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1.
J Fluoresc ; 32(3): 983-992, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35230565

RESUMO

Chirality plays a pivotal role in drugs, agrochemicals and food additives et al. The enantiomers of a chiral molecule often show huge difference in bioactivity, metabolism, and toxicity et al. thereby, the recognition of chiral molecules shows an increasingly important priority. In this paper, a novel method for chiral fluorescence recognition based on anthracene fluorescent dyes (AD) ⊂ water-soluble pillar[5] arene containing phosphonic acid group (PWP[5]) is developed. The AD as guest molecule can complex with PWP [5] to form 1:1 AD ⊂ PWP[5] assembly, and this assembly can be further used as a fluorescent probe to identify D/L-phenylalanine and D/L-phenylalaninol by fluorescent titration. The fluorescence intensity of the assembly was significantly reduced for D-phenylalanine and D-phenylalaninol, while L-phenylalanine or L-phenylalaninol was added to AD ⊂ PWP[5] assembly, the fluorescence intensity of the assembly almost unchanged. Hence, the chiral recognition based on assembly between the achiral fused ring fluorescent dye and achiral PWP[5] was developed.


Assuntos
Calixarenos/química , Corantes Fluorescentes , Compostos de Amônio Quaternário/química , Água , Antracenos , Fluorescência , Corantes Fluorescentes/química , Fenilalanina , Ácidos Fosforosos
2.
BMC Med Res Methodol ; 20(1): 84, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293277

RESUMO

BACKGROUND: Predictive models within epilepsy are frequently developed via Cox's proportional hazards models. These models estimate risk of a specified event such as 12-month remission. They are relatively simple to produce, have familiar output, and are useful to answer questions about short-term prognosis. However, the Cox model only considers time to first event rather than all seizures after starting treatment for example. This makes assessing change in seizure rates over time difficult. Variants to the Cox model exist enabling recurrent events to be modelled. One such variant is the Prentice, Williams and Peterson - Total Time (PWP-TT) model. An alternative is the negative binomial model for event counts. This study aims to demonstrate the differences between the three approaches, and to consider the benefits of the PWP-TT approach for assessing change in seizure rates over time. METHODS: Time to 12-month remission and time to first seizure after randomisation were modelled using the Cox model. Risk of seizure recurrence was modelled using the PWP-TT model, including all seizures across the whole follow-up period. Seizure counts were modelled using negative binomial regression. Differences between the approaches were demonstrated using participants recruited to the UK-based multi-centre Standard versus New Antiepileptic Drug (SANAD) study. RESULTS: Results from the PWP-TT model were similar to those from the conventional Cox and negative binomial models. In general, the direction of effect was consistent although the variables included in the models and the significance of the predictors varied. The confidence intervals obtained via the PWP-TT model tended to be narrower due to the increase in statistical power of the model. CONCLUSIONS: The Cox model is useful for determining the initial response to treatment and potentially informing when the next intervention may be required. The negative binomial model is useful for modelling event counts. The PWP-TT model extends the Cox model to all included events. This is useful in determining the longer-term effects of treatment policy. Such a model should be considered when designing future clinical trials in medical conditions typified by recurrent events to improve efficiency and statistical power as well as providing evidence regarding changes in event rates over time.


Assuntos
Anticonvulsivantes , Carbamazepina , Epilepsias Parciais , Epilepsia Generalizada , Convulsões , Anticonvulsivantes/efeitos adversos , Carbamazepina/uso terapêutico , Ensaios Clínicos como Assunto , Epilepsias Parciais/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Humanos , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico
3.
Exp Dermatol ; 28(11): 1336-1340, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31278779

RESUMO

Psoriatic skin is characterized by a deregulated profile of miRNAs that are contributing in disease development. In this study, we focus on miR-31, one of the upregulated miRNAs known to promote keratinocytes proliferation and migration. Moreover, miR-31 expression induction was dependent on a large panel of cytokines including IL-22. Here, we aimed at investigating the relationship between miR-31-5p and IL-22 axis; and by searching novel molecular target for miR-31-5p in keratinocytes. Our data identify a direct correlation between miR-31-5p and IL-22 in psoriasis with Pwp1 as new potential target. These findings confirm the important role of miR-31 in psoriasis onset and provide a basis for further investigations in miRNAs field in context of skin diseases.


Assuntos
Interleucinas/metabolismo , MicroRNAs/metabolismo , Psoríase/metabolismo , Animais , Imiquimode , Camundongos , Interleucina 22
4.
Geoderma ; 324: 18-36, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30122789

RESUMO

In rainfed crop production, root zone plant-available water holding capacity (RZ-PAWHC) of the soil has a large influence on crop growth and the yield response to management inputs such as improved seeds and fertilisers. However, data are lacking for this parameter in sub-Saharan Africa (SSA). This study produced the first spatially explicit, coherent and complete maps of the rootable depth and RZ-PAWHC of soil in SSA. We compiled geo-referenced data from 28,000 soil profiles from SSA, which were used as input for digital soil mapping (DSM) techniques to produce soil property maps of SSA. Based on these soil properties, we developed and parameterised (pedotransfer) functions, rules and criteria to evaluate soil water retention at field capacity and wilting point, the soil fine earth fraction from coarse fragments content and, for maize, the soil rootability (relative to threshold values) and rootable depth. Maps of these secondary soil properties were derived using the primary soil property maps as input for the evaluation rules and the results were aggregated over the rootable depth to obtain a map of RZ-PAWHC, with a spatial resolution of 1 km2. The mean RZ-PAWHC for SSA is 74 mm and the associated average root zone depth is 96 cm. Pearson correlation between the two is 0.95. RZ-PAWHC proves most limited by the rootable depth but is also highly sensitive to the definition of field capacity. The total soil volume of SSA potentially rootable by maize is reduced by one third (over 10,500 km3) due to soil conditions restricting root zone depth. Of these, 4800 km3 are due to limited depth of aeration, which is the factor most severely limiting in terms of extent (km2), and 2500 km3 due to sodicity which is most severely limiting in terms of degree (depth in cm). Depth of soil to bedrock reduces the rootable soil volume by 2500 km3, aluminium toxicity by 600 km3, porosity by 120 km3 and alkalinity by 20 km3. The accuracy of the map of rootable depth and thus of RZ-PAWHC could not be validated quantitatively due to absent data on rootability and rootable depth but is limited by the accuracy of the primary soil property maps. The methodological framework is robust and has been operationalised such that the maps can easily be updated as additional data become available.

5.
Behav Cogn Psychother ; 46(1): 101-114, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28903792

RESUMO

BACKGROUND: Little is understood about the relationship between therapist competence and the outcomes of patients treated for common mental health disorders. Furthermore, the evidence is yet to extend to competence in the delivery of low-intensity cognitive behavioural interventions. Understanding this relationship is essential to the dissemination and implementation of low-intensity cognitive behavioural interventions. AIMS: The aim of this study was to explore the relationship between Psychological Well-being Practitioner (PWP) competence and patient outcome within the framework of the British government's Improving Access to Psychological Therapies (IAPT) initiative. METHOD: Forty-seven PWPs treating 3688 patients participated. Relationships between PWP scores on three observed standardized clinical examinations and reliable change in patients' symptoms of anxiety and depression were explored at two time points: during the year-long training phase, and over a 12-month follow-up. RESULTS: Results indicated that patients treated by qualified PWPs achieved superior outcomes than those treated by trainees. Little support was found for a general association between practitioner competence in delivering low-intensity cognitive behavioural interventions and patient outcome, either during or post-training; however, significantly more patients of the most competent PWPs demonstrated reliable improvement in their symptoms of anxiety and depression than would be expected by chance alone and fewer deteriorated compared with those treated by the least competent PWPs. CONCLUSION: Results were indicative of a complex, non-linear relationship, with patient outcome affected by PWP status (trainee or qualified) and by competence at its extremes. The implications of these results for the dissemination and implementation of low-intensity cognitive behavioural interventions are discussed.


Assuntos
Ansiedade/psicologia , Ansiedade/terapia , Competência Clínica/estatística & dados numéricos , Terapia Cognitivo-Comportamental/normas , Depressão/psicologia , Depressão/terapia , Adulto , Transtornos de Ansiedade/psicologia , Transtornos de Ansiedade/terapia , Transtorno Depressivo/psicologia , Transtorno Depressivo/terapia , Feminino , Humanos , Masculino , Resultado do Tratamento
6.
Stem Cells ; 33(3): 661-73, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25335925

RESUMO

Leukemia inhibitory factor/Stat3 signaling is critical for maintaining the self-renewal and differentiation potential of mouse embryonic stem cells (mESCs). However, the upstream effectors of this pathway have not been clearly defined. Here, we show that periodic tryptophan protein 1 (Pwp1), a WD-40 repeat-containing protein associated with histone H4 modification, is required for the exit of mESCs from the pluripotent state into all lineages. Knockdown (KD) of Pwp1 does not affect mESC proliferation, self-renewal, or apoptosis. However, KD of Pwp1 impairs the differentiation potential of mESCs both in vitro and in vivo. PWP1 chromatin immunoprecipitation-seq results revealed that the PWP1-occupied regions were marked with significant levels of H4K20me3. Moreover, Pwp1 binds to sites in the upstream region of Stat3. KD of Pwp1 decreases the level of H4K20me3 in the upstream region of Stat3 gene and upregulates the expression of Stat3. Furthermore, Pwp1 KD mESCs recover their differentiation potential through suppressing the expression of Stat3 or inhibiting the tyrosine phosphorylation of STAT3. Together, our results suggest that Pwp1 plays important roles in the differentiation potential of mESCs.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Células-Tronco Embrionárias/metabolismo , Proteínas Nucleares/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Células-Tronco Embrionárias/citologia , Fibroblastos/citologia , Fibroblastos/metabolismo , Células HEK293 , Humanos , Camundongos , Proteínas Nucleares/genética , Transdução de Sinais
7.
J Enzyme Inhib Med Chem ; 31(sup3): 33-40, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27353461

RESUMO

Declining efficiency of antibiotic-inhibitor combinatorial therapies in treating beta-lactamase mediated resistance necessitates novel inhibitor development. Allosteric inhibition offers an alternative to conventional drugs that target the conserved active site. Here, we show that the evolutionarily conserved PWP triad located at the N-terminus of the H10 helix directly interacts with the allosteric site in TEM-1 beta-lactamase and regulates its activity. While point mutations in the PWP triad preserve the overall secondary structures around the allosteric site, they result in a more open and dynamic global structure with decreased chemical stability and increased aggregation propensity. These mutant enzymes with a less compact hydrophobic core around the allosteric site displayed significant activity loss. Detailed sequence and structure conservation analyses revealed that the PWP triad is an evolutionarily conserved motif unique to class A beta-lactamases aligning its allosteric site and hence is an effective potential target for enzyme regulation and selective drug design.


Assuntos
Sítio Alostérico , Sequência Conservada , Evolução Molecular , beta-Lactamases/química , beta-Lactamases/metabolismo , Sítio Alostérico/efeitos dos fármacos , Motivos de Aminoácidos , Desenho de Fármacos , Ativação Enzimática/efeitos dos fármacos , Modelos Moleculares , Mutação Puntual , Ureia/farmacologia , beta-Lactamases/genética
8.
Behav Cogn Psychother ; 44(4): 431-43, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26365006

RESUMO

BACKGROUND: "Stress Control" (SC) has been adopted as a core intervention in step 2 of Improving Access to Psychological Therapies (IAPT) services, but contemporary evidence of effectiveness has lagged behind service uptake. AIMS: To investigate the acceptability and effectiveness of SC and to explore moderators of outcome. METHOD: Analysis of acceptability (via attendance rates) and effectiveness (via IAPT minimum dataset). RESULTS: SC was well tolerated with 73.3% of all patients and 75.4% of "clinical cases" attending three or more sessions. Of the 546 "clinical cases" attending SC and not in receipt of other interventions, 37% moved to recovery. Attendance improved outcome; for those patients attending all SC sessions the recovery rate rose to 59.2%. CONCLUSION: SC appears a well-tolerated and effective intervention that enables large numbers to gain access to treatment in an organizationally efficient manner. Attendance is important in facilitating SC outcomes and research evaluating attendance interventions are needed.


Assuntos
Transtornos de Ansiedade/terapia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Psicoterapia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos de Ansiedade/psicologia , Terapia Cognitivo-Comportamental/métodos , Aconselhamento/métodos , Inglaterra , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Psicoterapia de Grupo/métodos , Estresse Psicológico/terapia
9.
Biochem Cell Biol ; 92(3): 191-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24754225

RESUMO

Nine WD-repeat containing proteins in human SSU processome components have been found in a HeLa cell nuclear matrix fraction. In these proteins, t-UTP sub-complex components, i.e., CIRH1A, UTP15, and WDR43, were shown to be immobilized in the fibrillar centers of nucleoli in living cells. In this study, the dynamics of the remaining six proteins fused with green fluorescent protein (GFP), i.e., PWP2-GFP, TBL3-GFP, GFP-UTP18, GFP-NOL10, GFP-WDR46, and GFP-WDSOF1, were examined in living cells. The findings were as follows. (i) The majority of UTP-B sub-complex components, i.e., PWP2-GFP, TBL3-GFP, and GFP-UTP18, are localized to the dense fibrillar component and granular component regions in nucleoli; (ii) When rRNA transcription is suppressed, the majority of GFP-fused UTP-B sub-complex components are localized in the cap and body regions of nucleoli. (iii) The mobility of these proteins except for GFP-WDSOF1, and half of GFP-UTP18 and GFP-WDR46, respectively, is very low in living cells. (iv) When rRNA transcription is suppressed, the mobility of these proteins except for GFP-WDSOF1 is accelerated but still slow. These findings and others suggest that these WD-repeat proteins other than GFP-WDSOF1 found in the nuclear matrix fraction bind tightly to some macro-protein complexes and act as a scaffold or a core for the complexes in nucleoli.


Assuntos
Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Ribonucleoproteínas/química , Ribonucleoproteínas/metabolismo , Células HeLa , Humanos , Processamento Pós-Transcricional do RNA , RNA Ribossômico/genética , RNA Ribossômico/metabolismo
10.
Heliyon ; 10(11): e32409, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38933950

RESUMO

Identification of novel biomarkers for prediction of disease course and prognosis is needed to reduce morbidity of liver hepatocellular carcinoma (LIHC/HCC) patients. Although dysregulated Periodic tryptophan protein 1 homolog (PWP1/endonuclein) expression has been detected in several tumors, the potential regulatory effect of PWP1 on LIHC remains uncertain. Here we evaluated the expression of PWP1 using multiple online platforms, and demonstrated that PWP1 upregulation was consistently observed in LIHC relative to non-tumor liver tissues and correlated with unfavorable prognosis. Moreover, HCC prognosis was significantly influenced by the methylation status of various CpG sites in the PWP1 gene. Lastly, we provide direct evidence that PWP1 acts as a driver of HCC progression by showing that siRNA-mediated PWP1 silencing significantly suppressed HCC cell proliferation in vitro. These data strongly suggest that PWP1 silencing may be an effective therapeutic strategy to treat LIHC.

11.
Comput Methods Programs Biomed ; 254: 108254, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38905989

RESUMO

BACKGROUND AND OBJECTIVES: Episodes of Freezing of Gait (FoG) are among the most debilitating motor symptoms of Parkinson's Disease (PD), leading to falls and significantly impacting patients' quality of life. Accurate assessment of FoG by neurologists provides crucial insights into patients' conditions and disease symptoms. This proposed strategy involves utilizing a Weighted Fuzzy Logic Controller, Kalman Filter, and Kaiser-Meyer-Olkin test to detect the gait parameters while walking, resting, and standing phases. Parameters such as neuromodulation format, intensity, duration, frequency, and velocity are computed to pre-empt freezing episodes, thus aiding their prevention. METHOD: The AiCarePWP is a wearable electronics device designed to identify instances when a patient is on the brink of experiencing a freezing episode and subsequently deliver a brief electrical impulse to the patient's shank muscles to stimulate movement. The AiCarePWP wearable device aims to identify impending freezing episodes in PD patients and deliver brief electrical impulses to stimulate movement. The study validates this innovative approach using plantar insoles with a 3D accelerometer and electrical stimulator, analysing data from the inertial measuring unit and plantar-pressure foot data to detect and predict FoG. RESULTS: Using a Convolutional Neural Network-based model, the study evaluated 47 gait features for their ability to differentiate resting, standing, and walking conditions. Variable selection was based on sensitivity, specificity, and overall accuracy, followed by Principal Component Analysis and Varimax rotation to extract and interpret factors. Factors with eigenvalues exceeding 1.0 were retained, and 37 features were retained. CONCLUSION: This study validates CNN's effectiveness in detecting FoG during various activities. It introduces a novel cueing method using electrical stimulation, which improves gait function and reduces FoG incidence in PD patients. Trustworthy wearable devices, based on Artificial Intelligence of Things (AIoT) and Artificial Intelligence of Medical Things (AIoMT), have been developed to support such interventions.


Assuntos
Aprendizado Profundo , Transtornos Neurológicos da Marcha , Marcha , Doença de Parkinson , Dispositivos Eletrônicos Vestíveis , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/complicações , Transtornos Neurológicos da Marcha/fisiopatologia , Redes Neurais de Computação , Masculino , Feminino , Lógica Fuzzy , Algoritmos , Acelerometria/instrumentação , Idoso , Caminhada
12.
Diagnostics (Basel) ; 13(20)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37892065

RESUMO

Kidney tumors represent a significant medical challenge, characterized by their often-asymptomatic nature and the need for early detection to facilitate timely and effective intervention. Although neural networks have shown great promise in disease prediction, their computational demands have limited their practicality in clinical settings. This study introduces a novel methodology, the UNet-PWP architecture, tailored explicitly for kidney tumor segmentation, designed to optimize resource utilization and overcome computational complexity constraints. A key novelty in our approach is the application of adaptive partitioning, which deconstructs the intricate UNet architecture into smaller submodels. This partitioning strategy reduces computational requirements and enhances the model's efficiency in processing kidney tumor images. Additionally, we augment the UNet's depth by incorporating pre-trained weights, therefore significantly boosting its capacity to handle intricate and detailed segmentation tasks. Furthermore, we employ weight-pruning techniques to eliminate redundant zero-weighted parameters, further streamlining the UNet-PWP model without compromising its performance. To rigorously assess the effectiveness of our proposed UNet-PWP model, we conducted a comparative evaluation alongside the DeepLab V3+ model, both trained on the "KiTs 19, 21, and 23" kidney tumor dataset. Our results are optimistic, with the UNet-PWP model achieving an exceptional accuracy rate of 97.01% on both the training and test datasets, surpassing the DeepLab V3+ model in performance. Furthermore, to ensure our model's results are easily understandable and explainable. We included a fusion of the attention and Grad-CAM XAI methods. This approach provides valuable insights into the decision-making process of our model and the regions of interest that affect its predictions. In the medical field, this interpretability aspect is crucial for healthcare professionals to trust and comprehend the model's reasoning.

13.
Epilepsy Behav Rep ; 21: 100579, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36620478

RESUMO

Radiofrequency thermocoagulation (RF-TC) is a wide-used procedure for drug-resistant epilepsy. The technique is considered safe with an overall risk of 1.1% of permanent complications, mainly focal neurological deficits. We report the case of a patient with drug-resistant epilepsy who complained of immediate seizure worsening and an unexpected event seven months following RF-TC. A 35-year-old male with drug-resistant epilepsy from the age of 18 years underwent stereoelectroencephalography (SEEG) implantation for a right peri-silvian polymicrogyria. He was excluded from surgery due to extent of the epileptogenic zone and the risk of visual field deficits. RF-TC was attempted to ablate the most epileptogenic zone identified by SEEG. After RF-TC, the patient reported an increase in seizure severity/frequency and experienced episodes of postictal psychosis. Off-label cannabidiol treatment led to improved seizure control and resolution of postictal psychosis. Patients with polymicrogyria (PwP) may present with a disruption of normal anatomy and the co-existence between epileptogenic zone and eloquent cortex within the malformation. RF-TC should be considered in PwP when they are excluded from surgery for prognostic and palliative purposes. However, given the complex interplay between pathological and electrophysiological networks in these patients, the remote possibility of clinical exacerbation after RF-TC should also be taken into account.

14.
Brain Sci ; 12(6)2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35741634

RESUMO

A major proportion of people with Parkinson's disease (PwP) in Germany has written an advance directive (AD). Unfortunately, these ADs are unclear for PD-specific endpoints. We previously established consensus-based recommendations for disease-specific content of an AD in PwP. However, the implementation of those recommendations and the consulting of AD creation and modification in PwP remains to be evaluated. This study aimed to investigate the practical use of PD-specific recommendations for ADs in outpatient settings. A total of 87 physicians (45 general practitioners (GPs) and 42 neurologists, 10% response rate) answered a self-constructed semiquantitative questionnaire. The participants were asked to evaluate the suggested PD-specific recommendations for ADs and the supply of palliative care in the outpatient setting. Overall, the vast majority of treating physicians agreed on the usefulness of the newly constructed PD-specific recommendations. Consultations to discuss information about PD-specific ADs were scarce with short durations. Only 24% of participating physicians implemented the PD-specific recommendations in their daily practice. GPs and neurologists agreed on the benefit of disease-specific recommendations for ADs. In future, a more general integration of these recommendations in routine care might improve specific AD creation of PwP and advanced care planning.

15.
ACS Appl Mater Interfaces ; 14(6): 8353-8360, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35067039

RESUMO

Low-acidity polymer electrolyte membranes are essential to polymer electrolyte fuel cells (PEFCs) and water electrolysis systems, both of which are expected to be next-generation energy and hydrogen sources. We developed a new type of high-performance polymer electrolyte membrane (PEM) in which the core particles are precisely electrolyte polymer coated and filled into binder resin. Cellulose nanocrystals (CNCs), which have attracted attention as light, rigid, and sustainable materials, were selected as the core material for the filler. The CNC surface was coated with a new block copolymer containing a proton conductive polymer of poly(vinylphosphonic acid) (PVPA) and a hydrophobic polymer of polystyrene (PS) using RAFT polymerization with particles (PwP) we developed. The pelletized fillers and the filler-filled polycarbonate membranes achieved proton conductivities of over 10-2 S/cm with lower activation energies and much weaker acidity than the Nafion membrane.

16.
Onco Targets Ther ; 13: 10025-10037, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116587

RESUMO

PURPOSE: The significance of periodic tryptophan protein 1 (PWP1) expression in human cancer and its molecular mechanism of action have not been reported so far. MATERIALS AND METHODS: Immunohistochemistry was performed to analyze the expression of PWP1 in non-small cell lung cancer (NSCLC) tissues and statistical analysis was applied to analyze the relationship between PWP1 expression and the clinicopathological factors. The effects of PWP1 on NSCLC proliferation and invasion were determined by colony formation, transwell and MTT assays. Western blot analysis (WB), dual-luciferase reporter gene assays and immunofluorescence staining were performed to demonstrate whether PWP1 stimulates Wnt pathway and inhibits Hippo pathway. Co-immunoprecipitation (Co-ip) assays were used to confirm the potential role of PWP1 in Wnt and Hippo signaling pathways. RESULTS: PWP1 expression in NSCLC was higher than that in normal bronchial epithelium and normal submucosal glands. In addition, PWP1 expression had a positive correlation with poor differentiation, high pathological tumor-node-metastasis (TNM) stage, and lymph node metastasis. Kaplan-Meier database demonstrated that the overall survival time of patients with high PWP1 expression was significantly shorter than that of patients with low PWP1 expression. Mechanistically, we found that PWP1 could interact with DVL2 to upregulate ß-catenin (thereby activating the Wnt pathway), whereas PWP1 could interact with Merlin (NF2) to downregulate p-MST1 (thereby inhibiting the Hippo signaling pathway). The effects of PWP1 on promoting the Wnt pathway or inhibiting the Hippo pathway were offset in DVL2- or Merlin-knockdown cells transiently overexpressing PWP1. CONCLUSION: PWP1 expression in NSCLC was correlated with poor prognosis. PWP1 enhanced the activity of the Wnt pathway by interacting with DVL2, whereas PWP1 inhibited the activity of the Hippo pathway by interacting with Merlin. Together, these two effects promoted the detrimental biological behaviors of NSCLC cells.

17.
Biol Open ; 7(11)2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-30361412

RESUMO

PWP1 is a chromatin binding protein with an important role in animal growth control downstream of mTOR-mediated nutrient sensing. PWP1 has been shown to control tissue growth by promoting the transcription of 5.8S, 18S and 28S ribosomal RNAs (rRNAs) by RNA polymerase I (Pol I). Concomitantly with Pol I, RNA Polymerase III (Pol III) contributes to ribosome biogenesis by transcribing 5S rRNA in the nucleoplasm. Pol III activity is also closely controlled by nutrient-dependent signaling, however, how the activities of Pol I and Pol III are coordinated in response to nutrient-derived signals remains insufficiently understood. Experiments in Drosophila larvae and human cells reported here show that PWP1 associates with the chromatin at the 5S rDNA loci and is needed for nutrient-induced expression of 5S rRNA. Similar to the Pol I target rDNAs, PWP1 epigenetically maintains 5S rDNA in a transcription competent state. Thus, as a common regulator of Pol I and Pol III, PWP1 might contribute to coordinated control of ribosomal gene expression in response to nutrition.This article has an associated First Person interview with the first author of the paper.

18.
J Am Coll Cardiol ; 62(12): 1103-1111, 2013 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-23831444

RESUMO

OBJECTIVES: The aim of the present study was to elucidate right ventricular (RV) function and structure in patients with chronic obstructive pulmonary disease (COPD) without pulmonary hypertension (PH). BACKGROUND: There is little knowledge of RV function and remodeling in COPD without PH. METHODS: Thirty-four controls and 98 patients with COPD were included. The study patients were divided into 2 groups by right heart catheterization: no PH (mean pulmonary artery pressure [mPAP] <25 mm Hg) and PH (mPAP ≥25 mm Hg). The echocardiographic tissue Doppler imaging variables of RV isovolumic acceleration, peak systolic strain, and RV myocardial performance index were measured at the basal free wall, and RV wall thickness and RV internal dimension were measured in the RV outflow tract. RESULTS: The increases in RV wall thickness and RV dimension were more evident when comparing controls with the no PH group (3.5 ± 0.5 mm to 5.5 ± 1.0 mm [p < 0.01] and 1.5 cm ± 0.2 to 2.0 ± 0.5 cm [p < 0.01]) than comparing the no PH group with the PH group (5.5 ± 1.0 mm to 6.6 ± 1.1 mm [p < 0.01] and 2.0 cm ± 0.5 to 2.1 ± 0.3 cm [p = NS]), respectively. Similarly, RV isovolumic acceleration, performance index, and strain deteriorated significantly when comparing controls with the no PH group and comparing the no PH group with the PH group (p < 0.01). Significant correlations were observed between mPAP and RV isovolumic acceleration, performance index, strain, and RV wall thickness (p < 0.01). RV impairment and increased RV wall thickness and RV dimensions were present even at slight elevations of mPAP (18 ± 3 mm Hg) in the no PH group. CONCLUSIONS: The present study showed that impaired RV systolic function, hypertrophy, and dilation were present even at a slight increase of mPAP, which indicates an early impact on RV function and structure in patients with COPD. RV isovolumic acceleration, performance index, and strain could detect subclinical disease and separate controls from those with no PH.


Assuntos
Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Disfunção Ventricular Direita/etiologia , Remodelação Ventricular , Idoso , Estudos de Casos e Controles , Ecocardiografia Doppler/estatística & dados numéricos , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/patologia , Análise de Regressão , Sístole , Disfunção Ventricular Direita/diagnóstico por imagem
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