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1.
Eur J Clin Pharmacol ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32157329

RESUMO

PURPOSE: To evaluate the influence of three proton pump inhibitors (PPIs) on plasma voriconazole (VOR) concentrations and characterize potential drug-drug interactions (DDIs) between VOR and three PPIs (omeprazole, lansoprazole, and pantoprazole) in Chinese patients with malignant hematological diseases. METHODS: A simple and reliable 2D-HPLC with internal quality control method was used to ensure accurate concentration measurements. A total of 194 patients in this retrospective study were divided into control (N = 59), omeprazole (OME, N = 57), lansoprazole (LAN, N = 26), and pantoprazole (PAN, N = 52) groups for comparison of plasma VOR trough concentrations. To further validate our retrospective analysis of clinical data, we used molecular docking simulation to analyze the binding affinity of PPIs to the cytochrome P450 2C19 (CYP2C19) and cytochrome P450 3A4 (CYP3A4) enzymes that are integral to the metabolism of PPIs and VOR. RESULTS: Our findings indicated that VOR trough concentrations were significantly higher in patient on PPIs compared with those who were not (P = 0.012). Patients on LAN (P < 0.01) or OME (P < 0.05) had significantly elevated VOR concentrations compared with the control group, whereas those on PAN did not. Although VOR trough concentrations were not significantly elevated with PAN, more patients in the PAN group reached therapeutic VOR concentrations than in any other group. CONCLUSION: In conclusion, our retrospective data analysis and molecular docking simulations results indicate that LAN and OME interact with VOR via CYP2C19 and CYP3A4 to increase VOR plasma concentrations. This study helps with selection of PPIs in Chinese patients with malignant hematological cancer administered VOR.

2.
Adv Mater ; : e2000827, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32134520

RESUMO

It is remarkably desirable and challenging to design reconfigurable ferromagnetic materials with high electrical conductivity. This has attracted great attention due to promising applications in many fields such as emerging flexible electronics and soft robotics. However, the shape and magnetic polarity of existing ferromagnetic materials with low conductivity are both hard to be reconfigured, and the magnetization of insulative ferrofluids is easily lost once the external magnetic field is removed. A novel reconfigurable ferromagnetic liquid metal (LM) plasticine (FM-LMP) with high electrical conductivity and transformed shape, which is prepared through homogenously mixing neodymium-iron-boron microparticles into the gallium-based LM matrix, and turning this liquid-like suspension into the solid-like plasticine by magnetization, is reported to achieve this. The induction magnetic field of FM-LMP is mainly attributed to the magnetic alignment of the dispersed ferromagnetic microparticles, which can be conveniently demagnetized by mechanical disordering and reversibly reconfigured through microparticle realignment by applying a weak magnetic field. FM-LMP with a low fraction of microparticles can be used as printable conductive ink for paper electronics, which are further exploited for applications including magnetic switching, flexible erasable magnetic recording paper, and self-sensing paper-based soft robotics using magnetic actuation.

3.
Food Chem ; 319: 126232, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32197213

RESUMO

Yeast ß-glucan (YG) adsorbs off-odor in silver carp mince due to its more porous structure. To explore adsorption behavior and mechanism, adsorption kinetics and thermodynamics of YG for 3 off-odor compounds (hexanal, 1-octen-3-ol and nonanal) were investigated by pseudo-first/second-order models and isothermal equations (Langmuir, Freundlich and Redlich-Peterson). Kinetic experiments indicated adsorption process followed pseudo-first-order model. Adsorption isotherms indicated 3 off-odors could easily be adsorbed by YG and adsorption capacity was in the order of 1-octene-3-ol > hexanal > nonanal. Thermodynamic result suggested adsorption of 3 off-odors by YG was endothermic and spontaneous, and was driven predominantly by physisorption and hydrophobic interaction. Consequently, the contents of 3 off-odors that released from mince/YG complex decreased by 22.8%, 29.9%, and 24.5% (p < 0.05), respectively, compared with those from mince without YG. Therefore, the addition of YG enhanced the binding capability to off-odors, thus reducing the release of off-odor from silver carp mince.

4.
Brain Imaging Behav ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125619

RESUMO

Deqi is taken as an indispensable requirement to achieve acupuncture efficacy. This study aimed to explore the central influence of deqi on the efficacy of acupuncture for functional dyspepsia (FD). 70 FD patients were randomized to receive 20 sessions' acupuncture treatment with (n = 35) and without deqi (n = 35). In each group, 25 FD patients randomly selected underwent functional magnetic resonance imaging (fMRI) scans before and after treatment. After group re-division according to deqi response, changes of amygdala subregions-based resting-state functional connectivity (rsFC) were compared between the acupuncture with and without obvious deqi group. The clinical changes of the Nepean Dyspepsia Symptom Index (NDSI) measuring FD symptoms were also used to further assess the correlation with amygdala subregions rsFC in FD patients. The decrease in the NDSI scores (pre-pos) in the obvious deqi group was significantly greater than that in the acupuncture without obvious deqi group (p < 0.05). Compared to the without obvious deqi group, the obvious deqi group showed significantly decreased the left basolateral amygdala (BLA) rsFC with bilateral insular (INS), putamen and middle/posterior cingulate cortex (MCC/PCC), right pallidum and hippocampus (HIPP) after treatment. The changed NDSI scores(pre-post) of all 41 FD patients was significantly positively correlated with their Fisher's transformed z value of the left BLA rsFC with left INS (r = 0.376, FDR corrected p = 0.015), and rsFC with right HIPP (r = 0.394, FDR corrected p = 0.015). The changed NDSI scores(pre-post) of the obvious deqi group was significantly negatively correlated with their Fisher's transformed z value of the right centromedial amygdala (CMA) rsFC with left medial prefrontal cortex (mPFC) (r = -0.463, p = 0.035). The results tested the hypothesis that the advantage of deqi on efficacy is related to affecting the BLA and CMA rsFC. It suggested that deqi might influence the abnormal rsFC within the salience network (SN), and participate in the adaptive modulation of disrupted relationship between the SN and default mode network (DMN).

5.
J Clin Lab Anal ; : e23239, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125733

RESUMO

BACKGROUND: MicroRNAs (miRNAs) is a class of functional regulator of tumorigenesis of human cancer including hepatocellular carcinoma (HCC). However, the potential clinical significance of serum exosomal miR-320d in HCC has not been elucidated. METHODS: Real-time reverse transcription PCR was used to detect the expression pattern of serum exosomal miR-320d in patients with HCC, and the correlation between the deregulation of serum exosomal miR-320d and the clinical outcome of HCC was explored. The biological function of exosomal miR-320d in HCC was also investigated. RESULTS: Our results showed that the expression levels of exosomal miR-320d were remarkably reduced in the serum samples of HCC patients and the culture medium of HCC cell lines compared with their respective controls. Serum exosomal miR-320d could differentiate the HCC patients from healthy controls with high accuracy. In addition, its level was remarkably increased in the HCC patients who had received surgical treatment. Moreover, reduced serum exosomal miR-320d was associated with advanced tumor stage, positive lymph node metastasis, and poorly differentiated tumors. HCC patients with lower serum exosomal miR-320d had shorter overall and disease-free survival. Low serum exosomal miR-320d was identified to be an independent unfavorable prognostic factor for HCC. Finally, overexpression of miR-320d inhibited the proliferation and invasion of HCC cells, and BMI1 was demonstrated to be a direct target of miR-320d. CONCLUSION: Taken together, serum exosomal miR-320d could be a potential non-invasive biomarker for the diagnosis and prognosis of HCC.

6.
Int J Clin Pharm ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32048122

RESUMO

Like other countries, China has been experiencing drug shortages during the past years, including drugs on the National Essential Medicine List and emergency drugs. Drug shortages have raised public concerns in China and have severe impacts on all stakeholders in the supply chain, especially patients and hospitals. Recently, Chinese governments have ramped up several measures to ensure a steady supply of essential and first-aid drugs. In this commentary, we share our experiences of addressing drug shortages at Hunan Province, central China. We focus on the establishment of a provincial drug shortage monitoring center, and the Center's efforts to standardize practices on the management of drug shortages and identify therapeutic alternatives for drugs in short supply based on international best practices.

7.
Surg Endosc ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32072279

RESUMO

BACKGROUND: Bleeding control as one of the major challenges in laparoscopic pancreaticoduodenectomy (LPD) necessitates a considerable anatomical knowledge of the blood supply to the pancreatic head so as to improve the safety of this surgery. This study aimed towards a better understanding of the anatomical features of the dorsal pancreatic artery (DPA), as well as its clinical significance in LPD. METHOD: Thirteen Chinese cadaveric specimens were used to study the blood supply of the pancreatic head. Twelve of them were perfused with latex, and the other fresh one was used to build the intraorganic structure model of the pancreas by mold casting. Between July 2018 and June 2019, a total of thirty-five consecutive patients without vascular encasement, who underwent LPD in our institute, were performed with computed tomography as a preoperative detection of the DPA. The DPA was ligated prior to uncinate process dissection in seventeen patients ("early DPA ligation" group), as the others were assigned into the control group. RESULTS: In the thirteen cadaveric specimens, the DPA originates, respectively, from the splenic artery (46.1%), superior mesenteric artery (38.5%), common hepatic artery (7.7%) and right gastroepiploic artery (7.7%). The right branch of the DPA gives off terminal arteries to form an "inner ring" in the pancreatic head, which communicates with the pancreaticoduodenal arterial arches by plenty of collateral arteries. As compared to the control group, the "early DPA ligation" group showed a significantly lower mean blood loss (218 ± 111 vs 320 ± 162, P = 0.038), as well as shorter mean resection time (121 ± 23 vs 136 ± 22, P = 0.049). CONCLUSION: The DPA is one of the major blood supplies to the pancreatic head. A ligation of DPA prior to dissection of the uncinate process can help to completely block the blood supply to the pancreatic head, and therefore improve surgical outcome and safety in LPD.

8.
J Cell Physiol ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31957875

RESUMO

Long noncoding RNA (lncRNA) has been considered as potentially critical regulators in pancreatic ductal adenocarcinoma (PDAC). In this study, we prospectively investigate the effect and mechanism of lncRNA integrin subunit beta 2-anti-sense RNA 1 (ITGB2-AS1) on regulation of PDAC progression. The expression of ITGB2-AS1 and its target were analyzed by quantitative real-time polymerase chain reaction and in situ hybridization. 3-(4,5-Dimethylthiazol-z-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, wound healing, and transwell assays were used to investigate the influence of ITGB2-AS1 on cell proliferation, cell cycle, migration, and invasion, respectively. The interaction between ITGB2-AS1 and its target was determined via luciferase activity assay and RNA immunoprecipitation. The subcutaneous xenotransplanted tumor model was established and employed to detect the tumorigenic function of ITGB2-AS1, which was evaluated by western blot analysis, immunohistochemistry, and hematoxylin and eosin staining. The results showed that ITGB2-AS1 was elevated in both PDAC tumor tissues and cell lines, predicting a poor prognosis in PDAC patients. Knocking down of ITGB2-AS1 suppressed PDAC cell proliferation, invasion, and migration but induced cell apoptosis in vitro. Moreover, ITGB2-AS1 could target and inhibit the expression of miR-4319 and miR-4319-targeted and -suppressed serine/threonine kinase RAF1. ITGB2-AS1 promoted PDAC progression via inhibition of miR-4319. Interference of ITGB2-AS1 could suppress in vivo tumorigenic ability of PDAC via downregulation of RAF1. In conclusion, ITGB2-AS1 promoted PDAC progression via sponging miR-4319 to upregulate RAF1, suggesting the potential therapeutic target ability of ITGB2-AS1 in PDAC.

9.
J Vasc Res ; : 1-10, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31968349

RESUMO

Diabetes mellitus (DM)-induced impairment of collateral formation has been demonstrated in subjects with coronary artery disease, which contributes to unfavorable prognosis among diabetic individuals. In our previous studies, thioredoxin1 (Trx1) activity was shown to be decreased in diabetic cardiac tissues, but the reason of Trx1 inactivation and whether it mediates the impaired angiogenesis in ischemic myocardium is still to be identified. As thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of Trx, is overexpressed in DM due to carbohydrate response element within its promoter, we hypothesized that inhibition of Trx1 by enhanced TXNIP expression in endothelial cells may play a role in hyperglycemia-induced impairment of angiogenesis. In the present study, we found that high glucose-mediated increase of TXNIP expression and TXNIP-Trx1 interaction induced the impairment in endothelial cell function and survival, since these detrimental effects are rescued by silencing TXNIP with small interfering RNA. In diabetic mice, TXNIP knockdown or recombinant human Trx1 treatment counteracted the impairment of angiogenesis, alleviated myocardial ischemic injury, and improved survival rate. All these data implicate that TXNIP upregulation and subsequently the increased formation of TXNIP-Trx1 complex is a novel pathologic pathway by which DM induces insufficient angiogenesis and thereby exacerbates myocardial ischemia injury.

10.
Biochem Biophys Res Commun ; 523(1): 147-152, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-31836141

RESUMO

Hepatocellular carcinoma which is featured with the extensive vascularization is the third most frequent cause of cancer-related deaths with limited therapeutic options, particularly for advanced disease. Cobimetinib, a MEK inhibitor, has been approved for the treatment of melanomas with a BRAF mutation. In this work, we investigated the efficacy of cobimetinib in sensitive and resistant HCC cells. Using a panel of HCC cell lines and normal hepatocellular cells as control, we showed that cobimetinib is active against HCC cells and spare normal hepatocellular cells. Cobimetinib at nanomolar concentration inhibited proliferation and induced apoptosis in sorafenib-resistant HCC cells (Hep3B-r), suggesting its ability to overcome HCC resistance to standard of care. This was further demonstrated by our results that cobimetinib significantly augmented the inhibitory effects of sorafenib and doxorubicin in HCC cells. Notably, cobimetinib dose-dependently inhibited tumor angiogenesis by inhibiting HCC endothelial cell (HCCEC) growth, survival and capillary network work formation. Cobimetinib suppressed ERK/RSK without affecting JNK or p38 signaling pathways in Hep3B-r and HCCEC cells. In addition, cobimetinib negatively influenced the apoptosis pathways by increasing pro-apoptotic protein Bim and decreasing anti-apoptotic proteins Mcl-1 and Bcl-2. In addition, we validated the in vitro findings in HCC xenograft mouse model and demonstrated that cobimetinib inhibited ERK signaling, promoted apoptosis, and was active against resistant HCC growth and angiogenesis in vivo, without causing significant toxicity in mice. Our findings support the clinical trials of cobimetinib for HCC treatment and highlight the therapeutic value of inhibiting MEK/ERK/RSK to overcome HCC resistance.

11.
Cardiovasc Res ; 116(3): 645-657, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31241142

RESUMO

AIMS: Either insufficient or excessive autophagy causes cellular death and contributes to myocardial ischaemia/reperfusion (I/R) injury. However, mechanisms controlling the 'right-level' of autophagy in the heart remains unidentified. Thioredoxin-interacting protein (TXNIP) is a pro-oxidative molecule knowing to contribute to I/R injury. However, whether and how TXNIP may further inhibit suppressed autophagy or promote excessive cardiac autophagy in I/R heart has not been previously investigated. METHODS AND RESULTS: Wild type or gene-manipulated adult male mice were subjected to myocardial I/R. TXNIP was increased in myocardium during I/R. Cardiac-specific TXNIP overexpression increased cardiomyocytes apoptosis and cardiac dysfunction, whereas cardiac-specific TXNIP knock-out significantly mitigated I/R-induced apoptosis and improved cardiac function. Importantly, TXNIP overexpression significantly promoted cardiac autophagy and TXNIP knock-out significantly inhibited cardiac autophagy. In vitro studies demonstrated that TXNIP increased autophagosome formation but inhibited autophagosome clearance during myocardial reperfusion. Atg5 siRNA significantly decreased hypoxia/reoxygenation induced apoptosis in cardiomyocytes with TXNIP overexpression. Mechanistically, TXNIP suppressed autophagosome clearance via increasing reactive oxygen species (ROS) level. However, TXNIP-increased autophagosome formation was not mediated by ROS as a ROS scavenger failed to block increased autophagosome formation in TXNIP overexpression heart. Finally, TXNIP directly interacted and stabilized Redd1 (an autophagy regulator), resulting in mTOR inhibition and autophagy activation. Redd1 knock-down significantly reduced autophagy formation and ameliorated I/R injury in TXNIP overexpression hearts. CONCLUSIONS: Our results demonstrated that increased TXNIP-Redd1 expression is a novel signalling pathway that contributes to I/R injury by exaggerating excessive autophagy during reperfusion. These observations advance our understanding of the mechanisms of myocardial I/R injury.

12.
Huan Jing Ke Xue ; 41(1): 368-376, 2020 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854939

RESUMO

The Shen-Fu region is an important urban area in northeast China. We report on a study of the distribution of polybrominated diphenyl ethers (PBDEs) in representative topsoil from this region. In the summer of 2016, 72 soil samples from three cities (Shenyang, Fushun, and Shen-Fu New City) were collected, which covered four land use types:urban, rural residential, cultivated, and woodland. We report on the concentrations, compositions, and distributions of 14 PBDEs in soil and explore their sources, and additionally undertake human exposure analysis and health risk assessments. The results showed that the concentration of ∑14PBDEs in the topsoil ranged from 0.279-50.719 ng·g-1(dry weight), with a mean of (10.466±9.246) ng·g-1. The concentrations of PBDEs was ranked for the cities as:Fushun > Shenyang > Shen-Fu New City > background, and for different land use types as:urban land > rural residential land > cultivated land > forest. Deca-PBDE had the highest proportion of all congeners, accounting for 81.25%-89.23% of all PBDEs. Source analysis indicated that commercial Deca-PBDE was the main source, contributing 66.06% of the total Deca-PBDE according to principal component analysis/multiple linear regression (PCA-MLR). Among five different age groups assessed for exposure, children in Fushun had the highest exposure dose:(20.98±25.01) ng·(kg·d)-1. In terms of different land types, the highest exposure dose was for children living in urban areas:(18.54±20.27) ng·(kg·d)-1. The non-oncogenic health risks in the Shen-Fu region are of a relatively low level.


Assuntos
Monitoramento Ambiental , Éteres Difenil Halogenados/análise , Poluentes do Solo/análise , Criança , China , Cidades , Humanos , Medição de Risco
13.
Huan Jing Ke Xue ; 40(7): 3369-3377, 2019 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854740

RESUMO

To study the vertical distribution characteristics of polycyclic aromatic hydrocarbons (PAHs) in the soils from different land use types during urbanization, three land use types (urban land, cultivated land, and woodland) were selected in the eastern part of Shenyang, where urbanization is occurring rapidly. In each case, five soil samples were obtained from different depths (0-1 m). Change in the concentrations of PAHs, vertical migration factors, and the distribution and sources of PAHs were analyzed in the vertical soil profiles. Total concentrations of PAHs in the different soil type were ordered as follows:city 1 (513.19-12689.04 µg·kg-1); dry field (36.18-7196.10 µg·kg-1); paddy field (70.92-747.53 µg·kg-1); city 2 (19.39-636.47 µg·kg-1); and woodland (4.79-349.24 µg·kg-1). PAHs were mainly trapped in shallow soils in urban and forest land, but can migrate deeper into the soil profile in cultivated land. High-ring PAHs were abundant at depths of 0-30 cm, while low-ring PAHs were abundant deeper in the soil profiles. SOM had a significant effect on the vertical distribution of PAHs, and the physical and chemical properties of PAHs had a significant influence on their migration ability. However, combustion sources from industrial activities and transportation in the region are still considered the main sources of PAHs despite the fact that some low-ring PAHs derive from petroleum product inputs.

14.
Front Behav Neurosci ; 13: 241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31680896

RESUMO

Transcranial ultrasound stimulation (TUS; f < 1 MHz) is a promising approach to non-invasive brain stimulation. Transcranial magneto-acoustic stimulation (TMAS) is a technique of neuromodulation for regulating neuroelectric-activity utilizing a magnetic-acoustic coupling electric field generated by low-intensity ultrasound and magnetic fields. However, both techniques use the physical means of low-intensity ultrasound and can induce the response of the motor cortex. Therefore, it is necessary to distinguish the difference between the two techniques in the regulation of neural activity. This study is the first to quantify the amplitude and response latency of motor cortical electromyography (EMG) in mice induced by TMAS and TUS. The amplitude of EMG (2.73 ± 0.32 mV) induced by TMAS was significantly greater than that induced by TUS (2.22 ± 0.33 mV), and the EMG response latency induced by TMAS (101.25 ± 88.4 ms) was significantly lower than that induced by TUS (181.25 ± 158.4 ms). This shows that TMAS can shorten the response time of nerve activity and enhance the neuromodulation effect of TUS on the motor cortex. This provides a theoretical basis for revealing the physiological mechanisms of TMAS and the treatment of neuropsychiatric diseases using it.

15.
Brain Behav ; 9(12): e01469, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31724337

RESUMO

OBJECTIVE: This study aims to explore the curative effect of dl-3-n-butylphthalide (NBP) on patients with acute cerebral infarction (ACI) and its effects on serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and hypersensitive C-reactive protein (hs-CRP) levels. METHODS: A total of 136 ACI patients treated in our hospital, who met the criteria, were selected and randomly divided into two groups: control group (n = 60, including 28 males and 32 females) and treatment group (n = 76, including 32 males and 44 females). Patients in the control group were treated with routine drug therapy, while patients in the treatment group were treated with NBP on this basis. A dose of 100 ml was administered by intravenous injection for 2 times/day, for 14 days. The curative effect was evaluated using the National Institute of Health Stroke Scale (NIHSS) and Barthel index (BI) self-care ability. The levels of the two factors in serum were measured using enzyme-linked immunosorbent assay, and the changes in levels of these two factors in serum at different time points before and after treatment were compared between the two groups. RESULTS: (a) Lp-PLA2 and hs-CRP levels in the treatment group after treatment were significantly lower than those before treatment and those in the control group after treatment (p < .05). (b) The NIHSS and BI scores in the treatment group were significantly lower after treatment than before treatment and those in the control group after treatment (p < .05). CONCLUSION: Dl-3-n-butylphthalide can improve the expression of Lp-PLA2 and hs-CRP in serum in ACI patients. Furthermore, NBP has significant efficacy in inhibiting inflammation and improving neurological symptoms.

16.
Onco Targets Ther ; 12: 7149-7156, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564899

RESUMO

Background: GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is involved in various biological functions, including cell growth, metastasis, differentiation, apoptosis, and RNA metabolism. In current study, we aimed to investigate the effect of G3BP1 on gastric cancer (GC). Methods: The expression of G3BP1 in GC tissues and cell lines was assessed by immunohistochemistry and Western blotting. Correlations of G3BP1 expression with clinicopathological and prognosis of GC patients were evaluated. The functions of G3BP1 in regulating proliferation, migration and invasion of GC cell were investigated using small interfering RNA (siRNA) strategies. Preliminary exploration of its underlying mechanism using Western blotting. Results: G3BP1 expression was upregulated in GC tissues compared with adjacent tissues, and the higher G3BP1 expression was correlated with poor prognosis. G3BP1 knockdown decreased GC cell proliferation, migration and invasion. Mechanistically, silencing of G3BP1 inhibits the activation of the transforming growth factor (TGF)-ß/Smad signaling pathway in GC cells. Conclusion: G3BP1 plays an important role in the progression of GC as an oncogene and may become a new therapeutic target.

17.
PLoS One ; 14(10): e0224352, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31648284

RESUMO

OBJECTIVES: The primary objective of this study was to establish a novel method to assess the effect of imipenem/cilastatin (IMP) on liver function laboratory indexes in Chinese underage inpatients (inpatients aged <18 year-old). METHODS: A retrospective study was conducted in 188 underage inpatients who received IMP in Xiangya Hospital from January 2016 to April 2018. Demographic data and clinical information of these inpatients were collected. As there was no reference interval of minors, the occurrence of abnormal liver function was estimated by that of adults, temporarily. A new concept (mean-variance induced by drug, MVID) was introduced to analyze the characteristics of total bilirubin (TBil), direct bilirubin (DBil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Effect of MVID of TBil, DBil, ALT and AST in different patients (aged<1 year old and aged ≥ 1 year old) were compared by Mann-Whitney U test. RESULTS: Estimating by reference intervals of adults, 57.4% underage inpatients (108/188) had abnormal liver function. According to the probability distribution curve of MVID, IMP can cause the increase of AST in 24% (0.62-0.38) Chinese underage inpatients, and the increase of ALT in 20% (0.60-0.40) Chinese underage inpatients. And liver protecting drugs can decrease MVID of ALT and AST. There were not statistically significant differences in MVID of TBil, DBil, ALT and AST in different patients (aged<1 year old and aged ≥ 1 year old); P value was 0.711, 0.734, 0.067 and 0.086, respectively. CONCLUSION: IMP can affect the liver function of 20-24% Chinese underage inpatients mainly by increasing the AST and ALT. IMP may induce hepatocellular injury, but not cholestasis. And liver protecting drugs can reverse the side effects caused by IMP. Age may not affect the effect of IMP on liver function.

18.
Medicine (Baltimore) ; 98(42): e17412, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626095

RESUMO

BACKGROUND: Long non-coding RNA colon cancer-associated transcript 2 (CCAT2) is a 1752-bp lncRNA transcribed from m8q24 genomic region. A lot of investigations have confirmed the involvement of CCAT2 in the tumorigenesis of many cancer types. Previous studies found that over-expression of CCAT2 significantly promoted cell migration and proliferation, and inhibited apoptosis of HCC cells. In the present investigation, the clinical value and prognostic significance of CCAT2 were investigated. METHODS: The 122 pairs of HCC tissues and adjacent normal liver tissues were acquired between September 2013 and February 2018. The expression levels of CCAT2 in HCC tissues and their corresponding adjacent normal liver tissues were examined by RT-qPCR analysis. Survival was calculated using the Kaplan-Meier method and analyzed using the log-rank test. Independent prognostic indicators were determined in the multivariate analysis using Cox's proportional hazard model. RESULTS: CCAT2 expression levels were significantly increased in HCC tissues compared to that in their normal counterparts (P < .001). CCAT2 expression was significantly correlated with vascular invasion (P = .001), histopathologic grading (P = .001), distant metastasis (P = .002) and TNM stage (P = .018). A Kaplan-Meier survival curve showed that the overall survival rate of HCC patients in high CCAT2 expression group markedly decreased as compared with that of low CCAT2 expression group (P = .016). In addition, COX multivariate analysis showed that high expression of CCAT2 was an independent risk factor for predicting shorter overall survival time in HCC (HR = 2.126, 95%CI:1.273-8.775, P = .021). CONCLUSIONS: Taken together, this research revealed that lncRNA CCAT2 may serve as a potential biomarker for predicting overall survival time in HCC.


Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima/genética
19.
Technol Cancer Res Treat ; 18: 1533033819871300, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31564215

RESUMO

Non-coding RNAs, originally considered junk gene products, have taken center stage in view of their significant involvement in a spectrum of biological processes during human development, thereby offering novel therapeutic targets for improvement of treatment options. Accumulating evidence has demonstrated non-coding RNA dysfunction across various human cancers. In particular, microRNAs have emerged as key regulatory molecules in cancer biology. MicroRNAs are noninvasive, readily accessible biomarkers that can be effectively applied for diagnosis and prognosis of different tumor types, including colon cancer. In this study, we reanalyzed the available data with bioinformatics tools to identify differentially expressed microRNAs in colon cancer cells. The top 3 upregulated microRNAs (miR-10, miR-199, and miR-122) in colon cancer cells were further validated in tissues of clinical patients via reverse transcription-quantitative polymerase chain reaction. Our results showed that miR-122 significantly promotes the proliferation and invasion ability of SW480 and SW620 cells through inhibition of Aldolase, Fructose-Bisphosphate A (ALDOA) expression. We further summarized recent advances in our understanding of the functional relevance of microRNAs in cancer development and discussed the possible implications of specific microRNAs in colon cancer. This study extends our knowledge of microRNA involvement in colon cancer biology and presents novel candidates for the development of attractive therapeutic strategies.


Assuntos
Carcinogênese/genética , Neoplasias do Colo/genética , Frutose-Bifosfato Aldolase/genética , MicroRNAs/genética , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias do Colo/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia
20.
Front Oncol ; 9: 855, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552179

RESUMO

Objective: To investigate the role of myeloid-derived suppressor cells (MDSC) in cancer progression after the stress of operative removal and the potential treatment value of MDSC depletion. Summary Background Data: Surgery is the most important treatment strategy in breast cancer. Recent research has provided evidence that operations may promote cancer metastases under some circumstances. Methods: A mouse model of breast cancer (administration of the murine breast cancer 4T1 cells subcutaneously) and the stress of operation were used to compare immune responses and survival outcomes. Flow cytometry was performed to detect the expression of CD11b and Gr1 MDSCs in tumor tissues and lung metastases. Cytokine levels were detected with three-color flow cytometry and enzyme-linked immunosorbent assay (ELISA). MDSCs were isolated and co-cultured with 4T1 cells to identify any morphological change with immunofluorescence. The anti Gr-1 antibody was used to detect the function of the anti-Gr1 treatment in breast cancer. Results: The operative stress impaired the overall survival, leading to an increased number of MDSCs that preferentially infiltrated the tumor microenvironment and promoted tumor metastasis. In both in vitro and in vivo assays, MDSCs induced the epithelial-mesenchymal transition (EMT) of tumor cells through the up-regulation of TGF-beta1, VEGF, and IL-10. Furthermore, a treatment strategy of MDSC depletion was found to reduce pulmonary metastases after operations. Conclusions: The stress of operation could impair the overall survival in mice. The infiltrated MDSCs appear to induce EMT of tumor cells and increase metastases through the up-regulation of TGF-beta1, VEGF, and IL-10 levels. MDSC depletion could be a promising treatment strategy to prevent immune evasion after operations.

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