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1.
Sci Rep ; 14(1): 9324, 2024 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654056

RESUMO

This study constructs a composite indicator system covering the core dimensions of medical equipment input and output. Based on this system, an innovative cone-constrained data envelopment analysis (DEA) model is designed. The model integrates the advantages of the analytic hierarchy process (AHP) with an improved criterion importance through intercriteria correlation (CRITIC) method to determine subjective and objective weights and employs game theory to obtain the final combined weights, which are further incorporated as constraints to form the cone-constrained DEA model. Finally, a bidirectional long short-term memory (Bi-LSTM) model with an attention mechanism is introduced for integration, aiming to provide a novel and practical model for evaluating the effectiveness of medical equipment. The proposed model has essential reference value for optimizing medical equipment management decision-making and investment strategies.


Assuntos
Equipamentos e Provisões , Humanos , Modelos Teóricos , Teoria dos Jogos , Algoritmos
2.
Materials (Basel) ; 17(6)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38541549

RESUMO

Organic semiconductors (OSCs), especially small molecule semiconductors, have received increasing attention due to their good designability and variability. Phase transitions and interfacial properties have a decisive influence on device performance. Here, 2-Dodecyl-7-phenyl[1]benzothieno[3,2-b][1]benzothiophene (Ph-BTBT-12) devices are treated with low-power laser annealing, which is able to avoid the influence of the dewetting effect on the hole mobility of organic semiconductor materials. Ultraviolet ozone treatment and self-assembled monolayer treatment can improve the performance and stability of the device. Moreover, after low-temperature thermal annealing, the hole mobility of the device can even reach as high as 4.80 cm2 V-1 s-1, and we tested the optical response of the device to the ultraviolet wavelength and found that its maximum optical responsivity was 8.2 AW-1.

3.
Respiration ; : 1-11, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38422997

RESUMO

INTRODUCTION: Distinguishing between malignant pleural effusion (MPE) and benign pleural effusion (BPE) poses a challenge in clinical practice. We aimed to construct and validate a combined model integrating radiomic features and clinical factors using computerized tomography (CT) images to differentiate between MPE and BPE. METHODS: A retrospective inclusion of 315 patients with pleural effusion (PE) was conducted in this study (training cohort: n = 220; test cohort: n = 95). Radiomic features were extracted from CT images, and the dimensionality reduction and selection processes were carried out to obtain the optimal radiomic features. Logistic regression (LR), support vector machine (SVM), and random forest were employed to construct radiomic models. LR analyses were utilized to identify independent clinical risk factors to develop a clinical model. The combined model was created by integrating the optimal radiomic features with the independent clinical predictive factors. The discriminative ability of each model was assessed by receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). RESULTS: Out of the total 1,834 radiomic features extracted, 15 optimal radiomic features explicitly related to MPE were picked to develop the radiomic model. Among the radiomic models, the SVM model demonstrated the highest predictive performance [area under the curve (AUC), training cohort: 0.876, test cohort: 0.774]. Six clinically independent predictive factors, including age, effusion laterality, procalcitonin, carcinoembryonic antigen, carbohydrate antigen 125 (CA125), and neuron-specific enolase (NSE), were selected for constructing the clinical model. The combined model (AUC: 0.932, 0.870) exhibited superior discriminative performance in the training and test cohorts compared to the clinical model (AUC: 0.850, 0.820) and the radiomic model (AUC: 0.876, 0.774). The calibration curves and DCA further confirmed the practicality of the combined model. CONCLUSION: This study presented the development and validation of a combined model for distinguishing MPE and BPE. The combined model was a powerful tool for assisting in the clinical diagnosis of PE patients.

4.
Med Eng Phys ; 122: 104073, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38092490

RESUMO

OBJECTIVE: Ambulatory arterial stiffness index (AASI) is an index which indicates arterial stiffness. This work aims to explore the mathematical relationship between AASI and mean value of PP (PP‾), and reveal the importance of PP‾ during AASI estimating. Meanwhile, a well-performing AASI estimation model is presented. METHODS: To evaluate AASI, electrocardiograph (ECG) signal, photoplethysmogram (PPG) signal and arterial blood pressure (ABP) are used as the source of AASI estimation. Features are extracted from the above three signals. Meanwhile, fitting curve analysis and regression models are implemented to describe the relationship between AASI and PP‾. RESULTS: Among three fitting curves on AASI and PP‾, cubic polynomial curve performs best. The introduction of feature PP‾ in AASI estimation reduced LR's MAE from 0.0556 to 0.0372, SVMR's MAE from 0.0413 to 0.0343 and RFR's MAE from 0.0386 to 0.0256. All three estimation models obtain considerable improvement, especially on the previous worst-performing linear regression. SIGNIFICANCE: This work presents the mathematical association between AASI and PP‾. AASI estimation using regression models can be significantly improved by involving PP‾ as its key feature, which is not only meaningful for exploring the connection between vascular elasticity function and pulse pressure, but also hold importance for the diagnosis of cardiovascular arteriosclerosis and atherosclerosis at the early stage.


Assuntos
Rigidez Vascular , Pressão Sanguínea/fisiologia , Modelos Lineares , Elasticidade
5.
J Stroke Cerebrovasc Dis ; 32(12): 107395, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37839303

RESUMO

BACKGROUND: Our previous study found that hyperbaric oxygen (HBO) attenuated cognitive impairment in mice induced by cerebral ischemia-reperfusion injury (CIRI). However, its mechanism of action is not fully understood. In this study, we aimed to establish a rat model of cerebral ischemia-reperfusion, explore the possible role of ferroptosis in the pathogenesis of CIRI, and observe the effect of HBO on ferroptosis-mediated CIRI. METHODS: Sprague Dawley (SD) rats were randomly divided into control, model, Ferrostatin-1 (Fer-1), HBO and Fer-1+ HBO groups. Morris water maze, myelin basic protein (MBP) and ß-tubulin immunoreactivity were assessed to evaluate the neuroprotective effects of HBO on cerebral ischemia reperfusion injury. Ferroptosis were examined to investigate the mechanism underlying the effects of HBO. RESULTS: Our result showed that Fer-1 and HBO improved learning and memory ability in the navigation trail and probe trail of the Morris water maze and increased MBP and ß-tubulin immunoreactivity of the cortex in the model rats. The levels of ferritin, malondialdehyde (MDA) and glutathione (GSH) in the serum were also reversed by Fer-1 and HBO treatment. Mitochondrial cristae dissolution and vacuolization were observed in the model group by transmission electron microscopy and these conditions were improved in the Fer-1 and HBO groups. Furthermore, Fer-1 and HBO treatment reversed Prostaglandin-Endoperoxide Synthase 2 (PTGS2), Iron Responsive Element Binding Protein 2 (IREB2), acyl-CoA synthetase long chain family member 4 (ACSL4) and Solute Carrier Family 7 Member 11 (SLC7A11) mRNA levels and Transferrin Receptor 1 (TFR1), ferritin light chain (FTL), ferritin heavy chain 1 (FTH1), glutathione peroxidase 4 (GPX4), Nuclear factor E2-related factor 2 (Nrf2), lysophosphatidylcholine acyltransferase 3 (LPCAT3), c-Jun N-terminal kinase (JNK), phosphorylated c-Jun N-terminal kinase (P-JNK) phosphorylated Extracellular signal-regulated protein kinase (P-ERK) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) protein levels. The above changes were more pronounced in Fer-1+ HBOGroup. DISCUSSION: The results of the present study indicated that HBO improves cerebral ischemia-reperfusion injury in rats, which may be related to inhibition of ferroptosis. This also means that ferroptosis may become a new target of HBO against CIRI.


Assuntos
Isquemia Encefálica , Ferroptose , Oxigenoterapia Hiperbárica , Traumatismo por Reperfusão , Ratos , Camundongos , Animais , Ratos Sprague-Dawley , Oxigenoterapia Hiperbárica/métodos , Tubulina (Proteína) , Oxigênio , Isquemia Encefálica/terapia , MAP Quinases Reguladas por Sinal Extracelular , Proteínas Quinases JNK Ativadas por Mitógeno , Traumatismo por Reperfusão/patologia , 1-Acilglicerofosfocolina O-Aciltransferase
6.
ACS Appl Mater Interfaces ; 15(19): 23573-23582, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37141554

RESUMO

Artificial synapse networks capable of massively parallel computing and mimicking biological neural networks can potentially improve the processing efficiency of existing information technologies. Semiconductor devices functioning as excitatory and inhibitory synapses are crucial for developing intelligence systems, such as traffic control systems. However, achieving reconfigurability between two working modes (inhibitory and excitatory) and bilingual synaptic behavior in a single transistor remains challenging. This study successfully mimics a bilingual synaptic response using an artificial synapse based on an ambipolar floating gate memory comprising tungsten selenide (WSe2)/hexagonal boron nitride (h-BN)/ molybdenum telluride (MoTe2). In this WSe2/h-BN/MoTe2 structure, ambipolar semiconductors WSe2 and MoTe2 are inserted as channel and floating gates, respectively, and h-BN serves as the tunneling barrier layer. Using either positive or negative pulse amplitude modulations at the control gate, this device with bipolar channel conduction produced eight distinct resistance states. Based on this, we experimentally projected that we could achieve 490 memory states (210 hole-resistance states + 280 electron-resistance states). Using the bipolar charge transport and multistorage states of WSe2/h-BN/MoTe2 floating gate memory, we mimicked reconfigurable excitatory and inhibitory synaptic plasticity in a single device. Furthermore, the convolution neural network formed by these synaptic devices can recognize handwritten digits with an accuracy of >92%. This study identifies the unique properties of heterostructure devices based on two-dimensional materials as well as predicts their applicability in advanced recognition of neuromorphic computing.

7.
Front Med (Lausanne) ; 10: 1239795, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38239616

RESUMO

Introduction: In the rapidly evolving field of digital public health, effective management of medical equipment is critical to maintaining high standards of healthcare service levels and operational efficiency. However, current decisions to replace large medical equipment are often based on subjective judgments rather than objective analyses and lack a standardized approach. This study proposes a multi-criteria decision-making model that aims to simplify and enhance the medical equipment replacement process. Methods: The researchers developed a multi-criteria decision-making model specifically for the replacement of medical equipment. The model establishes a system of indicators for prioritizing and evaluating the replacement of large medical equipment, utilizing game theory to assign appropriate weights, which uniquely combines the weights of the COWA and PCA method. In addition, which uses the GRA method in combination with the TOPSIS method for a more comprehensive decision-making model. Results: The study validates the model by using the MRI equipment of a tertiary hospital as an example. The results of the study show that the model is effective in prioritizing the most optimal updates to the equipment. Significantly, the model shown a higher level of differentiation compared to the GRA and TOPSIS methods alone. Discussion: The present study shows that the multi-criteria decision-making model presented provides a powerful and accurate tool for optimizing decisions related to the replacement of large medical equipment. By solving the key challenges in this area as well as giving a solid basis for decision making, the model makes significant progress toward the field of management of medical equipment.

8.
Sci Rep ; 11(1): 14601, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272434

RESUMO

Pulmonary fibrosis is a devastating disease, and the pathogenesis of this disease is not completely clear. Here, the medical records of 85 Covid-19 cases were collected, among which fibrosis and progression of fibrosis were analyzed in detail. Next, data independent acquisition (DIA) quantification proteomics and untargeted metabolomics were used to screen disease-related signaling pathways through clustering and enrichment analysis of the differential expression of proteins and metabolites. The main imaging features were lesions located in the bilateral lower lobes and involvement in five lobes. The closed association pathways were FcγR-mediated phagocytosis, PPAR signaling, TRP-inflammatory pathways, and the urea cycle. Our results provide evidence for the detection of serum biomarkers and targeted therapy in patients with Covid-19.


Assuntos
COVID-19/complicações , Fibrose Pulmonar/complicações , Adolescente , Adulto , COVID-19/diagnóstico , Feminino , Humanos , Pulmão/patologia , Masculino , Metabolômica , Pessoa de Meia-Idade , Proteômica , Fibrose Pulmonar/diagnóstico , Transdução de Sinais , Adulto Jovem
9.
Front Pharmacol ; 12: 626307, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33776768

RESUMO

Background: Emulsified isoflurane is a novel intravenous general anesthetic obtained by encapsulating isoflurane molecules into emulsion. The formulation of emulsion has been improved according to the latest regulations of the China Food and Drug Administration. This study was designed to compare the bioequivalence of the new and previous formulation emulsion of isoflurane. Methods: In a single-center, single-dose, double-blinded, randomized, two-period crossover study, healthy volunteers received intravenous injection of 30 mg/kg of isoflurane with either previous formulation of emulsion isoflurane (PFEI) or new formulation of emulsion isoflurane (NFEI). Arterial and venous blood samples were obtained for geometric mean test/reference ratios of Cmax, AUC0-t, and AUC0-∞, as well as their 90% confidence interval (CI90) as the primary outcome. The secondary outcomes were safety measurements such as vital signs, 12-lead electrocardiography, adverse effects, and laboratory tests; and anesthesia efficacy was assessed by Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score, bispectral index (BIS), and loss/recovery of eyelash reflex. Results: 24 subjects were eligible, of which 21 completed the whole experiment (NFEI n = 21, PFEI n = 23). Arterial geometric mean test/reference ratios of Cmax, AUC0-t, and AUC0-∞ were 104.50% (CI90 92.81%-117.65%), 108.23% (94.51%-123.96%), and 106.53% (93.94%∼120.80%), respectively. The most commonly seen adverse effects for NFEI and PFEI were injection pain (38.1% vs. 34.8%), hypotension (19.0% vs. 13.0%), apnea (14.3% vs. 17.4%), and upper airway obstruction (14.3% vs. 13.0%). No severe adverse effect was observed. The effectiveness of general anesthesia was similar between the two formulations. Conclusion: The CI90 of Cmax, AUC0-t, AUC0-∞, NFEI, and PFEI were within the range of 80%-125%, suggesting bioequivalence between NFEI and PFEI. The safety and anesthesia effectiveness were also similar.

10.
Med Chem ; 15(5): 459-471, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30569869

RESUMO

Hyperbaric Oxygenation Therapy (HBOT) is used as an adjunctive method for multiple diseases. The method meets the routine treating and is non-invasive, as well as provides 100% pure oxygen (O2), which is at above-normal atmospheric pressure in a specialized chamber. It is well known that in the condition of O2 deficiency, it will induce a series of adverse events. In order to prevent the injury induced by anoxia, the capability of offering pressurized O2 by HBOT seems involuntary and significant. In recent years, HBOT displays particular therapeutic efficacy in some degree, and it is thought to be beneficial to the conditions of angiogenesis, tissue ischemia and hypoxia, nerve system disease, diabetic complications, malignancies, Carbon monoxide (CO) poisoning and chronic radiation-induced injury. Single and combination HBOT are both applied in previous studies, and the manuscript is to review the current applications and possible mechanisms of HBOT. The applicability and validity of HBOT for clinical treatment remain controversial, even though it is regarded as an adjunct to conventional medical treatment with many other clinical benefits. There also exists a negative side effect of accepting pressurized O2, such as oxidative stress injury, DNA damage, cellular metabolic, activating of coagulation, endothelial dysfunction, acute neurotoxicity and pulmonary toxicity. Then it is imperative to comprehensively consider the advantages and disadvantages of HBOT in order to obtain a satisfying therapeutic outcome.


Assuntos
Oxigenoterapia Hiperbárica , Animais , Doenças Cardiovasculares/terapia , Humanos , Hipóxia/terapia , Isquemia/terapia , Neovascularização Fisiológica/fisiologia , Doenças do Sistema Nervoso/terapia
11.
Oncotarget ; 9(9): 8241-8252, 2018 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-29492191

RESUMO

Impaired angiogenesis contributes to delayed wound healing in aging. Hyaluronan (HA) has a close relationship with angiogenesis and wound healing. However, HA content decreases with age. In this study, we used high molecular weight HA (HMW-HA) (1650 kDa), and investigated its effects on wound healing in old rats by local injection. We found that HMW-HA significantly increases proliferation, migration and tube formation in endothelial cells, and protects endothelial cells against apoptosis. Local injection of HMW-HA promotes wound healing by increasing angiogenesis in old rats. HMW-HA increases the phosphorylation of Src, ERK and AKT, leading to increased angiogenesis, suggesting that local injection of HMW-HA promotes wound healing in elderly patients.

12.
Neurochem Res ; 43(3): 531-539, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29313212

RESUMO

In this study, we examined whether hyperbaric oxygen (HBO2) plays a detoxification role in withdrawal symptoms in a morphine-dependent rat model. The model was established through injections of morphine at increasing doses for 7 days. Withdrawal symptoms were induced by naloxone injection on the 8th day. The detoxification effect of HBO2 was evaluated using the withdrawal symptom scores, biochemical indices and neurotransmitters. Compared with the model group, HBO2 therapy significantly attenuated the withdrawal symptom scores, body weight loss and the level of norepinephrine level, whereas it increased the dopamine level and tyrosine hydroxylase expression in the nucleus accumbens. Moreover, HBO2 therapy substantially alleviated the NO, NOS, cAMP, and cGMP levels. Our findings indicate that HBO2 can effectively alleviate withdrawal symptoms induced by morphine dependence, and these effects may be attributed to the modulation of monoaminergic neurotransmitters and the suppression of the NO-cGMP signaling pathway.


Assuntos
Oxigenoterapia Hiperbárica , Morfina/farmacologia , Neurotransmissores/metabolismo , Óxido Nítrico/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Animais , Masculino , Dependência de Morfina/metabolismo , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Núcleo Accumbens/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Síndrome de Abstinência a Substâncias/tratamento farmacológico
13.
Life Sci ; 183: 50-59, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28666765

RESUMO

AIMS: Our experiments were designed to study the effect of diltiazem (DIL) combined with superoxide dismutase (SOD) on myocardial ischemia-reperfusion (MIRI) injury in a rat model. MAIN METHODS: Fifty rats were randomly separated into sham, ischemia-reperfusion (IR), DIL (5mg/kg), SOD (10,000U/kg) and combinatorial therapy (DIL plus SOD) groups. MIRI was induced by ligating the left anterior descending coronary artery for 30min and then reperfusing for 60min. The cardioprotective effects of combinatorial therapy were evaluated using hemodynamics, biochemical indices, histopathology and apoptotic-related proteins and gene expression. KEY FINDINGS: Compared with the IR group, combinatorial therapy significantly improved cardiac function and decreased arrhythmia, myocardial infarction area and release of myocardial enzyme. In addition, combinatorial therapy protected the myocardial cell structure as well as markedly alleviated oxidative stress, resulting in upregulation of Bcl-2 and adenine nucleotide transporter-1 expression as well as downregulation of Bax, caspase-3 and cleaved caspase-3 expression. SIGNIFICANCE: Our results indicated that DIL combined with SOD can provide protection against MIRI in rats, and these effects may be attributed to a reduction in oxygen stress damage, attenuation of calcium overload, and inhibition of cell apoptosis.


Assuntos
Cardiotônicos/farmacologia , Diltiazem/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/farmacologia , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Cardiotônicos/administração & dosagem , Diltiazem/administração & dosagem , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/administração & dosagem
14.
Curr Top Med Chem ; 17(21): 2440-2455, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28474551

RESUMO

Addiction is a chronic, relapsing disease of the brain that includes drug-induced compulsive seeking behavior and consumption of drugs. Dopamine (DA) is considered to be critical in drug addiction due to reward mechanisms in the midbrain. In this article, we review the major animal models in addictive drug experiments in vivo and in vitro. We discuss the relevance of the structure and pharmacological function of DA receptors. To improve the understanding of the role of DA receptors in reward pathways, specific brain regions, including the Ventral tegmental area, Nucleus accumbens, Prefrontal cortex, and Habenula, are highlighted. These factors contribute to the development of novel therapeutic targets that act at DA receptors. In addiction, the development of neuroimaging method will increase our understanding of the mechanisms underlying drug addiction.


Assuntos
Comportamento Aditivo , Encéfalo/metabolismo , Dopamina/metabolismo , Receptores Dopaminérgicos/metabolismo , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Animais , Agonistas de Dopamina/química , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/química , Antagonistas de Dopamina/farmacologia , Recompensa
15.
Med Chem ; 13(6): 569-576, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28494727

RESUMO

BACKGROUND: Toll-like receptor-2 (TLR2) and Toll-like receptor-4 (TLR4) have been reported to play a crucial role in tuberculosis, however, little is known about their expression in tuberculous pleuritis. OBJECTIVE: The goal of this work is to explore the expressions of TLR2 and TLR4 in tuberculous pleuritis and their predominant expressions on cells. METHODS: Levels of soluble TLR2 and TLR4 by enzyme linked immunosorbent assay (ELISA) in 58 patients with tuberculous pleural effusion (PE) and 43 patients with malignant PE were determined. The related genes were analyzed by RT-PCR and the membrane expressions of TLR2 and TLR4 on CD3+, CD14+, and CD19+ monocytes were assessed by using flow cytometry in 20 of 58 patients with tuberculous pleuritis. RESULTS: Our results showed that the levels of ADA, IL-27 and IFN-γ in tuberculous PE were obviously higher than in malignant PE. Moreover, the concentrations of soluble TLR2 and soluble TLR4 in PE were significantly higher than those in peripheral blood of the same patients, as well as the levels of soluble TLR2 in tuberculous PE were significantly higher than those in malignant effusions. Furthermore, the levels of TLR2, TLR4 and IFN-γ mRNA expression were marked increased in the tuberculous PE when compared with the correspondent serum. Importantly, we found that the predominant expressions of TLR2 in monocyte were on CD19 B cells, and the predominant expressions of TLR4 were on CD14 monocytes/macrophages. CONCLUSION: Our findings provided the evidence of a role for TLRs expression in tuberculous PE.


Assuntos
Regulação da Expressão Gênica , Derrame Pleural/complicações , Derrame Pleural/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Tuberculose Pulmonar/complicações , Adulto , Feminino , Humanos , Interferon gama/genética , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Derrame Pleural/genética , Derrame Pleural/imunologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor 2 Toll-Like/sangue , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/sangue , Receptor 4 Toll-Like/genética
16.
Mol Pharm ; 14(5): 1742-1753, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28358987

RESUMO

Although liver fibrosis is a major public health issue, there is still no effective drug therapy in the clinic. Fibroblast growth factor-inducible 14 (Fn14), a membrane receptor highly specifically expressed in activated hepatic stellate cells (HSCs), is the key driver of liver fibrosis, and thus, it has a great potential as a novel target for the development of effective treatment. Here, we identified a d-enantiomeric peptide ligand of Fn14 through mirror-image mRNA display. This included the chemical synthesis of a d-enantiomer of the target protein (extracellular domain of Fn14), identification of an l-peptide ligand of d-Fn14 using a constructed mRNA peptide library, and identification of a d-enantiomer of the l-peptide, which is a ligand of the natural Fn14 for reasons of symmetry. The obtained d-peptide ligand showed strong binding to Fn14 while maintaining high proteolytic resistance. As a targeting moiety, this d-peptide successfully mediated high selectivity of activated HSCs for liposomal vehicles compared to that of other major cell types in the liver and significantly enhanced the accumulation of liposomes in the liver fibrosis region of a carbon tetrachloride-induced mouse model. Moreover, in combination with curcumin as an encapsulated load, a liposomal formulation conjugated with this d-peptide showed powerful inhibition of the proliferation of activated HSCs and reduced the liver fibrosis to a significant extent in vivo. This Fn14-targeting strategy may represent a promising approach to targeted drug delivery for liver fibrosis treatment. Meanwhile, the mirror-image mRNA display can provide a new arsenal for the development of d-peptide-based therapeutics against a variety of human diseases.


Assuntos
Curcumina/uso terapêutico , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , Peptídeos/uso terapêutico , RNA Mensageiro/genética , Receptor de TWEAK/metabolismo , Animais , Tetracloreto de Carbono/toxicidade , Linhagem Celular , Curcumina/química , Endocitose/efeitos dos fármacos , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , Lipossomos/química , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Peptídeos/química , Receptor de TWEAK/agonistas
17.
Neurochem Res ; 42(4): 1240-1253, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28078611

RESUMO

Our previous study demonstrated that hyperbaric oxygen (HBO) improved cognitive impairments mainly by regulating oxidative stress, inflammatory responses and aging-related gene expression. However, a method for preventing cognitive dysfunction has yet to be developed. In the present study, we explored the protective effects of HBO on the cholinergic system and apoptosis in D-galactose (D-gal)-treated mice. A model of aging was established via systemic intraperitoneal injection of D-gal daily for 8 weeks. HBO was administered during the last 2 weeks of D-gal injection. Our results showed that HBO in D-gal-treated mice significantly improved behavioral performance on the open field test and passive avoidance task. Studies on the potential mechanisms of this effect showed that HBO significantly reduced oxidative stress and blocked the nuclear factor-κB pathway. Moreover, HBO significantly increased the levels of choline acetyltransferase and acetylcholine and decreased the activity of acetylcholinesterase in the hippocampus. Furthermore, HBO markedly increased expression of the anti-apoptosis protein Bcl-2 and glial fibrillary acidic protein meanwhile decreased expression of the pro-apoptosis proteins Bax and caspase-3. Importantly, there was a significant reduction in expression of Aß-related genes, such as amyloid precursor protein, ß-site amyloid cleaving enzyme-1 and cathepsin B mRNA. These decreases were accompanied by significant increases in expression of neprilysin and insulin-degrading enzyme mRNA. Moreover, compared with the Vitamin E group, HBO combined with Vitamin E exhibited significant difference in part of the above mention parameters. These findings suggest that HBO may act as a neuroprotective agent in preventing cognitive impairments.


Assuntos
Apoptose/fisiologia , Neurônios Colinérgicos/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/prevenção & controle , Galactose/toxicidade , Oxigenoterapia Hiperbárica/métodos , Animais , Apoptose/efeitos dos fármacos , Neurônios Colinérgicos/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Distribuição Aleatória , Vitamina A/farmacologia , Vitamina A/uso terapêutico
18.
Sleep Breath ; 18(2): 375-82, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24072550

RESUMO

BACKGROUND: The prevalence, profiles, and potential risk factors of snoring and obstructive sleep apnea-hypopnea syndrome (OSAHS) in China are largely unknown. OBJECTIVES: This study aims to investigate the prevalence, profiles, and potential risk factors for snoring and OSAHS in Guangxi, China, and the association between OSAHS and ethnicity. METHODS: Urban and rural population-based cluster samples were randomly selected in each of eight counties/cities. All residents aged 14 years or older in the selected clusters were interviewed using a standardized questionnaire. A subject was considered to have clinically diagnosed OSAHS if snoring was loud and habitual, breathing pauses were observed, and the subject experienced excessive daytime sleepiness. RESULTS: Among 12,742 sampled subjects, 10,819 completed the questionnaire (response rate = 84.9%). The overall OSAHS prevalence was 4.1% (men, 5.7% (5.1-6.3%); women, 2.4% (2.0-2.9%); Zhuang people, 3.2% (2.8-3.7%); Han people 6.0% (5.2-6.8%).The overall rate of habitual snoring was 11.5 % (men, 17.1% (16.1-18.1%); women, 5.6% (5.0-6.2%)). Univariate analysis showed that the OSAHS prevalence was significantly higher among the following groups: urban residents, elderly individuals, smokers, drinkers, those with higher body mass indexes (BMI), those with more years of schooling, those with nasal problems, those whose parents are Han, and those who usually sleep in prone position. However, multiple logistic regression analysis revealed that only urban residency, age, smoking status, drinking status, and BMI were the risk factors for OSAHS. CONCLUSIONS: OSAHS is prevalent in individuals aged 14 years or older in Guangxi, China. Han and Zhuang people differ significantly in their obstructive sleep apnea (OSA) prevalence, but this difference is explained by the combination of classic OSA risk factors.


Assuntos
Povo Asiático/estatística & dados numéricos , Apneia Obstrutiva do Sono/etnologia , Apneia Obstrutiva do Sono/epidemiologia , Adolescente , Adulto , Idoso , Índice de Massa Corporal , China , Comparação Transcultural , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Apneia Obstrutiva do Sono/diagnóstico , Adulto Jovem
19.
Chin Med J (Engl) ; 121(17): 1656-61, 2008 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-19024094

RESUMO

BACKGROUND: Triggering receptors expressed on myeloid cells (TREM) proteins are a family of cell surface receptors expressed broadly by cells of the myeloid lineage. The aim of this study was to investigate the clinical significance of soluble TREM-1 (sTREM-1) in pleural effusions, and to determine the effects of pneumonia on pleural sTREM-1 concentrations. METHODS: Pleural fluid was collected from 109 patients who presented to the respiratory institute (35 with malignant pleural effusion, 31 with tuberculous pleural effusion, 21 with bacterial pleural effusion, and 22 with transudate). The concentrations of sTREM-1, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were determined in effusion and serum samples by enzyme linked immunosorbent assay (ELISA). RESULTS: The concentrations of sTREM-1 in bacterial pleural effusion were significantly higher than those in malignant, tuberculous, and transudative groups (all P < 0.001). An sTREM-1 cutoff value of 768.1 ng/L had a sensitivity of 86% and a specificity of 93%. Pleural sTREM-1 levels were positively correlated with levels of TNF-alpha and IL-1beta. Patients with complicating bacterial pneumonia did not have elevated concentration of sTREM-1 in pleural effusion when compared with patients without pneumonia. CONCLUSIONS: Determination of pleural sTREM-1 may improve the ability of clinicians to differentiate pleural effusion patients of bacterial origin from those with other etiologies. The occurrence of bacterial pneumonia did not affect pleural sTREM-1 concentrations.


Assuntos
Glicoproteínas de Membrana/análise , Derrame Pleural/metabolismo , Receptores Imunológicos/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Humanos , Interleucina-1beta/análise , Pessoa de Meia-Idade , Derrame Pleural/diagnóstico , Pneumonia/metabolismo , Estudos Prospectivos , Receptor Gatilho 1 Expresso em Células Mieloides , Fator de Necrose Tumoral alfa/análise
20.
Chin Med J (Engl) ; 121(7): 581-6, 2008 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-18466675

RESUMO

BACKGROUND: Active suppression by CD4+CD25+ regulatory T lymphocytes plays an important role in the down-regulation of T cell responses to foreign and self-antigens. This study was conducted to analyze whether the CD4+CD25+ regulatory T cells exist and function normally in tuberculous pleural effusion. METHODS: The percentages of CD4+CD25+ T cells in pleural effusion and peripheral blood from patients with tuberculous pleurisy and peripheral blood from healthy control subjects were determined by flow cytometry. The expression of forkhead transcription factor Foxp3 was also examined. CD4+CD25+ and CD4+CD25(-) T cells from pleural effusion and blood were isolated, and were cultured to observe the effects of CD4+CD25+ T cells on proliferation response of CD4+CD25(-) T cells in vitro. RESULTS: There were increased numbers of CD4+CD25+ T cells in tuberculous pleural effusion compared with peripheral blood from both patients with tuberculous pleurisy and normal subjects, and these cells demonstrated a constitutive high-level expression of Foxp3. Moreover, CD4+CD25+ T cells mediated potent inhibition of proliferation response of CD4+CD25(-) T cells. CONCLUSION: The increased CD4+CD25+ T cells in tuberculous pleural effusion express a high level of Foxp3 transcription factor, while potently suppressing the proliferation of CD4+CD25(-) T cells.


Assuntos
Derrame Pleural/imunologia , Linfócitos T Reguladores/fisiologia , Tuberculose Pleural/imunologia , Adulto , Feminino , Fatores de Transcrição Forkhead/análise , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Derrame Pleural/etiologia , Tuberculose Pleural/etiologia
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