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1.
Exp Eye Res ; 240: 109825, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38360087

RESUMO

The cause of Posner-Schlossman syndrome (PSS) remains unknown and its frequent recurrence may eventually lead to irreversible damage of the optic nerve. The influence of immune factors in the pathophysiology of PSS is gaining more and more interest. Increasing evidence suggests that gut dysbiosis plays vital roles in a variety of neurodegenerative and immune-related diseases. However, alterations of the gut microbiota in PSS patients have not been well defined yet. In this study, 16S rRNA sequencing was used to explore the difference of gut microbiota between PSS patients and healthy controls, and the correlation between the microbiota profile and clinical features was also analyzed. Our data demonstrated a significant increase of Prevotella and Prevotellaceae, and a significant reduction of Bacteroides and Bacteroidaceae in PSS patients, and KEGG analysis showed dysfunction of gut microbiota between PSS patients and healthy controls. Interestingly, further analysis showed that the alteration of gut microbiota was correlated with the PSS attack frequency of PSS. This study demonstrated the gut microbiota compositional profile of PSS patients and speculated the risk microbiota of PSS, which is expected to provide new insights for the diagnosis and treatment of PSS.


Assuntos
Microbioma Gastrointestinal , Microbiota , Humanos , RNA Ribossômico 16S/genética
2.
BMC Med ; 20(1): 130, 2022 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-35369871

RESUMO

BACKGROUND: Hundreds of millions of doses of coronavirus disease 2019 (COVID-19) vaccines have been administered globally, but progress on vaccination varies considerably between countries. We aimed to provide an overall picture of COVID-19 vaccination campaigns, including policy, coverage, and demand of COVID-19 vaccines. METHODS: We conducted a descriptive study of vaccination policy and doses administered data obtained from multiple public sources as of 8 February 2022. We used these data to develop coverage indicators and explore associations of vaccine coverage with socioeconomic and healthcare-related factors. We estimated vaccine demand as numbers of doses required to complete vaccination of countries' target populations according to their national immunization program policies. RESULTS: Messenger RNA and adenovirus vectored vaccines were the most commonly used COVID-19 vaccines in high-income countries, while adenovirus vectored vaccines were the most widely used vaccines worldwide (180 countries). One hundred ninety-two countries have authorized vaccines for the general public, with 40.1% (77/192) targeting individuals over 12 years and 32.3% (62/192) targeting those ≥ 5 years. Forty-eight and 151 countries have started additional-dose and booster-dose vaccination programs, respectively. Globally, there have been 162.1 doses administered per 100 individuals in target populations, with marked inter-region and inter-country heterogeneity. Completed vaccination series coverage ranged from 0.1% to more than 95.0% of country target populations, and numbers of doses administered per 100 individuals in target populations ranged from 0.2 to 308.6. Doses administered per 100 individuals in whole populations correlated with healthcare access and quality index (R2 = 0.59), socio-demographic index (R2 = 0.52), and gross domestic product per capita (R2 = 0.61). At least 6.4 billion doses will be required to complete interim vaccination programs-3.3 billion for primary immunization and 3.1 billion for additional/booster programs. Globally, 0.53 and 0.74 doses per individual in target populations are needed for primary immunization and additional/booster dose programs, respectively. CONCLUSIONS: There is wide country-level disparity and inequity in COVID-19 vaccines rollout, suggesting large gaps in immunity, especially in low-income countries.


Assuntos
Vacinas contra COVID-19 , COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , Programas de Imunização , Políticas , Cobertura Vacinal
3.
Anal Chem ; 93(10): 4528-4535, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33657320

RESUMO

Developing novel microelectronic devices for electrochemical measurements and electrochemiluminescence (ECL) study is of great importance. Herein, we fabricated a submicrometer-sized dual carbon electrode (DCE) and investigated its annihilation ECL behavior under steady-state conditions for the first time. The oxidation and reduction of the model luminophore, [Ru(bpy)3]2+, occurred separately at the two sides of the DCE, and the electrogenerated ions then diffused to the gap between the two electrodes to generate the excited-state intermediate [Ru(bpy)3]2+* and ECL emission. Compared with other types of two-electrode systems, the prepared DCE possesses a smaller total size and an ultrasmall interelectrode distance of 60 nm or less, which could result in a shorter diffusion time and an amplified ECL signal without the purification of the solvent and supporting electrolytes. On the basis of the constructed ECL microscopic platform, we successfully obtained a stable and confined ECL signal in the vicinity of the electrode tip. Furthermore, a two-dimensional finite element method simulation of this model system was performed to quantitively analyze the concentration profiles of the electrogenerated species around the tip of the DCE and predict the concentrations of [Ru(bpy)3]2+* with various gap distances. The simulation results also proved that the higher concentrations of [Ru(bpy)3]2+* could be achieved with a smaller distance with a possible amplification factor of 6 (compared with the concentration when the gap distance is greater than 300 nm). This work provides an experimental model for further improvement of ECL efficiency and broadens the availability for annihilation ECL applications in small confined spaces.

4.
Am J Emerg Med ; 39: 21-23, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32829991

RESUMO

Left ventricular free wall rupture (LVFWR) is a rare and fatal mechanical complication following an acute myocardial infarction (AMI). Cases of survival after LVFWR due to ST-segment elevation myocardial infarction (STEMI) treated with a conservative treatment strategy are extremely rare. In this case, a 55-year-old male patient with several cardiovascular risk factors presented to the emergency department with symptoms of ongoing chest pain and syncope. The patient's electrocardiogram was in sinus rhythm with ST-elevation on I, aVL, and V4-6 leads. His myoglobin and troponin I levels were elevated. Due to the unstable hemodynamic state of the patient, bedside echocardiography was performed. The echocardiography indicated LVFWR after AMI. Pericardiocentesis was used to restore a satisfactory hemodynamic state in the patient. Following the initial treatment, the patient opted for a conservative treatment strategy and was uneventfully discharged after 19 days.


Assuntos
Ruptura Cardíaca Pós-Infarto/diagnóstico por imagem , Ruptura Cardíaca Pós-Infarto/etiologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Tratamento Conservador , Ecocardiografia , Eletrocardiografia , Ruptura Cardíaca Pós-Infarto/terapia , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Pericardiocentese , Resultado do Tratamento
5.
Anal Chem ; 92(2): 1890-1897, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31920079

RESUMO

In this work, fullerenols were found to be able to enhance the ECL signals of the luminol and H2O2 system and were employed for the first time as a reducing, catalyzing, and stabilizing agent in the one-step fast synthesis of fullerenols@AuNPs in only 5 min. First, the prepared fullerenols@AuNPs were applied to fabricate a label-free immunosensor for the detection of human cardiopathy biomarker (cardiac troponin I, cTnI). Second, using the fullerenols@AuNPs as biolabels to establish a sandwich-type immunosensor and catalyzing in situ copper-stained reaction to generate Cu particles capped on the fullerenols@AuNPs, and then a novel electrochemical stripping chemiluminescent (ESCL) method was developed for detection of cTnI and IgG with about 20 times more sensitive than the former one. At the process of ESCL detection, Cu2+was stripped from Cu@fullerenols@AuNPs with significant increase of the ECL signals. This can be attributed to the fact that the fullerenols@AuNPs nanoparticles and the Cu2+ have excellent conductivity and could facilitate the decomposition of H2O2 to generate various reactive oxygen species (ROSs), thereby accelerating the ECL process. Both immunosensors show high sensitivity and selectivity to cTnI and IgG detection with a wide linear range from fg/mL to ng/mL and the low limits of detection down to fg/mL for cTnI and IgG, respectively.


Assuntos
Fulerenos/química , Imunoglobulina G/análise , Nanopartículas Metálicas/química , Troponina I/análise , Anticorpos Imobilizados/imunologia , Cobre/química , Técnicas Eletroquímicas/métodos , Ouro/química , Humanos , Peróxido de Hidrogênio/química , Imunoensaio/métodos , Imunoglobulina G/imunologia , Limite de Detecção , Luminescência , Medições Luminescentes/métodos , Luminol/química , Troponina I/imunologia
6.
Analyst ; 145(3): 873-879, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31845932

RESUMO

In this work, an Au-Ag alloy nanourchin (Au-Ag alloy NU) based electrochemiluminescent (ECL) sensor for the measurement of cardiac troponin I (cTnI) was developed. The as-prepared Au-Ag alloy NUs exhibited higher specific surface area and better conductivity owing to their unique urchin-like morphology, which resulted in excellent electrocatalytic activity towards H2O2 in the luminol-H2O2 ECL system. We have found that the Au-Ag alloy NUs could enhance the ECL signal in the luminol-H2O2 solution. Based on these facts, a facile and label-free ECL immunosensor has been constructed for the analysis of cTnI, a cardiac biomarker, with a wide linear range of 3.5 pg mL-1-350 µg mL-1. This novel ECL immunosensor has good stability and reproducibility, showing potential application in clinical diagnostics. In addition, a non-enzymatic electrochemical sensor for H2O2 was also fabricated, with a wide linear detection range of 100 nM-200 µM, a low limit of detection of 45 nM and a fast response time (less than 2 s).

7.
Ecotoxicol Environ Saf ; 190: 110090, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31874405

RESUMO

Cadmium (Cd), a toxic heavy metal, restrains the growth and development of plants and threatens global food safety. Many studies on the alleviation of heavy metal toxicity by exogenous phytohormones have emerged, but reports on tea (Camellia sinensis) are still scarce. In this study, the effects of indole acetic acid (IAA) (2 µM and 10 µM) on Cd uptake and on the physiological and biochemical characteristics of the 'Xiangfeicui' tea cultivar were investigated for the first time. The order of Cd accumulation in tea seedlings was root > stem > mature leaf > tender leaf. Under Cd stress (30 mg kg-1), photosynthetic pigment levels, antioxidant enzyme activity, root vigor, root IAA content, and the levels of most metabolites (including caffeine, soluble sugar, total amino acids, some amino acid components, and most catechins) were significantly reduced, while levels of malondialdehyde, proline, epicatechin, and some amino acids increased. We therefore propose that by reducing Cd accumulation, exogenous IAA can lessen the adverse effects of Cd on the physiology and biochemistry of tea seedlings, promoting the growth of healthier tea plants.


Assuntos
Cádmio/análise , Camellia sinensis/química , Ácidos Indolacéticos/metabolismo , Poluentes do Solo/análise , Antioxidantes/metabolismo , Cádmio/metabolismo , Cádmio/toxicidade , Fotossíntese/efeitos dos fármacos , Reguladores de Crescimento de Plantas/metabolismo , Folhas de Planta/metabolismo , Plântula/efeitos dos fármacos , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidade , Chá
8.
Nature ; 504(7480): 437-40, 2013 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-24226772

RESUMO

Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic ß-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.


Assuntos
Proteínas de Transporte/antagonistas & inibidores , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Proteínas Adaptadoras de Transdução de Sinal , Animais , Glicemia/metabolismo , Proteínas de Transporte/metabolismo , Núcleo Celular/enzimologia , Cristalografia por Raios X , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/enzimologia , Modelos Animais de Doenças , Hepatócitos , Humanos , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Hiperglicemia/enzimologia , Hipoglicemiantes/química , Fígado/citologia , Fígado/enzimologia , Fígado/metabolismo , Masculino , Modelos Moleculares , Especificidade de Órgãos , Fosforilação/efeitos dos fármacos , Piperazinas/química , Piperazinas/metabolismo , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Ligação Proteica/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Ratos , Ratos Wistar , Sulfonamidas/química , Sulfonamidas/metabolismo , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico
9.
Anal Chem ; 90(4): 2826-2832, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29411611

RESUMO

In many electrochemiluminescent (ECL) systems, coreactants play crucial roles in the redox-induced light emission process at the electrode surface. In this work, a novel and environment-friendly nanoplatform for ECL immunosensing enabled by triethanolamine (TEOA)-modified gold nanoparticles (TEOA@AuNPs) is reported. The monodisperse TEOA@AuNPs are fabricated by one-pot synthesis using TEOA as both reducing and stabilizing agent. Then the TEOA@AuNPs-modified electrode not only acted as coreactant for Ru(bpy)32+ ECL system but also provided a carrier for antibody 1 to form label-free immunosensor through an interaction between antigen and antibody. The unique structure of the TEOA@AuNPs loaded a large amount of coreactant of Ru(bpy)32+, which shortened the electron-transfer distance from the AuNPs surface to the appended TEOA molecules, thereby greatly enhancing the ECL efficiency and amplifying the ECL signal. In addition, Ru(bpy)32+-doped silica (RuSiO2) nanoparticles and antibody 2 were combined to form a composite for labels and a sandwich-type ECL immunosensor has been constructed. The possible mechanism of those ECL systems have also been proposed and confirmed by the EC-MS hyphenated technique. The human cardiopathy biomarker, cardiac troponin I (cTnI), was detected in a wide linear concentration range and the limit of detection (LOD) was 34 or 5.5 fg mL-1 by using the proposed label-free or labeling ECL immunoassay method.


Assuntos
Técnicas Eletroquímicas , Etanolaminas/química , Ouro/química , Imunoensaio , Medições Luminescentes , Nanopartículas Metálicas/química , Biomarcadores/análise , Eletrodos , Humanos , Tamanho da Partícula , Propriedades de Superfície , Troponina I/análise
10.
Anal Chem ; 90(19): 11622-11628, 2018 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-30207703

RESUMO

A simple strategy for one-step fabrication of tris(bipyridine)ruthenium(II) (Ru(bpy)32+)-functionalized metal-organic framework (Ru-MOF) thin films using a self-assembly approach assisted by an electrochemical way was introduced. In this protocol, the electrochemically driven cooperative reaction of Ru(bpy)32+ as an electrochemiluminescent (ECL) probe and a structure-directing agent, trimesic acid (H3btc) as a ligand, and Zn(NO3)2 as the Zn2+ source leads to an one-step and simultaneous synthesis and deposition of the MOF onto the electrode surface. Characterization of the Ru-MOF thin films was performed with scanning electron microscopy, Fourier transform infrared, and X-ray photoelectron spectroscopy. Scanning ion conductance microscopy was specially applied in situ to image the topography and thickness of the Ru-MOF thin films. The Ru-MOF thin films as a sensing platform show excellent ECL behavior because of plenty of Ru(bpy)32+ molecules encapsulated in the frameworks. On the basis of the Ru-MOF modified electrodes, an ultrasensitive label-free ECL immunosensing method for the human heart-type fatty-acid-binding protein has been developed with a wide linear response range (150 fg mL-1-150 ng mL-1) and a very low limit of detection (2.6 fg mL-1). The prepared immunosensor also displayed excellent stability and good specificity in the test of practical samples.


Assuntos
Proteínas de Ligação a Ácido Graxo/análise , Imunoensaio/métodos , Estruturas Metalorgânicas/química , Rutênio/química , 2,2'-Dipiridil/química , Técnicas Eletroquímicas , Eletrodos , Proteínas de Ligação a Ácido Graxo/imunologia , Humanos , Imunoensaio/instrumentação , Limite de Detecção , Medições Luminescentes
11.
Trends Neurosci ; 47(4): 243-245, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38453567

RESUMO

In a recent study, Profes, Tiroumalechetty, and colleagues used the in vivo proximity ligation technique TurboID to scrupulously characterize the interactome of the intracellular domain (ICD) of neurexin, revealing that this domain may be involved in presynaptic actin assembly by interacting with actin-associated proteins.


Assuntos
Actinas , Neurexinas , Humanos , Actinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Sinapses/metabolismo , Moléculas de Adesão Celular Neuronais/metabolismo
12.
Nutrients ; 16(17)2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39275258

RESUMO

Our previous studies have demonstrated that konjac glucomannan (KGM) can prevent dysbiosis induced by antibiotics. While exercise may also impact the gut microbiome, there are limited studies reporting its protective effect on antibiotic-induced dysbiosis. Therefore, this study investigated the preventive and regulatory effects of a combination of 6-week exercise and KGM intervention on antibiotic-induced dysbiosis in C57BL/6J mice compared with a single intervention. The results showed that combined exercise and KGM intervention could restore the changes in the relative abundance of Bacteroides (3.73% with CTL versus 14.23% with ATBX versus 4.46% with EK) and Prevotellaceae_Prevotella (0.33% with CTL versus 0.00% with ATBX versus 0.30% with EK) induced by antibiotics (p < 0.05), and minimized the Bray-Curtis distance induced by antibiotics (0.55 with CTL versus 0.81 with ATBX versus 0.80 with EXC versus 0.83 with KGM versus 0.75 with EK). Compared with the combined intervention, exercise intervention also produced a certain level of recovery effects; the relative abundance of Rikenellaceae (1.96% with CTL versus 0.09% with ATBX versus 0.49% with EXC) was restored, while KGM supplementation showed the best preventive effect. In addition, the combination of exercise and KGM significantly enriched microbial purine metabolic pathways (p < 0.05). These findings indicate that combining exercise with KGM could be a promising approach to reducing the side effects of antibiotics on the gut microbiome.


Assuntos
Antibacterianos , Disbiose , Microbioma Gastrointestinal , Mananas , Camundongos Endogâmicos C57BL , Condicionamento Físico Animal , Animais , Mananas/farmacologia , Disbiose/prevenção & controle , Disbiose/induzido quimicamente , Antibacterianos/farmacologia , Antibacterianos/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Masculino , Terapia Combinada
13.
Biomed Eng Lett ; 14(5): 1037-1048, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39220035

RESUMO

In clinical practice, obstetricians use visual interpretation of fetal heart rate (FHR) to diagnose fetal conditions, but inconsistencies among interpretations can hinder accuracy. This study introduces MTU-Net3+, a deep learning model designed for automated, multi-task FHR analysis, aiming to improve diagnostic accuracy and efficiency. The proposed MTU-Net3 + was built upon the UNet3 + architecture, incorporating an encoder, a decoder, full-scale skip connections, and a deep supervision module, and further integrates a self-attention mechanism and bidirectional Long Short-Term Memory layers to enhance its performance. The MTU-Net3 + model accepts the preprocessed 20-minute FHR signals as input, outputting categorical probabilities and baseline values for each time point. The proposed MTU-Net3 + model was trained on a subset of a public database, and was tested on the remaining data of the public database and a private database. In the remaining public datasets, this model achieved F1 scores of 84.21% for deceleration (F1.Dec) and 61.33% for acceleration (F1.Acc), with a Root Mean Square Baseline Difference (RMSD.BL) of 3.46 bpm, 0% of points with an absolute difference exceeding 15 bpm(D15bpm), a Synthetic Inconsistency Coefficient (SI) of 44.82%, and a Morphological Analysis Discordance Index (MADI) of 7.00%. On the private dataset, the model recorded an RMSD.BL of 1.37 bpm, 0% D15bpm, F1.Dec of 100%, F1.Acc of 87.50%, an SI of 12.20% and a MADI of 2.79%. The MTU-Net3 + model proposed in this study performed well in automated FHR analysis, demonstrating its potential as an effective tool in the field of fetal health assessment.

14.
Nutrients ; 16(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38892536

RESUMO

The diversity and functionality of gut microbiota may play a crucial role in the function of human motor-related systems. In addition to traditional nutritional supplements, there is growing interest in microecologics due to their potential to enhance sports performance and facilitate post-exercise recovery by modulating the gut microecological environment. However, there is a lack of relevant reviews on this topic. This review provides a comprehensive overview of studies investigating the effects of various types of microecologics, such as probiotics, prebiotics, synbiotics, and postbiotics, on enhancing sports performance and facilitating post-exercise recovery by regulating energy metabolism, mitigating oxidative-stress-induced damage, modulating immune responses, and attenuating bone loss. Although further investigations are warranted to elucidate the underlying mechanisms through which microecologics exert their effects. In summary, this study aims to provide scientific evidence for the future development of microecologics in athletics.


Assuntos
Atletas , Desempenho Atlético , Exercício Físico , Microbioma Gastrointestinal , Probióticos , Humanos , Desempenho Atlético/fisiologia , Probióticos/administração & dosagem , Microbioma Gastrointestinal/fisiologia , Exercício Físico/fisiologia , Prebióticos/administração & dosagem , Simbióticos/administração & dosagem , Metabolismo Energético , Estresse Oxidativo , Suplementos Nutricionais , Recuperação após o Exercício
15.
Sci Rep ; 14(1): 8013, 2024 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580754

RESUMO

Hepatocellular carcinoma (HCC) seriously threatens human health, mostly developed from liver fibrosis or cirrhosis. Since diethylnitrosamine (DEN) and carbon tetrachloride (CCl4)-induced HCC mouse model almost recapitulates the characteristic of HCC with fibrosis and inflammation, it is taken as an essential tool to investigate the pathogenesis of HCC. However, a comprehensive understanding of the protein expression profile of this model is little. In this study, we performed proteomic analysis of this model to elucidate its proteomic characteristics. Compared with normal liver tissues, 432 differentially expressed proteins (DEPs) were identified in tumor tissues, among which 365 were up-regulated and 67 were down-regulated. Through Gene Ontology (GO) analysis, Ingenuity Pathway Analysis (IPA), protein-protein interaction networks (PPI) analysis and Gene-set enrichment analysis (GSEA) analysis of DEPs, we identified two distinguishing features of DEN and CCl4-induced HCC mouse model in protein expression, the upregulation of actin cytoskeleton and branched-chain amino acids metabolic reprogramming. In addition, matching DEPs from the mouse model to homologous proteins in the human HCC cohort revealed that the DEN and CCl4-induced HCC mouse model was relatively similar to the subtype of HCC with poor prognosis. Finally, combining clinical information from the HCC cohort, we screened seven proteins with prognostic significance, SMAD2, PTPN1, PCNA, MTHFD1L, MBOAT7, FABP5, and AGRN. Overall, we provided proteomic data of the DEN and CCl4-induced HCC mouse model and highlighted the important proteins and pathways in it, contributing to the rational application of this model in HCC research.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas Experimentais , Neoplasias Hepáticas , Camundongos , Animais , Humanos , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteômica , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/metabolismo , Dietilnitrosamina/efeitos adversos , Cirrose Hepática/patologia , Modelos Animais de Doenças , Proteínas de Ligação a Ácido Graxo
16.
J Lipid Res ; 54(2): 325-32, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23204296

RESUMO

Elevated triglyceride (TG) and cholesterol levels are risk factors for cardiovascular disease and are often associated with diabetes and metabolic syndrome. Recent reports suggest that fibroblast growth factor (FGF)19 and FGF21 can dramatically improve metabolic dysfunction, including hyperglycemia, hypertriglyceridemia, and hypercholesterolemia. Due to their similar receptor specificities and co-receptor requirements, FGF19 and FGF21 share many common properties and have been thought to be interchangeable in metabolic regulation. Here we directly compared how pharmacological administration of recombinant FGF19 or FGF21 proteins affect metabolism in B6.V-Lep(ob)/J leptin-deficient mice. FGF19 and FGF21 equally improved glucose parameters; however, we observed increased serum TG and cholesterol levels after treatment with FGF19 but not with FGF21. Increases in serum TGs were also observed after a 4-day treatment with FGF19 in C57BL6/J mice on a high-fat diet. This is in contrast to many literature reports that showed significant improvements in hyperlipidemia after chronic treatment with FGF19 or FGF21 in high-fat diet models. We propose that FGF19 has lipid-raising and lipid-lowering actions mediated through different FGF receptors and target tissues, and the results described here provide a potential mechanism that may explain the inconsistency in the reported effects of FGF19 on lipid metabolism.


Assuntos
Fatores de Crescimento de Fibroblastos/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Animais , Linhagem Celular , Colesterol/sangue , Dieta/efeitos adversos , Fatores de Crescimento de Fibroblastos/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Obesidade/sangue , Obesidade/etiologia , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/metabolismo , Triglicerídeos/sangue
17.
Bioorg Med Chem Lett ; 23(24): 6625-8, 2013 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-24215889

RESUMO

A series of urea based calcimimetics was optimized for potency and oral bioavailability. Crucial to this process was overcoming the poor pharmacokinetic properties of lead thiazole 1. Metabolism-guided modifications, characterized by the use of metabolite identification (ID) and measurement of time dependent inhibition (TDI) of CYP3A4, were essential to finding a compound suitable for oral dosing. Calcimimetic 18 exhibited excellent in vivo potency in a 5/6 nephrectomized rat model and cross-species pharmacokinetics.


Assuntos
Hiperparatireoidismo Secundário/tratamento farmacológico , Tiazóis/química , Tiazóis/uso terapêutico , Ureia/análogos & derivados , Administração Oral , Animais , Disponibilidade Biológica , Meia-Vida , Hiperparatireoidismo Secundário/metabolismo , Hiperparatireoidismo Secundário/patologia , Masculino , Hormônio Paratireóideo/metabolismo , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Receptores de Detecção de Cálcio/química , Receptores de Detecção de Cálcio/metabolismo , Tiazóis/farmacocinética
18.
Neuropsychiatr Dis Treat ; 19: 1725-1739, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37546518

RESUMO

Objective: To assess the therapeutic impacts of exercise, massage, and music interventions on college students experiencing depression by employing a mesh meta-analysis approach. This research intends to offer valuable insights to aid in the development of non-pharmaceutical treatment strategies for depression. Methods: We conducted a thorough search across various databases including Cochrane, PubMed, Embase, Web of Science, CNKI, and Wanfang to explore the effects of music, massage, aerobic exercise, fitness Qigong, yoga, tai chi, ball games, strength training, dance, whole body vibration training, and high-intensity interval training on the treatment of depression in college students. The search period was from January 1, 2023, which marks the establishment of each database. Subsequently, a mesh meta-analysis was performed using the "Stata 15.1" software, incorporating outcome indicators from 24 included literature comprising a total of 1458 patients. Results: Based on the ranking of the optimal intervention effects of various non-pharmaceutical methods, the order, from highest to lowest probability, was as follows: high-intensity interval training (96%), yoga (94.90%), dance (78.30%), music (73.30%), ball games (62.50%), strength training (51.70%), aerobic training (45.30%), tai chi (35.40%), vibration training (27.30%), massage (20.10%), qigong (14.30%), and no intervention (1.00%). This ranking aligns closely with the findings obtained from pairwise comparisons between different interventions. Conclusion: High-intensity interval training is likely to yield the most effective therapeutic results for college students with depression. In the pairwise comparison of different interventions, High-intensity interval training is also better than most interventions. However, to establish its intervention effect more conclusively, further validation through additional high-quality randomized controlled trials is necessary.

19.
Nutrients ; 15(19)2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37836491

RESUMO

Excessive exercise without adequate rest can lead to overtraining syndrome, which manifests a series of side effects, including fatigue, gut dysbiosis, and decremental sports performance. Konjac glucomannan (KGM) is a plant polysaccharide with numerous health-improving effects, but few studies reported its effects on the gut microbiome, endurance, and strength in an overtraining model. This study assessed the effect of KGM on gut microbiome, endurance, and strength in mice with excessive exercise. Three doses of KGM (1.25, 2.50, and 5.00 mg/mL) were administrated in drinking water to mice during 42 days of a treadmill overtraining program. The results showed that excessive exercise induced a significant microbial shift compared with the control group, while a high dose (5.00 mg/mL) of KGM maintained the microbial composition. The proportion of Sutterella in feces was significantly increased in the excessive exercise group, while the moderate dose (2.50 mg/mL) of KGM dramatically increased the relative abundance of Lactobacillus and SCFA production in feces. Additionally, the moderate dose and high dose of KGM counteracted the negative effects of excessive exercise on strength or/and endurance (43.14% and 39.94% increase through a moderate dose of KGM, Bonferroni corrected p < 0.05, compared with the excessive exercise group). Therefore, it suggests that KGM could prevent overtraining and improve sports performance in animal models.


Assuntos
Microbioma Gastrointestinal , Animais , Camundongos , Mananas/farmacologia , Polissacarídeos , Fezes
20.
Influenza Other Respir Viruses ; 17(1): e13067, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36394198

RESUMO

BACKGROUND: Estimation of influenza disease burden is crucial for optimizing intervention strategies against seasonal influenza. This study aimed to estimate influenza-associated excess respiratory and circulatory (R&C) and all-cause (AC) mortality among older adults aged 65 years and above in mainland China from 2011 to 2016. METHODS: Through a systematic review, we collected influenza-associated excess R&C and AC mortality data of older adults aged 65 years and above for specific cities/provinces in mainland China. Generalized linear models were fitted to estimate the corresponding excess mortality for older adults by province and nationwide, accounting for the potential variables of influenza virus activity, demography, economics, meteorology, and health service. All statistical analyses were conducted using R software. RESULTS: A total of 9154 studies were identified in English and Chinese databases, and 11 (0.1%) were included in the quantitative synthesis after excluding duplicates and screening the title, abstract, and full text. Using a generalized linear model, the estimates of annual national average influenza-associated excess R&C and AC mortality among older adults aged 65 years and above were 111.8 (95% CI: 92.8-141.1) and 151.6 (95% CI: 127.6-179.3) per 100,000 persons, respectively. Large variations in influenza-associated excess R&C and AC mortality among older adults were observed among 30 provinces. CONCLUSIONS: Influenza was associated with substantial excess R&C and AC mortality among older adults aged 65 years and above in China from 2011 to 2016. This analysis provides valuable evidence for the introduction of the influenza vaccine into the National Immunization Program for the elderly in China.


Assuntos
Vacinas contra Influenza , Influenza Humana , Orthomyxoviridae , Idoso , Humanos , Influenza Humana/complicações , Influenza Humana/epidemiologia , Estações do Ano , China/epidemiologia
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