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This study investigated the effects of ultrasound-assisted soybean lecithin (SL) on the rehydration behavior and physical properties of egg white protein powder (EWPP) and its ability to enhance the efficacy of EWPP instant solubility. The results of rehydration, including wettability and dispersibility, indicated that ultrasound (200 W)-assisted SL (5 g/L) addition had the shortest wetting time and dispersion time, which were 307.14 ± 7.00 s and 20.95 ± 2.27 s, respectively. In terms of powder properties, the EWPP with added SL had lower lightness, moisture content and bulk density. In addition, the increase in average particle size, net negative charge, free sulfhydryl group content and surface hydrophobicity indicated that ultrasound treatment facilitated the protein structures unfolding and promoted the formation of SL-EWP complexes. Overall, our study provided a new perspective for the food industry regarding using ultrasound technology to produce instant EWPP with higher biological activity and more complete nutritional value.
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Metal/carbon nanotubes (CNTs) have been attractive hybrid systems due to their high specific surface area and exceptional catalytic activity, but their challenging synthesis and dispersion impede their extensive applications. Herein, we report a facile and green approach towards the fabrication of metal/CNT composites, which utilizes a versatile glycopeptide (GP) both as a stabilizer for CNTs in water and as a reducing agent for noble metal ions. The abundant hydrogen bonds in GP endow the formed GP-CNTs with excellent plasticity, enabling the availability of polymorphic CNT species from dispersion to viscous paste, gel, and even to dough by increasing their concentration. The GP molecules can reduce metal precursors at room temperature without additional reducing agents, enabling the in situ immobilization of metal nanoparticles (e.g. Au, Ag, Pt, and Pd) on the CNT surface. The combination of the excellent catalytic properties of Pd particles with photothermal conversion capability of CNTs makes the Pd/CNT composite a promising catalyst for the fast degradation of organic pollutants, as demonstrated by a model catalytic reaction using 4-nitrophenol (4-NP). The conversion of 4-NP using the Pd/CNT composite as the catalyst has increased by 1.6-fold under near infrared light illumination, benefiting from the strong light-to-heat conversion effect of CNTs. Our proposed strategy opens a new avenue for the synthesis of CNT composites as a sustainable and versatile catalyst platform.
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Sugars played an important role in the processing of products such as cakes, however, their high-calorie character often posed a health risk to consumers. Therefore, this paper aimed to better investigate the effect of sugar substitutes on the improvement of egg white foaming properties and angle cake digestibility characteristics. It was demonstrated that the addition of erythritol improved the surface properties of egg whites, thus enhancing their foaming properties. Particularly, when the erythritol substitution was 50 %, the sugar-egg white complex structure unfolded and had the best foaming capacity. On this basis, the baking performance of angel cakes with sucrose replaced by erythritol was analyzed. When the erythritol substitution was lower than 50 %, the specific volume and the baking loss rate of the cakes were basically unchanged, and the texture and sensory taste of the cakes were all excellent. Finally, the gastrointestinal digestive kinetic analysis suggested that erythritol substitution for sucrose was beneficial for reducing blood glucose levels in vivo. Furthermore, for the MgCl2-based samples, both the degree of protein destruction after digestion was weakened and the glucose-lowering effect was better exerted. Overall, this study provided a new theoretical basis for the low-calorie sugar-substituted health food products development in the future.
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Eritritol , Sacarosa , Cinética , Edulcorantes/análisis , Azúcares , DigestiónRESUMEN
This study aims to investigate the mechanism of magnesium ions regulated ovalbumin-lysozyme (OVA-LYS) heteroprotein aggregation behavior via aggregation kinetics model, exploring the relationship between differential aggregation behavior and protein molecular structure, intermolecular interactions and thermal stability. Results showed that the aggregation rate (kapp) and maximum absorbance (Amax) of the OVA-LYS heteroprotein complex were located between OVA and LYS. Meanwhile, the thermal denaturation temperature (Td) and denaturation enthalpy (ΔH) were between the values of OVA and LYS as well. Compared with OVA, the thermal stability of the OVA-LYS heteroprotein complex increased owing to the electrostatic interactions between OVA and LYS, resulting in slower aggregation rate and lower aggregation degree. Molecular dynamics simulations revealed the molecular conformational changes during OVA-LYS binary protein binding and the stability of the complex conformation. Moreover, MgCl2 weakened the OVA-LYS interactions through Debye shielding while increasing thermal stability, allowing the two proteins to aggregate into amorphous precipitates rather than spherical coacervates. Overall, this study provides information to further understand the regulation mechanism of proteins differential aggregation behavior by ions.
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Magnesio , Muramidasa , Ovalbúmina/química , Muramidasa/química , Termodinámica , IonesRESUMEN
Lithium-sulfur batteries with high energy density still confront many challenges, such as polysulfide dissolution, the large volume change of sulfur, and fast capacity fading in long-term cycling. Herein, a naturally abundant clay material, halloysite, is introduced as a sulfur host material in the cathode of Li-S batteries. Nickel oxide nanoparticles are embedded into the halloysite nanotubes (NiO@Halloysite) by hydrothermal and calcination treatment to improve the affinity of halloysite nanotubes to polysulfides. The NiO@Halloysite composite loaded with sulfur (S/NiO@Halloysite) is employed as the cathode of Li-S batteries, which combines the physical confinements of tubular halloysite particles and good chemical adsorption ability of NiO. The S/NiO@Halloysite electrode exhibits a high discharge capacity of 1205.47 mAh g-1 at 0.1 C. In addition, it demonstrates enhanced cycling stability, retaining ≈60% of initial capacity after 450 cycles at 0.5 C. The synthesized NiO@Halloysite can provide a promising prospect and valuable insight into applying natural clay materials in Li-S batteries.
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Dam-induced hydrological alterations and eco-environmental impacts have significant implications, however, these concern issues in large floodplain systems are less well understood. The present study shows a first attempt to adopt a quasi-three-dimensional groundwater flow modeling FEFLOW (Finite Element subsurface FLOW system) to investigate the influences of a proposed hydraulic dam on groundwater dynamics in the largest floodplain lake of the Yangtze River basin (Poyang Lake, China). The FEFLOW model was successfully constructed and has the ability to represent the hydrodynamics of floodplain groundwater flow. Model simulations indicate that, in general, the dam is likely to increase the groundwater levels across the floodplain during different hydrological phases. The responses of floodplain groundwater levels to the dam during the dry and recession phases are stronger (â¼2-3 m) than the rising and flooding phases (<2 m). Under the natural condition, the floodplain groundwater may recharge the lake during the dry and recession phases, and discharge the lake during the rising and flooding phases. However, the dam regulation may alter the natural recharge-discharge patterns, forming a generally gaining condition of the floodplain groundwater. The proposed dam is most likely to reduce the groundwater flow velocity (â¼<1 m/d) relative to the natural condition (up to 2 m/d) during different hydrological phases, and it may also alter the floodplain groundwater flow direction during the dry and recession phases. Additionally, the floodplain groundwater system is mainly characterized by losing state (-4.5 × 106 m3/yr) under the natural condition, while the dam-induced groundwater system exhibits an overall gaining state (9.8 × 106 m3/yr). The current research findings contribute to future water resources assessment and management by providing a foundation for assessing associated eco-environmental changes of the large lake-floodplain system.
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Agua Subterránea , Lagos , Ríos , China , HidrologíaRESUMEN
BACKGROUND: Group B Streptococcus (GBS), also referred as Streptococcus agalactiae, is one of the leading causes of life-threatening invasive diseases such as bacteremia, meningitis, pneumonia and urinary tract infection in pregnant women and neonates. Rates of GBS colonization vary by regions, but large-sample studies on maternal GBS status are limited in southern China. As a result, the prevalence of GBS among pregnant women and its associated risk factors and the efficacy of intrapartum antibiotic prophylaxis (IAP) intervention in preventing adverse pregnancy and neonatal outcomes remain poorly understood in southern China. METHODS: To fill this gap, we retrospectively analyzed demographic and obstetrical data of pregnant women who have undergone GBS screening and delivered between 2016 and 2018 in Xiamen, China. A total of 43,822 pregnant women were enrolled and only a few GBS-positive women did not receive IAP administration. Possible risk factors for GBS colonization were assayed by univariate and multivariate logistic regression analysis. Generalized linear regression model was applicated to analyze whether IAP is one of the impact factors of the hospital length of stay of the target women. RESULTS: The overall GBS colonization rate was 13.47% (5902/43,822). Although women > 35 years old (P = 0.0363) and women with diabetes mellitus (DM, P = 0.001) had a higher prevalence of GBS colonization, the interaction between ages and GBS colonization was not statistically significant in Logistic Regression analysis (adjusted OR = 1.0014; 95% CI, 0.9950, 1.0077). The rate of multiple births was significantly dropped in GBS-positive group than that of GBS-negative group (P = 0.0145), with no significant difference in the rate of fetal reduction (P = 0.3304). Additionally, the modes of delivery and the incidences of abortion, premature delivery, premature rupture of membranes, abnormal amniotic fluid and puerperal infection were not significantly different between the two groups. The hospitalization stays of the subjects were not influenced by GBS infection. As for neonatal outcomes, the cases of fetal death in maternal GBS-positive group did not statistically differ from that in maternal GBS-negative group. CONCLUSION: Our data identified that pregnant women with DM are at high risk of GBS infection and IAP is highly effective in prevention of adverse pregnancy and neonatal outcomes. This stressed the necessity of universal screening of maternal GBS status and IAP administration to the target population in China, and women with DM should be considered as priorities.
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Complicaciones Infecciosas del Embarazo , Nacimiento Prematuro , Infecciones Estreptocócicas , Recién Nacido , Embarazo , Femenino , Humanos , Adulto , Profilaxis Antibiótica , Estudios Retrospectivos , Streptococcus agalactiae , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Antibacterianos/uso terapéutico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/prevención & control , Factores de Riesgo , Embarazo Múltiple , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/diagnóstico , Nacimiento Prematuro/tratamiento farmacológicoRESUMEN
Solar-driven water purification is considered as an effective and sustainable technology for water treatment using green solar energy. One major goal for practical applications is to improve the solar evaporation performance by the design of novel photothermal materials, with optimized heat localization and water transport pathways to achieve reduced energy consumption for water vaporization. Recently, some emerging materials like polymers, metal-organic frameworks (MOFs), covalent organic frameworks (COFs) and also single molecules were employed to construct novel solar evaporation systems. In this minireview, we present an overview of the recent efforts on materials development for water purification systems. The state-of-the-art applications of these emerging materials for solar-driven water treatment, including desalination, wastewater purification, sterilization and energy production, are also summarized.
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BACKGROUND: Post-stroke spasticity (PSS) is a major cause of disability, leading to severely impaired upper-limb flexibility and ability to walk and move, significantly affecting the quality of life of cerebral infarction patients. There is currently no recognized effective therapy. Alternatively, Chinese traditional medicine has shown promise for PSS treatment. In this regard, the BSLSF has been reported to be effective; however, its underlying mechanism remains unclear. OBJECTIVE: The objective of this study is to clarify the main targets and pathways of Baishao Luoshi Formula (BSLSF) during PSS treatment, laying the foundation for further research on its pharmacological effects. METHODS: In this study, network pharmacology and experimental verification were conducted to explore the potential mechanism of BSLSF systematically. After obtaining active ingredients of BSLSF from the TCMSP database, SwissTarget-Prediction and PharMapper were used to uncover BSLSF targets. PSS-related targets were gathered with GeneCards and Online Mendelian Inheritance in Man. The differentially expressed genes between BSLSF and PSS were identified by a Venn plot. The drugactive ingredient-target interaction network and Protein-protein interaction (PPI) were constructed using Cytoscape and further analyzed using the MCC algorithm of CytoHubba plugin. Then, Pathway enrichment and GO biological process enrichment analyses were performed. Subsequently, a mice model of middle cerebral artery occlusion (MCAO) was established for the in vivo experiments. RESULTS: We found that AKT1, TNF, CASP3, VEGFA, and CREB1 were potential targets during PSS treatment. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that the mechanism of PSS was closely related to synaptic plasticity. And the immunohistochemical staining showed that BSLSF protected against ischemic stroke via the CCR5/CREB signaling pathway and probably affected synaptic plasticity. CONCLUSION: our study validated that treatment with BSLSF protected against ischemic stroke via the CCR5/CREB signaling pathway and could affect synaptic plasticity. In a sense, this study provides the basis for further extensive and in-depth analysis of BSLSF, enabling the quest for new drug targets at the same time.
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Accidente Cerebrovascular Isquémico , Farmacología en Red , Animales , Ratones , Calidad de Vida , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Algoritmos , Bases de Datos Factuales , Simulación del Acoplamiento MolecularRESUMEN
Based on the study's thorough logging records from 74 wells, grain size analysis, spatial analysis of sand thickness and sand ratio, and pertinent regional geological data, a sedimentary microfacies analysis of the Bayanchagan area is conducted using one sand layer as a unit. In addition, the reservoir's microscopic characteristics are summarized, and the location of advantageous reservoir areas is predicted. The principal reservoir rock types in the research region are determined to be lithic arkose and feldspathic lithic sandstone, and reservoir physical attributes are also quite poor. Intergranular dissolution pores make up the bulk of reservoir space types, which also include primary pores, secondary dissolution pores, and micro-fractures. Additionally, the delta front and delta plain subfacies are recognized. Eight more sedimentary microfacies are found: sheet sand, estuary bar, underwater distributary channel, underwater distributary bay, overflow thin sand, floodplain, and distributary channel under water. In a sedimentary environment with water penetration, the entire reservoir was produced. The delta diversion plain deposit makes up the lower portion of the FIII, FII, and FI oil layer groups, while the delta front deposit makes up the top portion of the FI oil layer group. The reservoirs may be divided into three groups: type I reservoirs, type II reservoirs, and type III reservoirs by thorough examination of the facies, microstructure, mercury intrusion characteristics, and other criteria. Among these, type I and type II reservoirs with substantial thicknesses, which are favorable for hydrocarbon accumulation, are the main focus of favorable oil and gas area exploration. The investigation's conclusions are instructive for future research.
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Geología , Arena , Facies , Humanos , Agua , Pozos de AguaRESUMEN
The cell membrane fluidity was very important in adipogenesis and galloyl groups on polyphenolic structures could enhance their antiadipogenic activity. However, the effect of polyphenols on membrane fluidity and the role of galloyl groups in fluidity changes remain unclear. Therefore, the present study chose structurally different polyphenols to compare their effects on the membrane morphology and fluidity of 3T3-L1 preadipocytes, and then the reasons behind the changes of membrane fluidity induced by galloylated polyphenols were explored from structural and molecular insights using liposome model and molecular dynamic simulation technology. Our results indicated that galloylated polyphenols could significantly change 3T3-L1 cell membrane morphology and decrease membrane fluidity, while non-galloylated ones could not. The membrane interference effect of polyphenols was enhanced as the number of galloyl groups increased. Morever, the decrease in membrane fluidity induced by galloylated polyphenols was due to the disturbance of polyphenols on lipid alkyl chains in the cell membrane. Galloylated polyphenols could not only locate in the polar head, but also insert into hydrophobic center of lipid bilayer to interfere with the lipid alkyl chains arrangement, thus decreasing the membrane fluidity and showing strong affinity for the membrane. In addition, differences in position of galloyl groups in polyphenols induced distinct effect on cell membranes interactions, thus affecting the binding manner and bioactivity. The results expanded the understanding on the strong antiadipogenic activity of galloylated polyphenols through the aspect of their effects on cell membrane by both experimental and theoretically simulated ways.
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Fluidez de la Membrana , Polifenoles , Células 3T3-L1 , Animales , Membrana Celular , Membrana Dobles de Lípidos/química , Ratones , Polifenoles/química , Polifenoles/farmacologíaRESUMEN
Solar-driven water generation is a sustainable water treatment technology, helping to relieve global water scarcity issues. However, this technology faces great challenges due to the high energy consumption of water evaporation yielding low evaporation rates. Here, a covalent organic framework (COF)/graphene dual-region hydrogel, containing hydrophilic and hydrophobic regions in one material, is developed through a facile in situ growth strategy. The hydrophilic COF is covering parts of the hydrophobic graphene regions. Through accurate control of both wetting regions, the hybrid hydrogel shows effective light-harvesting, tunable wettability, optimized water content, and lowered energy demand for water vaporization. Acting as solar absorber, the dual-region hydrogel exhibits a steam generation rate as high as 3.69 kg m-2 h-1 under 1 sun irradiation (1 kW m-2), which competes well with other state-of-the-art materials. Furthermore, this hydrogel evaporator can be used to produce drinkable water from seawater and sewage, demonstrating the potential for water treatment.
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Interferon stimulated gene 15 (ISG15) is one of the most robustly upregulated interferon stimulated genes (ISGs) and also a ubiquitin-like modifier which has been reported to play an important role in host defense against pathogens. Cytosolic nucleic acids detected by DNA sensors induce type â interferons (IFN-â s) and ISGs in host cells. Streptococcus pneumoniae (S. pn) autolysin LytA triggers bacterial lysis and then S. pn-derived genomic DNA (hereafter referred to as S. pn-DNA) can be released and accumulates in the cytoplasm of host cells. However, it remains elusive whether LytA-mediated S. pn-DNA release is involved in ISG15 induction. Here we verified that ISG15 conjugation system can be widely activated by S. pn and cytosolic S. pn-DNA in host cells. Moreover, the phagocytosis of macrophages to the mutant strain S. pn D39 ΔlytA was enhanced when compared to S. pn D39, which in turn increased S. pn-DNA uptake into macrophages and augmented ISG15 expression. ISG15 might upregulate proinflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) in macrophages and further promoted the clearance of S. pn in the absence of LytA. These results indicate that S. pn autolysis blunts ISG15 induction through preventing bacteria internalization and reducing cytosolic S. pn-DNA accumulation in macrophages, revealing a new strategy of S. pn for avoiding elimination. This study will help us to further understand the role of ISG15 during S. pn infection as well as the regulatory mechanisms of immune responses mediated by bacterial autolysis and bacterial DNA.
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Proteínas Bacterianas/metabolismo , Citocinas/metabolismo , Citoplasma/microbiología , ADN Bacteriano/metabolismo , Macrófagos/metabolismo , Macrófagos/microbiología , N-Acetil Muramoil-L-Alanina Amidasa/metabolismo , Streptococcus pneumoniae/metabolismo , Animales , Citosol/metabolismo , Interacciones Huésped-Patógeno , Interferón beta/farmacología , Ratones , Modelos Biológicos , Mutación/genética , Fagocitosis , Células RAW 264.7 , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinas/metabolismoRESUMEN
OBJECTIVE: K+-Cl- cotransporter-2 (KCC2), which primarily extrudes chloride in mature neurons, triggers hemiplegia limb spasticity after ischemic stroke by affecting neuronal excitability. Our previous study revealed that the Chinese herb Baishaoluoshi Decoction decreases hemiplegia limb spasticity in poststroke spasticity (PSS) patients. This study aimed at elucidating on the effects of Baishaoluoshi Decoction on the BDNF/TrKB-KCC2 pathway in PSS rat models. METHODS: Middle cerebral artery occlusion (MCAO) was adopted for the establishment of PSS rat models. Muscle tension was evaluated by Modified Ashworth Scale. Nissl staining and transmission electron microscopy were used to measure the protective effects of Baishaoluoshi Decoction on ischemic injury-induced neuronal damage due to MCAO. Expression levels of BDNF, TrKB, and KCC2 in brain tissues around the infarct and brainstem were detected by immunohistochemical staining. RESULTS: It was found that Baishaoluoshi Decoction suppressed hemiplegia limb spasticity and alleviated the damage in neurons and synapses in PSS rat models. Importantly, the expression of BDNF, TrKB, and KCC2 in brain tissues around the infarct and brainstem were significantly upregulated after treatment with low-dose and high-dose Baishaoluoshi Decoction. CONCLUSION: Suppression of spasticity by Baishaoluoshi Decoction in PSS rat models may be correlated with upregulated BDNF/TrKB-KCC2 pathway, which may be a complementary therapeutic strategy for PSS.
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Encéfalo/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Accidente Cerebrovascular Isquémico/complicaciones , Espasticidad Muscular/etiología , Animales , Encéfalo/patología , Factor Neurotrófico Derivado del Encéfalo/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Receptor trkB/efectos de los fármacos , Receptor trkB/metabolismo , Transducción de Señal/efectos de los fármacos , Simportadores/efectos de los fármacos , Simportadores/metabolismo , Cotransportadores de K ClRESUMEN
Lung cancer is the primary cause of cancer-related deaths, and the persistent inflammation is inextricably linked with the lung cancer tumorigenesis. Pro-inflammatory cytokine interleukin-33 (IL-33) is able to serve as a potent modulator of cancer. Mounting evidence indicates IL-33 has significant effect on lung cancer progression by regulating host immune response, but the current opinions about the function and mechanism of IL-33 in lung cancer are still controversial. Meanwhile, antibacterial peptide LL-37 also exerts a momentous effect on immune responses to lung cancer. LL-37 is regarded as versatile, including antimicrobial activities, chemotaxis and immunoregulation. However, the immunomodulatory mechanism of IL-33 and LL-37 in lung cancer remains thoroughly not defined. Here, we determined the secretion of LL-37 was up-regulated in lung cancer serum samples. Similarly, the expression of CRAMP was enhancive in macrophages after co-cultured with lung cancer cells. Moreover, we expounded that IL-33 could up-regulate LL-37 secretion in macrophages, resulting in the massive releases of IL-6 and IL-1ß. Additionally, LL-37 cooperated with IL-33 to increase the phosphorylation of p38 MAPK and NF-κB p65 pathways, and augmented IL-6 and IL-1ß secretion, which resulting in the proliferation of lung cancer cells in vitro. In conclusion, our study identified that IL-33 aggravated the inflammation of lung cancer by increasing LL-37 expression in macrophages, thereby promoting lung cancer cell proliferation in vitro. It is contributed to our present understanding of the immunomodulatory relationship between pro-inflammatory cytokines and antibacterial peptides in the tumor immune response, and offer a novel perspective for controlling the progress of lung cancer.
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Péptidos Catiónicos Antimicrobianos/biosíntesis , Citocinas/biosíntesis , Mediadores de Inflamación/metabolismo , Interleucina-33/metabolismo , Neoplasias Pulmonares/metabolismo , Macrófagos/metabolismo , Biomarcadores , Línea Celular Tumoral , Humanos , Inmunomodulación , Neoplasias Pulmonares/inmunología , Macrófagos/inmunología , Transducción de Señal , CatelicidinasRESUMEN
BACKGROUND: Age-related macular degeneration (AMD) is a devastating eye disease causing irreversible vision loss in the elderly. Retinal pigment epithelium (RPE), the primary cell type that is afflicted in AMD, undergoes programmed cell death in the late stages of the disease. However, the exact mechanisms for RPE degeneration in AMD are still unresolved. The prevailing theories consider that each cell death pathway works independently and without regulation of each other. Building upon our previous work in which we induced a short burst of inflammasome activity in vivo, we now investigate the effects of prolonged inflammasome activity on RPE cell death mechanisms in rats. METHODS: Long-Evans rats received three intravitreal injections of amyloid beta (Aß), once every 4 days, and were sacrificed at day 14. The vitreous samples were collected to assess the levels of secreted cytokines. The inflammasome activity was evaluated by both immunohistochemistry and western blot. The types of RPE cell death mechanisms were determined using specific cell death markers and morphological characterizations. RESULTS: We found robust inflammasome activation evident by enhanced caspase-1 immunoreactivity, augmented NF-κB nuclear translocalization, increased IL-1ß vitreal secretion, and IL-18 protein levels. Moreover, we observed elevated proteolytic cleavage of caspase-3 and gasdermin D, markers for apoptosis and pyroptosis, respectively, in RPE-choroid tissues. There was also a significant reduction in the anti-apoptotic factor, X-linked inhibitor of apoptosis protein, consistent with the overall changes of RPE cells. Morphological analysis showed phenotypic characteristics of pyroptosis including RPE cell swelling. CONCLUSIONS: Our data suggest that two cell death pathways, pyroptosis and apoptosis, were activated in RPE cells after exposure to prolonged inflammasome activation, induced by a drusen component, Aß. The involvement of two distinct cell death pathways in RPE sheds light on the potential interplay between these pathways and provides insights on the future development of therapeutic strategies for AMD.
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Apoptosis/fisiología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Epitelio Pigmentado de la Retina/citología , Epitelio Pigmentado de la Retina/metabolismo , Animales , Femenino , Piroptosis/fisiología , Ratas , Ratas Long-Evans , Roedores , Transducción de Señal/fisiología , Cuerpo Vítreo/citología , Cuerpo Vítreo/metabolismoRESUMEN
BACKGROUND: Recent work on Alzheimer's disease (AD) diagnosis focuses on neuroimaging modalities; however, these methods are expensive, invasive, and not available to all patients. Ocular imaging of biomarkers, such as drusen in the peripheral retina, could provide an alternative method to diagnose AD. OBJECTIVE: This study compares macular and peripheral drusen load in control and AD eyes. METHODS: Postmortem eye tissues were obtained from donors with a neuropathological diagnosis of AD. Retina from normal donors were processed and categorized into younger (<55 years) and older (>55 years) groups. After fixation and dissection, 3-6 mm punches of RPE/choroid were taken in macular and peripheral (temporal, superior, and inferior) retinal regions. Oil red O positive drusen were counted and grouped into two size categories: small (<63 µm) and intermediate (63-125 µm). RESULTS: There was a significant increase in the total number of macular and peripheral hard drusen in older, compared to younger, normal eyes (p<0.05). Intermediate hard drusen were more commonly found in the temporal region of AD eyes compared to older normal eyes, even after controlling for age (p<0.05). Among the brain and eye tissues from AD donors, there was a significant relationship between cerebral amyloid angiopathy (CAA) severity and number of temporal intermediate hard drusen (r=0.78, p<0.05). CONCLUSION: Imaging temporal drusen in the eye may have benefit for diagnosing and monitoring progression of AD. Our results on CAA severity and temporal intermediate drusen in the AD eye are novel. Future studies are needed to further understand the interactions among CAA and drusen formation.
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Enfermedad de Alzheimer/metabolismo , Retina/metabolismo , Drusas Retinianas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Biomarcadores/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Retina/química , Retina/patología , Drusas Retinianas/patologíaRESUMEN
RATIONALE: Age-related macular degeneration (AMD) is one of the leading causes of blindness among the elderly. Due to its complex etiology, current treatments have been insufficient. Previous studies reveal three systems closely involved in AMD pathogenesis: lipid metabolism, oxidation and inflammation. These systems are also involved in Alzheimer's disease, atherosclerosis and glomerulonephritis. Understanding commonalities of these four diseases may provide insight into AMD etiology. OBJECTIVES: To understand AMD pathogenesis by analogy and suggest ideas for future research, this study summarizes main commonalities in disease pathogenesis of AMD, Alzheimer's disease, atherosclerosis and glomerulonephritis. METHODS: Articles were identified through PubMed, Ovid Medline and Google Scholar. We summarized the common findings and synthesized critical differences. RESULTS: Oxidation, lipid deposition, complement activation, and macrophage recruitment are involved in all four diseases shown by genetic, molecular, animal and human studies. Shared genetic variations further strengthen their connection. Potential areas for future research are suggested throughout the review. CONCLUSIONS: The four diseases share many steps of an overall framework of pathogenesis. Various oxidative sources cause oxidative stress. Oxidized lipids and related molecules accumulate and lead to complement activation, macrophage recruitment and pathology. Investigations that arise under this structure may aid us to better understand AMD pathology.
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Enfermedad de Alzheimer/patología , Aterosclerosis/patología , Glomerulonefritis/patología , Metabolismo de los Lípidos/inmunología , Degeneración Macular/patología , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/inmunología , Enfermedad de Alzheimer/metabolismo , Animales , Apolipoproteínas/genética , Apolipoproteínas/inmunología , Aterosclerosis/genética , Aterosclerosis/inmunología , Aterosclerosis/metabolismo , Colesterol/metabolismo , Activación de Complemento , Proteínas del Sistema Complemento/genética , Proteínas del Sistema Complemento/inmunología , Expresión Génica , Variación Genética , Glomerulonefritis/genética , Glomerulonefritis/inmunología , Glomerulonefritis/metabolismo , Humanos , Inflamación , Metabolismo de los Lípidos/genética , Macrófagos/inmunología , Macrófagos/patología , Degeneración Macular/genética , Degeneración Macular/inmunología , Degeneración Macular/metabolismo , Estrés OxidativoRESUMEN
Lung cancer is one of the leading causes of cancer-related mortality, and responds badly to existing treatment. Thus, it is of urgent need to identify novel diagnostic markers and therapeutic targets. Increasing evidences have indicated that long non-coding RNAs (lncRNAs) play an important role in initiation and progression of lung cancer. However, the role of lncRNA Taurine upregulated 1 (TUG1) in lung adenocarcinoma (LAD) progression is not well known. In this study, we determined the diagnostic value of TUG1 in LAD patients, and further uncovered the underlying functional mechanism. Our results showed that TUG1 was significantly upregulated in LAD cells and serum samples. Receiver operator characteristic (ROC) analysis suggested a relatively higher area under the curve (AUC) of TUG1 (0.756) contrast to cyfra21-1 (0.619). In addition, high TUG1 level was associated with enhanced tumor size, degree of differentiation, lymph node metastases, distant metastasis and TNM stage. Cell functional assays showed that knockdown of TUG1 suppressed LAD cell viability and promoted cell apoptosis. We then sought to reveal the underlying regulatory mechanism, and the pro-apoptotic protein BAX was then identified as the downstream target of TUG1. Gain and loss functional assays showed that inhibition of BAX reversed the induced apoptosis by TUG1 knockdown. Finally, RNA immunoprecipitation and Chromatin immunoprecipitation revealed that TUG1 suppressed BAX expression through physically interacting with EZH2. In conclusion, lncRNA TUG1 is a promising diagnostic marker for LAD patients and suppression of TUG1 levels could be a future direction to promote the prognosis of LAD patients.