively, our study supports the notion that NMDAR/Ca2+/calpain is mechanistically involved in anesthesia and surgery-induced BDNF/TrkB signaling disruption and cognitive impairments in aging mice, which provides one possible therapeutic target for POCD.

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