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1.
J Cell Physiol ; 235(1): 254-266, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31237697

RESUMO

Accumulated evidence suggested the importance of the Rho/Rho-kinase (ROCK) signaling pathway in cancer proliferation and invasion. However, its role in colorectal carcinoma (CRC) is not well understood. This study evaluated the effect of ROCK signaling pathway on CRC behavior on the basis of a novel Rho/ROCK inhibitor RKI-1447. Here, we found RKI-1447 could drastically suppress HCT-8 and HCT-116 cell growth and promoted apoptosis. Our in vitro data indicated suppressed cytoskeletal dynamics induced by RKI-1447 inhibition on mitochondrial respiration, which was evidenced by basal and maximal respiration rates, and ATP production. Simultaneously, cellular basal and maximal glycolytic rates, and glycolytic capacity were also reduced in response to RKI-1447. Moreover, RKI-1447 caused excessive reactive oxygen species generation and membrane depolarization as well as activated ER-stress. We also demonstrated CHOP is essential for RKI-1447 induced cell apoptosis. Finally, we proved inhibition of ROCK by RKI-1447 could effectively inhibit CRC growth in vivo. Taken together, this study demonstrated that inhibition of ROCK signaling pathway by RKI-1447 could suppress CRC via cytoskeleton associated mitochondrial dysfunction and cellular bioenergetics disruption. Our data suggest RKI-1447 may be an attractive antitumor drug candidate for the treatment of CRC.

2.
Methods Mol Biol ; 2055: 119-132, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31502149

RESUMO

A high level of microsatellite instability (MSI-H+) is an emerging predictive and prognostic biomarker for immunotherapy response in cancer. Recently, MSI-H+ has been detected in a variety of cancer types, in addition to the classical cancers associated with Lynch Syndrome. Clinical testing for MSI-H+ is currently performed primarily through traditional polymerase chain reaction (PCR) or immunohistochemistry (IHC) assays. However, next-generation sequencing (NGS)-based approaches have been developed which have multiple advantages over traditional assays. For instance, NGS has the ability to interrogate thousands of microsatellite loci compared with just 5-7 loci that are detected by PCR. In this chapter, we detail the biochemical and computational steps to detect MSI-H+ from analysis of paired tumor and normal samples through NGS. We begin with DNA extraction, describe sequencing library preparation and quality control (QC), and outline the bioinformatics steps necessary for sequence alignment, preprocessing, and MSI-H+ detection using the software tool MANTIS. This workflow is intended to facilitate more widespread usage and adaptation of NGS-powered MSI detection, which can be eventually standardized for routine clinical testing.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117407, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31404760

RESUMO

As expired medical products can be repackaged and sold by unscrupulous counterfeiters, it is essential to find a rapid and convenient method for distinguishing expired and unexpired drugs. Standard detection methods such as high-performance liquid chromatography (HPLC) and thin-layer chromatography are complex, time-consuming, and require organic solvents (that are environmentally unfriendly). Additionally, the Pharmacopoeia publications do not include information about identifying expired drugs. In this study, we proposed a novel method for identifying expired medications based on Raman spectra and verified it using >20 types of expired (Old) and unexpired (New) drugs, each type from the same manufacturer. A portable Raman spectrometer was used to collect Raman spectra of all samples and the similarities between the Old and New drugs (SN-O) were evaluated. Drugs with SN-O values <0.9 were classified directly as expired drugs. For drugs with SN-O values >0.9, the content of active pharmaceutical ingredient (API) might be so low (below or around 10 wt%) that its Raman signal is largely obscured by that of the excipients. In such cases, changes in the API content are undetectable using the portable instrument. Therefore, we adopted Raman mapping technology and established a virtual imaging map to locate areas of high API content. The similarities between the Old or New spectrum and that of the API (SO-A and SN-A, respectively) were calculated after removing the signal from the excipients. Our novel methods provide a precise, rapid, convenient, and environmentally friendly way to identify expired drugs that is more effective than the standard HPLC assay.

4.
J Nanosci Nanotechnol ; 20(4): 2138-2143, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492222

RESUMO

With the higher and higher application level of medical technology, more and more genetic diseases have been diagnosed. Nucleic acid, as an important genetic material, has been found to have important functions in the storage and transmission of the genetic information in the replication and synthesis of proteins. As the first step in nucleic acid detection experiments, nucleic acid extraction performance is associated with the purity of target nucleic acid samples, which is very important for the downstream steps. In this paper, we employed the magnetic bead for extracting nucleic acids based on the platform of large liquid handling workstation and designed a matching magnetic separation module. It was shown that the temperature control block designed in this paper has reliable stability, high accuracy by using the incremental PID algorithm, with the control accuracy up to ±0.5 °C, and the control stabilization time is about 90 s, which can satisfy the experimental requirements. Besides, the average magnetic bead transfer rate of this module was further verified by mimicking the manual magnetic bead nucleic acid extraction process. The results proved that the module has an excellent performance with the average magnetic bead transfer rate greater than 95% and the magnetic bead transfer rate in each well greater than 90%, which could be consistent with the experimental indictors of nucleic acid extraction.

5.
J Nanosci Nanotechnol ; 20(4): 2165-2170, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492225

RESUMO

The high-throughput nucleic acid detection system provides a good solution for detecting nucleic acids more safely, rapidly and accurately, which greatly improves the detection efficiency. Highthroughput nucleic acid detection mainly includes three steps: signal acquisition, signal amplification and signal processing. Therefore, obtaining the purified nucleic acid is the primary task of the nucleic acid detection, and the quality of the nucleic acid has a significant impact on results. In this paper, we employed the magnetic nanoparticle technology for extracting nucleic acids based on the platform of large liquid handling workstation and designed a matching vibrating module. The involved steps of core method, magnetic bead nucleic acid extraction technology, are mainly concerned with the cell lysis, nucleic acid binding, nucleic acid purification and magnetic particles elution. During the extraction process, specific temperature is required for the lysis and elution. It was shown that the temperature control part designed in this paper has the reliable stability, high accuracy by using the incremental proportion-integration-differentiation (PID) algorithm, with the control accuracy up to ±0.5 °C. The temperature regulating time is about 90 s, which can meet the experimental requirements. Besides, the vibrating uniformity of this module was further verified by protein concentration test, which proved that the module has the excellent performance and can be consistent with the experimental indictors of the nucleic acid extraction.

6.
Opt Express ; 27(22): 32349-32359, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31684449

RESUMO

Recently, ghost imaging has been attracting attention because its mechanism could lead to many applications inaccessible to conventional imaging methods. However, it is challenging for high-contrast and high-resolution imaging, due to its low signal-to-noise ratio (SNR) and the demand of high sampling rate in detection. To circumvent these challenges, we propose a ghost imaging scheme that exploits Haar wavelets as illuminating patterns with a bi-frequency light projecting system and frequency-selecting single-pixel detectors. This method provides a theoretically 100% image contrast and high-detection SNR, which reduces the requirement of high dynamic range of detectors, enabling high-resolution ghost imaging. Moreover, it can highly reduce the sampling rate (far below Nyquist limit) for a sparse object by adaptively abandoning unnecessary patterns during the measurement. These characteristics are experimentally verified with a resolution of 512×512 and a sampling rate lower than 5%. A high-resolution (1000×1000×1000) 3D reconstruction of an object is also achieved from multi-angle images.

7.
Opt Express ; 27(20): 29248-29260, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684662

RESUMO

A novel strategy for colorimetric and surface-enhanced Raman scattering (SERS) dual-mode sensing of the lead ions (Pb2+) was established based on gluconate ion (Gluc) modified and 2-Naphthalenethiol (2-NT) tagged Au-Ag core-shell nanoparticles (NPs). Due to the complex formation between adsorbed Gluc and Pb2+, the addition of Pb2+ can induce the aggregation of Gluc/2-NT@Au@Ag NPs. Correspondingly, the aggregated Gluc/2-NT@Au@Ag NPs caused a significant difference in the color and SERS intensity. As a result, such Gluc/2-NT@Au@Ag NPs can achieve the sensing of Pb2+ using both colorimetric and SERS signals as the indicator, which features with wide response range from 10-11 to 10-5 M, rapid screening and high sensitivity (with a limit of detection (LOD) of 0.185 pM). Furthermore, such dual-mode sensor was demonstrated not to be responsive to other cations, and facilitate the sensing of real samples in practical environment. With rapid screening ability and outstanding sensitivity, we anticipate that this method would holding great potential for the applications in environmental monitoring.

8.
J Glaucoma ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31688374

RESUMO

PRéCIS:: The overall incidence of postoperative suspected glaucoma and glaucoma after congenital cataract surgery is low; however, the identification of associated risk factors helps to monitor susceptible individuals and to provide real-time surveillance and timely intervention. PURPOSE: Pediatric patients who have undergone surgery for congenital or infantile cataracts have a risk of developing suspected glaucoma and glaucoma, but the current evidence does not address our understanding of the incidence and associated risk factors of suspected glaucoma/glaucoma for application in clinical standard care. Therefore, this study investigated the incidence of and risk factors for suspected glaucoma/glaucoma in patients who have undergone surgery for congenital/infantile cataracts. METHODS: This study used a prospective cohort of 241 eyes from 241 patients 10 years of age or younger who had congenital/infantile cataract surgeries and were recruited from January 2011 to December 2016 at the Zhongshan Ophthalmic Center. Pediatric patients who underwent cataract surgery were classified into two groups according to intraocular lens (IOL) implantation. The patients' baseline characteristics and the incidence and risk factors for suspected glaucoma/glaucoma were assessed. RESULTS: The incidence of suspected glaucoma after cataract surgery was 10.70% (26 of 241 eyes; 95% confidence interval [CI], 6.88% to 14.70%). The rate of suspected glaucoma developing into glaucoma was 26.92% (7 of 26 eyes; 95% CI, 9.87% to 43.97%), and the incidence of glaucoma was 2.90% (7 of 241 eyes; 95% CI, 0.79% to 5.03%). Our study revealed that the incidence of suspected glaucoma/glaucoma in patients who did not receive IOL implantation was 13.91% (21 of 151 eyes; 95% CI, 8.39% to 19.42%), and the incidence in patients who received IOL implantation was 5.56% (5 of 90 eyes; 95% CI, 8.23% to 10.28%). The preoperative central corneal thickness (hazard ratio [HR], 1.003; 95% CI, 1.001 to 1.004; P=0.004) and a family history of congenital cataracts (HR, 2.314; 95% CI, 1.004 to 5.331; P=0.049) were significant risk factors in patients without IOL implantation. Patient age at the time of cataract surgery was not a statistically significant risk factor for the development of suspected glaucoma/glaucoma in patients without IOL implantation. CONCLUSIONS: Identification of the incidence of and risk factors for suspected glaucoma/glaucoma may help clinicians monitor susceptible individuals and provide timely surveillance and interventions in a clinical setting. Age at the time of cataract surgery was not a risk factor for suspected glaucoma/glaucoma in patients without IOL implantation, and this may allow the timing window for pediatric cataract surgery to be expanded and support new insights into the optimal timing of surgery for standard care.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31679693

RESUMO

Obesity and its associated non-alcoholic fatty liver disease (NAFLD) have become epidemic medical problems worldwide; however, the current available therapeutic options are limited. Farnesoid X receptor (FXR) has recently emerged as an attractive target for obesity treatment. Here we demonstrate that isotschimgine (ITG), a constituent in genus Ferula, as a novel FXR agonist with anti-obesity and anti-hepatic steatosis effects. The results showed that ITG activated the FXR transactivity and bound with the ligand binding dormain (LBD) of FXR with gene reporter assays and AlphaScreen assays. In high-fat diet-induced obese (DIO) mice, ITG lowered body weight and fat mass, improved insulin resistance and hepatic steatosis. Mechanistic studies showed that ITG altered the expression levels of FXR downstream genes, lipid synthesis and energy metabolism genes in the liver of mice. Our findings suggest that ITG is a novel FXR agonist and may be a potential therapeutic choice for obesity associated with NAFLD.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31682026

RESUMO

BACKGROUND AND AIM: Clear visualization of the small bowel is a requirement for satisfactory video capsule endoscopy (VCE). The aim of this study was to identify the optimal dose and timing of polyethylene-glycol (PEG) for small-bowel preparation before VCE. METHODS: 410 patients were enrolled in this prospective randomized trial. All patients fasted for 12 h and ingested 320 mg simethicone 30 min before swallowing the capsule. Patients were randomized into 5 groups: Group A (no PEG), Group B (1 L PEG, 12 h before VCE), Group C (2 L PEG, 12 h before VCE), Group D (1 L PEG, 4 h before VCE), and Group E (2 L PEG, 4 h before VCE). The primary endpoint was small bowel visualization quality (SBVQ), and the secondary endpoints were patient acceptability and diagnosis rate of VCE. RESULTS: Excellent SBVQ was achieved in 27 (32.5%) of Group A, 38 (46.3%) of Group B, 40 (48.2%) of Group C, 55 (66.3%) of Group D and 43 (54.4%) of Group E. The percentage of excellent SBVQ in Group D was significantly more than in Group A (66.3% vs. 32.5%, P < 0.001), and diagnostic rate in the distal segment was higher (28.9% vs. 10.8%, P = 0.0035). Patient acceptance of 1 L PEG was better than of 2 L PEG (P < 0.005). CONCLUSIONS: Small bowel cleansing with 1 L PEG given 4 h before VCE was the optimal preparation for visualization of the bowel and patient acceptance. (ClinicalTrials.gov, ID: NCT02486536).

11.
Transbound Emerg Dis ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31682070

RESUMO

Infectious bronchitis virus (IBV) causes respiratory diseases in chickens and poses an economic threat to the poultry industry worldwide. Despite vaccine use, there have been field outbreaks of IBV in Taiwan. This study aimed to characterize the emerging IBV variants circulating in Taiwan. The analysis of the structural protein genes showed that these variants emerged through frequent recombination events among Taiwan strains, China strains, Japan strains and vaccine strains. Cross-neutralization tests revealed that two of the variants exhibited novel serotypes. Clinicopathological assessment showed that two of the variants caused high fatality rates of 67% and 20% in one-day-old SPF chicks, and all the variants possessed multiorgan tropisms, including trachea, proventriculus and urogenital tissues. Furthermore, the commercial live attenuated Mass-type vaccine conferred poor protection against these variants. This study identified novel genotypes, serotypes, and pathotypes of emerging IBV variants circulating in Taiwan. There is an urgent need for effective countermeasures against these variant strains.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31682102

RESUMO

Activity and immobilization of catalysts in liquid-phase reactions seem not to coexist. We report here the excellent activity of MoOx nanoparticles (NPs) catalyst for D-glucose epimerization to D-mannose and the electrical immobilization of NPs in a flow reaction. Prior to that, a green and one-pot method to synthesize the MoOx NPs (3.05 nm) via oxidizing metal Mo by hydrogen peroxide was presented. The NPs overwhelmed the reported catalysts including epimerase for D-glucose epimerization, originating from a strong interaction between the NPs and the reactant that was demonstrated by ex-situ and in-situ characterizations and theoretical calculations. The electrically charged feature of NPs inspired us to find a convenient way to "immobilize" them inside an activated carbon bed and thereby a flow reactor was assembled. The continuous epimerization was run under 24 V for 16 days with an almost unchanged activity and only 3.2% of total Mo was lost.

13.
Medicine (Baltimore) ; 98(44): e17677, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689784

RESUMO

The purpose of this retrospective study was to evaluate the visual quality, objective scattering index, aberration, etc after Implantable Collamer Lens with center hole (EVO-ICL) implantation to treat patients with hypermyopia (diopter > -10 D).A total of 30 eyes underwent EVO-ICL implantation. The uncorrected distance visual acuity (UDVA), best-corrected visual acuity (BCVA), equivalent spherical degree, aberration, visual quality parameters, and corneal endothelial cell density were compared preoperative and postoperative. Fill in the National Eye Institute Refractive Error Quality of Life Instrument-42 before and after surgery.The modulation transfer function (MTF), Optical Quality Analysis System (OQAS) II values (OV 100%, 20%, 9%), and Stahl ratio 1 and 3 months after surgery were higher than the respective preoperative values. The objective scatter index value increased 1 week after surgery, but decreased 1 and 3 months after surgery compared with the preoperative values. Total aberration (TA), total low-order aberration (tLOAs), and defocus decreased at 1 week and 3 months after EVO-ICL implantation. Total high-order aberration (tHOAs) and spherical aberration were significantly increased 1 week after surgery and decreased 3 months after surgery, and the difference was statistically significant. Astigmatism, coma, and clover were not significantly different in each time period. TA, tLOAs, tHOAs, defocus, and spherical aberration were higher at 1 week than 3 months after surgery. At 3 months after surgery, the scores of the patients' NEI-RQL-42 scale were all improved except that the glare was lower than that before surgery. There was no significant difference in the density of corneal endothelial cells before and 3 months after surgery.For patients with hypermyopia, the postoperative subjective and objective visual quality of EVO-ICL implantation was better than preoperative.

14.
Food Funct ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31691684

RESUMO

Seafood provides a range of health benefits due to its nutritional and bioactive components. However, the bioactive peptides derived from Mytilus edulis proteins were seldom reported, especially their beneficial effects related to bone growth in vitro and in vivo. In this study, the water soluble protein from Mytilus edulis was isolated and the osteogenic activity of Mytilus edulis protein was determined in vivo. The protein from Mytilus edulis was subjected to simulated digestion in vitro, and the hydrolysate of different stages for osteogenic activity by osteoblast proliferation. It was found that the hydrolysate, derived from proteins hydrolyzed by pepsin for 2 h and trypsin for 3 h, showed high osteogenic activity, which induced an increase of 35.56 ± 2.92% in mouse-MC3T3-E1-preosteoblast-cell growth and the alkaline-phosphatase activity was 2.94 ± 0.10 mU, which was an increase of 19.78% compared with that of the control. Moreover, the molecular weight distribution of the peptides and the composition of the free amino acids were determined in order to evaluate the nutritional properties. These findings showed that the water soluble protein from Mytilus edulis could be used in functional food as a bioactive ingredient, which would be beneficial for bone growth and health.

15.
Fitoterapia ; : 104392, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31669961

RESUMO

Previous studies have shown that mitomycin C (MMC) can prevent scar adhesion after joint surgery, but the specific mechanism underlying this effect remains unclear. The purpose of this study was to explore the specific mechanism by which MMC promotes fibroblast apoptosis and prevents joint adhesion. The effect of MMC on fibroblasts was assessed using cell counting kit-8 (CCK-8) assays, western blotting, and TUNEL staining. We used qRT-PCR to measure the expression of miR-21 in fibroblasts treated with MMC. Luciferase activity assays were used to determine the relationships between miR-21 and Programmed cell death 4 (PDCD4). The effects of miR-21 and PDCD4 on fibroblast apoptosis were assessed using flow cytometry and western blotting. HE staining was used to determine the role of miR-21 in scar tissue formation in a model of joint adhesion. The results showed that MMC induced apoptosis of fibroblasts and decreased the expression of miR-21. Moreover, miR-21 down-regulation also induced apoptosis of fibroblasts. PDCD4 was confirmed to be a direct target of miR-21 by luciferase activity assay. The results from the animal model indicated that miR-21 attenuated the effect of MMC on reducing the number of fibroblasts. Our study shows that MMC can induce fibroblast apoptosis and prevent joint adhesion by regulating the expression of miR-21 and its target PDCD4.

16.
Medicine (Baltimore) ; 98(45): e17671, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702619

RESUMO

INTRODUCTION: Injuries among children and adolescents remain a major public health problem in China. In the present study, we undertook a systematic review and meta-analysis of the published literature of epidemiological studies investigating injuries among children and adolescents in China and aimed to describe the status of injury among children and adolescents (aged 0-19 years) in China nationwide. A random-effects meta-analysis model was used to calculate the pooled prevalence of injury with 95% confidence intervals (CIs) across studies. The potential heterogeneity moderators were identified by subgroup and sensitivity analysis. A total of 775,615 children and adolescents were included in this study. Overall, the pooled injury prevalence among children and adolescents aged 0 to 19 years was 23.0% (95% CI 20.0%-27.0%) in studies using 1996 version of injury definition, and 13.0% (95% CI 10.0%-17.0%) in studies using 2004 version of injury definition. Relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded consistent results. CONCLUSION: Our study shows a moderately high injury prevalence among children and adolescents aged 0 to 19 years in China, more prevention policies and programs should be urgently developed to decrease the occurrence of child and adolescent injury.

17.
Appl Opt ; 58(27): 7552-7557, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31674407

RESUMO

Based on a parallel phase compensation scheme, we propose an efficient wavefront shaping method using a spatial light modulator (SLM) for quickly generating a series of focused spots through a multimode fiber (MMF). The compensated phase mask obtained by a two-step phase-shifting technique is loaded to the SLM for generating a focused spot at an arbitrary target position out of the fiber facet. Furthermore, the parallel algorithm we present makes it possible to obtain a series of compensated phase masks, which could be used to generate a series of focused spots at different locations. We experimentally obtained 100 tightly focused spots, with an average focused efficiency of 21.60% and an average focused diameter of 1.9240 µm, and only one-time parallel-compensated phase retrieval is required without multiple iteration optimization.

18.
Appl Opt ; 58(30): 8282-8289, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31674500

RESUMO

The paper introduces a silica-on-silicon monolithic integrated cyclic arrayed waveguide grating (AWG) with Mach-Zehnder interference (MZI) filters and arrayed vertical reflecting mirrors in silicon to realize effective and stable optical transmission between waveguides and photodiodes. The cyclic AWG acts as both multiplexer over the L-band for upstream traffic and demultiplexer over the C-band for downstream traffic. The integrated chip, including AWG, MZI filters, and arrayed reflecting mirrors, has been made successfully with a 6.0 dB insertion loss, which is less than the discrete devices. At the same time, the arrayed reflecting mirrors are more stable than separate reflectors.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31677186

RESUMO

BACKGROUND AND AIM: Treatment modalities of variceal bleeding or rebleeding for extrahepatic portal vein obstruction (EHPVO) are limited and their long-term results and prognostic factors are unclear. This study aimed at assessing the long-term results of EHPVO treated with current recommendations and investigating the influencing factors. METHODS: Between 2009 and 2016, 302 consecutive patients with EHPVO were included. Watch-and-wait policy was applied for those with no (n=59) or small varices (n=55), nonselective beta-adrenergic blocker (NSBB) and NSBB plus endotherapy were for primary (n=115) and secondary prophylaxis (n=87), transjugular intrahepatic portosystemic shunt (TIPS) or combination therapy was for those with recurrent bleeding (n=92). RESULTS: The median follow-up was 58.8 months. The 1-, 3-, and 5-year cumulative rates were 3.6%, 19.2%, 32.3% for small varices development and 4.5%, 30.9%, 53.4% for large varices development. The 1-, 3-, and 5-year cumulative rates were 11.1%, 20.9%, 34.9% for first variceal bleeding and 16.0%, 26.9%, 33.6% for variceal rebleeding. For those with recurrent variceal bleeding, only TIPS (n = 37, technical success rate: 90.2%) was associated with a reduced risk of variceal rebleeding (1-, 3-, 5-year: 5.6%, 11.7%, 21.9%). The 1-, 3-, and 5-year survival rates were 96.9%, 95.8%, 91.9%. Prothrombotic factors and anticoagulation did not influence the risk of variceal bleeding, rebleeding and survival. CONCLUSIONS: By applying the same variceal management as recommended for patients with liver cirrhosis, patients with non-cirrhotic EHPVO showed a similar development of varices and variceal bleeding. This is also true for the beneficial effect of TIPS to prevent rebleeding.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31666981

RESUMO

Microorganisms enhance fitness by prioritizing catabolism of available carbon sources using a process known as carbon catabolite repression (CCR). Planktonically grown Pseudomonas aeruginosa is known to prioritize the consumption of organic acids including lactic acid over catabolism of glucose using a CCR strategy termed "reverse diauxie." P. aeruginosa is an opportunistic pathogen with well-documented biofilm phenotypes that are distinct from its planktonic phenotypes. Reverse diauxie has been described in planktonic cultures, but it has not been documented explicitly in P. aeruginosa biofilms. Here a combination of exometabolomics and label-free proteomics was used to analyze planktonic and biofilm phenotypes for reverse diauxie. P. aeruginosa biofilm cultures preferentially consumed lactic acid over glucose, and in addition, the cultures catabolized the substrates completely and did not exhibit the acetate secreting "overflow" metabolism that is typical of many model microorganisms. The biofilm phenotype was enabled by changes in protein abundances, including lactate dehydrogenase, fumarate hydratase, GTP cyclohydrolase, L-ornithine N(5)-monooxygenase, and superoxide dismutase. These results are noteworthy because reverse diauxie-mediated catabolism of organic acids necessitates a terminal electron acceptor like O2, which is typically in low supply in biofilms due to diffusion limitation. Label-free proteomics identified dozens of proteins associated with biofilm formation including 16 that have not been previously reported, highlighting both the advantages of the methodology utilized here and the complexity of the proteomic adaptation for P. aeruginosa biofilms. Documenting the reverse diauxic phenotype in P. aeruginosa biofilms is foundational for understanding cellular nutrient and energy fluxes, which ultimately control growth and virulence.

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