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1.
Proc Natl Acad Sci U S A ; 120(33): e2305717120, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37549287

RESUMO

Great progress has been made in identifying positive regulators that activate adipocyte thermogenesis, but negative regulatory signaling of thermogenesis remains poorly understood. Here, we found that cardiotrophin-like cytokine factor 1 (CLCF1) signaling led to loss of brown fat identity, which impaired thermogenic capacity. CLCF1 levels decreased during thermogenic stimulation but were considerably increased in obesity. Adipocyte-specific CLCF1 transgenic (CLCF1-ATG) mice showed impaired energy expenditure and severe cold intolerance. Elevated CLCF1 triggered whitening of brown adipose tissue by suppressing mitochondrial biogenesis. Mechanistically, CLCF1 bound and activated ciliary neurotrophic factor receptor (CNTFR) and augmented signal transducer and activator of transcription 3 (STAT3) signaling. STAT3 transcriptionally inhibited both peroxisome proliferator-activated receptor-γ coactivator (PGC) 1α and 1ß, which thereafter restrained mitochondrial biogenesis in adipocytes. Inhibition of CNTFR or STAT3 could diminish the inhibitory effects of CLCF1 on mitochondrial biogenesis and thermogenesis. As a result, CLCF1-TG mice were predisposed to develop metabolic dysfunction even without external metabolic stress. Our findings revealed a brake signal on nonshivering thermogenesis and suggested that targeting this pathway could be used to restore brown fat activity and systemic metabolic homeostasis in obesity.


Assuntos
Adipócitos Marrons , Biogênese de Organelas , Animais , Camundongos , Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/metabolismo , Homeostase , Obesidade/genética , Obesidade/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Termogênese/fisiologia
2.
Small ; 20(28): e2308483, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38329171

RESUMO

Phosphates featuring a 3D framework offer a promising alternative to aqueous sodium-ion batteries, known for their safety, cost-effectiveness, scalability, high power density, and tolerance to mishandling. Nevertheless, they often suffer from poor reversible capacity stemming from limited redox couples. Herein, N-containing Na2VTi(PO4)3 is synthesized for aqueous sodium-ion storage through multi-electron redox reactions. It demonstrates a capacity of 155.2 mAh g-1 at 1 A g-1 (≈ 5.3 C) and delivers an ultrahigh specific energy of 55.9 Wh kg-1 in a symmetric aqueous sodium-ion battery. The results from in situ X-ray diffraction analysis, ex situ X-ray photoelectron spectroscopy analysis, and first-principle calculations provide insights into the local chemical environment of sodium ions, the mechanisms underlying capacity decay during cycling, and the dynamics of ion and electron transfer at various states of charge. This understanding will contribute to the advancement of electrode materials for aqueous sodium-ion batteries.

3.
J Biol Chem ; 298(2): 101544, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34971706

RESUMO

Uncontrolled gluconeogenesis results in elevated hepatic glucose production in type 2 diabetes (T2D). The small ubiquitin-related modifier (SUMO)-specific protease 2 (SENP2) is known to catalyze deSUMOylation of target proteins, with broad effects on cell growth, signal transduction, and developmental processes. However, the role of SENP2 in hepatic gluconeogenesis and the occurrence of T2D remain unknown. Herein, we established SENP2 hepatic knockout mice and found that SENP2 deficiency could protect against high-fat diet-induced hyperglycemia. Pyruvate- or glucagon-induced elevation in blood glucose was attenuated by disruption of SENP2 expression, whereas overexpression of SENP2 in the liver facilitated high-fat diet-induced hyperglycemia. Using an in vitro assay, we showed that SENP2 regulated hepatic glucose production. Mechanistically, the effects of SENP2 on gluconeogenesis were found to be mediated by the cellular fuel sensor kinase, 5'-AMP-activated protein kinase alpha (AMPKα), which is a negative regulator of gluconeogenesis. SENP2 interacted with and deSUMOylated AMPKα, thereby promoting its ubiquitination and reducing its protein stability. Inhibition of AMPKα kinase activity dramatically reversed impaired hepatic gluconeogenesis and reduced blood glucose levels in SENP2-deficient mice. Our study highlights the novel role of hepatic SENP2 in regulating gluconeogenesis and furthers our understanding of the pathogenesis of T2D.


Assuntos
Proteínas Quinases Ativadas por AMP , Cisteína Endopeptidases , Diabetes Mellitus Tipo 2 , Hiperglicemia , Sumoilação , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Glicemia/metabolismo , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Gluconeogênese , Glucose/metabolismo , Hiperglicemia/metabolismo , Fígado/metabolismo , Camundongos , Peptídeo Hidrolases/metabolismo
4.
Biochem Biophys Res Commun ; 681: 225-231, 2023 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-37783121

RESUMO

The commitment of mesenchymal stem cells (MSCs) to preadipocytes and the termination of differentiation to adipocytes are critical for maintaining systemic energy homeostasis. However, our knowledge of the molecular mechanisms governing the commitment of MSCs to preadipocytes and the subsequent termination of their differentiation into adipocytes remain limited. Additionally, the role of Sox6 sex-determining region Y (SRY)-box6 (Sox6), a transcription factor that regulates gene transcription, is reportedly involved in various cellular processes, including adipogenesis; however, its function in regulating preadipocyte development and the factors involved in the termination of adipogenic differentiation remain unexplored. Therefore, we investigated the role of Sox6 in regulating the differentiation of adipocytes by monitoring the effects of its overexpression in C3H10T1/2 cells (in vitro) and C57BL/6J mouse (in vivo) models of adipogenesis. We observed lower Sox6 expression in the adipose tissue of obese mice than that in control mice. Sox6 overexpression inhibited the differentiation of MSC by directly binding to the lysyl oxidase (Lox) and preadipocyte factor 1 (Pref1) promoters, which was potentiated by histone deacetylase-1(HDAC1). Our findings suggest that Sox6 is a key regulator of MSC commitment to adipocytes; therefore, targeting the Sox6-mediated regulation of this process could offer potential therapeutic avenues for addressing obesity and related metabolic disorders.


Assuntos
Adipogenia , Células-Tronco Mesenquimais , Animais , Camundongos , Adipogenia/genética , Diferenciação Celular/genética , Camundongos Endogâmicos C57BL , Proteína-Lisina 6-Oxidase/genética , Proteína-Lisina 6-Oxidase/metabolismo , Fatores de Transcrição SOXD/genética , Fatores de Transcrição SOXD/metabolismo
5.
Eur Radiol ; 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37848772

RESUMO

OBJECTIVES: To develop an automatic computer-based method that can help clinicians in assessing spine growth potential based on EOS radiographs. METHODS: We developed a deep learning-based (DL) algorithm that can mimic the human judgment process to automatically determine spine growth potential and the Risser sign based on full-length spine EOS radiographs. A total of 3383 EOS cases were collected and used for the training and test of the algorithm. Subsequently, the completed DL algorithm underwent clinical validation on an additional 440 cases and was compared to the evaluations of four clinicians. RESULTS: Regarding the Risser sign, the weighted kappa value of our DL algorithm was 0.933, while that of the four clinicians ranged from 0.909 to 0.930. In the assessment of spine growth potential, the kappa value of our DL algorithm was 0.944, while the kappa values of the four clinicians were 0.916, 0.934, 0.911, and 0.920, respectively. Furthermore, our DL algorithm obtained a slightly higher accuracy (0.973) and Youden index (0.952) compared to the best values achieved by the four clinicians. In addition, the speed of our DL algorithm was 15.2 ± 0.3 s/40 cases, much faster than the inference speeds of the clinicians, ranging from 177.2 ± 28.0 s/40 cases to 241.2 ± 64.1 s/40 cases. CONCLUSIONS: Our algorithm demonstrated comparable or even better performance compared to clinicians in assessing spine growth potential. This stable, efficient, and convenient algorithm seems to be a promising approach to assist doctors in clinical practice and deserves further study. CLINICAL RELEVANCE STATEMENT: This method has the ability to quickly ascertain the spine growth potential based on EOS radiographs, and it holds promise to provide assistance to busy doctors in certain clinical scenarios. KEY POINTS: • In the clinic, there is no available computer-based method that can automatically assess spine growth potential. • We developed a deep learning-based method that could automatically ascertain spine growth potential. • Compared with the results of the clinicians, our algorithm got comparable results.

6.
Food Microbiol ; 113: 104283, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37098436

RESUMO

Salmonella is a common chicken-borne pathogen that causes human infections. Data below the detection limit, referred to as left-censored data, are frequently encountered in the detection of pathogens. The approach of handling the censored data was regarded to affect the estimation accuracy of microbial concentration. In this study, a set of Salmonella contamination data was collected from chilled chicken samples using the most probable number (MPN) method, which consisted of 90.42% (217/240) non-detect values. Two simulated datasets with fixed censoring degrees of 73.60% and 90.00% were generated based on the real-sampling Salmonella dataset for comparison. Three methodologies were applied for handling left-censored data: (i) substitution with different alternatives, (ii) the distribution-based maximum likelihood estimation (MLE) method, and (iii) the multiple imputation (MI) method. For each dataset, the negative binomial (NB) distribution-based MLE and zero-modified NB distribution-based MLE were preferable for highly censored data and resulted in the least root mean square error (RMSE). Replacing the censored data with half the limit of quantification was the next best method. The mean concentration of Salmonella monitoring data estimated by the NB-MLE and zero-modified NB-MLE methods was 0.68 MPN/g. This study provided an available statistical method for handling bacterial highly left-censored data.


Assuntos
Galinhas , Modelos Estatísticos , Humanos , Animais , Simulação por Computador , Funções Verossimilhança
7.
Molecules ; 28(13)2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37446762

RESUMO

We optimized an ultrasound-assisted extraction process of Phellinus linteus mycelium polysaccharides (PLPs) and studied their monosaccharide composition and bacteriostatic properties. Based on a single-factor experiment, a three-factor, three-level Box-Behnken design was used to optimize the ultrasound-assisted extraction process of PLP, using the yield of PLP as the index. The chemical composition and monosaccharide composition of PLP were determined by chemical analysis and HPLC analysis, respectively. Microscopic morphological analysis of the surface of PLP was performed via swept-surface electron microscopy. The bacteriostatic properties of PLP were determined using the spectrophotometric turbidimetric method. The results showed that the best extraction process of PLP with ultrasonic assistance achieved a result of 1:42 g/mL. In this method, the ultrasonic temperature was 60 °C, ultrasonic extraction was performed for 20 min, and the yield of PLP was 12.98%. The monosaccharide composition of PLP mainly contains glucose (Glc), mannose (Man), galactose (Gal), and glucuronic acid (GlcA). The intracellular polysaccharide of Phellinus igniarius Mycelia (PIP) is an irregular spherical accumulation, the surface is rough and not smooth, and the extracellular polysaccharide (PEP) is a crumbly accumulation. PIP has a stronger inhibitory ability for S. aureus and E. coli and a slightly weaker inhibitory effect for B. subtilis; the inhibitory effect of PEP on S. aureus, E. coli, and B. subtilis is slightly inferior to that of PIP.


Assuntos
Escherichia coli , Staphylococcus aureus , Humanos , Polissacarídeos/farmacologia , Polissacarídeos/química , Monossacarídeos
8.
Hepatology ; 74(4): 1864-1883, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33934381

RESUMO

BACKGROUND AND AIMS: NAFLD, characterized by aberrant triglyceride accumulation in liver, affects the metabolic remodeling of hepatic and nonhepatic tissues by secreting altered hepatokines. Small ubiquitin-related modifier (SUMO)-specific protease 2 (SENP2) is responsible for de-SUMOylation of target protein, with broad effects on cell growth, signal transduction, and developmental processes. However, the role of SENP2 in hepatic metabolism remains unclear. APPROACH AND RESULTS: We found that SENP2 was the most dramatically increased SENP in the fatty liver and that its level was modulated by fed/fasted conditions. To define the role of hepatic SENP2 in metabolic regulation, we generated liver-specific SENP2 knockout (Senp2-LKO) mice. Senp2-LKO mice exhibited resistance to high-fat diet-induced hepatic steatosis and obesity. RNA-sequencing analysis showed that Senp2 deficiency up-regulated genes involved in fatty acid oxidation and down-regulated genes in lipogenesis in the liver. Additionally, ablation of hepatic SENP2 activated thermogenesis of adipose tissues. Improved energy homeostasis of both the liver and adipose tissues by SENP2 disruption prompted us to detect the hepatokines, with FGF21 identified as a key factor markedly elevated in Senp2-LKO mice that maintained metabolic homeostasis. Loss of FGF21 obviously reversed the positive effects of SENP2 deficiency on metabolism. Mechanistically, by screening transcriptional factors of FGF21, peroxisome proliferator-activated receptor alpha (PPARα) was defined as the mediator for SENP2 and FGF21. SENP2 interacted with PPARα and deSUMOylated it, thereby promoting ubiquitylation and subsequent degradation of PPARα, which in turn inhibited FGF21 expression and fatty acid oxidation. Consistently, SENP2 overexpression in liver facilitated development of metabolic disorders. CONCLUSIONS: Our finding demonstrated a key role of hepatic SENP2 in governing metabolic balance by regulating liver-adipose tissue crosstalk, linking the SUMOylation process to metabolic regulation.


Assuntos
Tecido Adiposo/metabolismo , Cisteína Endopeptidases/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , PPAR alfa/metabolismo , Animais , Cisteína Endopeptidases/metabolismo , Dieta Hiperlipídica , Metabolismo Energético/genética , Ácidos Graxos/metabolismo , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Humanos , Lipogênese/genética , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/genética , Obesidade/metabolismo , Sumoilação , Termogênese/genética , Ubiquitinação
9.
Surg Endosc ; 36(10): 7827-7838, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35882666

RESUMO

BACKGROUND: During postoperative follow-up, the visible range of maxillary sinus (MS) is limited, even combining 0° and 70° rigid endoscopes together. Flexible endoscope has been used in larynx examinations for a long time, but rarely in nasal cavity and sinus. We aimed to evaluate the application values of rigid and flexible endoscopes for visualization of MS. METHODS: We followed up 70 patients with lesions in MS via both rigid and flexible endoscopes. In addition, we used thin-slice CT image of the sinus to create a MS model and divided it into two parts for 3D printing. The inner surface of the 3D-printed sinus was marked with grid papers of the same size (5 mm × 5 mm), then the visual range under rigid endoscopes with different angle and flexible endoscopes was calculated and analyzed. RESULTS: In clinical follow-up, we found that flexible endoscopy can reach where rigid endoscopy cannot, which is more sensitive than medical imaging. Endoscopes showed the largest observation range of the posterolateral wall, more than half of which can be visualized by 0° endoscope. Almost all of the posterolateral wall can be revealed under 45° endoscope, 70° endoscope and flexible endoscope. The visual range of each wall under flexible endoscope is generally greater than that under rigid endoscopes, especially of the anterior wall, medial wall and inferior wall. CONCLUSION: There was obviously overall advantage of using flexible endoscope in postoperative follow-up of MS lesions. Flexible endoscopy can expand the range of observation, and improve the early detection of the recurrent lesion. We recommend flexible endoscope as a routine application.


Assuntos
Endoscopia , Seio Maxilar , Endoscópios , Endoscopia/métodos , Humanos , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/cirurgia , Impressão Tridimensional
10.
Eur Arch Otorhinolaryngol ; 279(5): 2485-2492, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34510259

RESUMO

OBJECTIVE: The aim of this analysis was to evaluate the prognostic significance of inflammatory biomarkers (NLR, dNLR, PLR and LMR) in NPC patients. METHODS: This was a retrospective analysis of 111 NPC patients from January 2013 and December 2016. Receiver-operating characteristic (ROC) curve was plotted to determine the cut-off values of these inflammatory biomarkers. Univariate analysis and multivariate Cox regression model were used to evaluate the association between these parameters and progression-free survival (PFS) and overall survival (OS). RESULTS: The optimal critical value of NLR was 2.02, by which cases were divided into high NLR group (NLR ≥ 2.02) and low NLR group (NLR < 2.02). The elevated NLR was significantly associated with decreased OS (P = 0.009) and remained significant in multivariate analysis (HR 8.48, 95% CI 1.69-42.46, P = 0.009). CONCLUSIONS: The before treatment NLR may be an independent prognostic biomarker for OS in patients with NPC. NLR, dNLR and PLR might be a useful complement to TNM staging in the prognosis evaluation of NPC patients.


Assuntos
Neoplasias Nasofaríngeas , Neutrófilos , Biomarcadores , Humanos , Linfócitos/patologia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/terapia , Neutrófilos/patologia , Prognóstico , Estudos Retrospectivos
11.
Psychol Health Med ; 26(3): 333-346, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33241941

RESUMO

Chronic pain is a significant public health problem with emotional and disabling factors, which may not completely respond to current medical treatments such as opioids. The systematic review and meta-analysis aimed to examine the effectiveness and safety of MBCT for patients with chronic pain. Database searches of PubMed, Medline, EMBASE, the Cochrane Library, PsycINFO, Web of Science, Scopus and CINAHL up to 15 October 2019. Included studies assessed with the Cochrane risk-of-bias tool. Eight RCTs involved 433 patients, including chronic low back pain, fibromyalgia, migraine, rheumatoid arthritis and mix etiology. MBCT intervention demonstrated a short-term improvement on depression mood [standardized mean difference -0.72; 95% confidence interval = -1.22 to -0.22, p = 0.005] compared with usual care and was associated with short-term improvement in mindfulness compared with non-MBCT [SMD 0.51; 95% CI = 0.01 to 1.01, p = 0.04]. Between-group differences in pain intensity, pain inference and pain acceptance were not significant at short- or long-term follow-up. Compared to active treatments, MBCT intervention not found significant differences in either short- or long-term outcomes. MBCT showed short-term efficacious on depressed mood and mindfulness of chronic pain patients. Longer follow-ups, large sample and rigorous RCTs that can be best understand remaining uncertainties needed.


Assuntos
Dor Crônica/terapia , Terapia Cognitivo-Comportamental/métodos , Atenção Plena , Dor Crônica/psicologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
12.
J Tissue Viability ; 30(3): 324-330, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34176736

RESUMO

Here, we aimed to build a nomogram model to estimate the probability of nasogastric tube-associated pressure injuries (NTAPIs) in intensive care unit(ICU)patients. This prospective cohort study included 219ICU patients with nasogastric tube between September 2019 and January 2020.Univariate and multivariate logistic regression analyses were used to develop the nomogram model. The resulting nomogram was tested for calibration, discrimination, and clinical usefulness. Of the included patients, 58 developed NTAPIs, representing an incidence rate of 26.5%. Binary logistic regression analysis revealed that the prediction nomogram included C-reactive protein, vasopressor use, albumin level, nasogastric tube duration, and Sequential Organ Failure Assessment score. The value of these predictors was again confirmed using theLasso regression analysis. Internal validation presented a good discrimination of the nomogram, with an area under the curve value of 0.850, and good calibration (Hosmer-Lemeshow test, P = 0.177). The decision curve analysis also demonstrated preferable net benefit along with the threshold probability in the prediction nomogram. The nomogram model can accurately predict the risk factors for NTAPIs, to formulate intervention strategies as early as possible to reduce NTAPI incidence.


Assuntos
Intubação Gastrointestinal/efeitos adversos , Nomogramas , Úlcera por Pressão/etiologia , Adulto , Idoso , Área Sob a Curva , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Intubação Gastrointestinal/métodos , Intubação Gastrointestinal/normas , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Úlcera por Pressão/fisiopatologia , Desenvolvimento de Programas/métodos , Estudos Prospectivos , Curva ROC , Fatores de Risco
13.
Int Wound J ; 18(6): 777-786, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33960668

RESUMO

The knowledge, attitude, and practice of nurses in intensive care units (ICUs) are determinants for the efficacy of preventing the medical device-related pressure injury (MDRPI). The aim of this study was to determine the level and factors of knowledge, attitude, and practice of nurses' ICUs on preventing medical MDRPI in western China. An annual cross-sectional study was conducted in hospitals of western China from May 2020 to September 2020. Nurses' knowledge and attitudes were assessed using Clinical Nurses Prevention MDRPI of Critically Ill Patients for the Knowledge, Attitude, Practice Assessment Scale. SPSS software version 25.0 and independent t-test, Chi-square, Fisher exact, one-way analysis of variance, and multiple linear regression tests were used for data analysis. A total of 1002 nurses in ICUs from 37 hospitals in Gansu Province, China, participated in this study. The scores of overall KAP, knowledge, attitudes, and practice were 149.17 ± 24.62, 53.83 ± 12.23, 37.24 ± 6.35 and 58.10 ± 9.83, respectively. There was a positive and significant relationship between three variables. Findings revealed that nurses' knowledge score in the Tertiary hospital was higher than scores of other hospitals as 3.840 units. Moreover, the knowledge score and practice score of nurses with bachelor's degree or above were higher than other nurses and are 0.978 and 1.106 units, respectively. Based on the findings, practice of nurses increased by 0.992 units, with a 1-year increase in work experience of nurses in the ICU. The levels of knowledge, attitude, and practice of nurse in ICUs on preventing MDRPI were acceptable. The findings of the study highlight that a comprehensive approach should be conducted for raising the level of knowledge, attitude, and practice of nurses' ICUs on preventing medical MDRPI, as well as improving the quality of care for critically ill patients.


Assuntos
Competência Clínica , Conhecimentos, Atitudes e Prática em Saúde , Enfermeiras e Enfermeiros , Úlcera por Pressão/prevenção & controle , China , Estudos Transversais , Humanos , Unidades de Terapia Intensiva , Inquéritos e Questionários
14.
Med Sci Monit ; 26: e923618, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32614806

RESUMO

BACKGROUND The aim of this study was to explore the upregulated nuclear factor kappaB (NF-kappaB)/microRNA-155 (miR-155) in regulating inflammatory responses and relapse of chronic rhinosinusitis (CRS) with nasal polyps (NP), which underlies the molecular mechanism of glucocorticoid treatment. MATERIAL AND METHODS The study recruited 25 patients with eosinophilic (Eos) CRSwNP, 25 patients with Non-Eos CRSwNP, 25 patients with CRS without NP (CRSsNP) and 30 patients with nasal septum deviation (control group). The expression of NF-kappaB/miR-155 and inflammatory cytokines was detected in epithelial tissue specimens. Additionally, a mouse model of Eos CRSwNP was established, and the mice were treated by NF-kappaB inhibitor, miR-155 antagomir, or dexamethasone (DEX) to explore the role of NF-kB/miR-155 and the anti-inflammatory effects of glucocorticoid treatment. RESULTS Results showed that the expression level of NF-kappaB/miR-155 was significantly elevated in the Eos CRSwNP group, accompanied by the upregulation of cytokines: tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-4, IL-5 (P<0.05) compared with the control group, the CRSsNP group or the Non-Eos CRSwNP group. The upregulation of NF-kappaB/miR-155 increased inflammatory mediator cyclooxygenase2 (COX2) while decreasing anti-inflammatory mediator Src homology-2 domain-containing inositol 5-phosphatase 1 (SOCS1), which resulted in the aberrant expression pattern of cytokines in the mice model. DEX treatment inhibited the expression of cytokines and decreased the relapse rate of Eos CRSwNP via inhibiting NF-kappaB/miR-155 (P<0.05). CONCLUSIONS The upregulation of NF-kappaB/miR-155 was crucial in mediating the aberrant expression of inflammatory cytokines in Eos CRSwNP. This molecular mechanism is a concern with the high relapse rate of Eos CRSwNP. However, glucocorticoid treatment inhibited the relapse of CRSwNP via downregulation of NF-kappaB/miR-155.


Assuntos
MicroRNAs/genética , NF-kappa B/metabolismo , Sinusite/genética , Adulto , Animais , Doença Crônica , Citocinas/genética , Modelos Animais de Doenças , Feminino , Expressão Gênica , Perfilação da Expressão Gênica/métodos , Glucocorticoides/metabolismo , Humanos , Masculino , Camundongos , MicroRNAs/metabolismo , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Pólipos Nasais/genética , Pólipos Nasais/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Recidiva , Rinite/complicações , Rinite/metabolismo , Rinite/patologia , Sinusite/metabolismo , Ativação Transcricional , Transcriptoma
15.
Sensors (Basel) ; 20(6)2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32178463

RESUMO

Image classification is a fundamental task in remote sensing image processing. In recent years, deep convolutional neural networks (DCNNs) have experienced significant breakthroughs in natural image recognition. The remote sensing field, however, is still lacking a large-scale benchmark similar to ImageNet. In this paper, we propose a remote sensing image classification benchmark (RSI-CB) based on massive, scalable, and diverse crowdsourced data. Using crowdsourced data, such as Open Street Map (OSM) data, ground objects in remote sensing images can be annotated effectively using points of interest, vector data from OSM, or other crowdsourced data. These annotated images can, then, be used in remote sensing image classification tasks. Based on this method, we construct a worldwide large-scale benchmark for remote sensing image classification. This benchmark has large-scale geographical distribution and large total image number. It contains six categories with 35 sub-classes of more than 24,000 images of size 256 × 256 pixels. This classification system of ground objects is defined according to the national standard of land-use classification in China and is inspired by the hierarchy mechanism of ImageNet. Finally, we conduct numerous experiments to compare RSI-CB with the SAT-4, SAT-6, and UC-Merced data sets. The experiments show that RSI-CB is more suitable as a benchmark for remote sensing image classification tasks than other benchmarks in the big data era and has many potential applications.

16.
J Biol Chem ; 292(28): 11740-11750, 2017 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-28572510

RESUMO

Polycystic ovary syndrome is a common endocrine disorder and a major cause of anovulatory sterility in women at reproductive age. Most patients with polycystic ovary syndrome have hyperandrogenism, caused by excess androgen synthesis. Bone morphogenetic protein 4 (BMP4) is an essential regulator of embryonic development and organ formation, and recent studies have also shown that BMP4 may be involved in female steroidogenesis process. However, the effect of BMP4 on hyperandrogenism remains unknown. Here, using a female mouse model of hyperandrogenism, we found that ovarian BMP4 levels were significantly decreased in hyperandrogenism. Elevated androgens inhibited BMP4 expression via activation of androgen receptors. Moreover, BMP4 treatment suppressed androgen synthesis in theca cells and promoted estrogen production in granulosa cells by regulating the expression of steroidogenic enzymes, including CYP11A, HSD3B2, CYP17A1, and CYP19A1 Consistently, knockdown of BMP4 augmented androgen levels and inhibited estrogen levels. Mechanistically, Smad signaling rather than the p38 MAPK pathway regulated androgen and estrogen formation, thereby mediating the effect of BMP4. Of note, BMP4-transgenic mice were protected against hyperandrogenism. Our observations clarify a vital role of BMP4 in controlling sex hormone levels and offer new insights into intervention for managing hyperandrogenism by targeting the BMP4-Smad signaling pathway.


Assuntos
Proteína Morfogenética Óssea 4/metabolismo , Modelos Animais de Doenças , Hiperandrogenismo/etiologia , Ovário/metabolismo , Síndrome do Ovário Policístico/fisiopatologia , Transdução de Sinais , Proteína Smad4/metabolismo , Androgênios/metabolismo , Androgênios/farmacologia , Animais , Proteína Morfogenética Óssea 4/antagonistas & inibidores , Proteína Morfogenética Óssea 4/genética , Células Cultivadas , Desidroepiandrosterona , Regulação para Baixo/efeitos dos fármacos , Estrogênios/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Células da Granulosa/patologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Ovário/efeitos dos fármacos , Ovário/patologia , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Interferência de RNA , Receptores Androgênicos/química , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Smad4/antagonistas & inibidores , Proteína Smad4/genética , Células Tecais/efeitos dos fármacos , Células Tecais/metabolismo , Células Tecais/patologia
17.
Molecules ; 23(7)2018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29954113

RESUMO

β-1,3-Glucanase is considered as a useful enzymatic tool for β-1,3-glucan degradation to produce (1→3)-linked β-glucan oligosaccharides with pharmacological activity properties. To validly isolate β-1,3-glucanase-producing microorganisms, the soil of Wolfiporia extensa, considered an environment rich in β-1,3-glucan-degrading microorganisms, was subjected to high throughput sequencing. The results demonstrated that the genera Streptomyces (1.90%) and Arthrobacter (0.78%) belonging to the order Actinomycetales (8.64%) in the phylum Actinobacteria (18.64%) were observed in soil for P. cocos cultivation (FTL1). Actinomycetes were considered as the candidates for isolation of glucan-degrading microorganisms. Out of 58 isolates, only 11 exhibited β-1,3-glucan-degrading activity. The isolate SYBCQL belonging to the genus Kitasatospora with β-1,3-glucan-degrading activity was found and reported for the first time and the isolate SYBC17 displayed the highest yield (1.02 U/mg) among the isolates. To check the β-1,3-glucanase contribution to β-1,3-glucan-degrading activity, two genes, 17-W and 17-Q, encoding β-1,3-glucanase in SYBC17 and one gene QLK1 in SYBCQL were cloned and expressed for verification at the molecular level. Our findings collectively showed that the isolates able to secrete β-1,3-glucanase could be obtained with the assistance of high-throughput sequencing and genes expression analysis. These methods provided technical support for isolating β-1,3-glucanase-producing microorganisms.


Assuntos
Glicosídeo Hidrolases/metabolismo , Actinobacteria/metabolismo , Arthrobacter/metabolismo , Biologia Molecular , Microbiologia do Solo , Streptomyces/metabolismo , Wolfiporia
18.
Biochem Biophys Res Commun ; 491(3): 814-820, 2017 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-28647369

RESUMO

Dysregulation of insulin signaling leads to type 2 diabetes mellitus (T2DM) and other metabolic disorders. Obesity is an important contributor to insulin resistance, and although the understanding of this relationship has improved in recent years, the mechanism of obesity-induced insulin resistance is not completely understood. Disorders of copper metabolism tend to accompany the development of obesity, which increases the risk of insulin resistance. Synthesis of cytochrome c oxidase 1 (SCO1) functions in the assembly of cytochrome c oxidase (COX) and cellular copper homeostasis. However, the role of SCO1 in the regulation of metabolism remains unknown. Here, we found that obese mice had higher expression of SCO1 and lower levels of copper in white adipose tissue (WAT) than did the control mice. Overexpression of SCO1 in adipocytes was associated with copper deficiency. Copper increased insulin sensitivity by decreasing the level of phosphatase and tensin homolog (PTEN) protein. Ectopic expression of SCO1 led to insulin resistance and was accompanied by a decrease in intracellular copper level, and addition of copper abolished the inhibitory effect of SCO1 on insulin sensitivity. Our results demonstrated a novel role of SCO1 in modulating insulin sensitivity via the regulation of copper concentration in WAT and suggested a potential therapeutic target for T2DM.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo Branco/metabolismo , Cobre/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/biossíntese , Resistência à Insulina , Insulina/metabolismo , Obesidade/metabolismo , Adipócitos/patologia , Tecido Adiposo Branco/patologia , Animais , Células Cultivadas , Regulação para Baixo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Chaperonas Moleculares , Obesidade/patologia
19.
J Magn Reson Imaging ; 45(4): 1005-1012, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27726238

RESUMO

PURPOSE: To explore the feasibility of parotid spin-lattice relaxation time in the rotating frame (T1ρ) MR imaging in the diagnosis of Sjögren's syndrome (SS) without morphological changes of the parotid glands. MATERIALS AND METHODS: The study enrolled 32 consecutive SS patients without morphological changes of parotid glands and 32 age- and gender-matched healthy volunteers who underwent parotid 3.0 Tesla MR imaging, including T1ρ sequences. Follow-up imaging was performed at 3 months. T1 signal intensities and T1ρ values of bilateral parotid glands were compared using paired samples t-test. Parotid T1 signal intensities and T1ρ values were compared using two independent samples t-test. Diagnostic performance of the parotid T1ρ values was evaluated by receiver operating characteristic analysis. The intraclass correlation coefficient (ICC) was calculated to evaluate the reproducibility of parotid T1ρ measurements. RESULTS: There were no significant differences of T1 signal intensities and T1ρ values between bilateral parotid glands in SS patients and healthy volunteers (P = 0.170, 0.886 and 0.942, 0.229). The parotid T1ρ values of SS patients (96.47 ± 15.38 ms) were significantly higher than those of healthy volunteers (84.25 ± 6.11 ms) (P < 0.001), while there were no significant differences of T1 signal intensities between SS patients and healthy volunteers (P = 0.655). With a cutoff value of 88.02 ms, the sensitivity and specificity of the parotid T1ρ value was 75.0% and 100.0% in the diagnosis of SS. The reproducibility of parotid T1ρ measurement was excellent (ICC: 0.934-0.995). CONCLUSION: Parotid T1ρ MR imaging held a potential role in diagnosing SS without morphological changes of parotid glands. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:1005-1012.


Assuntos
Imageamento por Ressonância Magnética/métodos , Glândula Parótida/diagnóstico por imagem , Síndrome de Sjogren/diagnóstico por imagem , Adolescente , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glândula Parótida/patologia , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Síndrome de Sjogren/patologia , Adulto Jovem
20.
J Magn Reson Imaging ; 46(5): 1409-1417, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28323371

RESUMO

PURPOSE: To explore the role of diffusion kurtosis imaging (DKI) of parotid glands in diagnosing Sjögren's syndrome (SS). MATERIALS AND METHODS: A total of 40 patients with SS and 40 healthy volunteers underwent 3.0T magnetic resonance imaging (MRI) including DKI, which generated the apparent diffusion coefficient (ADC), corrected diffusion (D), and diffusional kurtosis (K) values. The MR nodular grade was determined on the basis of MR morphological findings. RESULTS: The parotid ADC, D, and K values in patients with SS were significantly higher than those of healthy volunteers (P = 0.011, < 0.001, 0.022, respectively). The parotid ADC and D values in patients with SS of MR nodular grade 0 were significantly higher than those of healthy volunteers (all P < 0.001). The parotid D value showed an accuracy of 75.0% and 87.9% in diagnosing patients with SS and MR nodular grade 0, respectively. The parotid ADC and D values correlated negatively, while the K values correlated positively with the MR nodular grade significantly in patients with SS (r = -0.741, -0.605, 0.424, all P < 0.001). All parotid DKI parameters differed significantly among patients with SS at different MR nodular grades (all P < 0.001). CONCLUSION: Parotid DKI parameters hold great potential in diagnosing SS, especially in early-stage SS without MR morphological changes. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1409-1417.


Assuntos
Glândula Parótida/diagnóstico por imagem , Síndrome de Sjogren/diagnóstico por imagem , Síndrome de Sjogren/fisiopatologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto Jovem
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