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1.
Medicine (Baltimore) ; 99(3): e18868, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011509

RESUMO

BACKGROUND: Plenty of evidence has suggested that long non-coding RNAs (lncRNAs) have played a vital part may act as prognostic biomarkers in a variety of cancers. The aim of this study was to screen survival-related lncRNAs and to construct a lncRNA-based prognostic model in patients with cutaneous melanoma (CM). METHODS: We obtained lncRNAs expression profiles and clinicopathological data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. A lncRNA-based prognostic model was established in training set. The established prognostic model was evaluated, and validated in the validation set. Then, a prognostic nomogram combining the lncRNA-based risk score and clinicopathological characteristics was developed in training set, and assessed in the validation set. The accuracy of the model was evaluated by the discrimination and calibration plots. RESULTS: A total of 212 lncRNAs were identified to be differentially expressed in CM. After univariate analysis, LASSO penalized regression analysis, and multivariate analysis, 3 lncRNAs were used to construct risk score model. The proposed risk score model could divide patients into high-risk and low-risk groups with significantly different survival in both training set and validation set. The ROC curve showed good performance in survival prediction in both sets. Furthermore, the nomogram for predicting 3-, 5-, and 10-year OS was established based on lncRNA-based risk score and clinicopathologic factors. The prognostic accuracy of the risk model was confirmed by the discrimination and calibration plots in both training set and validation set. CONCLUSIONS: We established a novel three lncRNA-based risk score model and nomogram to predict overall survival of CM. The proposed nomogram may provide information for individualized treatment in CM patients.

2.
Pharmazie ; 75(1): 18-22, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-32033628

RESUMO

Salvia miltiorrhiza (Danshen) is typically used in the treatment of diabetic complications and is often co-prescribed with gliquidone in China. However, whether danshen affects the absorption of gliquidone has not been elucidated. In this study, the effects of an aqueous extract of danshen (danshen injection, DSI) and its primary compounds (danshensu, protocatechuic aldehyde, rosmarinic acid and salvianolic acid B) on gliquidone transport across Caco-2 monolayer cells was investigated. DSI enhanced the transport of gliquidone in Caco-2 cell monolayers from the apical (AP) to basolateral (BL) sides and from the BL to AP sides. Rosmarinic acid (RA) also significantly increased the Papp (AP-BL) value for gliquidone transport. Verapamil (a P-gp inhibitor) and Ko143 (a BCRP inhibitor) inhibited the BL-AP transport of gliquidone and promoted the AP-BL transport of gliquidone, whereas MK571 (an MRP1 inhibitor), probenecid (an MRP2 inhibitor), and benzbromarone (an MRP3 inhibitor) had no effect on gliquidone transport. RA also enhanced the intracellular accumulation of Rho123 and Hoechst 33342. The expression of P-gp and BCRP was significantly downregulated, and P-gp ATPase activity was promoted by RA in a dose-dependent manner. These results indicate that an aqueous extract of danshen can increase the transport of gliquidone in Caco-2 cell monolayers and that RA may be the primary compound associated with this activity, which is in agreement with RA simultaneously suppressing the function and expression of P-gp and BCRP.

3.
Int J Biol Macromol ; 149: 1084-1097, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32035151

RESUMO

This study presented the first purification and characterization of a hepatoprotective polysaccharide (PNPS-0.5 M) from the residue of Panax notoginseng (Burk.) F.H. Chen. This polysaccharide included a backbone of (4 â†’ 1)-linked GalA and branches of (1→)-linked Araf, (1→)-linked Rhap, and (5 â†’ 1)-linked Araf and had an extremely high molecular weight (2600 kDa). We investigated the hepatoprotective effects of PNPS-0.5 M on mice with alcoholic liver damage (ALD). After administration of PNPS-0.5 M, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and hepatic malondialdehyde (MDA) were reduced to normal. In contrast, hepatic levels of alcohol dehydrogenase (ADH) and the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were elevated to normal. Further investigations indicated that PNPS-0.5 M activated Nrf2 signaling as a protective mechanism against Cyp2e1 toxicity in ALD mice. Meanwhile, it strengthened the ADH pathway and suppressed the CAT pathway of alcohol metabolism to prevent peroxide accumulation, thereby ameliorating ALD. In the present study, we describe a novel acidic polysaccharide from P. notoginseng with hepatoprotective activity that facilitates the development and utilization of P. notoginseng resources.

4.
Lipids Health Dis ; 19(1): 5, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31926562

RESUMO

BACKGROUND: Real-world evidence of low-density lipoprotein cholesterol (LDL-C) goal attainment rates for Asian patients is deficient. The objective of this study was to assess the status of dyslipidemia management, especially in high-risk patients with cardiovascular disease (CVD) including stroke and acute coronary syndrome (ACS). METHODS: This was a retrospective cohort study of 514,866 subjects from the National Health Insurance Service-National Health Screening Cohort database in Korea. Participants were followed up from 2002 to 2015. Subjects with a high-risk of CVD prior to LDL-C measurement and subjects who were newly-diagnosed for high-risk of CVD following LDL-C measurement were defined as known high-risk patients (n = 224,837) and newly defined high-risk patients (n = 127,559), respectively. Data were analyzed by disease status: stroke, ACS, coronary heart disease (CHD), peripheral artery disease (PAD), diabetes mellitus (DM) and atherosclerotic artery disease (AAD). RESULTS: Overall, less than 50% of patients in each disease category achieved LDL-C goals (LDL-C < 70 mg/dL in patients with stroke, ACS, CHD and PAD; and LDL-C < 100 mg/dL in patients with DM and AAD). Statin use was observed in relatively low proportions of subjects (21.5% [known high-risk], 34.4% [newly defined high-risk]). LDL-C goal attainment from 2009 to 2015 steadily increased but the goal-achiever proportion of newly defined high-risk patients with ACS remained reasonably constant (38.7% in 2009; 38.1% in 2015). CONCLUSIONS: LDL-C goal attainment rates in high-risk patients with CVD and DM in Korea demonstrate unmet medical needs. Proactive management is necessary to bridge the gap between the recommendations of clinical guidelines and actual clinical practice.

5.
J Clin Lab Anal ; : e23216, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31967356

RESUMO

BACKGROUND: Clinically, D-dimer (DD) levels are mainly used to exclude diseases such as deep venous thrombosis (DVT). In clinical testing, DD assays can be subjected to interference that may cause false results, which directly affect the clinical diagnosis. Our hypothesis was that the 95% confidence intervals (CIs) of the fibrin degradation product (FDP)/DD and fibrinogen (Fib)/DD ratios were used to identify these false results and corrected via multiple dilutions. METHODS: In total, 16 776 samples were divided into three groups according to the DD levels detected by Sysmex CS5100 and CA7000: Group A, DD ≥ 2.0 µg/mL fibrinogen equivalent unit (FEU); group B, 0.5 < DD < 2.0 µg/mL FEU; and group C, DD ≤ 0.5 µg/mL FEU. The 95% CIs of the FDP/DD and Fib/DD ratios were calculated. Six abnormal DD results were found according to the 95% CIs. For verification, we performed multiple dilutions, compared the results with those of other instruments, and tested the addition of heterophilic blocking reagent (HBR). RESULTS: The median and 95% CI of the FDP/DD ratio were 3.76 and 2.25-8.15 in group A, 5.63 and 2.86-10.58 in group B, 10.23 and 0.91-47.71 in groups C, respectively. For the Fib/DD ratio, the 95% CIs was 0.02-2.21 in group A, 0.68-8.15 in group B, and 3.82-55.27 in groups C. Six abnormal results were identified after multiple dilutions, by comparison with other detection systems, and after HBR addition. CONCLUSIONS: The FDP/DD ratio is more reliable for identifying false results. If the FDP/DD ratio falls outside the 95% CI, it should be verified by different methods.

6.
Mol Med Rep ; 21(2): 623-630, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31974593

RESUMO

Placental structural abnormalities and dysfunction in those with gestational diabetes mellitus (GDM) can lead to increased placental permeability, which is in turn related to a poorer maternal and fetal prognosis. The present study sought to assess whether increased placental permeability in rats with GDM was accompanied by alterations in tight junction (TJ) factors and to evaluate the impact of low molecular weight heparin (LMWH) on these factors. The present study was conducted using pregnant female rats that were randomized into control, GDM and GDM + LMWH groups. Diabetes was induced via intraperitoneal administration of streptozotocin to rats in the GDM and GDM + LMWH groups, whereas rats in the GDM + LMWH group received daily subcutaneous LMWH starting on day 5 of pregnancy. On gestational day 16, all rats were sacrificed and Evans Blue (EB) assay was used to gauge vascular permeability based on EB dye leakage. Transmission electron microscopy was further used to assess TJ structures, and the TJ proteins zonular occludens­1 (ZO­1) and occludin (OCLN) were assessed using immunohistochemistry and western blotting. Blood samples were obtained from the abdominal aorta for ELISA measurements of advanced glycation end products (AGEs) concentrations, and placental receptor for AGEs (RAGE) and vascular endothelial growth factor (VEGF) expression was assessed using reverse transcription­quantitative PCR. In addition, western blotting was used to measure placental NF­κB. Compared with in the control group, EB leakage was markedly increased in GDM group rats; this was associated with reduced ZO­1 and OCLN expression. Conversely, LMWH attenuated this increase in placental permeability in rats with GDM and also mediated a partial recovery of ZO­1 and OCLN expression. Blood glucose and serum AGEs concentrations did not differ between the GDM and GDM + LMWH groups. Furthermore, LMWH treatment resulted in decreases in RAGE and VEGF mRNA expression levels, which were upregulated in the GDM group, whereas it had the opposite effect on the expression of NF­κB. In conclusion, GDM was associated with increased placental permeability and this may be linked with changes in TJs. LMWH intervention mediated protection against this GDM­associated shift in placental permeability via the RAGE/NF­κB pathway.

7.
Biomacromolecules ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31955566

RESUMO

Current therapy for liver failure and concomitant hyperbilirubinemia faces the challenge of poor hemocompatibility and bleeding risks associated with the anticoagulant injection. Herein, heparin-mimetic biomacromolecule (HepMBm) with a similar degree of sulfation and anticoagulant properties to heparin was synthesized by imitating the structure of natural biomacromolecule heparin. Then HepMBm was used to prepare nanocomposite spheres based on reduced graphene oxide (rGO). The formation of a dual-network structure in the spheres endowed the spheres with improved dimensional stability. The proposed spheres exhibited outstanding blood compatibilities and excellent self-anticoagulant properties. The bilirubin adsorption experiments and whole blood bilirubin removal assay indicated that the spheres exhibited high bilirubin removal capability from whole blood (The removal ratio was 99.69%.). The spheres open new routes for a therapeutic strategy without a plasma separation system and heparin pump, which may be a step toward a lightweight wearable artificial liver.

8.
BMC Cancer ; 20(1): 28, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924176

RESUMO

BACKGROUND: Pyroptosis belongs to a novel inflammatory programmed cell death pathway, with the possible prognosis of endometrial cancer related to the terminal protein GSDMD. Hydrogen exerts a biphasic effect on cancer by promoting tumor cell death and protecting normal cells, which might initiate GSDMD pathway-mediated pyroptosis. METHODS: We performed immunohistochemical staining and western immunoblotting analysis to observe expression of NLRP3, caspase-1, and GSDMD in human and xenograft mice endometrial cancer tissue and cell lines. We investigated treatment with hydrogen could boost ROS accumulation in endometrial cancer cells by intracellular and mitochondrial sources. GSDMD shRNA lentivirus was used to transfect endometrial cancer cells to investigate the function of GSDMD protein in pyroptosis. Propidium iodide (PI) staining, TUNEL assay, measurement of lactate dehydrogenase (LDH) release and IL-1ß ELISA were used to analysis pyroptosis between hydrogen-supplemented or normal culture medium. We conducted in vivo human endometrial tumor xenograft mice model to observe anti-tumor effect in hydrogen supplementation. RESULTS: We observed overexpression of NLRP3, caspase-1, and GSDMD in human endometrial cancer and cell lines by IHC and western immunoblotting. Hydrogen pretreatment upregulated ROS and the expression of pyroptosis-related proteins, and increased the number of PI- and TUNEL-positive cells, as well as the release of LDH and IL-1ß, however, GSDMD depletion reduced their release. We further demonstrated that hydrogen supplementation in mice was sufficient for the anti-tumor effect to inhibit xenograft volume and weight of endometrial tumors, as mice subjected to hydrogen-rich water displayed decreased radiance. Tumor tissue sections in the HRW groups presented moderate-to-strong positive expression of NLRP3, caspase-1 and GSDMD. Hydrogen attenuated tumor volume and weight in a xenograft mouse model though the pyroptotic pathway. CONCLUSIONS: This study extended our original analysis of the ability of hydrogen to stimulate NLRP3 inflammasome/GSDMD activation in pyroptosis and revealed possible mechanism (s) for improvement of anti-tumor effects in the clinical management of endometrial cancer.

9.
J Lipid Res ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941672

RESUMO

Zinc metallopeptidase STE24 (ZMPSTE24) is essential for the conversion of farnesyl-prelamin A to mature lamin A, a key component of the nuclear lamina. In the absence of ZMPSTE24, farnesyl-prelamin A accumulates in the nucleus and exerts toxicity, causing a variety of disease phenotypes. By ~4 months of age, both male and female Zmpste24-/- mice manifest a near-complete loss of adipose tissue, but it has never been clear whether this phenotype is a direct consequence of farnesyl-prelamin A toxicity in adipocytes. To address this question, we generated a conditional knockout Zmpste24 allele and used it to create adipocyte-specific Zmpste24-knockout mice. To boost farnesyl-prelamin A levels, we bred in the "prelamin A-only" Lmna allele. Gene expression, immunoblotting, and immunohistochemistry experiments revealed that adipose tissue in these mice had decreased Zmpste24 expression along with strikingly increased accumulation of prelamin A. In male mice, Zmpste24 deficiency in adipocytes was accompanied by modest changes in adipose stores (an 11% decrease in body weight, a 23% decrease in body fat mass, and significantly smaller gonadal and inguinal white adipose depots). No changes in adipose stores were detected in female mice, likely because prelamin A expression in adipose tissue is lower in female mice. Zmpste24 deficiency in adipocytes did not alter the number of macrophages in adipose tissue, nor did it alter plasma levels of glucose, triglycerides, or fatty acids. We conclude that ZMPSTE24 deficiency in adipocytes, and the accompanying accumulation of farnesyl-prelamin A, reduces adipose tissue stores, but only modestly and only in male mice.

10.
Int J Pharm ; 576: 119031, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31953082

RESUMO

This study developed novel ionic liquids (ILs) based on amino acids. We first screened 15 methyl amino acid ester hydrochlorides ([AAC1]Cl) for their skin permeation enhancements using 5-Fluorouracil (5-Fu) and Hydrocortisone (HC) as model drugs. Glycine methyl ester hydrochloride ([GlyC1]Cl), L-proline methyl ester hydrochloride ([L-ProC1]Cl), and L-leucine methyl ester hydrochloride ([L-LeuC1]Cl) were selected, and their ester sites were modified with different carbon chains (C8 and C12). The resulting ILs showed improved permeation to the two drugs. TEWL and CLSM assays revealed the moderation effects of the modified ILs on skin barrier function, whereas L-proline dodecyl ester hydrochloride ([ProC12]Cl) and L-leucine dodecyl ester hydrochloride ([L-LeuC12]Cl) exhibited the strongest activities. Permeation mechanisms were further investigated by ATR-FTIR, solid-NMR, SEM, and TEM analyses. The results suggested that [L-ProC12]Cl and [L-LeuC12]Cl combined the advantages of amino acid esters and IL solvent and could interact with the intercellular lipid domain by the multi-functions of lipid fluidization and lipid extraction, which were observed in a dosage- and time-dependent manner. Additionally, pathological examination suggested that the amino acid ester-based ILs (AAE-ILs) had good biocompatibility. In conclusion, this study has generated novel chemical penetration enhancers (CPEs) based on AAE-ILs and may be potentially utilized in drug transdermal delivery systems (TDDSs).

11.
J Cell Mol Med ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31990147

RESUMO

The purpose of the present study was to evaluate the anti-cancer property of Lobetyolin on colorectal cancer and explore its potential mechanism. Lobetyolin was incubated with HCT-116 cells in the absence or presence of ASCT2 inhibitor Benser or p53 inhibitor Pifithrin-α. The levels of glutamine, glutamic acid, α-ketoglutarate, ATP and GSH were determined to measure the glutamine metabolism. Annexin V-FITC/PI staining and TUNEL assay were applied to estimate the apoptotic condition. The levels of ASCT2 were examined by RT-qPCR, Western blot and immunofluorescence staining. The expressions of cleaved-caspase-3, caspase-3, cleaved-caspase-7, caspase-7, cleaved-PARP, PARP, p53, p21, bax and survivin were detected using Western blot analysis. As a result, the treatment with Lobetyolin effectively induced apoptosis and glutamine metabolism in HCT-116 cells through ASCT2 signalling. The inhibition of ASCT2 reduced the glutamine-related biomarkers and augmented the apoptotic process. We further found that the effect of Lobetyolin on HCT-116 was related to the expressions of p21 and bax, and transportation of p53 to nucleus. The inhibition of p53 by Pifithrin-α promoted the inhibitory effect of Lobetyolin on ASCT2-mediated apoptosis. Lobetyolin also exerted anti-cancer property in nude mice. In conclusion, the present work suggested that Lobetyolin could induce the apoptosis via the inhibition of ASCT2-mediated glutamine metabolism, which was possibly governed by p53.

12.
Int J Oncol ; 56(1): 69-84, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31789398

RESUMO

The present study aimed to evaluate the correlation of integrin α7 (ITGA7) with clinicopathological characteristics and overall survival (OS) in patients with tongue squamous cell carcinoma (TSCC), and to investigate the effect of ITGA7 knockdown on proliferation, apoptosis and stemness of TSCC cells in vitro. ITGA7 expression was measured in tumor tissues and paired adjacent normal tissues from 60 patients with TSCC using immunohistochemistry. ITGA7 expression in human TSCC cell lines and normal oral keratinocytes was measured using quantitative PCR and western blotting. Lentiviruses carrying short hairpin (sh) RNA targeting ITGA7 were used to knockdown its expression in CAL­27 and HSC­4 cells, and then proliferation, apoptosis and stemness were measured. In addition, CAL­27 and HSC­4 cancer stem cells (CSCs) were constructed and their ITGA7 expression was measured. The results demonstrated that ITGA7 was upregulated in the tumor tissues compared with the paired adjacent tissues, and its high expression was correlated with worse pathological grade, N stage, TNM stage and OS. In vitro, ITGA7 expression levels were demonstrated to be increased in the TSCC CAL­27, SCC­9, HSC­4 and SCC­25 cell lines compared to the normal HOK cell line. In CAL­27 and HSC­4 cells, ITGA7 knockdown inhibited cell proliferation, promoted apoptosis, increased CD24 expression, decreased CD44 and CD133 expression, reduced drug resistance to cisplatin and attenuated sphere formation efficiency. Finally, ITGA7 expression levels were greatly elevated in CAL­27 and HSC­4 CSCs compared with parental CAL­27 and HSC­4 cells. In conclusion, ITGA7 knockdown inhibited tumor cell proliferation and stemness in TSCC cells. These findings indicated that ITGA7 might serve as a potential marker for CSCs and may correlate with worse clinical features and prognosis in TSCC.

13.
Mol Pharm ; 17(1): 338-348, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31793786

RESUMO

The synergy of chemotherapy and antiangiogenesis therapy is a new strategy for cancer treatment. In this paper, a well-developed core-shell nanoparticle loaded with gambogic acid (GA), heparin (HP), and the immunoadjuvant cytosine-phosphate-guanine oligonucleotide (CpG ODN), called GHC NP, was constructed to treat hepatocellular carcinoma. GHC NPs with liver targeting activity can effectively inhibit tumor cell proliferation and angiogenesis. With the delivery of nanocarriers and the assistance of GA and HP, the GHC NPs can more effectively upregulate cytotoxic T cell (CTL) levels, promote helper T cell (Th cell) differentiation, and induce Th1 immune responses in long-term treatment compared with single CpG ODN. This synergistically enhanced immunotherapy might have universal application in cancer treatments.

14.
Clin Chim Acta ; 501: 66-71, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31756311

RESUMO

OBJECTIVE: To screen long non-coding RNA (lncRNA) related to glucokinase regulatory protein gene (GCKR), its differential expression was analyzed in patients with Type 2 diabetes mellitus (T2DM) and control samples. The correlation of lncRNA with GCKR was verified and its potential value as a molecular marker of T2DM was assessed. METHODS: Lymphocyte RNA was extracted from five patients with T2DM and five patients with non-T2DM. The expression profiles of circulating lncRNAs and mRNAs were obtained by microarray. Bioinformatics analysis was used to screen lncRNAs associated with the GCKR gene in 127 patients with T2DM and 130 patients with non-T2DM were selected. The expression levels of the GCKR gene and lncRNA (ENST00000588707.1 and TCONS_00004187) in the T2DM group and control group were verified by real-time PCR. Additionally, a correlation analysis was conducted. The value of circulating ENST00000588707.1 and TCONS_00004187 as biomarkers for the diagnosis of T2DM was performed by receiver operating characteristic curve analysis. RESULTS: We identified 68 lncRNAs and 74 mRNAs differentially expressed from the expression profile. Compared with the control group, the expression levels of the GCKR gene and lncRNA ENST00000588707.1 and TCONS_00004187 in the T2DM group were significantly lower (P < 0.05). The correlation analysis revealed that ENST00000588707.1 and TCONS_00004187 were correlated with GCKR gene expression and glycolipid metabolism (P < 0.05). ROC analysis showed that the area under the curve value of ENST00000588707.1 between T2DM patients and non-T2DM patients was 0.816 (95% CI: 0.764-0.869, sensitivity 72.0%, specificity 80.3%) and the AUC value of TCONS_00004187 was 0.826 (95% CI: 0.774-0.879, sensitivity 81.6%, specificity 61.3%). CONCLUSION: lncRNA ENST0000588707.1 and TCONS_00004187 could serve as potential biomarkers for T2DM, which could involve in glycolipid metabolism by regulating the GCKR gene.

15.
J Cell Biochem ; 121(3): 2534-2542, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31692047

RESUMO

Lung cancer is the dominating cause of cancer-induced death and can be classified into small cell lung cancer and non-small cell lung cancer (NSCLC). Lung adenocarcinoma (LUAD) is the most common histological subtype of NSCLC and its pathology remains unclear. Mounting reports have revealed that lncRNAs could regulate cellular activities in cancers. Yet the role of ZFPM2 antisense RNA 1 (ZFPM2-AS1) in LUAD has not been elucidated. Using GEPIA online dataset, we identified the amplification of ZFPM2-AS1 in LUAD tissues. Through quantitative real-time reverse transcription-polymerase chain reaction analysis, we observed an upregulation of ZFPM2-AS1 in LUAD cell lines. Conducting loss-of-function assays, we found that ZFPM2-AS1 depletion impaired cell viability, suppressed cell migration, and reversed epithelial-mesenchymal transition progress in LUAD cells. Mechanism investigation manifested that ZFPM2-AS1 was distributed in the cytoplasm of LUAD cells. Moreover, ZFPM2-AS1 functioned as a molecular sponge of miR-511-3p, which was a suppressor in LUAD. Moreover, ZFPM2-AS1 sponged miR-511-3p and thereby deregulated AF4/FMR2 family member 4 (AFF4), a target of miR-511-3p. At length, rescue assays indicated that AFF4 overexpression revived the inhibiting effects of ZFPM2-AS1 knockdown on the biological processes in LUAD. All in all, this study uncovered the function and the mechanism of ZFPM2-AS1 in LUAD.

16.
Talanta ; 208: 120460, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816722

RESUMO

Probing the level and activity of alkaline phosphatases (ALP) is of great significance for biomedical research on cellular functions and clinical diagnosis of cancers. Herein, a novel dual-colored carbon dots (CDs)-based ratiometric fluorescent sensor was constructed to accomplish high sensitive and accurate determination of ALP relyed on the difference of fluorescence resonance energy transfer (FRET) between blue light emitted CDs (B-CDs)-MnO2 nanohybrid and yellow light emitted CDs (Y-CDs)-MnO2 nanohybrid. The ratiometric fluorescent sensor enabled sensitive discrimination of ALP against other enzymes in a linear range of 0.1-500 U/L with a limit of detection of 0.02 U/L. The lower error and signal fluctuation, more satisfactory LODs and higher R value (R2 = 0.99552) of the ratiometric sensing platform than single signal detection mode (R2 = 0.85231; R2 = 0.64260) indicated the superiority of the ratiometric fluorescence detection mode.Besides, the excellent analytical performance towards ALP in biological system demonstrated the potential application in clinical diagnosis.

17.
J Mater Chem B ; 8(3): 568-577, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31854426

RESUMO

Rapid endothelialization and prevention of restenosis are two vital challenges for the preparation of a small-diameter vascular graft (SDVG), while postoperative infection after implantation is often neglected. In the present study, carboxymethyl chitosan (CMC) and chitosan (CS) were chosen as the anti-thrombotic and anti-bacterial components, respectively; and then an asymmetric vascular graft was fabricated by co-electrospinning of poly(ε-caprolactone) (PCL)/CMC and PCL/CS. The mechanical properties of the asymmetric vascular graft were much better than those of the native vessels. In vitro blood compatibility tests indicated that the inner layer of the graft could inhibit thrombosis effectively. The outer layer of the graft had a certain anti-bacterial effect owing to the addition of chitosan. Besides, the inner layer of the graft could greatly promote the growth of endothelial cells. It is believed that the asymmetric SDVG with anti-thrombotic and anti-bacterial functions could contribute to the future clinical implantation of tissue engineered vascular grafts.

18.
J Biol Chem ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822558

RESUMO

The Maf proteins including c-Maf, MafA and MafB are critical transcription factors in myelomagenesis. Previous studies demonstrated that Maf proteins are processed by the ubiquitin-proteasome pathway but the mechanisms remain elusive. The present study applied mass spectrometry to identify MafB ubiquitination-associated proteins and found that the ubiquitin-specific protease USP7 was present in the MafB interactome. Moreover, USP7 also interacted with c-Maf and MafA and blocked their polyubiquitination and degradation. Consistently, knockdown of USP7 resulted in Maf protein degradation along with increased polyubiquitination levels. The action of USP7 thus promoted Maf transcriptional activity as evidenced by luciferase assays and by the upregulation of the expression of Maf-modulated genes. Furthermore, USP7 was upregulated in myeloma cells and it was negatively associated with the survival of myeloma patients. USP7 promoted myeloma cell survival, and when it was inhibited by its specific inhibitor P5091, myeloma cell lines underwent apoptosis. These results therefore demonstrated that USP7 is a deubiquitinase of Maf proteins and promotes MM cell survival in association with Maf stability. Given the significance of USP7 and Maf proteins in myeloma genesis, targeting the USP7/Maf axle is a potential strategy to the precision therapy of MM.

19.
Onco Targets Ther ; 12: 8955-8960, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802905

RESUMO

Chimeric antigen receptor (CAR)-modified T cell therapy is increasingly administered for hematological malignancies. Cytokine release syndrome (CRS) is a common and severe complication of CAR-T therapy. In the present case, a 62-year-old male patient was diagnosed with relapsed and refractory multiple myeloma (RRMM). Treated with CART-CD19/BCMA therapy, his symptoms remitted, during which occasional but severe CRS associated with coagulation disorder still appeared, as evidenced by the coexistence of a huge thrombosis and bleeding tendency. Through the First Generation Sequencing, we extracted genomic DNA from the patient's peripheral blood to analyze the distribution of polymorphism at the -572C/G site of the promoter of IL-6 gene. The results showed that the genotype of -572C/G promoter polymorphism was CC, indicating that high level of IL-6 and -572C/G polymorphism might be associated with the risk of thrombotic disorders. We concluded that immediate diagnosis and appropriate treatment of coagulopathy could reduce CRS-related mortality.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31838832

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) infects the lower respiratory airway of humans, leading to severe acute respiratory failure. Unlike human dipeptidyl peptidase 4 (hDPP4), a receptor for MERS-CoV, mouse DPP4 (mDPP4) failed to support MERS-CoV infection. Consequently, diverse transgenic mouse models expressing hDPP4 have been developed using diverse methods, although some models show no mortality and/or only transient and mild-to-moderate clinical signs following MERS-CoV infection. Additionally, overexpressed hDPP4 is associated with neurological complications and breeding difficulties in some transgenic mice, resulting in impeding further studies. Here, we generated stable hDPP4-transgenic mice that were sufficiently susceptible to MERS-CoV infection. The transgenic mice showed weight loss, decreased pulmonary function, and increased mortality with minimal perturbation of overexpressed hDPP4 after MERS-CoV infection. In addition, we observed histopathological signs indicative of progressive pulmonary fibrosis, including thickened alveolar septa, infiltration of inflammatory monocytes, and macrophage polarization as well as elevated expression of profibrotic molecules and acute inflammatory response in the lung of MERS-CoV-infected hDPP4-transgenic mice. Collectively, we suggest that this hDPP4-transgenic mouse is useful to enable understanding of the pathogenesis of MERS-CoV infection and for antiviral research and vaccine development against the virus.

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