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1.
Artigo em Inglês | MEDLINE | ID: mdl-32215933

RESUMO

The efficacy of dexmedetomidine in the prevention of postoperative delirium (POD) remains ambiguous, however, it has been used to reduce the incidence of delirium in elderly patients. Here, we conducted a meta-analysis study for assessing the effects of dexmedetomidine on POD among elderly patients following non-cardiac surgery. A systematic literature search was performed against the PubMed, EMBASE, Cochrane Library, and Web of Science databases, and all relevant literature published till November 30, 2019, were considered. Our analysis included 16 randomised controlled trials conducted with 4534 patients for exploring the effects of dexmedetomidine on POD in elderly patients following non-cardiac surgery. It was observed that the overall incidence of POD was significantly lower in the dexmedetomidine group than in the control group (risk ratio (RR)0.51, 95% confidence interval (CI) 0.43-0.61, P<0.01). Similar results were obtained from subgroup analysis upon comparison of the placebo (RR 0.52, 95% CI 0.41-0.66, P<0.01, moderate quality of evidence), propofol-treated (RR 0.55, 95% CI 0.38-0.78, P<0.01, low quality of evidence), and midazolam-treated (RR 0.38, 95% CI 0.20-0.71, P<0.01, low quality of evidence) groups. Trial sequential analysis revealed that the cumulative z-value superseded the monitoring boundary and reached the required information size. However, patients who received dexmedetomidine had a higher incidence of bradycardia and hypotension. In conclusion, the meta-analysis revealed that dexmedetomidine appears to decrease the risk of POD in elderly patients following non-cardiac surgery. However, as some of the studies were heterogeneous and of low quality, high quality trials are necessary for drawing more definitive conclusions.

2.
Bioresour Technol ; 306: 123102, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32179399

RESUMO

The cultivation of microalgae in municipal wastewater not only purifies the wastewater but also transforms nutrients into biomass that contains high-value lipids. In this study, conventional static bottom-magnetic field (bottom-MF) equipment and cost-effective bypass-magnetic field (bypass-MF) equipment were designed and independently coupled with a microalgae-wastewater system in different positions to evaluate the effect of magnetic field (MF) on microalgae biomass production and lipid accumulation. When the MF equipment was applied in the wastewater pretreatment unit, the bottom-MF pretreatment mode exhibited a more beneficial effect on subsequent biomass and lipid accumulation. However, when the MF equipment was applied in the microalgae-wastewater culture unit, there was no significant difference between the bottom-MF and bypass-MF modes. The results of the orthogonal experiment suggested the optimum conditions for lipid production were wastewater pretreatment by bottom-MF at 5000 Gs for 1 h, followed by microalgae-wastewater culture treatment by bypass-MF at 5000 Gs for 3 h.

3.
Bioresour Technol ; 306: 123162, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32197194

RESUMO

Herein, a novel innovative lipid co-extraction strategy using the biodiesel-producing microalga Chlorella pyrenoidosa and planktonic cladoceran Daphnia was proposed. Co-extraction occurred as Daphnia ingested and digested microalgal cells in a pre-treatment process; thereafter, lipids from these organisms were extracted. Composition of fatty acids from C. pyrenoidosa and Daphnia were appropriate as potential biodiesel feedstocks. Daphnia had different absorption and conversion capacities of various fatty acids from C. pyrenoidosa, which showed potential for improving biodiesel characteristics. Linoleic acid (LA, C18:2n-6) and alpha-linolenic acid (ALA, C18:3n-3) were absorbed significantly into the body of Daphnia. The optimal lipid extraction and fatty acid methyl esters (FAMEs) recovery rates were up to 41.08% and 12.35%, respectively, which were greater than that of the traditional lipid extraction method due to the rich oil content of Daphnia. Overall, this lipid co-extraction process serves a potential Daphnia utilization as an economical, green, low-energy way for microalgae biodiesel production.

5.
Am J Kidney Dis ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32197881

RESUMO

RATIONALE & OBJECTIVE: Hematuria is the most typical presentation of immunoglobulin A nephropathy (IgAN); however, its role in disease progression is still controversial. This study aimed to evaluate the association of hematuria and progression of IgAN. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A cohort of 1,333 patients with IgAN treated at a Chinese referral hospital with a median follow-up of 45 months. PREDICTORS: Microhematuria was evaluated in fresh urine using a fully automated urine particle analyzer (automated method) and urine sediment examination by a skilled examiner (manual method). Hematuria was characterized as a time-varying attribute; namely, average hematuria level was calculated for every 6-month period for each patient during follow-up. Remission was defined as average red blood cell count ≤5/high-power field (manual method) or ≤28 red blood cells/µL (automated method) during the first 6 months of follow-up. OUTCOMES: Composite event of 50% decline in estimated glomerular filtration rate or development of kidney failure. ANALYTICAL APPROACH: Multivariable cause-specific hazards models to analyze the relationship between hematuria and the composite kidney disease progression event. RESULTS: Time-varying hematuria during follow-up was an independent risk factor for the composite kidney disease progression event (HR, 1.46; 95% CI, 1.13-1.87; P = 0.003). Hematuria remission during the 6 months after diagnosis was associated with a significantly lower rate of the composite kidney disease progression event (HR, 0.41; 95% CI, 0.28-0.61; P < 0.001). A significant interaction was detected between remission of proteinuria and remission of hematuria during the first 6 months (P < 0.001). The association between remission of hematuria and kidney disease progression was detectable (HR, 0.46; 95% CI, 0.32-0.68) within the subpopulation with persistent proteinuria (protein excretion > 1.0 g/d during the first 6 months), but not among patients whose proteinuria had remitted (HR, 0.64; 95% CI, 0.31-1.29; P = 0.2). The 2 techniques for hematuria evaluation were strongly and significantly linearly correlated (r = 0.948; P < 0.001), and results using these 2 methods were consistent. LIMITATIONS: A single-center retrospective study. Proportional hazards regression incorporating time-varying covariates may create time-varying confounding. The predictive value of reductions in hematuria was not directly evaluated. CONCLUSIONS: Level of hematuria was independently associated with kidney disease progression, whereas hematuria remission was associated with improved kidney outcomes in IgAN among patients with persistent proteinuria. Additionally, to monitor IgAN progression, automated methods to evaluate hematuria hold promise as a replacement for manual evaluation of urinary sediment.

6.
Mol Ther Nucleic Acids ; 20: 345-358, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-32199130

RESUMO

Osteoporosis is characterized by the reduction of bone mineral density and deterioration of bone quality which leads to high risk of fractures. Some microRNAs (miRNAs) have been confirmed as potential modulators of osteoblast differentiation to maintain bone mass maintenance. We aimed to clarify whether miR-122 could regulate osteoblast differentiation in ovariectomized rats with osteoporosis. miR-122 was upregulated and Purkinje cell protein 4 (PCP4) was downregulated in ovariectomized rats. PCP4 was identified as a target of miR-122 by dual-luciferase reporter gene assay. We transfected isolated osteoblasts from ovariectomized rats with miR-122 mimic or inhibitor or PCP4 overexpression vectors. Proliferation and differentiation of osteoblasts were repressed by the overexpression of miR-122 but enhanced by overexpression of PCP4. miR-122 could induce the activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway, while PCP4 blocked this pathway. Rescue experiments further demonstrated that the inhibiting effects of miR-122 on osteoblast differentiation could be compensated by activation of the PCP4 or inhibition of JNK signaling pathway. Collectively, our data imply that miR-122 inhibits osteoblast proliferation and differentiation in rats with osteoporosis, highlighting a novel therapeutic target for osteoporotic patients.

7.
Bioresour Technol ; 304: 123000, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32088625

RESUMO

An increasing interest is devoted to combined microbial electrolysis cell-anaerobic digestion (MEC-AD) system which could convert waste activated sludge into biogas. In this study series tests were initially conducted to study the effect of alkaline pretreatment on AD system and the results showed that alkaline pretreatment could promote the dissolution of organic matters in the sludge and thus improve the methane production. Then, the methane production in combined MEC-AD system fed with alkaline-pretreated sludge was investigated. The results indicated that the methane productions increased by 37% and 42% when applied voltage was 0.5 V and 0.8 V. The microbial electrochemical system strongly promoted the growth of Euryarchaeota (Methanosaeta and Methanobacterium). Meanwhile, the abundance of Paraclostridium increased from 17.9% to 38.5% when applied voltage was 0.8 V, suggesting an enhanced fermentation and acetogenesis process. The results of energy balance estimation indicated that MEC-AD system at 0.5 V could achieve higher net energy output.


Assuntos
Reatores Biológicos , Esgotos , Anaerobiose , Eletrólise , Metano , Eliminação de Resíduos Líquidos
8.
Nat Commun ; 11(1): 1066, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32103013

RESUMO

Around 70 Mha of land cover changes (LCCs) occurred in Europe from 1992 to 2015. Despite LCCs being an important driver of regional climate variations, their temperature effects at a continental scale have not yet been assessed. Here, we integrate maps of historical LCCs with a regional climate model to investigate air temperature and humidity effects. We find an average temperature change of -0.12 ± 0.20 °C, with widespread cooling (up to -1.0 °C) in western and central Europe in summer and spring. At continental scale, the mean cooling is mainly correlated with agriculture abandonment (cropland-to-forest transitions), but a new approach based on ridge-regression decomposing the temperature change to the individual land transitions shows opposite responses to cropland losses and gains between western and eastern Europe. Effects of historical LCCs on European climate are non-negligible and region-specific, and ignoring land-climate biophysical interactions may lead to sub-optimal climate change mitigation and adaptation strategies.

9.
J Mol Biol ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32105730

RESUMO

Noncoding RNAs (ncRNAs), such as lncRNAs, circRNAs and pri-miRNAs, play important roles in physiological and pathological processes. Recently, it was demonstrated that they could encode proteins or peptides. However, relevant information is scattered across numerous published articles, which is inconvenient for the exploration of ncRNA translation by researchers. In this study, we presented an ncEP database, which records the low-throughput experimentally validated (LTEV) proteins or peptides encoded by ncRNAs, from published articles. Collectively, ncEP contains 80 entries including 74 proteins or peptides, 22 lncRNAs, 11 circRNAs, 9 pri-miRNAs and 37 other ncRNAs across 18 species from more than 50 articles of over 2000 candidate articles. We have provided a user-friendly interface for users to search, browse, visualize, download and submit data. In summary, ncEP provides a relatively comprehensive repository of the LTEV proteins or peptides encoded by ncRNAs and will enrich the knowledge for translation process. ncEP is freely available at http://www.jianglab.cn/ncEP/.

10.
iScience ; 23(2): 100841, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-32058955

RESUMO

Tissue repair is a protective response after injury, but repetitive or prolonged injury can lead to fibrosis, a pathological state of excessive scarring. To pinpoint the dynamic mechanisms underlying fibrosis, it is important to understand the principles of the cell circuits that carry out tissue repair. In this study, we establish a cell-circuit framework for the myofibroblast-macrophage circuit in wound healing, including the accumulation of scar-forming extracellular matrix. We find that fibrosis results from multistability between three outcomes, which we term "hot fibrosis" characterized by many macrophages, "cold fibrosis" lacking macrophages, and normal wound healing. This framework clarifies several unexplained phenomena including the paradoxical effect of macrophage depletion, the limited time-window in which removing inflammation leads to healing, and why scar maturation takes months. We define key parameters that control the transition from healing to fibrosis, which may serve as potential targets for therapeutic reduction of fibrosis.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32023025

RESUMO

By using Ti3C2Tx quantum dots as interlayer spacers, Ti3C2Tx nanosheets/Ti3C2Tx quantum dots/RGO (reduced graphene oxide) fiber (M6M3RG1) is prepared by a wet-spinning method; it shows good capacitance and excellent flexibility. The M6M3RG1 fiber electrode possesses a novel network structure and a maximum volumetric capacitance of 542 F cm-3, and its capacitance and flexibility are affected by the amount of Ti3C2Tx quantum dots. Also, the Ti3C2Tx/PEDOT:PSS [poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)] fiber (M7P3) is prepared by injecting a homogeneous suspension of Ti3C2Tx nanosheets and PEDOT:PSS into a bath of 98 wt % H2SO4. The M6M3RG1 fiber is used as the positive electrode, and the M7P3 fiber is used as the negative electrode; a M6M3RG1//M7P3 asymmetric, flexible, solid-state supercapacitor is assembled in a PVA-H2SO4 gel electrolyte. The assembled device exhibits a volumetric capacitance of 53.1 F cm-3 and a good cycle stability of 96.6% after 5000 cycles. It also shows outstanding flexibility and mechanical properties; for example, the volumetric capacitance has no obvious change after the device is bent at 90° for 500 times. Moreover, its voltage window can be expanded to 1.5 V, and a maximum volumetric energy density of 16.6 mWh cm-3 can be achieved. This work will open up a new application area for new wearable energy storage devices based on the Ti3C2Tx fibers.

12.
Biomolecules ; 10(1)2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31906487

RESUMO

The phytochemical investigation of Fraxinus hupehensis led to the isolation and characterization of ten compounds which were identified as fraxin (1), fraxetin (2), esculetin (3), cichoriin (4), euphorbetin (5), kaempferol-3-O-ß-rutinoside (6), oleuropein (7), linoleic acid (8), methyl linoleate (9), and ß-sitosterol (10). Structures of the isolated constituents were characterized by 1H NMR, 13C NMR and HRMS. All the compounds, except compounds 3 and 4, were isolated for the first time from this plant. Further, this was the first report for the occurrence of compound 5 in the Fraxinus species. Antifungal activity evaluation showed that compound 2 exhibited significant inhibitory effects against Bipolaris maydis, Sclerotium rolfsii, and Alternaria solani with EC50 values of 0.31 ± 0.01 mmol/L, 10.50 ± 0.02 mmol/L, and 0.40 ± 0.02 mmol/L respectively, compared to the positive control, Carbendazim, with its EC50 values of 0.74 ± 0.01 mmol/L, 1.78 ± 0.01 mmol/L and 1.41 ± 0.00 mmol/L. Herbicidal activity tests showed that compounds 8-10 had strong inhibitory effects against the roots of Echinochloa crus-galli with EC50 values of 1.16 ± 0.23 mmol/L, 1.28 ± 0.58 mmol/L and 1.33 ± 0.35 mmol/L respectively, more potently active than that of the positive control, Cyanazine, with its EC50 values of 1.56 ± 0.44 mmol/L. However, none of the compounds proved to be active against the tested bacteria (Erwinia carotovora, Pseudomonas syringae, and Ralstonia solanacearum).

13.
Chin Med J (Engl) ; 133(3): 277-284, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31929371

RESUMO

BACKGROUND: High levels of plasma homocysteine occur almost uniformly in patients with end-stage renal disease (ESRD). IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and a common cause of ESRD in young adults. Here, we aimed to detect whether homocysteine was elevated and associated with clinical-pathologic manifestations of IgAN patients and tested its causal effects using a two-sample Mendelian randomization (MR) approach. METHODS: For observational analysis, 108 IgAN patients, 30 lupus nephritis (LN) patients, 50 minimal change disease (MCD) patients, and 206 healthy controls were recruited from April 2014 to April 2015. Their plasma homocysteine was measured and clinical-pathologic manifestations were collected from medical records. For MR analysis, we further included 1686 IgAN patients. The missense variant methylenetetrahydrofolate reductase C677T (rs1801133) was selected as an instrument, which was genotyped by TaqMan allele discrimination assays. RESULTS: Majority of IgAN patients (93.52%, 101/108) showed elevated levels of plasma homocysteine (>10 µmol/L). Plasma homocysteine in IgAN patients was significantly higher than that in MCD patients (median: 18.32 vs. 11.15 µmol/L, Z = -5.29, P < 0.01) and in healthy controls (median: 18.32 vs. 10.00 µmol/L, Z = -8.76, P < 0.01), but comparable with those in LN patients (median: 18.32 L vs. 14.50 µmol/L, Z = -1.32, P = 0.19). Significant differences were observed in sub-groups of IgAN patients according to quartiles of plasma homocysteine for male ratio (22.22% vs. 51.85% vs. 70.37% vs. 70.37%, χ = 14.29, P < 0.01), serum creatinine (median: 77.00 vs. 100.00 vs. 129.00 vs. 150.00 µmol/L, χ = 34.06, P < 0.01), estimated glomerular filtration rate (median: 100.52 vs. 74.23 vs. 52.68 vs. 42.67 mL·min·1.73 m, χ = 21.75, P < 0.01), systolic blood pressure (median: 120.00 vs. 120.00 vs. 125.00 vs. 130.00 mmHg, χ = 2.97, P = 0.05), diastolic blood pressure (median 80.00 vs. 75.00 vs. 80.00 vs. 81.00 mmHg, χ = 11.47, P < 0.01), and pathologic tubular atrophy and interstitial fibrosis (T) (T0/T1/T2: 62.96%/33.33%/3.70% vs. 29.63%/40.74%/29.63% vs. 24.00%/48.00%/28.00% vs. 14.81%/37.04%/48.15%, χ = 17.66, P < 0.01). The coefficient of each rs1801133-T allele on homocysteine levels after controlling age and sex was 7.12 (P < 0.01). MR estimates showed causal positive effects of homocysteine on serum creatine (ß = 0.76, P = 0.02), systolic blood pressure (ß = 0.26, P = 0.02), diastolic blood pressure (ß = 0.20, P = 0.01), and pathologic T lesion (ß = 0.01, P = 0.01) in IgAN. CONCLUSIONS: By observational and MR analyses, consistent results were observed for associations of plasma homocysteine with serum creatinine, blood pressures, and pathologic T lesion in IgAN patients.

14.
Nat Prod Res ; : 1-7, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31937140

RESUMO

Two new ditetrahydrofuran lignans, named sieverlignans A and B (1 and 2), together with six known ones (3-8), were isolated from the aerial parts of Artemisia sieversiana. Their structures were established on the basis of spectroscopic analysis including HRMS, NMR spectra and circular dichroism experiments. All the compounds were evaluated for their anti-neuroinflammatory effects on the lipopolysaccharides (LPS)-induced nitric oxide production in BV-2 murine microglial cells. Compound 2 exhibited the significant activity with its IC50 value of 11.9 ± 0.8 µM, respectively, compared to a positive control quercetin with its IC50 value of 16.0 ± 1.1 µM.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 230: 118031, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31931357

RESUMO

Fluorescent and robust fibers based on gold nanoclusters-loaded alginate were successfully prepared by wet spinning of gold nanoclusters and alginate. The relationship between process conditions, mechanical properties, and fluorescent properties of fibers was investigated. The as-prepared fibers exhibited high mechanical strength (up to 7.09 cN/dtex) and remarkable red emission under ultraviolet excitation. The fibers could be used as a simple, low-cost, and high-selectivity fluorescent sensor for detecting Cu2+ and Hg2+ among various metal ions in aqueous solution, with a detection limit as low as 187.99 nM for Cu2+ and 82.14 nM for Hg2+, respectively. Furthermore, the novel fluorescent fibers were used as an anti-counterfeiting label through knitting into textile materials. The wet-spun functional fibers may be applied to the design of smart wearable sensors and flexible optical sensors.

16.
Lasers Med Sci ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31897814

RESUMO

While zona pellucida (ZP) breaching of day-3 frozen blastocysts embryos can increase the blastocyst hatching rate, compared with ZP thinning, the pregnancy and implantation rates are similar. The aim of this study was to compare pregnancy outcomes and the risks associated with frozen-thawed blastocysts between laser ZP breaching and laser ZP thinning. For the thinning group, ZP of thawed blastocyst was thinned to a length of 30-40 µm using laser between January 2013 and October 2015. On the other hand, for the breaching group, thawed blastocysts were breached with a 60-80 µm hole in the ZP using laser between November 2015 and April 2018. The implantation rate of ZP breaching (72.7%) was higher than that of ZP thinning (61.8%). In single frozen blastocyst transfer, the implantation rate, clinical pregnancy rate, and live birth rate of ZP breaching (73.9%, 73.9%, 61.8%, respectively) were significantly higher than those of ZP thinning (60.9%, 60.9%, 46.7%, respectively). The abortion rate, preterm birth rate, congenital malformation, birth defects, and birth weight did not significantly differ between the two groups. In conclusion, laser assisted hatching during single frozen blastocyst transfer using ZP breaching exhibit higher implantation, pregnancy, and live birth rates compared with ZP thinning. No significant differences were observed between the two assisted hatching methods in terms of adverse effects on pregnancy and newborns.

17.
Clin Cardiol ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31904110

RESUMO

BACKGROUND: Management of cardiac perforation caused by the lead of a cardiac implantable electronic device (CIED) is currently unclear. This study evaluated the outcomes of transvenous lead extraction (TLE) in patients with cardiac perforation caused by a transvenous lead. HYPOTHESIS: Removal of perforated lead by transvenous approach is safe and effective. METHODS: The medical records of all patients diagnosed with cardiac perforation by a pacing or defibrillator lead in Peking University People's Hospital from January 2008 to January 2019 were reviewed. We included patients who were managed by TLE. RESULTS: A total of 53 patients (30 men; mean age: 67 ± 15 years) with lead perforation managed by TLE were included. Most of the perforated leads (94.9%) were pacemaker leads. Forty-three leads (81.1%) were implanted within 1 year. Ten patients with a high risk of hemopericardium underwent percutaneous subxiphoid pericardial puncture prior to TLE. All 53 culprit leads were removed completely without major complications. Simple traction with or without a locking stylet was sufficient in 51 patients (96.2%). Forty-eight patients (90.6%) had a new active-fixation lead reimplanted. No patients showed evidence of new-onset or worsening pericardial effusion during the procedure and hospital stay. During a median follow-up time of 16 months, no recurrence of symptoms associated with lead perforation or CIED-related infection were reported. CONCLUSION: In most patients with lead perforation, TLE can be a safe and effective management approach.

18.
J Cell Mol Med ; 24(5): 3149-3156, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31970934

RESUMO

Recently, many studies have shown that microRNA (miR)-612 is involved in cancer progression. However, the role of miR-612 in cervical cancer remains unclear. The present study aims to investigate the biological effects of miR-612 on cervical cancer. The expression of miR-612 in cervical cancer tissues and cell lines was analysed by quantitative reverse transcription-polymerase chain reaction. The effect of miR-612 cell proliferation, migration, invasion and apoptosis was studied by appropriate methods. Protein expression was determined by Western blot analyses. Bioinformatics analysis and luciferase reporter assays were performed to clarify the relationship between miR-612 and nin one binding protein (NOB1). A xenograft model was established to examine the role of miR-612 in vivo tumorigenesis. Cervical cancer tissues and cell lines showed down-regulation of miR-612 expression, which was associated with the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage and lymph node metastasis. Functional assays revealed that miR-612 overexpression significantly suppressed cervical cancer cell proliferation, migration and invasion in vitro and delayed tumour growth in vivo. Mechanically, miR-612 targeted NOB1 in cervical cancer cells, revealing a negative correlation between miR-612 and NOB1in cervical cancer samples. NOB1 overexpression partially reversed the inhibitory effects of miR-612 overexpression in cervical cancer cells. Taken together, these findings indicate that miR-612 functions as a tumour suppressor in cervical cancer and suggest that miR-612 may be a potential target in the therapeutic intervention of this malignancy.

19.
Oncol Rep ; 43(2): 405-414, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894341

RESUMO

Living tumors are of great scientific value for clinical medicine and basic research, especially for drug testing. An increasing number of drug tests fail due to the use of imperfect models. The aim of the present study was to develop a novel method combining vitrification­based cryopreservation of tumor biopsies and precision­cut slice cultivation for the assessment of anticancer drug responses. Biological characteristics of rectal cancer liver metastasis biopsies could be retained by vitrification­based cryopreservation. The patient­derived xenograft models were successfully established using both fresh and warmed biopsy tissues. Precision­cut slicing provided a similar three­dimensional architecture and heterogeneity to the original tumor. The positive drug responses in the xenograft model were consistent with those in precision­cut slice cultures in vitro. The present study demonstrated that live tumor biopsies could be preserved using vitrification­based cryopreservation. The warmed tissues developed xenograft tumors, which were also useful for either in vivo or in vitro anticancer drug testing. Precision­cut slices derived from the warmed tissues provided an efficient tool to assess anticancer drug response in vitro.

20.
Life Sci ; 243: 117256, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31923419

RESUMO

AIMS: Chemotherapy and molecularly targeted therapy are main strategies for treatment of cancers. However, long-term treatment makes cancer cells acquire resistance to anti-cancer drugs, which severely limits the effects of cancer treatment. NcRNAs, especially miRNAs and lncRNAs, have been reported to play key roles in drug resistance and could restore drug responses in resistant cells. MAIN METHODS: We presented a network-based framework to systematically identify drug resistance associated miRNAs and lncRNAs. First, we constructed a comprehensive heterogeneous miRNA-lncRNA regulatory network through integrating curated miRNA regulations to lncRNA, and significantly co-expressed miRNA-miRNA, lncRNA-lncRNA and miRNA-lncRNA interactions for each cancer type. Second, random walk with restart (RWR) was utilized to identify novel drug resistance associated ncRNAs. KEY FINDINGS: We predicted 470 associations of 34 miRNAs and 79 lncRNAs for 27 drugs in 10 cancer types. In addition, leave-one-out cross validation (LOOCV) demonstrated the effectiveness of the proposed approach. Next, we also demonstrated that the integrated heterogeneous cancer-specific network achieved better performance than the general curated miRNA-lncRNA regulatory network. What's more, we found that the drug resistance associated ncRNAs validated by high-throughput technology was also a reliable source for prediction. SIGNIFICANCE: We proposed a new framework to identify novel and reliable drug resistance associated ncRNAs, which provides new perspectives for drug resistance mechanism and new guidance for clinical cancer treatment.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Algoritmos , Redes Reguladoras de Genes , Humanos , Neoplasias/classificação , Neoplasias/genética
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