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Surface plasmon polaritons and phonon polaritons offer a means of surpassing the diffraction limit of conventional optics and facilitate efficient energy storage, local field enhancement and highsensitivity sensing, benefiting from their subwavelength confinement of light. Unfortunately, losses severely limit the propagation decay length, thus restricting the practical use of polaritons. While optimizing the fabrication technique can help circumvent the scattering loss of imperfect structures, the intrinsic absorption channel leading to heat production cannot be eliminated. Here, we utilize synthetic optical excitation of complex frequency with virtual gain, synthesized by combining the measurements made at multiple real frequencies, to compensate losses in the propagations of phonon polaritons with dramatically enhanced propagation distance. The concept of synthetic complex frequency excitation represents a viable solution to the loss problem for various applications including photonic circuits, waveguiding and plasmonic/phononic structured illumination microscopy.
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MicroRNAs (miRNAs) are small non-coding RNAs that can actively participate in post-transcriptional regulation of genes. A number of studies have shown that miRNAs can serve as important regulators of cancer cell growth, differentiation, and apoptosis. They can also act as markers for the diagnosis and prognosis of certain cancers. To explore the potential prognosis-related miRNAs in liver cancer patients, to provide theoretical basis for early diagnosis and prognosis of liver cancer, as well as to provide a new direction for the targeted therapy of liver cancer. The miRNA expression profiles of liver cancer patients in the the Cancer Genome Atlas database were comprehensively analyzed and various prognostic-related miRNAs of liver cancer were screened out. The data was further subjected to survival analysis, prognostic analysis, gene ontology and kyoto encyclopedia of genes and genomes enrichment analysis, microenvironment analysis, and drug sensitivity analysis by R Language version 4.2.0. Finally, the screened miRNAs were further validated by different experiments. Thus, miNRAs involved in liver cancer diagnosis and prognosis were identified. MiRNA-3680-3p was found to be significantly different in 10 different cancers, including liver cancer, and was significantly associated with the microenvironment, survival, and prognosis of liver cancer patients. In addition, drug sensitivity analysis revealed that miRNA-3680-3p can provide a useful reference for drug selection in targeted therapy for liver cancer. MiRNA-3680-3p can serve as a biomarker for the diagnosis and prognosis of liver cancer patients and down-regulation of miRNA-3680-3p could significantly inhibit both the proliferation and migration of liver cancer cells.
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Biomarcadores Tumorais , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , MicroRNAs , Humanos , MicroRNAs/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Prognóstico , Proliferação de Células/genética , Progressão da Doença , Microambiente Tumoral/genética , Perfilação da Expressão Gênica , Apoptose/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Linhagem Celular TumoralRESUMO
OBJECTIVE: Intracranial infection is a common complication after neurosurgery and can increase the length of hospital stay, affect patient prognosis, and increase mortality. We aimed to investigate the value of the combined detection of cerebrospinal fluid (CSF) heparin-binding protein (HBP), interleukin-6 (IL-6), interleukin-10 (IL-10), and procalcitonin (PCT) for post-neurosurgical intracranial infection. METHODS: This study assessed the diagnostic values of CSF HBP, IL-6, IL-10, PCT levels, and combined assays for post-neurosurgical intracranial infection with the area under the receiver operating characteristic (ROC) curve by retrospectively analysing biomarkers of post-neurosurgical patients. RESULTS: The CSF HBP, IL-6, IL-10, and PCT levels were significantly higher in the infected group than the uninfected group and the control group (P < 0.001). The indicators in the groups with severe intracranial infections were significantly higher than those in the groups with mild intracranial infections (P < 0.001), and the groups with poor prognoses had significantly higher indexes than the groups with good prognoses. According to the ROC curve display, the AUC values of CSF HBP, IL-6, IL-10, and PCT were 0.977 (95 % CI 0.952-1.000), 0.973 (95 % CI 0.949-0.998), 0.884 (95 % CI 0.823-0.946), and 0.819 (95 % CI 0.733-0.904), respectively. The AUC of the combined test was 0.996 (95 % CI 0.989-1.000), which was higher than those of the four indicators alone. CONCLUSION: The combined detection can be an important indicator for the diagnosis and disease monitoring of post-neurosurgical intracranial infection.
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Biomarcadores , Interleucina-10 , Interleucina-6 , Pró-Calcitonina , Humanos , Pró-Calcitonina/líquido cefalorraquidiano , Pró-Calcitonina/sangue , Interleucina-10/líquido cefalorraquidiano , Masculino , Feminino , Interleucina-6/líquido cefalorraquidiano , Interleucina-6/sangue , Pessoa de Meia-Idade , Prognóstico , Biomarcadores/líquido cefalorraquidiano , Biomarcadores/sangue , Adulto , Idoso , Procedimentos Neurocirúrgicos/efeitos adversos , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/líquido cefalorraquidiano , Estudos Retrospectivos , Curva ROC , Proteínas de Transporte/líquido cefalorraquidiano , Proteínas do Líquido Cefalorraquidiano/análise , Peptídeos Catiônicos AntimicrobianosRESUMO
BACKGROUND: This study aimed to compare the diagnostic accuracy of four indicators, including waist-to-height ratio (WHTR), vascular adiposity index (VAI), TG/HDL-C, and BMI/HDL-C for metabolic syndrome (MS) in Chinese adults aged 40 years and above. Additionally, the study aimed to develop an efficient diagnostic model displayed by a nomogram based on individual's BMI and circulating HDL-C level. METHODS: A cross-sectional study was conducted on 699 participants aged 40 years and above. Quartiles of BMI/HDL-C, TG/HDL-C, VAI, and WHTR were used as independent variables, and metabolic syndrome was used as the dependent variable. Logistic regression was conducted to explore the impact of each parameter on the risk of MS. The areas under the receiver operating characteristics were compared to determine the accuracy of the indicators in diagnosing MS in the participants. Logistic regression was run to construct the nomograms, and the performance of the nomogram was assessed by a calibration curve. RESULTS: MS subjects had higher levels of BMI, BFM, PBF, VFA, AMC, WC, SCR, TG, and insulin, but lower LDH and HDL-C levels than the subjects without MS. The BMI/HDL-C ratio was positively correlated with the prevalence of MS and its components. The final diagnostic model included five variables: gender, BFM, WC, TG, and BMI/HDL-C. The model showed good calibration and discrimination power with an AUC of 0.780. The cut-off value for the nomogram was 0.623 for diagnosing MS. CONCLUSIONS: BMI/HDL-C ratio was an independent risk factor for MS in Chinese adults. BMI/HDL-C was significantly correlated with MS and its components. BMI/HDL-C was the most powerful diagnostic indicator compared to other indicators, including TG/HDL-C, VAI and WHTR for diagnosing MS. The nomogram drawn based on the diagnostic model provided a practical tool for diagnosing MS in Chinese adults.
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Índice de Massa Corporal , HDL-Colesterol , Diagnóstico Precoce , Síndrome Metabólica , Humanos , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , HDL-Colesterol/sangue , China/epidemiologia , Fatores de Risco , Idoso , Nomogramas , Biomarcadores/sangue , População do Leste AsiáticoRESUMO
This study investigated the stability of milk fat globule membrane (MFGM) protein under simulated gastrointestinal conditions using an in vitro enzymatic digestion method. The optimal hydrolysis conditions were determined by monitoring the changes in particle size and zeta-potential of MFGM protein hydrolysates over time. Furthermore, the distribution of small molecular weight peptides with antioxidant activity was explored through DEAE-52 combined with in vitro cell experiments. Two novel antioxidant peptides (TGIIT and IITQ) were identified based on molecular docking technology and evaluated their potential scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS+) radicals. TGIIT and IITQ also demonstrated remarkable abilities in promoting mitochondrial biogenesis and activating Keap1/Nrf2 signaling pathway, which can effectively counteract skeletal muscle dysfunction induced by oxidative stress. Thus, MFGM-derived antioxidant peptides have the potential to be employed in food to regulate muscle protein metabolism and alleviate sarcopenia.
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Antioxidantes , Glicolipídeos , Glicoproteínas , Gotículas Lipídicas , Fator 2 Relacionado a NF-E2 , Proteína 1 Associada a ECH Semelhante a Kelch , Antioxidantes/farmacologia , Simulação de Acoplamento Molecular , Peptídeos/farmacologia , DigestãoRESUMO
Atherosclerosis (AS) is the main cause of cardiovascular diseases. However, the role of AQP9 in AS is not well understood. In the present study, we predicted that miR-330-3p might regulate AQP9 in AS through bioinformatics analysis, and we established AS model using ApoE-/- mouse (C57BL/6) with high-fat diet (HFD). Hematoxylin and eosin (H&E) and Oil red O staining were used to determine atherosclerotic lesions. CCK8 and Ethyny1-2-deoxyuridine (EdU) assays were used to investigate human umbilical vein endothelial cells (HUVECs) proliferation after treatment with 100 µg/mL ox-LDL. Wound scratch healing and transwell assays were used to measure the cell invasion and migration ability. Flow cytometry assay was used to determine apoptosis and cell cycle. A dual-luciferase reporter assay was performed to investigate the binding of miR-330-3p and AQP9. We identified that the expression of miR-330-3p in AS mice model decreased while the expression level of AQP9 increased. miR-330-3p overexpression or down-regulation of AQP9 could reduce cell apoptosis, promote cell proliferation, and migration after ox-LDL treatment. Dual-luciferase reporter assay result presented that AQP9 was directly inhibited by miR-330-3p. These results suggest that miR-330-3p inhibits AS by regulating AQP9. miR-330-3p/AQP9 axis may be a new therapeutic target for AS.
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Aquaporinas , Aterosclerose , MicroRNAs , Humanos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Células Endoteliais , Apoptose/genética , Aterosclerose/genética , MicroRNAs/genéticaRESUMO
AIMS: The study was designed to explore the role of apolipoprotein E (ApoE) deficiency concomitant with dietary docosahexaenoic acid (DHA) treatment on brain ß-amyloid (Aß) and lipid levels. METHOD: A 5-month dietary DHA intervention was conducted in ApoE-deficient (ApoE-/- ) mice and wild-type C57BL/6J (C57 wt) mice. The Morris water maze test was performed to assess the behaviour of the animals. The cortical contents of soluble Aß1-40 and Aß1-42 were detected by enzyme-linked immunosorbent assay (ELISA). Cortical fatty acid levels were detected by gas chromatography. Gene and protein expression of molecules associated with cerebral Aß and lipid metabolism were measured using real-time polymerase chain reaction (PCR), Western blot and histological methods. RESULTS: DHA treatment increased the content of cortical DHA and n-3 polyunsaturated fatty acids (n-3 PUFAs) but decreased the ratio of n-6/n-3 PUFAs in ApoE-/- mice; whereas the content of cortical DHA and n-3 PUFAs in C57 wt mice remained unchanged after DHA treatment. Cerebral Fabp5 and Cd36 gene expression were significantly downregulated in DHA-fed C57 wt mice; cerebral Cd36 and Scarb1 gene expression were significantly upregulated, whereas Fabp5 gene expression was downregulated in DHA-fed ApoE-/- mice. In comparison with C57 wt mice, the content of cortical soluble Aß1-42 , total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) increased, whereas the level of high-density lipoprotein cholesterol (HDL-C) decreased in ApoE-/- mice. Interestingly, these differences were significantly reversed by DHA dietary treatment. CONCLUSION: DHA intervention has discrepant impacts on cerebral lipids, fatty acid transporter expression and soluble Aß levels in ApoE-/- and C57 wt mice, suggesting the modifying role of ApoE status on the responses of cerebral lipids and Aß metabolism to DHA treatment.
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Ácidos Docosa-Hexaenoicos , Ácidos Graxos , Camundongos , Animais , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos/metabolismo , Camundongos Endogâmicos C57BL , Apolipoproteínas E/genética , ColesterolRESUMO
Sargassum fusiforme polysaccharide (SFP) is a kind of biologically active macromolecule with biological functions. In this study, oxidative stress and high-fat HepG2â cell models were established to investigate its lipid-lowering activity and mechanism of action. It was found that SFP and its two isolated fractions had antioxidant effects on the cells. It was also found the polysaccharides decreased the content of total cholesterol and total triglyceride in the high-fat cells. RT-qPCR assays revealed that the three polysaccharides down-regulated the mRNA expression level of ACC, PPARγ, and SREBP-2. It could be concluded that the hypolipidemic effect of SFPs is achieved via multiple pathways, including the regulation on the expression level of lipid metabolism-related key enzymes and factors, and binding with bile acids. The hypolipidemic effect of SFPs could be partially due to their antioxidant activity. SFPs developed in the present work have potential as ingredients of functional foods with hypolipidemic effect.
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Sargassum , Humanos , Sargassum/química , Células Hep G2 , Polissacarídeos/farmacologia , Polissacarídeos/químicaRESUMO
Waste electrical and electronic equipment (WEEE) which contains various valuable and harmful materials is an inevitable waste in modern society. In order to resolve the pollution problems associated with WEEE treatment, a WEEE management system has been established in China. The main role of importers and manufacturers of electrical and electronic equipment (EEE) is to pay the treatment fees to facilitate the WEEE recycling in China. The announced treatment and subsidy fee is given by set, not by the weight of WEEE. There is no lesser green treatment fee for the producers which can produce environmentally friendly EEE in China. Also, the recovery of refrigerants from the foaming agent of refrigerators is not required in China. In total, 45 million sets of recycled WEEE were certified in 2020, a year that contains the most updated data. Among them, 48%, 14%, 20%, 10% and 8% are for TV, refrigerator, washing machine, computer and air conditioners, respectively. The spatial analysis indicates that the WEEE recycling activities are mainly concentrated on the mid-east and east regions of China. It also can be concluded that the certified amount of each province has higher positive correlation with provincial population than provincial GDP per capita and green recovery rate. It also clearly notes that the amount of recycled air conditioner is the lowest for each province. Thus, more effort should be conducted to increase the recycling of scrapped air conditioner in China.
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Low shear stress and pyroptosis both play an important role in the onset and development of atherosclerosis (AS). MicroRNAs (miRNAs) are a kind of short (18-22) nucleotide sequences that can bind to the 3'-untranslated region (3'-UTR) of messenger RNA, thereby regulating programmed cell death including pyroptosis. However, the function of miRNAs in cells subjected to shear stress conditions is unknown. Therefore, we conducted the current study to demonstrate the effect of low shear stress on pyroptosis and the underlying mechanism. Human umbilical vein endothelial cells (HUVECs) stimulated by undisturbed shear stress (5 dynes/cm2 ) were the experimental group while HUVECs without shear stress treatment were the control group in our experiments. We observed that shear stress can suppress mechanosensitive miR-181b-5p expression, accompanying the elevated expression of NLRP3 inflammasome-dependent pyroptosis. Introduction of miR-181b-5p could alleviate NLRP3 inflammasome-dependent pyroptosis. Luciferase assay showed specific binding of miR-181b-5p to the 3'-UTR of signal transduction and transcriptional activation factor 3 (STAT-3) gene. Inhibition of STAT-3 gene expression at the posttranscriptional level results in the alleviation of NLRP3 inflammasome-dependent pyroptosis. Besides, the silencing of STAT-3 reduced anti-miR-181b-5p-mediated HUVEC pyroptosis via regulating NLRP3 inflammasome activation. Given the role of mechanosensitive miR-181b-5p and STAT-3 in the shear stress-induced pyroptosis, regulation of their expression levels may be a promising strategy to control AS.
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Células Endoteliais da Veia Umbilical Humana/fisiologia , MicroRNAs/genética , Piroptose/genética , Piroptose/fisiologia , Fator de Transcrição STAT3/genética , Regiões 3' não Traduzidas/genética , Apoptose/genética , Células Cultivadas , Humanos , Inflamassomos/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Interferência de RNA/fisiologia , RNA Mensageiro/genética , Transdução de Sinais/genéticaRESUMO
Gracilaria lemaneiformis polysaccharide (GLP) exhibits good physiological activities, and it is more beneficial as it is degraded. After its degradation by hydrogen peroxide combined with vitamin C (H2O2-Vc) and optimized by Box-Behnken Design (BBD), a new product of GLP-HV will be generated. While using GLP as control, two products of GLP-H (H2O2-treated) and GLP-V (Vc-treated) were also produced. These products chemical characteristics (total sugar content, molecular weight, monosaccharide composition, UV spectrum, morphological structure, and hypolipidemic activity in vitro) were assessed. The results showed that the optimal conditions for H2O2-Vc degradation were as follows: H2O2-Vc concentration was 18.7 mM, reaction time was 0.5 h, and reaction temperature was 56 °C. The total sugar content of GLP and its degradation products (GLP-HV, GLP-H and GLP-V) were more than 97%, and their monosaccharides are mainly glucose and galactose. The SEM analysis demonstrated that H2O2-Vc made the structure loose and broken. Moreover, GLP, GLP-HV, GLP-H, and GLP-V had significantly inhibition effect on α-glucosidase, and their IC50 value were 3.957, 0.265, 1.651, and 1.923 mg/mL, respectively. GLP-HV had the best inhibition effect on α-glucosidase in a dose-dependent manner, which was the mixed type of competitive and non-competitive. It had a certain quenching effect on fluorescence of α-glucosidase, which may be dynamic quenching.
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Gracilaria , Hipolipemiantes/farmacologia , Polissacarídeos/farmacologia , alfa-Glucosidases/efeitos dos fármacos , Animais , Organismos Aquáticos , Hipolipemiantes/química , Concentração Inibidora 50 , Polissacarídeos/químicaRESUMO
The objective of the present study was to investigate the xanthine oxidase (XO) inhibitory effects of peptides purified and identified from round scad (Decapterus maruadsi) hydrolysates (RSHs). In this study, RSHs were obtained by using three proteases (neutrase, protamex and alcalase). Among them, the RSHs of 6-h hydrolysis by neutrase displayed the strongest XO inhibitory activity and had an abundance of small peptides (<500 Da). Four novel peptides were purified by immobilized metal affinity chromatography and identified by nano-high-performance liquid chromatography mass/mass spectrometry. Their amino acid sequences were KGFP (447.53 Da), FPSV (448.51 Da), FPFP (506.59 Da) and WPDGR (629.66 Da), respectively. Then the peptides were synthesized to evaluate their XO inhibitory activity. The results indicated that the peptides of both FPSV (5 mM) and FPFP (5 mM) exhibited higher XO inhibitory activity (22.61 ± 1.81% and 20.09 ± 2.41% respectively). Fluorescence spectra assay demonstrated that the fluorescence quenching mechanism of XO by these inhibitors (FPSV and FPFP) was a static quenching procedure. The study of inhibition kinetics suggested that the inhibition of both FPSV and FPFP was reversible, and the type of their inhibition was a mixed one. Molecular docking revealed the importance of π-π stacking between Phe residue (contained in peptides) and Phe914 (contained in the XO) in the XO inhibitory activity of the peptides.
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Inibidores Enzimáticos/química , Proteínas de Peixes/química , Peixes , Hidrolisados de Proteína/química , Xantina Oxidase/antagonistas & inibidores , Animais , Organismos Aquáticos , Cromatografia Líquida de Alta Pressão , Simulação de Acoplamento MolecularRESUMO
BACKGROUND: This is a case of lateral recess stenosis secondary occurred the discal fungus infection treated with percutaneous transforaminal endoscopic discectomy (PTED). There has been no relevant reports before. CASE PRESENTATION: A 49-year-old patient who had taken itraconazole for 13 months for lateral recess stenosis secondary occurred the discal fungus infection complained of gradually worsening radiating pain and numbness in the back and inguinal and inner thigh region of right side. In order to relieve the radiating neuralgia and reduce the damage to spinal stability, the minimally invasive PTED was performed.The patient's prognosis was assessed using Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS). During the follow-up, the patient's ODI and VAS scores were decreased significantly. The radiating pain in the inguinal and inner thigh region of right side were significantly alleviated and the discomfort caused by lower back instability was improved by plaster vest. DISCUSSION AND CONCLUSION: PTED not only avoids further damage to the stability of the lumbar spine, but also effectively relieves the symptoms of leg neuroradialgia caused by lateral recess stenosis secondary occurred the discal fungus infection.
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Aspergillus flavus , Discotomia Percutânea/métodos , Disco Intervertebral/cirurgia , Neuroaspergilose/cirurgia , Neuroendoscopia/métodos , Estenose Espinal/cirurgia , Aspergillus flavus/isolamento & purificação , Humanos , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/microbiologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/microbiologia , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Neuroaspergilose/diagnóstico por imagem , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/microbiologia , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Spinal cord injury (SCI) is a common and devastating disease, which results in systemic inflammatory response syndrome and secondary lung injury. Mitochondrial dysfunction and inflammation are closely related to lung injury in diverse disease models. No studies have demonstrated the effects of mitochondrial targeted peptide SS-31 in a mouse model of SCI-induced lung injury. METHODS: Immediately after injury, mice in the treatment groups received a daily, single-dose intraperitoneal injection of SS-31 and for the next 2 days. The sham and SCI groups also received a daily single dose of vehicle (DMSO and 0.9% NaCl, 1: 3). The lung tissue of mice was examined after SCI, and tissue damage, apoptosis, inflammation, and mitochondrial dysfunction were recorded. RESULTS: SS-31 treatment attenuated lung edema and tissue damage. Furthermore, SS-31 treatment reduced apoptosis of alveolar type II cells, the number of total macrophages and M1 macrophages, and neutrophil infiltration. Moreover, SS-31 treatment attenuated reactive oxygen species levels, reversed mitochondrial dysfunction and inhibited NLRP3 inflammasome activation. CONCLUSIONS: Collectively, our results demonstrate that SS-31 attenuates mitochondrial dysfunction, controls inflammatory responses, and alleviates the severity of lung damage in a mouse model of SCI-induced lung injury.
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Inflamação/prevenção & controle , Lesão Pulmonar/prevenção & controle , Oligopeptídeos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Traumatismos da Medula Espinal/complicações , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Interleucina-1beta/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/etiologia , Macrófagos/citologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Oligopeptídeos/farmacologia , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Spinal cord injury (SCI) is a devastating disease, which results in tissue loss and neurologic dysfunction. NLRP3 inflammasome plays an important role in the mechanism of diverse diseases. However, no studies have demonstrated the role of NLRP3 inflammasome and the effects of NLRP3 inflammasome inhibitors in a mouse model of SCI. We investigated whether inhibition of NLRP3 inflammasome activation by the pharmacologic inhibitor BAY 11-7082 or A438079 could exert neuroprotective effects in a mouse model of SCI. METHODS: SCI was performed using an aneurysm clip with a closing force of 30 g at the level of the T6-T7 vertebra for 1 min. Motor recovery was evaluated by an open-field test. Neuronal death was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling and Nissl staining. Mitochondrial dysfunction was determined by quantitative real-time polymerase chain reaction (qPCR), western blot, and detection of mitochondrial membrane potential level. Microglia/macrophage activation and astrocytic response were evaluated by immunofluorescence labeling. RESULTS: Inhibition of NLRP3 inflammasome activation by pharmacologic inhibitor BAY 11-7082 or A438079 reduced neuronal death, attenuated spinal cord anatomic damage, and promoted motor recovery. Furthermore, BAY 11-7082 or A438079 directly attenuated the levels of NLRP3 inflammasome and proinflammatory cytokines. Moreover, BAY 11-7082 or A438079 alleviated microglia/macrophage activation, neutrophils infiltration, and reactive gliosis, as well as mitochondrial dysfunction. CONCLUSIONS: Collectively, our results demonstrate that pharmacologic suppression of NLRP3 inflammasome activation controls neuroinflammation, attenuates mitochondrial dysfunction, alleviates the severity of spinal cord damage, and improves neurological recovery after SCI. These data strongly indicate that the NLRP3 inflammasome is a vital contributor to the secondary damage of SCI in mice.
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Sistemas de Liberação de Medicamentos , Inflamassomos/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Nitrilas/administração & dosagem , Piridinas/administração & dosagem , Traumatismos da Medula Espinal/prevenção & controle , Sulfonas/administração & dosagem , Tetrazóis/administração & dosagem , Animais , Sistemas de Liberação de Medicamentos/métodos , Feminino , Inflamassomos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologiaRESUMO
Mutant alleles of EXT1 or EXT2, two members of the EXT gene family, are causative agents in hereditary multiple exostoses, and their gene products function together as a polymerase in the biosynthesis of heparan sulfate. EXTL2, one of three EXT-like genes in the human genome that are homologous to EXT1 and EXT2, encodes a transferase that adds not only GlcNAc but also N-acetylgalactosamine to the glycosaminoglycan (GAG)-protein linkage region via an α1,4-linkage. However, both the role of EXTL2 in the biosynthesis of GAGs and the biological significance of EXTL2 remain unclear. Here we show that EXTL2 transfers a GlcNAc residue to the tetrasaccharide linkage region that is phosphorylated by a xylose kinase 1 (FAM20B) and thereby terminates chain elongation. We isolated an oligosaccharide from the mouse liver, which was not detected in EXTL2 knock-out mice. Based on structural analysis by a combination of glycosidase digestion and 500-MHz (1)H NMR spectroscopy, the oligosaccharide was found to be GlcNAcα1-4GlcUAß1-3Galß1-3Galß1-4Xyl(2-O-phosphate), which was considered to be a biosynthetic intermediate of an immature GAG chain. Indeed, EXTL2 specifically transferred a GlcNAc residue to a phosphorylated linkage tetrasaccharide, GlcUAß1-3Galß1-3Galß1-4Xyl(2-O-phosphate). Remarkably, the phosphorylated linkage pentasaccharide generated by EXTL2 was not used as an acceptor for heparan sulfate or chondroitin sulfate polymerases. Moreover, production of GAGs was significantly higher in EXTL2 knock-out mice than in wild-type mice. These results indicate that EXTL2 functions to suppress GAG biosynthesis that is enhanced by a xylose kinase and that the EXTL2-dependent mechanism that regulates GAG biosynthesis might be a "quality control system" for proteoglycans.
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Regulação Enzimológica da Expressão Gênica , Glicosaminoglicanos/metabolismo , Proteínas de Membrana/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , Fosfotransferases/metabolismo , Xilose/química , Alelos , Animais , Clonagem Molecular , Fibroblastos/metabolismo , Genes Supressores de Tumor , Genômica , Glicosiltransferases/metabolismo , Células HeLa , Humanos , Fígado/metabolismo , Camundongos , Camundongos Knockout , Mutação , N-Acetilglucosaminiltransferases/genética , Proteoglicanas/metabolismo , RNA Mensageiro/metabolismoRESUMO
Aiming to provide a basis for the application of Gynura divaricata (L.) DC polysaccharide (GDP) in functional foods, the hypoglycemic effects of GDP, and action mechanisms, were investigated. Results showed that GDP effectively inhibited α-glucosidase and remarkably increased the glucose absorption, glycogen content, and pyruvate kinase and hexokinase activities of insulin-resistant HepG2 cells, indicating its potent in vitro hypoglycemic effect. In streptozotocin-induced type 2 diabetes mice, GDP significantly improved various glycolipid metabolism-related indices in serum and liver, e.g., fasting blood glucose, oral glucose tolerance, glycosylated serum protein content, serum insulin level, antioxidant enzyme activities, TG, TC, LDL-C, and HDL-C levels, and hepatic glycogen content, and recovered the structure of gut microbiota to the normal level. It was also found that GDP significantly affected the expression of related genes in the PI3K/Akt, AMPK, and GS/GSK-3ß signaling pathways. Therefore, GDP regulates blood glucose possibly by directly inhibiting α-glucosidase, exerting antioxidant activity, and regulating intestinal microbiota.
Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Hipoglicemiantes , Polissacarídeos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Polissacarídeos/farmacologia , Polissacarídeos/administração & dosagem , Polissacarídeos/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/administração & dosagem , Masculino , Humanos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Asteraceae/química , alfa-Glucosidases/metabolismo , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Células Hep G2 , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Insulina/metabolismo , Insulina/sangue , Fígado/metabolismo , Fígado/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismoRESUMO
Rational design and preparation of a multiphase electrocatalyst for hydrogen evolution reaction (HER) has become a hot research topic, while applicable and pH versatility of vanadium tetrasulfide (VS4) and heptairon octasulfide (Fe7S8) composites have rarely been reported. Here, the facile topological sulfide self-template sacrifice method using FeV bimetallic MOFs is designed to obtain Fe7S8 coupled with VS4 heterostructures, enhancing the electron precipitation in the catalysts and attracts electrons to migrate. According to DFT simulations, the electronic coupling at the atomic orbital level and the modulation of interfacial electrons among various interfaces play a crucial role in enhancing the intermediate state process of the hydrogen evolution reaction (HER) across the entire pH range, promoting the optimal d-band centroid value (εd). Reassuringly, the prepared 3D Fe7S8/VS4 electrodes possessed excellent performances of η10 = 53 mV, η10 = 135 mV and η10 = 38 mV in a conventional three-electrode configuration in a 1 M KOH, 1 M Na2SO4, and 0.5 M H2SO4, and the stabilized currents can all be maintained for 48 h. This innovative design of in situ heterostructured materials constructed from dual transition metal sulfides provides inspiring ideas for the preparation of all-pH catalysts.
RESUMO
Catechins compounds from tea have demonstrated significant inhibitory effects on xanthine oxidase (XOD). However, the precise inhibitory mechanisms of the main catechins on XOD remain to be fully elucidated. This study explored the inhibition mechanisms and binding characteristics of five catechins (GC, EGC, EC, EGCG, and ECG) on XOD through a combination of inhibition kinetics, multi-spectroscopy analysis, molecular docking, and dynamics simulations. Among the catechins, EGCG and ECG exhibited the most potent inhibitory activities against XOD. All five catechins were found to exhibit mixed inhibition, affecting the hydrophobic groups and secondary structure of XOD predominantly through hydrophobic interactions and hydrogen bonding. Molecular dynamics simulations revealed that a 3,4,5-trihydroxybenzoic acid moiety at C3 position significantly enhances the binding affinity of EGCG and ECG to XOD. Additionally, the decrease of ß-sheet and random coil induced by EGCG and ECG was found to be crucial for enhancing inhibitory activity of XOD. In vitro cell experiments showed that EGCG and ECG significantly reduced high uric acid levels of BRL-3A cell. This study elucidates the inhibitory mechanisms of catechins on XOD, paving the way for their application as XOD inhibitors to combat hyperuricemia.
RESUMO
The exploration of bifunctional electrocatalysts with high activity, stability, and economy is of great significance in promoting the development of water splitting. Herein, a dual active sites heterostructure NiCoS/NC was designed to be derived in situ on 3D N-doped porous carbon (NC) using gelatin as a nitrogen and carbon source. The characterization of experiments suggests that nanoflower-like Ni2CoS4 (abbreviated as NiCoS) was randomly distributed on the NC substrate, and the sheet-like NC formed a highly open porous network structure resembling a honeycomb, which provided more accessible active sites for electrolyte ions. In addition, the special nanostructures of the catalyst materials help to promote the surface reconstruction to the real active substance NiOOH/CoOOH, and the double active sites synergistically reduce the overpotential of OER and improve its kinetics. DFT (Density-functional theory) calculations reveal the electronic coupling of NiCoS/NC in atomic orbitals, modulation of electrons by the heterointerface and N-doping, and synergistic effect of dual active sites improving the inherent catalytic activity. The NiCoS/NC composite electrocatalyst exhibited a 177 mV small OER overpotential and a 132 mV small HER overpotential with Faraday efficiencies as high as 96 % and 98 % at 10 mA cm-2 current density. In the two-electrode system, it also requires only an ultra-low voltage of 1.52 V to achieve a 10 mA cm-2 current density, and it shows excellent long-term water splitting stability. This provides a new idea for the development of transition metal-based bifunctional electrocatalysts.