Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.329
Filtrar
1.
Mol Med Rep ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31922216

RESUMO

Chemerin is a novel adipokine that regulates immune responses, adipocyte differentiation, and glucose metabolism. However, the role of chemerin in pancreatogenic diabetes mellitus (PDM) remains unknown. PDM is recognized as DM occurring secondary to chronic pancreatitis or pancreatic resection due to the loss of the loss of islet cell mass. The aim of the present study was to investigate the role of chemerin in PDM by collecting blooding samples from DM patients and establishing in vivo PDM model. The present study demonstrated that chemerin levels are decreased in the serum of patients with PDM and are negatively associated with the insulin resistance (IR) status. Chemerin levels also decreased during the development of PDM in C57BL/6 mice, together with increasing serum levels of interleukin­1 and tumor necrosis factor­α and decreasing mRNA expression levels of glucose transporter 2 (GLUT2) and pancreatic and duodenal homeobox 1 (PDX1). Treatment of PDM model mice with chemerin chemokine­like receptor 1 (CMKLR1) agonist, chemerin­9, elevated the serum levels of chemerin and mRNA expression levels of GLUT2 and PDX1, leading to the alleviation of glucose intolerance and IR in these animals. Together, the accumulated data indicated that chemerin may exert a protective function in PDM, perhaps by regulating perhaps by regulating GLUT2 and PDX1 expression, and that the restoration of the chemerin/CMKLR1 pathway may represent a novel therapeutic strategy for PDM.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31922352

RESUMO

OBJECTIVES: To assess the predictive value of the Global Registry of Acute Coronary Events (GRACE) discharge score for patients with stable coronary artery disease (SCAD) after percutaneous coronary intervention (PCI). BACKGROUND: The GRACE score is widely used for predicting the mortality of acute coronary syndrome patients. However, the predictive value of SCAD has not been sufficiently studied. METHODS: We studied 4,293 consecutive patients with SCAD who underwent PCI between January 2013 and December 2013. The primary endpoint was all-cause mortality and the secondary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: Among 3,915 patients with SCAD following PCI, there were 38 deaths and 394 MACCE during 2 years of follow-up. The GRACE discharge score was significantly higher for patients who died than for those who survived (86.97 ± 23.27 vs. 71.07 ± 19.84; p < .001). Risk stratification of the GRACE score indicated that the mortality risk of the intermediate-risk and high-risk groups were 3.23-fold (hazard ratio [HR], 3.23; range, 1.59-6.55; p = .001) and 15.31-fold higher (HR, 15.31; range, 4.43-51.62; p < .001), respectively, than that of the low-risk group. The MACCE risk for the intermediate-risk and high-risk groups were 1.28-fold (HR, 1.28; range, 1.02-1.62; p = .037) and 2.42-fold higher (HR, 2.42; range, 1.20-4.88; p = .014), respectively. The GRACE discharge score had prognostic value for mortality (area under the receiver operating characteristic curve, 0.692; p < .001). CONCLUSIONS: The GRACE discharge score is valuable for the risk stratification of death and MACCE, as well as for the prognosis to mortality for SCAD patients who have undergone PCI.

3.
Viruses ; 12(1)2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31906441

RESUMO

The transcription factor NF-κB plays a critical role in diverse biological processes. The NF-κB pathway can be activated by incoming pathogens and then stimulates both innate and adaptive immunity. However, many viruses have evolved corresponding strategies to balance NF-κB activation to benefit their replication. Pseudorabies virus (PRV) is an economically important pathogen that belongs to the alphaherpesvirus group. There is little information about PRV infection and NF-κB regulation. This study demonstrates for the first time that the UL24 protein could abrogate tumor necrosis factor alpha (TNF-α)-mediated NF-κB activation. An overexpression assay indicated that UL24 inhibits this pathway at or downstream of P65. Furthermore, co-immunoprecipitation analysis demonstrated that UL24 selectively interacts with P65. We demonstrated that UL24 could significantly degrade P65 by the proteasome pathway. For the first time, PRV UL24 was shown to play an important role in NF-κB evasion during PRV infection. This study expands our understanding that PRV can utilize its encoded protein UL24 to evade NF-κB signaling.

4.
Urol Oncol ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31952997

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) is the second common malignant tumor in the urinary system, and 85% of RCC cases are clear cell RCC (ccRCC). This study is designed to build a risk score system for ccRCC. METHODS: The gene methylation and expression data of ccRCC samples were downloaded from The Cancer Genome Atlas database (training set) and ArrayExpress database (validation set). The differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were identified by limma package, and their intersecting genes with negative Pearson correlation coefficients were remained using cor.test function. Prognosis-associated genes were identified by survival package, and the optimal DMGs were obtained using penalized package. After risk score system was built, nomogram survival model was constructed using rms package. Additionally, pathways were enriched for the DEGs between high- and low-risk groups using Gene Set Enrichment Analysis. RESULTS: There were 3,638 DMGs and 2,702 DEGs between tumor and normal samples. Among the 312 intersecting genes, 43 prognosis-associated genes were identified. A total of 13 optimal DMGs (BTBD19, ADAM8, BGLAP, TNFRSF13C, JPH4, BEST1, GNRH2, UBE2QL1, CHODL, GDF9, UPB1, KCNH3; and ADAMTSL4) were obtained for building the risk score system. After pathological M, pathological T, platelet qualitative, and RS status were revealed to be independent prognostic factors, a nomogram survival model was constructed. For the 920 DEGs between the high- and low-risk samples, 6 significant pathways were enriched. CONCLUSION: The 13-gene risk score system and the nomogram survival model might be used for prognostic prediction of ccRCC patients.

5.
Elife ; 92020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31958057

RESUMO

The RAS proteins are GTP-dependent switches that regulate signaling pathways and are frequently mutated in cancer. RAS proteins concentrate in the plasma membrane via lipid-tethers and hypervariable side-chain interactions in distinct nano-domains. However, little is known about RAS membrane dynamics and the details of RAS activation of downstream signaling. Here we characterize RAS in live human and mouse cells using single molecule tracking methods and estimate RAS mobility parameters. KRAS4b exhibits confined mobility with three diffusive states distinct from the other RAS isoforms (KRAS4a, NRAS, and HRAS); and although most of the amino acid differences between RAS isoforms lie within the hypervariable region, the additional confinement of KRAS4b is largely determined by the protein's globular domain. To understand the altered mobility of an oncogenic KRAS4b we used complementary experimental and molecular dynamic simulation approaches to reveal a detailed mechanism.

6.
ACS Appl Mater Interfaces ; 12(2): 2432-2444, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31845791

RESUMO

Discovering cathode materials composed of earth-abundant elements has become the current priority for developing sodium-ion batteries (SIBs) to meet the ever-increasing demand of large-scale energy storage. Herein, for the first time, layered NaxMO2 (M = Cu, Fe, Mn) cathodes are successfully prepared by directly using concentrated chalcopyrite ores as precursors. Greatly, impurity elements like Si and Ca are found to be crucial to tailoring the phase structure of as-obtained layered oxides as a P2 or O3 type, which removes the traditional concern that the impurities may restrict the utilization of natural ores. More interestingly, a certain amount of the Ca elements remaining in the Na sites through a self-doping process endows the P2-type products with enhanced structural stability. In half-cells, P2-type NaxMO2 with self-doped Ca elements shows superior rate capability and cycling stability (56 mAh g-1 at 5 C and 90% capacity retention after 100 cycles at 1 C). In contrast, less impurity elements are favorable for O3-type oxides to achieve a high capacity of 107 mAh g-1 at 0.1 C and 84% capacity retention after 200 cycles at 2 C. This new strategy would efficiently shorten the process for preparing electrode materials and open a feasible route to construct cheap and durable SIBs.

7.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(10): 903-909, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31814567

RESUMO

Objective To investigate the expression of C-C motif chemokine ligand 23 (CCL23) in hepatocellular carcinoma (HCC) and its clinical significance for survival and prognosis. Methods GEPIA, HCCDB, MetaScape, TIMER, TISIDB, Kaplan-Meier Plotter and other online databases were used to analyze the expression level of CCL23 in HCC, the functional notes of co-expression gene and its gene ontology (GO), the enrichment of Kyoto gene and genome encyclopedia (KEGG), the correlation between tumor cell purity, the expression of CCL23 in immune cells and its significance for survival and prognosis of patients. Results The expression of CCL23 in all stages of HCC was negatively correlated with the purity of HCC tumor cells. The short prognosis of HCC patients with low expression of CCL23 was poor. The GO function and KEGG pathway of CCL23 co-expressed gene in HCC were mainly enriched in immune cell activation and complement system activation. CCL23 was the strongest chemokine factor in HCC, and it could bind to multiple receptors including CC chemokine receptor 1 (CCR1), CCR2, CCR7 and CXC chemokine receptor 6 (CXCR6) to exert chemokine effect on immune cells, among which CD8+ T cells and macrophages have the most obvious chemokine effect. Conclusion The low expression of CCL23 in HCC tissue is not conducive to the development of anti-tumor immune defense in HCC patients and significantly shortens the survival of HCC patients.

8.
J Toxicol Environ Health A ; 82(21): 1113-1119, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31818208

RESUMO

Microcystin-LR (MC-LR), a cyclic heptapeptide toxin produced by cyanobacteria, was found to induce genotoxic actions in various types of cells. Some investigators reported that microcystin-LR acted as tumor initiator in the observed genotoxic action mediated by this cyanotoxin. However, the underlying mechanisms underlying MC-induced DNA damage in the human intestine epithelium cell line (NCM460) are not known. The purpose of this study was to examine the influence of 24 hr exposure to 5 or 10 µM MC-LR on intestinal DNA damage using NCM460 intestine cell line as a model. Data showed that MC-LR increased Olive tail moment (OTM) as evidenced by the comet assay, inhibited protein phosphatase 2A (PP2A) activity, elevated reactive oxygen species levels (ROS) and enhanced γ-H2AX and p-p53 protein expression levels. Results indicated that MC-LR produced intestinal DNA damage by inhibiting PP2A activity, activating p53 protein and subsequently initiating excess generation of ROS. These observations suggest that MC-LR-induced intestinal DNA damage involves a complex series of events that include oxidant stress, PP2A enzymic inhibition and activation of p53 protein.

9.
J Toxicol Environ Health A ; 82(21): 1129-1136, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31818223

RESUMO

Microcystin-LR (MC-LR) variant exposure poses a potential health hazard to ecosystem, animals, and humans. Previously investigators showed that autophagy plays a key role in MC-LR induced cytotoxicity immortalized murine ovarian granular KK-1 cells and rat Sertoli cells. Recently exposure to MC-LR via drinking water was reported to accumulate in mouse brain with associated adverse oxidant and inflammatory responses. However, autophagy the physiological mechanism required for cells to degrade their own impaired organelles to maintain their homeostasis has not been determined with respect to MC-LR actions on the central nervous system (CNS). Thus, the aim of this study was to examine the effects of MC-LR on autophagy using human neuroblastoma SK-N-SH cells as CNS model. Data demonstrated that after treatment with 15 or 30 µmol/L MC-LR for 48 hr significantly reduced survival rate was noted in SK-N-SH cells. MC-LR increased the expression levels of autophagy-related proteins light chain 3 (LC3) II/I and p62 in SK-N-SH cells, resulting in the accumulation of LC3 and increased intracellular free calcium ion levels. Data indicated that MC-LR induced adverse effects on the CNS as evidenced by decreased cellular survival associated with inhibition of autophagy flux and consequent enhanced autophagosomes accumulation.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31818687

RESUMO

OBJECTIVE: There is lack of standardized management and mobilization strategies after oral and maxillofacial reconstruction surgery. We used prospective randomized controlled trials to explore improvements in postoperative mobilization protocol in such patients. METHODS: A total of 149 patients were randomly divided into tracheotomy control group A (38 cases) and test group A (37 cases), nontracheotomy control group B (38 cases) and test group B (36 cases). Test group patients sat up in bed on the 2nd day after surgery and performed off-bed activity on the 3rd day, whereas control group patients sat up in bed on the 4th day postoperatively and performed off-bed activity on the 6th day. Objective evaluation included free flap success rate, postoperative complications, sleep time, and catheter removal time, among other parameters. Subjective evaluation included postoperative pain and comfort evaluation. RESULTS: The success rate of free flaps was 97.3% in test group A and 100% in the other groups. In terms of mean sleep time, 4.6 ± 1.0 h in test group A, which was longer than 4.1 ± 1.0 h in control group A (P = 0.034); 5.7 ± 1.4 h in test group B, which was longer than 4.9 ± 1.7 h in control group B (P = 0.026). Early activity makes catheter removal time (tracheal incision, nasogastric tube, urethral catheter) shorter and gets higher comfort evaluation scores in both test groups versus control groups (P < 0.05). CONCLUSIONS: The early mobilization protocol for patients undergoing free flap reconstruction was safe, and can effectively improve sleep, shorten the catheter indwelling time, and increase the patient's comfort level.

11.
J Clin Gastroenterol ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31789771

RESUMO

BACKGROUND: Serum hepatitis B e antigen (HBeAg) status is associated with the progression of chronic hepatitis B (CHB). The authors aimed to investigate the relationship between HBeAg status and liver pathology in CHB patients. METHODS: A total of 683 treatment-naive CHB patients who had undergone liver biopsy were retrospectively enrolled from 2 medical centers. Propensity score-matching (PSM) method was performed to adjust the imbalance of baseline confounders between HBeAg-positive and HBeAg-negative CHB patients. RESULTS: HBeAg-negative CHB patients (n=338) exhibited more advanced liver fibrosis than HBeAg-positive CHB patients (n=345) before PSM (P<0.001). However, there were no significant differences in the distribution of inflammation grades between HBeAg-positive and HBeAg-negative CHB patients (P=0.051). Of these 683 CHB patients, 123 patients were included in each group after PSM. HBeAg-negative CHB patients still showed significantly advanced liver fibrosis as compared with HBeAg-positive CHB patients (P=0.03) after PSM. Furthermore, the distribution of liver inflammation grades in the HBeAg-negative CHB patients was also more severe than patients with HBeAg-positive (P=0.037). HBeAg-negative status was identified as an independent risk factor of significant liver fibrosis (P=0.011) by multivariate analysis. CONCLUSIONS: HBeAg negativity is associated with more advanced liver fibrosis in CHB patients.

12.
Fitoterapia ; 140: 104442, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31790769

RESUMO

Averrhoa carambola L. (Oxalidaceae) was widely cultivated for fruits (star fruit), whereas the value of leaves remains to be discovered. Our study on the leaves yielded five flavan-3-ols (1-5) and two 2-diglycosyloxybenzoates. Their structures were determined by spectroscopic and chemical methods. Epicatechin-(5,6-bc)-4ß-(p-hydroxyphenyl)-dihydro-2(3H)-pyranone (1) and benzyl 2-ß-d-apiofuranosyl-(1 â†’ 6)-ß-d-glucopyranosyloxybenzoate (6) were new structures. 6-(S-2-Pyrrolidinone-5-yl)epicatechin (4) and 6-(R-2-pyrrolidinone-5-yl)epicatechin (5) were obtained as monomeric diastereomer for the first time and their absolute configurations were determined by electronic circular dichroism (ECD) computation. Epicatechin-(7,8-bc)-4α-(p-hydroxyphenyl)-dihydro-2(3H)-pyranone (2), epicatechin-(7,8-bc)-4ß-(p-hydroxyphenyl)-dihydro-2(3H)-pyranone (3), and methyl 2-ß-d-apiofuranosyl-(1 â†’ 6)-ß-d-glucopyranosyloxybenzoate (7) were not previously reported from the genus Averrhoa. Compounds 1-5 showed more potent 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical cation and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities and ferric reducing antioxidant power (FRAP) than l-ascorbic acid. Meanwhile 1 and 3 exhibited lipase and α-glucosidase inhibitory activities, respectively. The results clarified the structures of flavan-3-ols and 2-diglycosyloxybenzoates in the leaves and their antioxidant, lipase, and α-glucosidase inhibitory activities.

13.
J Exp Clin Cancer Res ; 38(1): 481, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801598

RESUMO

BACKGROUND: Although EGFR tyrosine kinase inhibitors (EGFR-TKIs) are beneficial to lung adenocarcinoma patients with sensitive EGFR mutations, resistance to these inhibitors induces a cancer stem cell (CSC) phenotype. Here, we clarify the function and molecular mechanism of shisa3 as a suppressor that can reverse EGFR-TKI resistance and inhibit CSC properties. METHODS: The suppresser genes involved in EGFR-TKI resistance were identified and validated by transcriptome sequencing, quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Biological function analyses, cell half maximal inhibitory concentration (IC50), self-renewal, and migration and invasion capacities, were detected by CCK8, sphere formation and Transwell assays. Tumorigenesis and therapeutic effects were investigated in nonobese diabetic/severe combined immunodeficiency (nod-scid) mice. The underlying mechanisms were explored by Western blot and immunoprecipitation analyses. RESULTS: We found that low expression of shisa3 was related to EGFR-TKI resistance in lung adenocarcinoma patients. Ectopic overexpression of shisa3 inhibited CSC properties and the cell cycle in the lung adenocarcinoma cells resistant to gefitinib/osimertinib. In contrast, suppression of shisa3 promoted CSC phenotypes and the cell cycle in the cells sensitive to EGFR-TKIs. For TKI-resistant PC9/ER tumors in nod-scid mice, overexpressed shisa3 had a significant inhibitory effect. In addition, we verified that shisa3 inhibited EGFR-TKI resistance by interacting with FGFR1/3 to regulate AKT/mTOR signaling. Furthermore, combinational administration of inhibitors of FGFR/AKT/mTOR and cell cycle signaling could overcome EGFR-TKI resistance associated with shisa3-mediated CSC capacities in vivo. CONCLUSION: Taken together, shisa3 was identified as a brake to EGFR-TKI resistance and CSC characteristics, probably through the FGFR/AKT/mTOR and cell cycle pathways, indicating that shisa3 and concomitant inhibition of its regulated signaling may be a promising therapeutic strategy for reversing EGFR-TKI resistance.

14.
Int Immunopharmacol ; 78: 106043, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31837574

RESUMO

Protectin DX (PDX) has been reported to have extensive anti-inflammatory effects. However, it is unknown whether PDX acts as an anti-inflammatory agent in the context of osteoarthritis (OA). This study aimed to evaluate the anti-inflammatory activity of PDX in vitro and in vivo in a model of OA. Primary rat chondrocytes were preincubated with PDX 1 h prior to IL-1ß treatment for 24 h. We found that PDX was nontoxic, and pretreatment with PDX increased cell viability in IL-1ß-induced chondrocytes. Preincubation with PDX also efficiently inhibited the degradation of type II collagen dose-dependently. Additionally, the expression of MMP-3, MMP-13, ADAMTS4, iNOS, COX-2, NO, and PGE2 decreased after IL-1ß stimulation when cells were preincubated with PDX. Moreover, PDX inhibited the increase in phosphorylated NF-κB p65 and IκBα upon IL-1ß stimulation, and the negative effects of IL-1ß on chondrocytes were partially blocked by treatment with pyrrolidine dithiocarbamate (PDTC), a selective NF-κB inhibitor. In addition, we found that PDX increased AMPK phosphorylation in IL-1ß-mediated chondrocytes. The phosphorylation of AMPK could be inhibited by compound C, a classic AMPK inhibitor. Compound C also remarkably reversed the decrease in p65 phosphorylation and MMP-13 expression caused by PDX. Furthermore, nuclear translocation of NF-κB was visible by immunofluorescence after PDX-induced AMPK activation. Additionally, we verified that PDX ameliorated cartilage degradation in monosodium iodoacetate (MIA)-induced OA rats through histological evaluation and ELISA of TNF-α in the serum and intra-articular lavage fluid. In conclusion, we have shown that PDX suppresses inflammation in chondrocytes in vitro and in vivo, likely through the AMPK/NF-κB signaling pathway. Our results suggest that PDX could be a useful novel therapeutic agent for OA treatment.

15.
J Toxicol Environ Health A ; 82(21): 1103-1112, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31825292

RESUMO

Microcystin-LR (MC-LR), a frequently occurring hepatotoxic cyanotoxin produced by cyanobacterial blooms, poses a great threat to human health. However, the precise molecular mechanisms underlying MC-LR-induced hepatotoxicity remain to be determined. Recent investigators found that in many human diseases circular RNAs (circRNAs) a class of endogenous non-coding RNAs played critical roles in disease outcomes. The aim of this study was to investigate whether circRNAs were involved in MC-LR-mediated hepatotoxicity using human normal liver cell line (HL7702). Using high-throughput sequencing analysis data demonstrated that expression levels of 3250, 3111, 3097, 3253 circRNAs were significantly altered at concentrations ranging from 1 to 10 µM MC-LR. Expression levels of hsa_circRNA_0000657 and hsa_circRNA_0000659 were down-regulated while hsa_circRNA_0003247 and hsa_circRNA_0001535 were up-regulated in all MC-LR-exposed groups. The high-throughput sequencing results of selected circRNAs differential expression genes (DEGs) levels were verified by real-time fluorescent quantitative PCR (qRT-PCR). Gene Ontology (GO) enrichment analysis showed that the functions of circRNAs significantly altered in HL7702 cells were predominantly associated with metabolism, systems development, and protein binding. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis data revealed that the target genes of differentially expressed circRNAs in HL7702 cells were involved in FoxO signaling pathway, protein processing in endoplasmic reticulum, Ras signaling pathway, cell cycle, PI3K-Akt signaling pathway, MAPK signaling pathway and pathways in cancer. In summary, evidence indicates that a correlation may exist between circRNAs and MC-LR-induced hepatotoxicity.

16.
Regen Med ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31829095

RESUMO

Aim: To determine the efficacy and safety of intracoronary infusion of autologous bone marrow mesenchymal stem cells (MSCINJ) in combination with intensive atorvastatin (ATV) treatment for patients with anterior ST-segment elevation myocardial infarction-elevation myocardial infarction. Patients & methods: The trial enrolls a total of 100 patients with anterior ST-elevation myocardial infarction. The subjects are randomly assigned (1:1:1:1) to receive routine ATV (20 mg/d) with placebo or MSCsINJ and intensive ATV (80 mg/d) with placebo or MSCsINJ. The primary end point is the absolute change of left ventricular ejection fraction within 12 months. The secondary end points include parameters in cardiac function, remodeling and regeneration, quality of life, biomarkers and clinical outcomes. Results & conclusion: The trial will implicate the essential of cardiac micro-environment improvement ('fertilizing') for cell-based therapy. Clinical Trial Registration: NCT03047772.

17.
Kaohsiung J Med Sci ; 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31859425

RESUMO

The present study explored a new downstream regulator of Stat-3 signaling, miR-499-5p and its target gene programmed cell death 4 (PDCD4) in cell survival and metastasis of gastric cancer. Our results showed that miR-499-5p is significantly upregulated in human gastric cancer cell line SGC-7901. We further demonstrated that miR-499-5p promotes gastric cancer cell proliferation and invasion in vitro. Mechanistically, we demonstrated that upregulation of miR-499-5p expression associated with inhibition of PDCD4; STAT3 transcriptional activation by IL-6 is crucial for the upregulation of miR-499-5p expression. These results indicate that the STAT3-miR-499-5p-PDCD4 signaling axis plays an important role in gastric cancer progression and a potentially therapeutic target for gastric cancer treatment.

18.
Jpn J Clin Oncol ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31868876

RESUMO

PURPOSE: Nomograms are intuitive tools for individualized cancer prognosis. We sought to develop a clinical nomogram for prediction of overall survival and cancer-specific survival for patients with colorectal cancer. METHODS: Patients with colorectal cancer diagnosed between 1988 and 2006 and those who underwent surgery were retrieved from the Surveillance, Epidemiology, and End Results database and randomly divided into the training (n = 119 797) and validation (n = 119 797) cohorts. Log-rank and multivariate Cox regression analyses were used in our analysis. To find out death from other cancer causes and non-cancer causes, a competing-risks model was used, based on which we integrated these significant prognostic factors into nomograms and subjected the nomograms to bootstrap internal validation and to external validation. RESULTS: The 1-, 3-, 5- and 10-year probabilities of overall survival in patients of colorectal cancer after surgery intervention were 83.04, 65.54, 54.79 and 38.62%, respectively. The 1-, 3-, 5- and 10-year cancer-specific survival was 87.36, 73.44, 66.22 and 59.11%, respectively. Nine independent prognostic factors for overall survival and nine independent prognostic factors for cancer specific survival were included to build the nomograms. Internal and external validation CI indexes of overall survival were 0.722 and 0.721, and those of cancer-specific survival were 0.765 and 0.766, which was satisfactory. CONCLUSIONS: Nomograms for prediction of overall survival and cancer-specific survival of patients with colorectal cancer. Performance of the model was excellent. This practical prognostic model may help clinicians in decision-making and design of clinical studies.

19.
Curr Pharm Des ; 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31880242

RESUMO

BACKGROUND: Ghrelin (GHRL) is a polypeptide, which can specifically bind to the GHSR. The expression of GHSR has significant differences in human normal and prostate cancer tissues. It is meaningful to find an effective diagnostic method for the diagnosis and prognosis of invasive/neuroendocrine prostate cancer. METHODS: GHRL and GHSR mRNAs level were determined by quantitative real-time polymerase chain reaction in PC tissues. The expression of GHRL and GHSR proteins were assessed respectively by western blot and immunohistochemistry. GHRL polypeptide probe was synthesized through standard solid-phase synthesis of polypeptide, and labeled with Alexa Fluor 660. Confocal microscope was used to capture fluorescence images. Living imaging analysis show tumor areas of different invasiveness in mice models. RESULTS: The level of GHRL and GHSR copy number amplification and mRNA expression were increased in invasive/neuroendocrine prostate cancer, and the protein expression of GHRL and GHSR were similarly boosting in NEPC. The GHRL polypeptide probe could effectively bind to GHSR. In PC3, we found that GHRL probe specifically bind to GHSR on cell membrane and accumulated in cells through internalization after binding. Living imaging in mice models showed that there were different signal intensities in tumor areas of different invasiveness. CONCLUSION: The GHSR and GHRL might be used to the molecular imaging diagnosis for invasive/neuroendocrine prostate cancer in future.

20.
Cell Biol Int ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31868949

RESUMO

Long non-coding RNAs (lncRNAs) were reported to be involved in the progression of osteoarthritis (OA). The aim of this work was to explore the functional role of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in OA. Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was employed to analyze the expression of microRNA (miR-193a)-3p, NEAT1, and sex-determining region Y-box protein 5 (SOX5), as well as the levels of pro-inflammatory cytokines interleukin-6 (IL-6), IL-1ß, tumor necrosis factor-α (TNF-α), and IL-8 in OA cartilage tissue and chondrocytes. In addition, flow cytometry was used to measure the apoptosis of chondrocytes. The protein levels of extracellular matrix ACAN, collagen type II α1 chain (Col2a1), matrix metalloproteinase-3 (MMP-3), MMP-13, a disintegrin, and metalloproteinase with thrombospondin motifs (ADAMTS)-5 and SOX5 were determined using western blot analysis. Dual-luciferase reporter assay was performed to determine the target relationship among NEAT1, miR-193a-3p, and SOX5. We found that miR-193a-3p expression was downregulated, while NEAT1 and SOX5 were upregulated in OA cartilage tissue and chondrocytes. Both upregulation of miR-193a-3p and knockdown of NEAT1 suppressed inflammation, apoptosis, and reduced the protein levels of MMP-3, MMP-13, and ADAMTS-5, while elevating ACAN and Col2a1 expression in chondrocytes. NEAT1 targeted miR-193a-3p, and SOX5 was targeted by miR-193a-3p. Silencing of miR-193a-3p reversed the NEAT1 knockdown-mediated effect on the inflammation, apoptosis, and production of the extracellular matrix. The introduction of SOX5 abolished the impact of the upregulation of miR-193a-3p on inflammation, apoptosis, and production of extracellular matrix in chondrocytes. In conclusion, NEAT1/miR-193a-3p/SOX5 axis regulates cartilage matrix degradation in human OA.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA