Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 76
Filtrar
Filtros adicionais











País/Região como assunto
Intervalo de ano
1.
Drug Test Anal ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31471998

RESUMO

Thermal sensitivity, as a practical measure of thermostability, is an interesting quality attribute that can be used in the quality control (QC) release of biopharmaceuticals. This article investigates circular dichroism (CD) spectroscopy and nano-differential scanning fluorimetry (nano-DSF) to evaluate the thermal stability of E.coli L-asparaginase (L-ASNase) for QC purposes. In CD, molar ellipticity as a function of temperature (from 20 to 80°C) was measured at 222 nm. Different L-ASNase samples dissolved in different diluents were investigated by determining the melting temperature (Tm ) from the first derivative curve as well as the slope of the fitted sigmoidal function of the temperature gradient CD data. The obtained Tm values could be correlated with the L-ASNase sample origin as well as with the pH of the diluent. The Tm values obtained from the CD data were moreover consistent with the Tm values determined by nano-DSF, confirming their reliability. Next to the Tm value, also the slope of the fitted sigmoidal CD-function was able to differentiate different L-ASNase samples, including unstressed from stressed protein. By using both the Tm and the curve slope, the thermal stability of L-ASNase was investigated, demonstrating and recommending the use of this heat-stress characteristic as a QC quality attribute of proteins, which can be applied to detect substandard and falsified proteins.

2.
Biochem Biophys Res Commun ; 518(2): 344-350, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31421827

RESUMO

Hippocampal SIRT1 dysfunction and gene variation have previously been found potentially involved in depressive and anxiety disorders. However, the exact role of SIRT1 in post-traumatic stress disorder (PTSD) is not well understood. Here, we employed multiple genetic and pharmacological approaches targeting SIRT1 to verify the effects of SIRT1 on SPS-induced PTSD-like behaviors and its potential cellular and molecular mechanisms. We first demonstrated that Sirt1 knockout mice showed milder PTSD-like behavior after single prolonged stress (SPS) induction than wild type mice. Moreover, the expression of SIRT1 in the ventral CA1 (vCA1) region of hippocampus showed no significant changes following SPS induction, but the activity of SIRT1 enzyme was significantly increased post-SPS. Osmotic administration of EX527 in vCA1, a SIRT1 inhibitor, was shown to normalize the SIRT1 activity in SPS mice. Mechanically, EX527 rescued the acetylation of helix-loop-helix transcription factor 2 (NHLH2) and transcriptionally inhibited the increase of MAO-A expression in the vCA1, which thus suppressed the decomposition of the neurotransmitter serotonin into 5-hydroxydoleacetic acid (5-HIAA). Morphologically, Golgi staining showed that EX527 treatment improved the abnormal neuronal structure plasticity in the vCA1 region after SPS, including reversing the atrophic dendrites and the decreased dendritic spines. Finally, SIRT1 inhibitor effectively alleviated fear conditioning responses and anxiety-like behaviors. Our study first demonstrated that the development of PTSD-like behaviors was causatively related to the abnormal increase of SIRT1 activity in the ventral hippocampal CA1 region. And we also provided evidence that SIRT1 inhibition might exert therapeutic effects on PTSD by maintaining serotonin homeostasis through transcriptional inhibition of MAO-A, and thereby remodeled synaptic plasticity in the vCA1 region.

3.
Rev Bras Anestesiol ; 2019 Aug 03.
Artigo em Português | MEDLINE | ID: mdl-31387740

RESUMO

BACKGROUND: Left double-lumen endotracheal tubes have been widely used in thoracic, esophageal, vascular, and mediastinal procedures to provide lung separation. Lacking clear objective guidelines, anesthesiologists usually select appropriately sized double-lumen endotracheal tubes based on their experience with 35 and 37Fr double-lumen endotracheal tubes, which are the most commonly used. We hypothesized the patients with a left main bronchus of shorter length (<40mm) had a greater chance of experiencing desaturation during one lung ventilation due to obstruction in the orifice of the left upper lobe with the bronchial tube. METHODS: We included 360 patients with a left double-lumen intubated between September 2014 and August 2015. The patient's age, sex, height, weight, and underlying disease were recorded along with type of surgical procedure and the desaturation episodes. In addition, the width of the trachea and the width and length of the left bronchus were measured using computed tomography. RESULT: Patients with a left main bronchus length of less than 40mm who underwent intubation with a left double-lumen endotracheal tubes had significantly higher incidence of desaturation (Odds Ratio (OR: 8.087)) during one-lung ventilation. Other related factors of patients identified to be at risk of developing hypoxia were diabetes mellitus (OR: 5.368), right side collapse surgery (OR: 4.933), and BMI (OR: 1.105). CONCLUSIONS: We identified that patients with a left main bronchus length of less than 40mm have a great chance of desaturation, especially if other desaturation risk factors are present.

4.
Plant J ; 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31259444

RESUMO

Centromeres mediate chromosome attachment to microtubules and maintain the integrity of chromosomes for proper segregation of the sister chromatids during cell division. Advances in the assembly of Triticeae genome sequences combined with the capacity to recover hybrid species derived from very distantly related species provides potential experimental systems for linking retrotransposon amplification and repositioning of centromeres via non-mendelian inheritance in partial amphiploid breeds. The decaploid tall wheatgrass (Thinopyrum ponticum) is one of the most successfully used perennial species in wheat breeding for generating translocation lines with valuable agronomic traits. We found that wheat centromere retrotransposons CRW and Quinta widely occur within the tall wheatgrass genome. In addition, one of the genome donors to Th. ponticum, Pseudoroegneria stipifolia (StSt), has been shown to have Abigail and a satellite repeat, CentSt. We also found two other centromeric retrotransposons, Abia and CL135 in Th. ponticum by ChIP-seq. Examination of partial amphiploid lines that were generated in the 1970s demonstrated extensive modification in centromere sequences using CentSt, Abigail and Abia as probes. We also detected that St-genome chromosomes were more enriched with Abigail and CentSt, whereas E-genome chromosomes were enriched with CRW and Quinta in tall wheatgrass and its closer relatives. It can be concluded that bursts of transposition of retrotransposons and repositioning of centromeres via non-mendelian segregation are common in partial amphiploids derived from interspecific hybrids. Practically speaking, our study reveals that the existence of homologous centromere functional sequences in both a donor and its receptor can substantially contribute to the successful transfer of alien genes into crop species. OPEN RESEARCH BADGES: This article has earned an Open Data Badge for making publicly available the digitally-shareable data necessary to reproduce the reported results. The data is available at https://www.ncbi.nlm.nih.gov/sra/SRR9089557; https://www.ncbi.nlm.nih.gov/sra/SRR9089558; https://www.ncbi.nlm.nih.gov/sra/SRR9089559; https://www.ncbi.nlm.nih.gov/sra/SRR9089560; https://www.ncbi.nlm.nih.gov/sra/SRR9089561; https://www.ncbi.nlm.nih.gov/sra/SRR9089562; https://www.ncbi.nlm.nih.gov/sra/SRR9089563; https://www.ncbi.nlm.nih.gov/sra/SRR9089564; https://www.ncbi.nlm.nih.gov/nuccore/MK999394; https://www.ncbi.nlm.nih.gov/nuccore/MK999395; https://www.ncbi.nlm.nih.gov/nuccore/MK999396.

5.
Anticancer Drugs ; 30(9): 948-952, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31283544

RESUMO

Pegylated liposomal doxorubicin (Peg-Dox) treatment resulted in a good outcome for patients with lymphoma and multiple myeloma, with reduced cardiotoxicity and an improved pharmacokinetic profile when compared to those of conventional doxorubicin. However, the use of Peg-Dox in myeloid neoplasms remains poorly studied. In this study, we first tested the role of Peg-Dox in the killing of myeloid cell lines and of primary myeloid leukemia cells. Then, a Peg-Dox-based protocol was used to treat patients with myeloid neoplasms. The results showed that the Peg-Dox and Peg-Dox-based protocols had a similar killing ability in myeloid cell lines and in primary myeloid leukemia cells compared to that of conventional doxorubicin. The complete remission rate was 87.5% and 100% for patients with refractory/relapsed acute myeloid leukemia and myelodysplastic syndrome with excess blasts, respectively, after treatment with Peg-Dox. All patients developed grade 3 or 4 hematological toxicity and recovered approximately 2 weeks after completing chemotherapy. No deaths or other severe complications were reported. Our results showed that Peg-Dox can be used in the treatment of myeloid neoplasms with high rates of complete remission and with mild complications.

6.
Nat Neurosci ; 22(8): 1223-1234, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31332372

RESUMO

Social deficit is a core clinical feature of autism spectrum disorder (ASD) but the underlying neural mechanisms remain largely unclear. We demonstrate that structural and functional impairments occur in glutamatergic synapses in the pyramidal neurons of the anterior cingulate cortex (ACC) in mice with a mutation in Shank3, a high-confidence candidate ASD gene. Conditional knockout of Shank3 in the ACC was sufficient to generate excitatory synaptic dysfunction and social interaction deficits, whereas selective enhancement of ACC activity, restoration of SHANK3 expression in the ACC, or systemic administration of an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-positive modulator improved social behavior in Shank3 mutant mice. Our findings provide direct evidence for the notion that the ACC has a role in the regulation of social behavior in mice and indicate that ACC dysfunction may be involved in social impairments in ASD.

7.
Can J Anaesth ; 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31338808

RESUMO

PURPOSE: Bioelectrical impedance analysis (BIA) is a technology that provides a rapid, non-invasive measurement of volume in body compartments and may aid the physician in the assessment of volume status. We sought to investigate the effect of BIA-measured volume status on duration of mechanical ventilation, 28-day mortality, and acute kidney injury requiring renal replacement therapy in a population of medical/surgical patients admitted to the intensive care unit (ICU). METHODS: Prospective observational study of adult patients who required mechanical ventilation within 24 hr of admission to ICU. Bioelectrical impedance analysis measured extracellular water (ECW) and total body water (TBW) and these measurements were recorded on days 1, 3, 5, and 7. RESULTS: A total of 36 patients were enrolled. Mean (standard deviation) age was 61.8 (21.3) years and 31% of patients were female. The majority were admitted from the emergency department or operating room. The most common diagnosis was sepsis. At 28 days, eight patients (22%) had died. There was no association between ECW/TBW ratio at day 1 and 28-day mortality (odds ratio, 1.2; 95% confidence interval [CI], 0.6 to 2.3) after adjusting for age, sex, and Acute Physiology and Chronic Health Evaluation II score. The median [interquartile range] number of ventilator days was 5 [2.5-7.5]. On day 1, for each 1% increase in the ECW/TBW ratio, there was a 1.2-fold increase in ventilator days (95% CI, 1.003 to 1.4; P = 0.05). It is notable that 20% of eligible patients could not be enrolled because medical equipment interfered with correct electrode placement. CONCLUSION: Bioimpedance-measured ECW/TBW on day 1 of admission to the ICU is associated with time on the ventilator. While this technology may be a useful adjunct to the clinical assessment of volume status, there are technical barriers to its routine use in a general ICU population.

8.
Talanta ; 203: 9-15, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31202354

RESUMO

Biosensors are rising technologies in the pharmaceutical field for medicine discovery, development and Quality Control (QC) stages. Surface acoustic wave (SAW) biosensor employs acoustic waves generated by oscillating a piezoelectric crystal quartz plate to meas. mass and viscosity, and allows to detect and quantify binding events between the analyte and an immobilized interacting ligand. We present here a SAW biosensor based approach for the functional quantification of Escherichia colil-asparaginase (E. colil-ASNase), using polyclonal antibody (pAb) as the interaction partner immobilized on the chip. Different immobilization strategies of pAb were initially evaluated, resulting in the BS3 activated amide coupling via protein G strategy as the final immobilization method. The method was validated by evaluating the selectivity, linearity, as well as accuracy (a recovery of 102.4%) and precision (RSD of 8.5%). The application of the validated method on different samples encompassing different lots of E. colil-ASNase, deamidated E. colil-ASNase and dry-heated E. colil-ASNase (80 °C, 10 min) indicated the suitability of the developed SAW method to quantify E. colil-ASNase. We suggest this SAW method can be adopted as a pharmaceutical QC method.

9.
J Anesth ; 33(3): 463-477, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31076946

RESUMO

Over the last decade, considerable progress has been made regarding infraclavicular brachial plexus block (ICB) in adults, especially since the introduction of ultrasound guidance. The advancements in ICB have been attributed to the development of various approaches to improve the success rate and reduce complications. This has also necessitated a unified nomenclature system to facilitate comparison among different approaches. This review aimed to propose an anatomical nomenclature system by classifying ICB approaches into proximal and distal ones to aid future research and provide practice advisories according to recent updates. We also comprehensively discuss various aspects of this nomenclature system. Our review suggests that ultrasound-guided ICB should be categorized as an advanced technique that should be performed under supervision and dual guidance. For one-shot block, the conventional distal approach is still preferred but should be modified to follow ergonomic practice, with the arm in the proper position. For continuous ICB, the proximal approach is promising for reducing local anesthetic volume and increasing efficacy. Nevertheless, further studies are warranted in this direction. We provide practice advisories to maximize safety and minimize adverse events, and recommend designing future studies on ICB according to these findings based on the unified nomenclature system.

10.
Nat Biomed Eng ; 3(5): 414, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30976071

RESUMO

In the version of this Article originally published, 'palmitoyltransferase ZDHHC3 (DHHC3)' was incorrectly referred to as an 'acetyltransferase' rather than an as an 'acyltransferase'; this has now been corrected in five instances. In Fig. 3a, the label for the bottom row of the blots was mistakenly written as 'GAPHD'; it should have read 'GAPDH'. In the two right-most panels of Fig. 4j, the antibody labels 'α-PD-L1' for the reciprocal co-immunoprecipitation of DHHC3 were incorrect; they should have been 'α-DHHC3'. These errors have been corrected in all versions of the Article.

11.
Nat Biomed Eng ; 3(4): 306-317, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30952982

RESUMO

Checkpoint blockade therapy targeting the programmed-death ligand 1 (PD-L1) and its receptor programmed cell death 1 promotes T-cell-mediated immunosurveillance against tumours, and has been associated with marked clinical benefit in cancer patients. Antibodies against PD-L1 function by blocking PD-L1 on the cell surface, but intracellular storage of PD-L1 and its active redistribution to the cell membrane can minimize the therapeutic benefits, which highlights the importance of targeting PD-L1 throughout the whole cell. Here, we show that PD-L1 is palmitoylated in its cytoplasmic domain, and that this lipid modification stabilizes PD-L1 by blocking its ubiquitination, consequently suppressing PD-L1 degradation by lysosomes. We identified palmitoyltransferase ZDHHC3 (DHHC3) as the main acetyltransferase required for the palmitoylation of PD-L1, and show that the inhibition of PD-L1 palmitoylation via 2-bromopalmitate, or the silencing of DHHC3, activates antitumour immunity in vitro and in mice bearing MC38 tumour cells. We also designed a competitive inhibitor of PD-L1 palmitoylation that decreases PD-L1 expression in tumour cells to enhance T-cell immunity against the tumours. These findings suggest new strategies for overcoming PD-L1-mediated immune evasion in cancer.

12.
Medicine (Baltimore) ; 98(11): e14903, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30882709

RESUMO

In the present study, we aimed to investigate the association between gestational diabetes mellitus (GDM) and the oral microbial imbalance in the second trimester of pregnancy.Three hundred thirtyone women in the second trimester of pregnancy who underwent prenatal examinations at the Third Affiliated Hospital of Soochow University from February 2018 to August 2018 were included in this study. Personal parameters including the age, education level, and body mass index (BMI) at 28 weeks of gestation were recorded. Gestational diabetes mellitus (GDM) was diagnosed according to the Standards of Medical Care in Diabetes-2011 recommended by American Diabetes Association (ADA). After the significant difference of each parameter was erased by a propensity-score matched (PSM) analysis at a 1:1 ratio, the oral health conditions and the oral flora in pregnant women with GDM were compared with those in nondiabetic pregnant women.Our data demonstrated that 65 of the 331 pregnant women (19.6%) were diagnosed with GDM. Results from the matched data including 59 matched pairs of pregnant women showed that the gingival index (GI), plaque index (PI), tooth mobility degree (TMD), probing depth (PD), and bleeding on probing (BOP) of pregnant women with GDM were higher or more severe than those of nondiabetic pregnant women (P < .05). The detection rate of tuberculosis bacilli, Black-pigmented bacteria, and Capnocytophaga in pregnant women with GDM was higher than those in nondiabetic pregnant women (P = .000, P = .026, and P = .030, respectively). In addition, pregnant women with GDM had fewer oral streptococci (P = .000) and lactobacilli (P = .000) and more oral anaerobic bacteria (P = .000), tuberculosis bacilli (P = .000), Black-pigmented bacteria (P = .007), Capnocytophaga (P = .000), and actinomycetes (P = .000).The detection rate and the number of oral bacteria in pregnant women with GDM were higher than those in nondiabetic pregnant women in the second trimester of pregnancy.


Assuntos
Bactérias/classificação , Diabetes Gestacional/fisiopatologia , Gestantes , Adolescente , Adulto , Bactérias/metabolismo , Índice de Massa Corporal , China , Feminino , Teste de Tolerância a Glucose/métodos , Humanos , Índice Periodontal , Gravidez , Fatores de Risco
13.
Air Med J ; 38(2): 106-114, 2019 Mar - Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30898281

RESUMO

OBJECTIVE: The air medical transportation industry has seen a steady rise in the use of mechanical circulatory support devices (eg, intra-aortic balloon pumps, ventricular assist devices, and extracorporeal membrane oxygenation) during transport missions, either for definitive management or repatriation. As these complex devices become more common, the industry will have to adapt to support their use in their clientele. The goal of this narrative review was to assess our current experiences regarding mechanical circulatory support devices in air medical transportation and to identify important factors to ensure successful transport. METHODS: We conducted a systematic search on MEDLINE and Embase using the following search terms: aeromedical transportation, air transportation, intra-aortic balloon pump, ventricular assist device, and extracorporeal membrane oxygenation. Results were cross-referenced to identify articles addressing both air medical transport and mechanical circulatory support devices. RESULTS: After a systematic review of the available literature, 49 articles addressing mechanical support devices transported by rotary wing and fixed wing aircraft were reviewed. In summary, our review encompassed 811 total aerial transports (152 by balloon pumps, 12 by ventricular assist devices, and 647 by extracorporeal membrane oxygenation). We found air medical transportation with these devices carried out in the public, private, or military sectors, to be safe, with low rates of serious adverse events. Dedicated training sessions focused on device troubleshooting and problem-solving during transport, optimal medical crew composition, predeparture logistical preparations, and on-demand specialist consultation can improve mission success. CONCLUSION: We report that air medical transportation of patients supported by mechanical circulatory support devices is safe. Complications can be mitigated by training and addressed either during the predeparture or in-transportation phase.

14.
J Chromatogr A ; 1590: 10-18, 2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-30609959

RESUMO

Boronate affinity materials are usually used for selective enrichment of cis-diol-containing compounds, mainly based on formation of pH-dependent cyclic ester between cis-diol and boronic acid. Recently, B-N coordination, or combined with hydrogen-bonding interaction, was employed as primary interaction for the extraction of nitrogen-containing compounds. However, there are no reports about the combination of hydrophobic (or π-π) interaction and B-N coordination for the extraction. Here, we prepared a novel hydrophobic phenyl-boronic acid polymer (PBAP) through initiator-free ring-opening polymerization. The adsorption experiment indicated that the PBAP could combine hydrophobic (or π-π) interaction and B-N coordination to enhance their adsorption capacity toward hydrophobic and nitrogen-containing compounds, for example sulfamethoxazole (SMX) and trimethoprim (TMP). In addition, the PBAP monolith synthesized in pipette tip was used as solid phase microextraction (SPME) sorbent with combination of ultra high performance liquid chromatography to extract and monitor SMX and TMP from animal-originated foodstuffs. The proposed method exhibited low limit of quantitation as 5.0 and 1.0 ng mL-1 for SMX and TMP, respectively. The recoveries at three spiked levels were between 92.4% to 100.5% for SMX, and 92.7% to 102.6% for TMP, with intra-day and inter-day relative standard deviations no more than 5.3% and 8.6%, respectively. These results well demonstrated that the combination of hydrophobic (or π-π) interaction and B-N coordination played an important role in the extraction of hydrophobic and nitrogen-containing compounds.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Resíduos de Drogas , Produtos da Carne/análise , Microextração em Fase Sólida/métodos , Sulfametoxazol , Trimetoprima , Ácidos Borônicos/química , Resíduos de Drogas/análise , Resíduos de Drogas/química , Resíduos de Drogas/isolamento & purificação , Polímeros/química , Sulfametoxazol/análise , Sulfametoxazol/química , Sulfametoxazol/isolamento & purificação , Trimetoprima/análise , Trimetoprima/química , Trimetoprima/isolamento & purificação
15.
Opt Express ; 26(22): 28682-28692, 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30470041

RESUMO

An acousto-optic modulation (AOM) detection method is demonstrated to detect the atomic Larmor precession frequency in an all-optical K-Rb atomic magnetometer operated in Spin-Exchange Relaxation Free (SERF) regime. Magnetic field sensitivity of 14 fT/Hz1/2 was achieved by employing the uniform design (UD) [Acta Math Appl Sin.3, 363 (1980)] and subsequently optimizing the AOM modulation conditions. Results were compared to those of Faraday and the balanced polarimetry method in the same magnetometer. The AOM detection method has several advantages, such as small volume, no extra magnetic shielding for the modulator, high measurement signal-to-noise ratio and stability. It has a good prospect for compact and multi-channel atomic magnetometers.

16.
Nat Chem Biol ; 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30397328

RESUMO

Expression of programmed cell death 1 (PD-1) ligand 1 (PD-L1) protects tumor cells from T cell-mediated immune surveillance, and immune checkpoint blockade (ICB) therapies targeting PD-1 and PD-L1 have exhibited significant clinical benefits. However, the relatively low response rate and observed ICB resistance highlight the need to understand the molecular regulation of PD-L1. Here we show that HIP1R targets PD-L1 to lysosomal degradation to alter T cell-mediated cytotoxicity. HIP1R physically interacts with PD-L1 and delivers PD-L1 to the lysosome through a lysosomal targeting signal. Depletion of HIP1R in tumor cells caused PD-L1 accumulation and suppressed T cell-mediated cytotoxicity. A rationally designed peptide (PD-LYSO) incorporating the lysosome-sorting signal and the PD-L1-binding sequence of HIP1R successfully depleted PD-L1 expression in tumor cells. Our results identify the molecular machineries governing the lysosomal degradation of PD-L1 and exemplify the development of a chimeric peptide for targeted degradation of PD-L1 as a crucial anticancer target.

17.
Cancer Biomark ; 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30452401

RESUMO

Cholangiocarcinoma (CCA) is a highly malignant and poorly differentiated bile duct cancer with an extremely poor prognosis, but the pathogenesis of CCA remains not well-known. Attention has been increasingly focused on long noncoding RNAs, which plays an important role in tumorigenesis. However, the roles of cancer specific lncRNA and its related competitive endogenous RNAs (ceRNA) network in CCA remain elusive. In this study, we comprehensively integrated expression profiles, including data on mRNAs, lncRNAs and miRNAs obtained from 36 CCA tissues and 9 normal tissues in The Cancer Genome Atlas. 1434 cancer specific lncRNAs, 68 miRNAs and 3538 mRNAs (|logFC|> 1, p< 0.05) were identified. Based on bioinformatics generated from miRcode, starBase, miRTarBase, TargetScan and miRDB, we constructed an lncRNA-miRNA-mRNA network (ceRNA network) in CCA. We constructed the lncRNA-miRNA-mRNA ceRNA network consisting of 206 molecules and 454 interactions. In addition, we used Cytoscape software to visualize the ceRNA network in WGCNA, 22 mRNA network modules were identified, five of which were significantly related to tumor grade and survival time. Moreover, three lncRNAs COL18A1-AS1, SLC6A1-AS1 and HULC were found to be significantly associated with overall survival. The present study provides novel insight for better understanding of lncRNA-related ceRNA network in CCA and useful resource for identifcation of novel biomarkers of CCA.

18.
Front Mol Neurosci ; 11: 296, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30197587

RESUMO

Chronic pain usually results in persistent anxiety, which worsens the life quality of patients and complicates the treatment of pain. Hippocampus is one of the few brain regions in many mammalians species which harbors adult neural stem cells (NSCs), and plays a key role in the development and maintenance of chronic anxiety. Recent studies have suggested a potential involvement of hippocampal neurogenesis in modulating chronic pain. Whether and how hippocampal NSCs are involved in the pain-associated anxiety remains unclear. Here, we report that mice suffering persistent neuropathic pain showed a quick reduction of active NSCs in the ventral dentate gyrus (vDG), which was followed by the decrease of neurogenesis and appearance of anxiety. Wnt/ß-catenin signaling, a key pathway in sustaining the active status of NSCs was suppressed in the vDG of mice suffering chronic pain. Depleting ß-catenin by inducible Nestin-Cre significantly reduced the number of active NSCs and facilitated anxiety development, while expressing stabilized ß-catenin amplified active NSCs and alleviated anxiety, indicating that Wnt activated NSCs is required for anxiety development under chronic pain. Treatment with Fluoxetine, the most widely used anxiolytic in clinic, significantly increased the proliferation of active NSCs and enhanced Wnt signaling. Interestingly, both ß-catenin manipulation and Fluoxetine treatment had no significant effects on the pain thresholds. Therefore, our data demonstrated an anxiety-specific response and contribution of activated NSCs to chronic pain through Wnt/ß-catenin signaling, which may be targeted for treating chronic pain- or other diseases-associated anxiety.

19.
Front Immunol ; 9: 1774, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30105035

RESUMO

Programmed death 1 (PD-1) and its two natural ligands PD-L1 and PD-L2 are responsible for delivering inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. In previous studies, PD-1 was found only expressed on the surface of immune cells, such as T cells and B cells while PD-1's ligands PD-L1 and PD-L2 were found expressed in some tumor cells. However, recent studies revealed intrinsic expression of PD-1 in melanoma and some other cancers. In melanoma cells, PD-1 can be activated by its ligand PD-L1 expressed by tumor cells, modulating downstream mammalian target of rapamycin signaling and promoting tumor growth independent of adaptive immunity. In addition to melanoma, PD-1 was also detected in liver cancer cells as well as in non-small lung cancer cells. Unlike its oncogenic functions in melanoma and hepatic carcinoma cells, PD-1 seemed to play a distinct role in lung cancer, as blockade of PD-1 instead promoted tumor cells proliferation. Tumor-intrinsic PD-1 expression seems to be widespread in many tumor types, according to our reanalysis on cancer transcriptomic and proteomic data. The multifaceted roles of PD-1 in tumor cells beyond immune checkpoint signaling may explain the differential therapeutic effects of anti-PD-1 and anti-PD-L1 drugs and provide crucial information when developing combinatorial approaches to enhance antitumor immunity.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA