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1.
Redox Biol ; 36: 101596, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32506038

RESUMO

Experimental and molecular epidemiological studies indicate important roles for adipose tissue or high-fat diet (HFD) in tumor growth and metastasis. Gastric cancer (GC) possesses a metastatic predilection for the adipocyte-rich peritoneum. However, the precise molecular relevance of HFD in the peritoneal metastasis of GC remains unclear. Here, we showed that HFD causes obvious fat accumulation and promotes peritoneal dissemination of GC in vivo. Peritoneum-derived adipocytes induces robust lipid droplet (LD) accumulation and fatty acid oxidation in GC cells through transcriptional upregulation of DGAT2 in a C/EBPα-dependent manner and prevents anoikis during peritoneal dissemination. Treatment of GC cells with FAs or coculture with adipocytes induces intracellular formation of LDs and production of NADPH to overcome oxidative stress in vitro. Importantly, overexpression of DGAT2 was identified as an independent predictor of poor survival that promotes lung and peritoneal metastasis of GC, and genetic or pharmacological inhibition of DGAT2, via disruption of lipid droplet formation in a lipid-rich environment, enhances the sensitivity of GC to anoikis in vitro and inhibits peritoneal metastasis in vivo. Overall, our findings highlight the notion that DGAT2 may be a promising therapeutic target in GC with peritoneal implantation and provide some evidence for uncovering the link between obesity and tumor metastasis.

2.
Mol Genet Genomic Med ; : e1349, 2020 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-32537941

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) have been identified as crucial regulatory factors in the occurrence and progression of osteosarcoma. METHODS: Quantitative real-time polymerase chain reaction was used for detecting small nucleolar RNA host gene 4 (SNHG4) and miR-377-3p in osteosarcoma cells and tissues. Kaplan-Meier method was applied for evaluating the association between SNHG4 expression and the overall survival of osteosarcoma patients. CCK8, EdU, flow cytometry, and transwell assay were performed to examine the cell proliferation, apoptosis, cycle, and migration of osteosarcoma cells. RESULTS: In our study, we found that lncRNA SNHG4 was highly expressed in osteosarcoma tissues and cell lines. Additionally, the SNHG4 expression was related to distant metastasis, TNM stage, and survival of osteosarcoma patients. Through SNHG4 knockdown, the proliferation of osteosarcoma cells was considerably restrained and the cell apoptosis was induced in vivo and in vitro. Moreover, downregulated SNHG4 inhibited the cell migration and epithelial-mesenchymal transition in HOS and MG63 cells. In mechanism, we found that SNHG4 acts as a competing endogenous RNA to sponge miR-377-3p, which is downregulated in osteosarcoma. Our results showed that there is a negative correlation between SNHG4 and miR-377-3p expression in osteosarcoma patients. CONCLUSION: Taken together, SNHG4 promotes cell proliferation and migration by sponging miR-377-3p in osteosarcoma.

3.
Medicine (Baltimore) ; 99(23): e20657, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502053

RESUMO

INTRODUCTION: Pancreaticopleural fistula (PPF) is a rare but serious complication of pancreatic disorders. As the clinical presentations of PPF are often deceptive, it can cause a delay in the timely diagnosis and proper treatment. PPF is extremely uncommon in pediatric patients, and diagnostic and management strategies for PPF among pediatric patients are scanty. PATIENT CONCERNS: A 12-year-old girl presented with cough and dyspnea owing to massive right-side pleural effusion confirmed by Chest X-ray. Biochemical examination of pleural effusion revealed a significant elevation of amylase level. Imaging modalities showed dilated pancreatic duct and fistulous tract connecting pancreatic duct and right thorax. DIAGNOSIS: Chronic pancreatitis with PPF was diagnosed. INTERVENTIONS: Medical therapy was initially attempted for 2 weeks. Endoscopic therapy with naso-pancreatic drainage tube placement was then performed without any complications after failed medical therapy. OUTCOMES: The patient has remained healthy and symptom-free during 2 years of follow-up. CONCLUSION: When pediatric patients presented with recurrent pleural effusion with unknown etiology, PPF should be taken into consideration. Pleural effusion amylase level is the most important laboratory test and magnetic resonance cholangiopancreatography is recommended to visualize the fistula. Optimal management of PPF should be based on pancreatic duct morphology.


Assuntos
Drenagem/métodos , Fístula Pancreática/cirurgia , Fístula do Sistema Respiratório/cirurgia , Criança , Pré-Escolar , Colangiopancreatografia Retrógrada Endoscópica/métodos , Feminino , Humanos , Masculino , Fístula Pancreática/diagnóstico por imagem , Derrame Pleural/diagnóstico por imagem , Fístula do Sistema Respiratório/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
4.
Sci Rep ; 10(1): 8178, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32424168

RESUMO

Neonatal morbidities are associated with long term neurological deficits in life and have also been associated with dysbiosis. We tested whether optimizing the neonate's microbiome through maternal probiotic supplementation can improve offspring's neurodevelopmental outcomes. Maternal LB supplementation, carried out by giving Lactobacillus acidophilus and Bifidobacterium infantis (LB) to pregnant C57/BL6J mice daily from E16 to weaning, significantly suppressed postnatal peripheral proinflammatory insult-induced systemic inflammation and normalized compromised blood-brain barrier permeability and tight junction protein expression in the offspring at pre-weaned age. Maternal LB exposure also regulated markers associated with leukocyte transendothelial migration, extracellular matrix injury and neuroinflammation. The suppressed neuroinflammation by maternal LB supplementation was associated with reduced astrocyte/microglia activation and downregulation of the transcriptional regulators CEBPD and IκBα. Furthermore, maternal LB supplementation promoted neuronal and oligodendrocyte progenitor cell development. Our study demonstrates the efficacy of maternal LB supplementation in modulating systemic and central nervous system inflammation as well as promoting neural/oligodendrocyte progenitor development in the offspring. This evidence suggests that maternal probiotic supplementation may be a safe and effective strategy to improve neurological outcomes in the offspring.

5.
Genes Dev ; 34(11-12): 785-805, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32381627

RESUMO

Dysregulation of the DNA/RNA-binding protein FUS causes certain subtypes of ALS/FTD by largely unknown mechanisms. Recent evidence has shown that FUS toxic gain of function due either to mutations or to increased expression can disrupt critical cellular processes, including mitochondrial functions. Here, we demonstrate that in human cells overexpressing wild-type FUS or expressing mutant derivatives, the protein associates with multiple mRNAs, and these are enriched in mRNAs encoding mitochondrial respiratory chain components. Notably, this sequestration leads to reduced levels of the encoded proteins, which is sufficient to bring about disorganized mitochondrial networks, reduced aerobic respiration and increased reactive oxygen species. We further show that mutant FUS associates with mitochondria and with mRNAs encoded by the mitochondrial genome. Importantly, similar results were also observed in fibroblasts derived from ALS patients with FUS mutations. Finally, we demonstrate that FUS loss of function does not underlie the observed mitochondrial dysfunction, and also provides a mechanism for the preferential sequestration of the respiratory chain complex mRNAs by FUS that does not involve sequence-specific binding. Together, our data reveal that respiratory chain complex mRNA sequestration underlies the mitochondrial defects characteristic of ALS/FTD and contributes to the FUS toxic gain of function linked to this disease spectrum.

6.
Chemistry ; 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32307737

RESUMO

Organic-inorganic metal halide perovskites (most notably CH 3 NH 3 PbI 3 ) have demonstrated remarkable physical attributes for photovoltaic and diverse optoelectronic applications, whereas the concerns on toxicity of the lead (Pb) content in chemical composition still motivate further exploration of new nontoxic candidates. Lead-free halide double perovskites (HDPs), designed by the rational chemical substitution of Pb 2+ with other nontoxic candidate elements, are recently booming as fascinating alternative to Pb-based counterparts. Herein, we overview recent advances in crystal structures, physical properties and versatile optoelectronic applications of lead-free HDPs, such as solar cells, photodetectors, X-ray detectors and light-emitting diodes. Perspectives to improve physical and photoelectric properties of the existing HDP materials have also been discussed that will favor future development of new lead-free HDP candidates.

7.
Nanoscale ; 12(15): 8133-8138, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32236237

RESUMO

Self-assembling peptide matrixes are powerful platforms for encouraging tissue regeneration, but are usually formed within seconds and remain relatively static in both structure and function throughout their application. For the first time, we have shown that it is possible to extend the time it takes for peptide self-assembly so as to allow for the dynamic building of a self-assembled system over days, in the presence of an enzyme. Specifically, K5 and K10 sequences were conjugated, via a thrombin-specific cleavage domain NleTPR/SFL, to prevent the nanofiber formation and form stable nanoparticles composed of (RADA)4-GG-NleTPR/SFL-K5 and (RADA)4-GG-NleTPR/SFL-K10 that act as nucleation sites for reassembling. Upon introduction of thrombin, a model enzyme, this system showed an extremely slow rate of nanofiber formation in a parallel direction that is in sharp contrast to the well-known rapid assembly of (RADA)4 systems with random networks. These bioresponsive materials may provide a novel platform for utilizing long-term enzymatic profiles to form new nanofibers within an existing matrix over long therapeutic timeframes.

8.
J Immunol ; 204(8): 2021-2032, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32253270

RESUMO

Mast cells are tissue-resident immune cells that are involved in inflammation and fibrosis but also serve beneficial roles, including tissue maintenance, angiogenesis, pathogen clearance, and immunoregulation. Their multifaceted response and the ability of their mediators to target multiple organs and tissues means that mast cells play important roles in numerous conditions, including asthma, atopic dermatitis, drug sensitivities, ischemic heart disease, Alzheimer disease, arthritis, irritable bowel syndrome, infections (parasites, bacteria and viruses), and cancer. As a result, mast cells have become an important target for drug discovery and diagnostic research. Recent work has focused on applying novel nanotechnologies to explore cell biology. In this brief review, we will highlight the use of nanomaterials to modify mast cell functions and will discuss the potential of these technologies as research tools for understanding mast cell biology.

9.
Genetics ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32345615

RESUMO

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a devastating neurodegenerative disorder lacking effective treatments. ALS pathology is linked to mutations in more than twenty different genes indicating a complex underlying genetic architecture that is effectively unknown. Here, in an attempt to identify genes and pathways for potential therapeutic intervention and explore the genetic circuitry underlying Drosophila models of ALS, we carry out two independent genome-wide screens for modifiers of degenerative phenotypes associated with the expression of transgenic constructs carrying familial ALS (fALS)-causing alleles of FUS (hFUSR521C) and TDP-43 (hTDP-43M337V). We uncover a complex array of genes affecting either - or both - of the two strains and investigate their activities in additional ALS models. Our studies indicate the pathway that governs Phospholipase D (PLD) activity as a major modifier of ALS-related phenotypes, a notion supported by data we generated in mice and others collected in humans.

11.
Medicine (Baltimore) ; 99(17): e19890, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332662

RESUMO

RATIONALE: Dabigatran is an anticoagulant medication that has been widely used to prevent strokes caused by atrial fibrillation, deep vein thrombosis, and pulmonary embolism. However, the potential adverse effect of dabigatran of gastrointestinal mucosal injury is often neglected, and even induces esophagitis. PATIENT CONCERNS: A 77-year-old woman was admitted to the hospital with symptoms of progressive retrosternal pain, upper abdominal discomfort, and dysphagia. DIAGNOSIS: Esophagogastroduodenoscopy showed longitudinal sloughing mucosal casts in the distal esophagus. Histological examination showed squamous epithelium with neutrophil infiltration, partial epithelial degeneration, and Helicobacter pylori. Based on a literature review, medical history, and imaging examination, the patient was diagnosed with dabigatran-induced esophagitis. INTERVENTIONS: The patient recovered with standard H. pylori eradication therapy and proton pump inhibitor without discontinuing dabigatran. OUTCOMES: After 2 weeks, the retrosternal pain and dysphagia were relieved and upper abdominal discomfort was attenuated. LESSONS: Our case highlights the importance of physicians' awareness of the clinical and endoscopic characteristics of dabigatran-induced esophagitis and the importance of H. pylori-associated tests and eradication if necessary for patients with long-term dabigatran treatment.


Assuntos
Dabigatrana/efeitos adversos , Esofagite/etiologia , Dor Abdominal/tratamento farmacológico , Dor Abdominal/fisiopatologia , Idoso , Antitrombinas/efeitos adversos , Antitrombinas/uso terapêutico , Dabigatrana/uso terapêutico , Transtornos de Deglutição/tratamento farmacológico , Transtornos de Deglutição/fisiopatologia , Endoscopia do Sistema Digestório/métodos , Esofagite/fisiopatologia , Feminino , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/patogenicidade , Humanos
12.
J Sep Sci ; 43(11): 2172-2179, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32130755

RESUMO

The present work reported a novel hydrophilic and selective solid-phase microextraction fiber by improved multiple co-polymerization method immobilization of tetracycline molecularly imprinted polymer on a stainless steel wire and directly coupled with high-performance liquid chromatography for sensitive determination of trace tetracyclines residues in animal derived foods. The developed molecularly imprinted polymer coated solid-phase microextraction fibers were characterized through scanning electron microscopy, Fourier transfer infrared spectroscopy, thermogravimetric analysis, and adsorption experiments, the fiber with cross-linked and porous structure was observed and high thermal and chemical stability. The maximum adsorption capacity of this fiber with good selectivity reached 2.35 µg/mg in aqueous matrices, and showed good repeatability (relative standard deviation ≤ 6.6%, n = 5) and satisfying reproducibility between fiber to fiber (relative standard deviation ≤ 7.8%, n = 5). Under the optimized solid-phase microextraction conditions, satisfactory linearity (5-1000 µg/L) and detection limits (0.38-0.72 µg/kg, S/N = 3) for all the tetracyclines were obtained. The practicality of this method was proved by adding tetracycline, oxytetracycline at three levels to milk, chicken, and fish samples with good recoveries of 77.3-104.4%.

14.
Environ Pollut ; 262: 114289, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32179217

RESUMO

Rice is a main source of dietary cadmium (Cd), thus, how to reduce the Cd concentration in brown rice has received extensive attention worldwide. In three acidic paddy soils slightly to moderately contaminated with Cd, a series of field experiments were conducted to evaluate the effects of different proportions of nitrogen-phosphorus-potassium (N-P-K) fertilizer (urea, calcium magnesium phosphate, and potassium carbonate, respectively) alone or coupled with a topdressing of manganese (Mn) fertilizer at the tillering stage on reducing Cd bioavailability in soil and uptake in rice. The rational application of N-P-K fertilizer not only provided the basic nutrients to promote the normal growth of rice but also increased soil pH and thereby reduced the Cd bioavailability in soil. The Mg(NO3)2-extracted Cd concentrations in the three soils were reduced by 26.46-56.53%, while TCLP-extracted Cd were reduced by 19.87-45.41%, with little influence on soil cation exchange capacity (CEC) and organic matter (OM). The application of Mn fertilizer at the tillering stage increased Mn and Cd sequestration in the iron plaque. The Mn content in iron plaque increased by 15.71-58.67% and a significant positive correlation between Cd and Mn was observed at the three sites. Collectively, this combined method of fertilization significantly reduced Cd accumulation in rice tissues, the Cd concentrations in roots of treated plants decreased by 11.18-37.78%, whereas the concentrations in straw decreased by 13.16-41.03%. Particularly to brown rice, in which accumulation decreased by 25.19-44.70%, 37.35-47.84%, and 38.00-60.88% in three typical paddy fields, but no significant effect was observed for the Cd translocation factors (TF) among rice tissues. Thus, the basal application of combined urea and alkaline inorganic fertilizers followed by topdressing of Mn fertilizer may be a promising and cost-effective tactics for the remediation of Cd-contaminated paddy soils.

15.
EBioMedicine ; 52: 102638, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014820

RESUMO

BACKGROUND: To improve the early diagnosis of hepatocellular carcinoma (HCC), more effective diagnostic biomarkers are needed. A combination of biomarkers is reported to distinguish individuals with early-stage HCC from at-risk individuals. METHODS: Participants in this study were recruited from six hospitals in China. Literature review was used to choose 19 candidate proteins, a case-control study in the discovery stage was used to identify five proteins (P5) that constituted a diagnostic model. In the training and validation stages, the effectiveness of P5 for detecting early-stage HCC was tested (cross-sectional study). Finally, a nested case-control study independent of the other stages was set up to evaluate the P5 in the preclinical diagnosis of HCC. FINDINGS: Between February 2013 and June 2017, a total of 1396 participants were recruited. A panel of 5 proteins (P5: OPN, GDF15, NSE, TRAP5 and OPG) showed high diagnostic accuracy when differentiating the early-stage HCC from the at-risk group, with AUCs of 0·892, 0·907 and 0·852 for the training stage, validation cohort 1 and cohort 2 data sets, respectively. In the prediction set, the sensitivity of P5 for diagnosing preclinical HCC increased with time, starting from 12 months before to the time of definitive clinical diagnosis (range, 46·15% to 86·67%). INTERPRETATION: The P5 panel has the potential to screen populations at high risk of developing HCC and can enable the early diagnosis of HCC. FUNDING: Research supported by grants from eight funds. All sources of funding were declared at the end of the text.

16.
Biomaterials ; 241: 119904, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32109705

RESUMO

Specific selectivity of vascular cells and antithrombogenicity are crucial factors for the long-term success of vascular implants. In this work, a novel concept of mussel-inspired "built-up" surface chemistry realized by sequential stacking of a copper-dopamine network basement, followed by a polydopamine layer is introduced to facilitate the combination of nitric oxide (NO) catalysis and vascular cell selectivity. The resultant "built-up" film allowed easy manipulation of the content of copper ions and the density of catechol/quinone groups, facilitating the multifunctional surface engineering of vascular devices. For example, the chelated copper ions in the copper-dopamine network endow a functionalized vascular stent with a durable release of NO via catalytic decomposition of endogenous S-nitrosothiol. Meanwhile, the catechol/quinone groups on the film surface allow the facile, secondary grafting of the REDV peptide to develop a selectivity for vascular cells, as a supplement to the functions of NO. As a result, the functionalized vascular stent perfectly combines the functions of NO and REDV, showing excellent antithrombotic properties and competitive selectivity toward the endothelial cells over the smooth muscle cells, hence impressively promotes re-endothelialization and improves anti-restenosis in vivo. Therefore, the first mussel-inspired "built-up" surface chemistry can be a promising candidate for the engineering of multifunctional surfaces.

17.
Cell Biol Int ; 44(4): 1009-1019, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31889385

RESUMO

Heart failure preceded by pathological cardiac hypertrophy is a leading cause of death. Long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) was reported to inhibit cardiomyocytes apoptosis, but the role and underlying mechanism of SNHG1 in pathological cardiac hypertrophy have not yet been understood. This study was designed to investigate the role and molecular mechanism of SNHG1 in regulating cardiac hypertrophy. We found that SNHG1 was upregulated during cardiac hypertrophy both in vivo (transverse aortic constriction treatment) and in vitro (phenylephrine [PE] treatment). SNHG1 overexpression attenuated the cardiomyocytes hypertrophy induced by PE, while SNHG1 inhibition promoted hypertrophic response of cardiomyocytes. Furthermore, SNHG1 and high-mobility group AT-hook 1 (HMGA1) were confirmed to be targets of miR-15a-5p. SNHG1 promoted HMGA1 expression by sponging miR-15a-5p, eventually attenuating cardiomyocytes hypertrophy. There data revealed a novel protective mechanism of SNHG1 in cardiomyocytes hypertrophy. Thus, targeting of SNHG1-related pathway may be therapeutically harnessed to treat cardiac hypertrophy.

18.
Autophagy ; 16(2): 271-288, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31007149

RESUMO

A switch from autophagy to apoptosis is implicated in chondrocytes during the osteoarthritis (OA) progression with currently unknown mechanism(s). In this study we utilized a flow fluid shear stress (FFSS) model in cultured chondrocytes and a unilateral anterior crossbite (UAC) animal model. We found that both FFSS and UAC actively induced endoplasmic reticulum stress (ERS) in the temporomandibular joints (TMJ) chondrocytes, as demonstrated by dramatic increases in expression of HSPA5, p-EIF2AK3, p-ERN1 and ATF6. Interestingly, both FFSS and UAC activated not only pro-death p-EIF2AK3-mediated ERS-apoptosis programs but also pro-survival p-ERN1-mediated autophagic flux in chondrocytes. Data from FFSS demonstrated that MTORC1, a downstream of p-ERN1, suppressed autophagy but promoted p-EIF2AK3 mediated ERS-apoptosis. Data from UAC model demonstrated that at early stage both the p-ERN1 and p-EIF2AK3 were activated and MTORC1 was inhibited in TMJ chondrocytes. At late stage, MTORC1-p-EIF2AK3-mediated ERS apoptosis were predominant, while p-ERN1 and autophagic flux were inhibited. Inhibition of MTORC1 by TMJ local injection of rapamycin in rats or inducible ablation of MTORC1 expression selectively in chondrocytes in mice promoted chondrocyte autophagy and suppressed apoptosis, and reduced TMJ cartilage loss induced by UAC. In contrast, MTORC1 activation by TMJ local administration of MHY1485 or genetic deletion of Tsc1, an upstream MTORC1 suppressor, resulted in opposite effects. Collectively, our results establish that aberrant mechanical loading causes cartilage degeneration by activating, at least in part, the MTORC1 signaling which modulates the autophagy and apoptosis programs in TMJ chondrocytes. Thus, inhibition of MTORC1 provides a novel therapeutic strategy for prevention and treatment of OA.Abbreviations : ACTB: actin beta; ATF6: activating transcription factor 6; BECN1: beclin 1; BFL: bafilomycin A1; CASP12: caspase 12; CASP3: caspase 3; DAPI: 4',6-diamidino-2-phenylindole; DDIT3: DNA-damage inducible transcript 3; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERS: endoplasmic reticulum stress; ERN1/IRE1: endoplasmic reticulum to nucleus signaling 1; FFSS: flow fluid shear stress; HSPA5/GRP78/BiP: heat shock protein 5; LAMP2: lysosome-associated membrane protein 2; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin complex 1; OA: osteoarthritis; PRKAA1/2/AMPK1/2: protein kinase, AMP-activated, alpha 1/2 catalytic subunit; RPS6: ribosomal protein S6; Rapa: rapamycin; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TG: thapsigargin; TMJ: temporomandibular joints; TSC1/2: tuberous sclerosis complex 1/2; UAC: unilateral anterior crossbite; UPR: unfolded protein response; XBP1: x-box binding protein 1.

19.
Hepatology ; 71(1): 112-129, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31148184

RESUMO

To identify hepatocellular carcinoma (HCC)-implicated long noncoding RNAs (lncRNAs), we performed an integrative omics analysis by integrating mRNA and lncRNA expression profiles in HCC tissues. We identified a collection of candidate HCC-implicated lncRNAs. Among them, we demonstrated that an lncRNA, which is named as p53-stabilizing and activating RNA (PSTAR), inhibits HCC cell proliferation and tumorigenicity through inducing p53-mediated cell cycle arrest. We further revealed that PSTAR can bind to heterogeneous nuclear ribonucleoprotein K (hnRNP K) and enhance its SUMOylation and thereby strengthen the interaction between hnRNP K and p53, which ultimately leads to the accumulation and transactivation of p53. PSTAR is down-regulated in HCC tissues, and the low PSTAR expression predicts poor prognosis in patients with HCC, especially those with wild-type p53. Conclusion: This study sheds light on the tumor suppressor role of lncRNA PSTAR, a modulator of the p53 pathway, in HCC.

20.
Anal Sci ; 36(1): 127-133, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31474662

RESUMO

A highly sensitive and selective electrochemical sensor has been fabricated by the electrodepositing of nickel hexacyanoferrate (NiHCF) on a Ni-Al layered double hydroxides (Ni-Al-LDH) modified Au electrode for the quantification of doxorubicin hydrochloride (DOX). The characterization of synthesized nanomaterials has been conducted by scanning electron microscopy, energy dispersive X-ray spectroscopy and electrochemical methods. The synergistic effect of NiHCF and Ni-Al-LDH not only excellently improves the performance of DOX electro-reduction, but also promotes electron transfer between DOX and the NiHCF/Ni-Al-LDH/Au sensor. The differential pulse voltammetric response of the NiHCF/Ni-Al-LDH/Au sensor shows a linear relationship with the concentration of DOX in the range of 1.0 × 10-8 - 6.2 × 10-6 mol L-1, a limit of detection of 1.9 × 10-9 mol L-1 (S/N = 3) and a sensibility of 14.71 A mol L-1 cm-2. The developed sensor exhibits good sensitivity, reproducibility, anti-interference and a long-term stability property. Furthermore, the NiHCF/Ni-Al-LDH/Au sensor has been successfully applied to determine DOX in biological samples and human blood serum samples.

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